Dr. Lentine is a tenured Associate Professor of Medicine at Saint Louis University, with joint appointments to SLUCOR and Internal Medicine/Nephrology Division. A California native, Dr. Lentine earned her MD degree from Stanford University, and also completed an Internal Medicine residency, Nephrology fellowship, and master’s degree in Clinical Epidemiology at Stanford. Upon moving to St. Louis, Dr. Lentine received additional fellowship training focused in transplant epidemiology and outcomes at Washington University. She joined the faculty of Saint Louis University in October 2004. Dr. Lentine is a clinical scientist whose work is grounded in novel application and integration of national registry, administrative claims data, and other electronic health information sources to address topics in nephrology and transplant-related epidemiology, outcomes and policy. Among her publications, Dr. Lentine is the first author of a New England Journal of Medicine article describing racial variation in medical outcomes after living donation, and served as the first author and co-chair of a Scientific Statement from the American Heart Association on pretransplant cardiac disease evaluation and management in press at Circulation (2012).
Abstract: BACKGROUND.: Innovation in renal transplant management would benefit from identification of early markers that accurately predict long-term graft survival. METHODS.: Data from the United States Renal Data System for kidney transplant recipients (1995-2004) were analyzed to develop prediction models for all-cause graft survival based on estimated glomerular filtration rate (eGFR), the presence or absence of acute rejection within 1 year, and recipient and donor demographic characteristics. The prediction models were applied to participants in the Belatacept Evaluation of Nephroprotection and Efficacy as First-line Immunosuppression Trial and Belatacept Evaluation of Nephroprotection and Efficacy as First-line Immunosuppression Trial-EXTended criteria donors trials comparing belatacept with cyclosporine in standard criteria donor (SCD) and expanded criteria donor (ECD) graft recipients, respectively, as an external validation of the model predictions in a diverse population. RESULTS.: Compared with eGFR 60 mL/min/1.73 m, the relative hazard for all-cause graft loss increased in an accelerating pattern with lower GFR to approximately eight and seven times, respectively, among SCD and ECD recipients with eGFR less than 15 mL/min/1.73 m. When applied to the clinical trial samples, the predicted differences in all-cause graft survival of less intensive belatacept versus cyclosporine at the second transplant anniversary (SCD: 3.9%, 95% confidence interval [CI]: 3.6% to 4.2%; ECD: 4.1%, 95% CI: 3.5% to 4.7%) were similar to observed differences (SCD: 4.2%, 97.3% CI: -1.3% to 10.1%; ECD: 1.4%, 97.3% CI: -7.5% to 10.2%). CONCLUSIONS.: Accurate models of long-term graft survival can be developed using eGFR, donor, and recipient characteristics. Long-term survival prediction models may provide an efficient method for assessing the impact of novel pharmaceutical agents and clinical management protocols.
Abstract: We examined United States Renal Data System (USRDS) data for adult kidney transplant recipients in 1995-2003 (n = 87 575) to investigate associations of 12-month renal function with long-term clinical outcomes. Estimated glomerular filtration rate (eGFR) was computed by the Modification of Diet in Renal Disease (MDRD) equation. Associations of eGFR at the first transplant anniversary with graft and patient-survival in years 1-9 post-transplant were evaluated by multivariate nonlinear regression with spline forms, adjusted for recipient, donor, and transplant factors. Regardless of donor type, the likelihood of graft failure and death increased significantly with lower eGFR. The impact of poor eGFR was more pronounced for graft failure than death. Relative effects were similar across donor types, but were strongest among living-donor recipients. For example, compared with reference eGFR of 80 ml/min/1.73 m2, 1-year eGFR of 20 ml/min/1.73 m2 was associated with adjusted hazards ratios for subsequent death-censored graft failure of 9.2 in living, 8.9 in standard criteria deceased, and 5.9 in expanded criteria deceased-donor recipients. First-year renal function after kidney transplantation has strong, nonlinear associations with subsequent allograft and patient survival regardless of donor type. Post-transplant eGFR may be a useful end-point for discriminating benefits of care strategies that differentially affect renal function.
Abstract: BACKGROUND: Reduced kidney function confers a higher risk of acute kidney injury at the time of an inciting event, such as sepsis. Whether the same is true in those with reduced renal mass from living kidney donation is unknown.METHODS: We conducted a population-based matched cohort study of all living kidney donors in the province of Ontario, Canada who underwent donor nephrectomy from 1992 to 2009. We manually reviewed the medical records of these living kidney donors and linked this information to provincial health care databases. Non-donors were selected from the healthiest segment of the general population.RESULTS: There were 2027 donors and 20 270 matched non-donors. The median age was 43 years (interquartile range 34-50) and individuals were followed for a median of 6.6 years (maximum 17.7 years). The primary outcome was acute dialysis during any hospital stay. Reasons for hospitalization included infectious diseases, cardiovascular diseases and hematological malignancies. Only one donor received acute dialysis in follow-up (6.5 events per 100 000 person-years), a rate which was statistically no different than 14 non-donors (9.4 events per 100 000 person-years).CONCLUSIONS: These results are reassuring for the practice of living kidney donation. Longer follow-up of this and other donor cohorts will provide more precise estimates about this risk.
Abstract: BACKGROUND: Limited data exist on correlates of psychological outcomes after kidney donation. METHODS: We used a database integrating Organ Procurement and Transplantation Network registrations for 4650 living kidney donors from 1987 to 2007 with administrative data of a U.S. private health insurer (2000-2007 claims) to identify depression diagnoses among prior living donors. The burden and demographic correlates of depression after enrollment in the insurance plan were estimated by Cox regression. Graft failure and death of the donor's recipient were examined as time-varying exposures. RESULTS: After start of insurance benefits, the cumulative frequency of depression diagnosis was 4.2% at 1 year and 11.5% at 5 years, and depression among donors was less common than among age- and gender-matched general insurance beneficiaries (rate ratio, 0.70; 95% confidence intervals [CI], 0.60-0.81). Demographic and clinical correlates of increased likelihood of depression diagnoses among the prior donors included female gender, white race, and some perioperative complications. After adjustment for donor demographic factors, recipient death (adjusted hazard ratio (aHR), 2.23; 95% CI, 1.11-4.48) and death-censored graft failure (aHR, 3.30; 95% CI, 1.49-7.34) were associated with two to three times the relative risk of subsequent depression diagnosis among nonspousal unrelated donors. There were trends toward increased depression diagnoses after recipient death and graft failure among spousal donors but no evidence of associations of these recipient events with the likelihood of depression diagnosis among related donors. CONCLUSIONS: Recipient death and graft loss predict increased depression risk among unrelated living donors in this privately insured sample. Informed consent and postdonation care should consider the potential impact of recipient outcomes on the psychological health of the donor.
Abstract: Abstract Objectives: Quantifying relationships of post-transplant renal function with healthcare costs is relevant to economic evaluations of standard and emerging therapies. Methods: Clinical and billing records for Medicare-insured kidney transplant recipients (1995-2003) were drawn from the United States Renal Data System. Estimated glomerular filtration rate (eGFR) at one-year post-transplant was computed with the abbreviated Modification of Diet in Renal Disease equation. Associations of eGFR with total Medicare payments in the second and third post-transplant years were examined by multivariate non-linear regression with spline forms. Adjustment covariates were drawn from the survival prediction model developed by the UNOS Kidney Allocation Review Committee. Results: The sample comprised 7,103 living donor (LD), 22,110 standard criteria deceased (SCD), and 2,594 expanded criteria deceased (ECD) donor transplant recipients. Regardless of donor type, lower one-year eGFR was associated with significantly increased expenditures during the second and the third years post-transplant. Marginal costs began to increase as eGFR fell below 45 mL/min/1.73 m(2) and rose in an accelerating manner. Compared to a reference eGFR of 75 mL/min/1.73 m(2), one-year eGFR of 20 ml/min/1.73 m(2) in SCD recipients was associated with approximately $17,500 and $18,200 higher adjusted payments in the second and third post-transplant years, respectively.(.) Patterns were similar among recipients of LD and ECD transplants. Limitations: The study sample was limited to Medicare beneficiaries who survived allograft function at the first transplant anniversary, which may limit generalizability of the findings. eGFR is a surrogate measure of renal function. The design is retrospective and changes in post-transplant management may alter long-term cost implication of renal function. Conclusions: Decreased renal function is significanlty associated with higher healthcare expenditures following kidney transplantation. Post-transplant eGFR may be a useful metric for discriminating the economic impact of care strategies that differentially affect renal function.
Abstract: We analyzed clinical factors and graft survival associated with complement-dependent microcytotoxicity (CDC) crossmatch (XM) positive (+) kidney transplants in 1995 to 2009 United Network of Sharing (UNOS) registry data. CDCXM negative (-) transplants were selected from centers and years in which at least one CDCXM+ transplant was performed at a given center in a given year. CDCXM+ and CDCXM- results were compared with bivariate and multivariate survival analysis. Our observations are as follows: (1) The risk of graft loss with CDCXM+ vs. CDCXM- results was markedly lower than the risk observed historically, e.g., living donor (LD)-CDCXM+ absolute all-cause graft survival reductions were 0.7% at 24 hours (P=0.007), 2.9% at one year (P <0.0001), 3.7% at five years (P<0.0001); deceased donor (DD)-CDCXM+ absolute graft survival reductions were 0.7% at 24 hours (P=0.02), 3.5% at one year (P <0.0001), 2.7% at five years (P=0.0009). On covariate adjustment, the only significant association of CDCXM+ vs. CDCXM- results was with one-year graft loss risk: LD aHR 1.44 (95% CI 1.05-1.96), DD aHR 1.33 (CI 1.10-1.61). (2) CDCXM+ transplantation was more commonly performed among groups disadvantaged with respect to transplant access, including sensitized, previously transplanted women and black recipients. (3) In CDCXM+ recipients, there was a high percentage of flow cytometry (FC) XM- and autoXM+ results. After removing these groups, outcomes with CDCXM+ results were relatively good. (4) CDCXM+/FCXM+ vs. CDCXM-/FCXM- graft loss risk was observed only in LD recipients transplanted at centers performing fewer than 10 such transplants during the study period: 11.0% reduction (P<0.0001) and aHR of 2.86 (CI 1.18-6.94) at one year; 14.7% reduction (P<0.0001) and aHR of 1.77 (CI 0.88-3.58) at five years. Although using CDCXM+ as a contraindication to transplantation has been associated with virtual elimination of hyperacute rejection, the negative effect of a CDCXM+ in contemporary practice is relatively small, questioning the value of the CDCXM as a standalone test.
Abstract: Chronic kidney disease is now widely accepted as an independent risk factor for coronary disease and the dialysis population may represent the highest risk subgroup. Among all dialysis patients, a cardiac cause of mortality has been estimated at 40%. In addition, prior studies have demonstrated that when cardiac catheterization is obtained in a consecutive series of asymptomatic diabetic patients on dialysis the rates of coronary disease can approach 50%. However, the ability to define the problem continues to be greater than the ability to treat or prevent it. Coronary revascularization strategies have limitations in the general population which are amplified in the dialysis population. The ability to accurately diagnose an acute coronary syndrome is more difficult, clinical outcomes have a smaller margin of benefit, and technical challenges result in higher complication rates. Recent data demonstrate an inverse relationship between glomerular filtration rate and the risk of presenting with an acute myocardial infarction rather than unstable angina suggesting that patients with CKD may have a unique pathophysiologic profile that is more prone to plaque rupture. However, these "vulnerable" plaques typically are associated with stenoses <50% prior to rupture and are thus poor targets for revascularization and perhaps best treated with medical therapy. Although the benefits of revascularization may continue to outweigh the risks in the context of acute coronary syndromes, preventive strategies would have to overcome the lower margin of benefit and higher complication rates.
Abstract: Living donors supply approximately 40% of renal allografts in the United States. Based on current data, perioperative mortality after donor nephrectomy is approximately 3 per 10,000 cases, and major and minor perioperative complications affect approximately 3% to 6% and 22% of donors, respectively. Donor nephrectomy does not appear to increase long-term mortality compared with controls, nor does it appear to increase ESRD risk among white donors. Within the donor population, the likelihood of postdonation chronic renal failure and medical comorbidities such as hypertension and diabetes appears to be relatively higher among some donor subgroups, such as African Americans and obese donors, but the impact of uninephrectomy on the lifetime risks of adverse events expected without nephrectomy in these subgroups has not yet been defined. As national follow-up of living donors in the United States is limited in scope, duration, and completeness, additional methods for quantifying risk among diverse living donors are needed. In addition to improved national collection of follow-up data, possible sources of information on donor outcomes may include focused studies with carefully defined control groups, and database integration projects that link national donor registration records to other data sources. Given the growth and evolving characteristics of the living donor population, as well as changes in surgical techniques, tracking of short- and long-term risks after living kidney donation is vital to support truly informed consent and to maintain public trust in living donation. The transplant community must persist in their efforts to accurately assess risk across demographically diverse living kidney donors.
Abstract: The ability to accurately predict a population's long-term survival has important implications for quantifying the benefits of transplantation. To identify a model that can accurately predict a kidney transplant population's long-term graft survival, we retrospectively studied the United Network of Organ Sharing data from 13,111 kidney-only transplants completed in 1988- 1989. Nineteen-year death-censored graft survival (DCGS) projections were calculated and compared with the population's actual graft survival. The projection curves were created using a two-part estimation model that (1) fits a Kaplan-Meier survival curve immediately after transplant (Part A) and (2) uses truncated observational data to model a survival function for long-term projection (Part B). Projection curves were examined using varying amounts of time to fit both parts of the model. The accuracy of the projection curve was determined by examining whether predicted survival fell within the 95% confidence interval for the 19-year Kaplan-Meier survival, and the sample size needed to detect the difference in projected versus observed survival in a clinical trial. The 19-year DCGS was 40.7% (39.8-41.6%). Excellent predictability (41.3%) can be achieved when Part A is fit for three years and Part B is projected using two additional years of data. Using less than five total years of data tended to overestimate the population's long-term survival, accurate prediction of long-term DCGS is possible, but requires attention to the quantity data used in the projection method.
Abstract: BACKGROUND: Mortality records identify cancer as the leading cause of death among living kidney donors, but information on the burden of cancer outside death records is limited in this population. METHODS: We examined a database wherein U.S. Organ Procurement and Transplantation Network identifiers for 4,650 living kidney donors in 1987 to 2007 were linked to administrative data of a U.S. private health insurer (2000-2007 claims) to identify postdonation cancer diagnoses. Skin cancer and non-skin cancer diagnoses were ascertained from International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes on billing claims. Donors were also matched one-to-one with general insurance beneficiaries by sex and age when benefits began. Diagnosis rates within observation windows were compared as rate ratios. RESULTS: The median time from donation to the end of plan insurance enrollment was 7.7 years, with a median observation period of 2.1 years. Skin cancer rates were similar among prior living donors in the observation period and nondonor controls (rate ratio, 0.91; 95% confidence interval [CI], 0.59-1.40). In contrast, the rate of total non-skin cancers was significantly less common among donors than among controls (rate ratio, 0.74; 95% CI, 0.55-0.99), although reduced relative risk was limited to donors captured earlier in relation to donation. Several cases of cancer diagnosis (uterine, melanoma, "other") were identified within the first year after donation. Prostate cancer diagnosis was significantly more common among living donors compared with controls (rate ratio, 3.80; 95% CI, 1.42-10.2). CONCLUSIONS: Continued study of cancer after kidney donation is warranted to ensure that evaluation, selection, and long-term follow-up support overall good health of the donor.
Abstract: Model for End-stage Liver Disease (MELD)-based allocation of deceased donor livers allows exceptions for patients whose score may not reflect their true mortality risk. We hypothesized that organ procurement organizations (OPOs) may differ in exception practices, use of exceptions may be increasing over time, and exception patients may be advantaged relative to other patients. We analyzed longitudinal MELD score, exception and outcome in 88 981 adult liver candidates as reported to the United Network for Organ Sharing from 2002 to 2010. Proportion of patients receiving an HCC exception was 0-21.4% at the OPO-level and 11.9-18.8% at the region level; proportion receiving an exception for other conditions was 0.0%-13.1% (OPO-level) and 3.7-9.5 (region-level). Hepatocellular carcinoma (HCC) exceptions rose over time (10.5% in 2002 vs. 15.5% in 2008, HR = 1.09 per year, p<0.001) as did other exceptions (7.0% in 2002 vs. 13.5% in 2008, HR = 1.11, p<0.001). In the most recent era of HCC point assignment (since April 2005), both HCC and other exceptions were associated with decreased risk of waitlist mortality compared to nonexception patients with equivalent listing priority (multinomial logistic regression odds ratio [OR] = 0.47 for HCC, OR = 0.43 for other, p<0.001) and increased odds of transplant (OR = 1.65 for HCC, OR = 1.33 for other, p<0.001). Policy advantages patients with MELD exceptions; differing rates of exceptions by OPO may create, or reflect, geographic inequity.
Abstract: Little is known about the influence of pre-transplant comorbidities on post-transplant expenditures. We estimated the associations between pre-transplant comorbidities and post-transplant Medicare costs, using several comorbidity classification systems. We included recipients of first-kidney deceased donor transplants from 1995 through 2002 for whom Medicare was the primary payer for at least one year pre-transplant (N = 25,175). We examined pre-transplant comorbidities as classified by International Classification of Diseases (ICD-9-CM) codes from Medicare claims with the Clinical Classifications Software (CCS) and Charlson and Elixhauser algorithms. Post-transplant costs were calculated from payments on Medicare claims. We developed models considering Organ Procurement and Transplantation Network (OPTN) variables plus: 1) CCS categories, 2) Charlson, 3) Elixhauser, 4) number of Charlson and 5) number of Elixhauser comorbidities, independently. We applied a novel regression methodology to account for censoring. Costs were estimated at individual and population levels. The comorbidities with the largest impact on mean Medicare payments included cardiovascular disease, malignancies, cerebrovascular disease, mental conditions and functional limitations. Skin ulcers and infections, rheumatic and other connective tissue disease and liver disease also contributed to payments and have not been considered or described previously. A positive graded relationship was found between costs and the number of pre-transplant comorbidities. In conclusion, we showed that expansion beyond the usually considered pre-transplant comorbidities with inclusion of CCS and Charlson or Elixhauser comorbidities increased the knowledge about comorbidities related to augmented Medicare payments. Our expanded methodology can be used by others to assess more accurately the financial implications of renal transplantation to Medicare and individual transplant centers.
Abstract: Accurate assessment of the impact of donor quality on liver transplant (LT) costs has been limited by the lack of a large, multicenter study of detailed clinical and economic data. A novel, retrospective database linking information from the University HealthSystem Consortium and the Organ Procurement and Transplantation Network registry was analyzed using multivariate regression to determine the relationship between donor quality (assessed through the Donor Risk Index [DRI]), recipient illness severity, and total inpatient costs (transplant and all readmissions) for 1 year following LT. Cost data were available for 9059 LT recipients. Increasing MELD score, higher DRI, simultaneous liver-kidney transplant, female sex, and prior liver transplant were associated with increasing cost of LT (P < 0.05). MELD and DRI interact to synergistically increase the cost of LT (P < 0.05). Donors in the highest DRI quartile added close to $12,000 to the cost of transplantation and nearly $22,000 to posttransplant costs in comparison to the lowest risk donors. Among the individual components of the DRI, donation after cardiac death (increased costs by $20,769 versus brain dead donors) had the greatest impact on transplant costs. Overall, 1-year costs were increased in older donors, minority donors, nationally shared organs, and those with cold ischemic times of 7-13 hours (P < 0.05 for all). In conclusion, donor quality, as measured by the DRI, is an independent predictor of LT costs in the perioperative and postoperative periods. Centers in highly competitive regions that perform transplantation on higher MELD patients with high DRI livers may be particularly affected by the synergistic impact of these factors.
Abstract: Liver transplantation has evolved over the past four decades into the most effective method to treat end-stage liver failure and one of the most expensive medical technologies available. Accurate understanding of the financial implication of recipient severity of illness is crucial to assessing the economic impact of allocation policies. A novel database of linked clinical data from the Organ Procurement and Transplantation Network with cost accounting data from the University HealthSystem Consortium was used to analyze liver transplant costs for 15,813 liver transplants. This data was then utilized to consider the economic impact of alternative allocation systems designed to increase sharing of liver allografts using simulation results. Transplant costs were strongly associated with recipient severity of illness as assessed by the MELD score (p < 0.0001); however, this relationship was not linear. Simulation analysis of the reallocation of livers from low MELD patients to high MELD using a two-tiered regional sharing approach (MELD 15/25) resulted in 88 fewer deaths annually at estimated cost of $17,056 per quality-adjusted life-year saved. The results suggest that broader sharing of liver allografts offers a cost-effective strategy to reduce the mortality from end stage liver disease.
Abstract: Hyperuricemia is common in patients with chronic kidney disease (CKD). We assessed the relationship of increased serum uric acid levels with cardiovascular risk across levels of kidney function.
Abstract: Expanding gaps between the number of patients awaiting transplantation and the number who receive organs in the United States has been associated with heightened disease severity among transplant candidates and more common use of organs from non-standard donors. We summarize data on the economic consequences of liver and renal allograft quality in contemporary practice. Policy makers and providers must work together to ensure that financial disincentives do not lead to wastage of lifesaving organs.
Abstract: Improved early kidney transplant outcomes limit the contemporary utility of standard clinical endpoints. Quantifying the relationship of renal function at 1 year after transplant with subsequent clinical outcomes and healthcare costs may facilitate cost-benefit evaluations among transplant recipients.
Abstract: In light of continued uncertainty regarding postkidney donation medical, psychosocial and socioeconomic outcomes for traditional living donors and especially for donors meeting more relaxed acceptance criteria, a meeting was held in September 2010 to (1) review limitations of existing data on outcomes of living kidney donors; (2) assess and define the need for long-term follow-up of living kidney donors; (3) identify the potential system requirements, infrastructure and costs of long-term follow-up for living kidney donor outcomes in the United States and (4) explore practical options for future development and funding of United States living kidney donor data collection, metrics and endpoints. Conference participants included prior kidney donors, physicians, surgeons, medical ethicists, social scientists, donor coordinators, social workers, independent donor advocates and representatives of payer organizations and the federal government. The findings and recommendations generated at this meeting are presented.
Abstract: We investigated associations between pre-transplant comorbidities, length of stay (LOS) and Medicare payments for transplant hospitalization.
Abstract: The complement-dependent microcytotoxicity crossmatch (CDCXM) is a standard method for evaluating the presence of preformed antibodies before transplantation. The flow cytometry crossmatch (FCXM) is more sensitive, but there is controversy regarding translation of its increased sensitivity to clinically relevant graft outcomes.
Abstract: Variation in kidney transplant access across the United States may motivate relocation of patients with ability to travel to better-supplied areas.
Abstract: Anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis is considered a "pauci-immune" disease, characterized by absent or mild glomerular tuft staining for immunoglobulin and/or complement. We describe a 72-year-old man with progressive renal failure over five months who was found to have P-ANCA associated crescentic glomerulonephritis. Renal biopsy also revealed immunofluorescence staining for Immunoglobulin G and C3. Treatment comprised corticosteroids, cyclophosphamide, and plasmapheresis but unfortunately kidney function did not recover, likely due to substantial interstitial fibrosis at diagnosis. This case illustrates that serologic evaluation for ANCAs should not be discounted when immune deposits are present. Prompt diagnosis is warranted.
Abstract: We carried out an analysis of the United States Renal Data System to determine the incidence, risk factors, prognosis, and costs associated with the diagnosis of renal cell carcinoma (RCC) after kidney transplantation.
Abstract: Characterizing relationships of kidney function to healthcare costs in polycystic kidney disease has applications for economic evaluations of standard and emerging therapies.
Abstract: Cardiovascular disease is the most common cause of death after kidney transplantation. However, uncertainties regarding the optimal assessment of cardiovascular risk in potential transplant candidates have produced controversy and inconsistency in pretransplantation cardiac evaluation practices. In this review, we consider the evidence supporting cardiac evaluation in kidney transplant candidates, generally focused on coronary artery disease, according to the World Health Organization principles for screening. The importance of pretransplant cardiac evaluation is supported by the high prevalence of coronary artery disease and the incidence and adverse consequences of acute coronary syndromes in this population. Testing for coronary artery disease may be performed noninvasively by using modalities that include nuclear myocardial perfusion studies and dobutamine stress echocardiography. These tests have prognostic value for mortality, but imperfect sensitivity and specificity for detecting angiographically defined coronary artery disease in patients with end-stage renal disease. Associations of angiographically-defined coronary artery disease with subsequent survival also are inconsistent, likely because plaque instability is more critical for infarction risk than angiographic stenosis. The efficacy and best methods of myocardial revascularization have not been examined in large contemporary clinical trials in patients with end-stage renal disease. Biomarkers, such as cardiac troponin, have prognostic value in end-stage renal disease, but require further study to determine clinical applications in directing more expensive and invasive cardiac evaluation.
Abstract: BACKGROUND: The relationship of body mass index (BMI) with heart failure (HF) risk before and after kidney transplant is not well described. METHODS: We examined United States Renal Data System records for 67,591 kidney transplant candidates (1995-2004) with Medicare insurance and BMI data at listing. Heart failure diagnoses were ascertained from Medicare billing claims. Body mass index was categorized per World Health Organization criteria. We modeled time-dependent associations (adjusted hazard ratio, aHR) of transplant with HF risk after listing compared with waiting in each BMI group by multivariable, stratified Cox regression. The time-dependent exposure variables partitioned relative risk of HF after transplant versus waiting into early (<or=90 days) and late (>90 days) posttransplant periods. RESULTS: The BMI distribution of listed candidates was as follows: 3.7% under, 40.4% normal, 32.0% over, 16.2% obese, and 7.7% morbidly obese weight. The prevalence of HF among patients awaiting transplant reached 57.4% by 3 years. Deceased-donor transplant was associated with increased early HF risk compared with continued waiting-aHRs ranged from 2.23 for normal-BMI to 2.82 for morbidly obese patients. However, transplant reduced the risk of HF in the late posttransplant period from 54% (aHR 0.46) in normal-BMI to 32% (aHR 0.68) for morbidly obese patients. Relative benefits were largest for normal-weight candidates who received live-donor transplants (aHR 0.31). CONCLUSIONS: Heart failure risk improves in obese patients in the long term after kidney transplant, but not as much as for nonobese patients. There is need for close monitoring and for new strategies to reduce HF risk in obese patients before and after transplant.
Abstract: We examined the relationship between the total cost incurred by liver transplantation (LT) recipients and their Model for End-Stage Liver Disease (MELD) score at the time of transplant. We used a novel database linking billing claims from a large private payer with the Organ Procurement and Transplantation Network registry. Included were adults who underwent LT from March 2002 through August 2007 (n = 990). Claims within the year preceding and following transplantation were analyzed according to the recipient's calculated MELD score. Cost was the primary endpoint and was assessed by the length of stay and charges. Transplant admission charges represented approximately 50% of the total cost of LT. MELD was a significant cost driver for pretransplant, transplant, and total charges. A MELD score of 28 to 40 was associated with additional charges of $349,213 (P < 0.05) in comparison with a score of 15 to 20. Pretransplant and transplant admission charges were higher by $152,819 (P < 0.05) and $64,286 (P < 0.05), respectively, in this higher MELD group. No differences by MELD score were found for posttransplant charges. Those in the highest MELD group also experienced longer hospital stays both in the pretransplant period and at the time of LT but did not have higher rates of re-admissions. In conclusion, high-MELD patients incur significantly higher costs prior to and at the time of LT. Following LT, the MELD score is not a significant predictor of cost or re-admission.
Abstract: We analyzed the United States Renal Data System registry to study the risks, predictors, and outcomes of transplant renal artery stenosis (TRAS) in contemporary practice.
Abstract: There are several case reports of rhabdomyolysis (RM) in renal transplant recipients, but the actual incidence of this complication is not known. Most of the reported cases have been attributed to drug-drug interactions with calcineurin inhibitors, with the majority of interactions reported between cyclosporine and 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins). Pharmacokinetic studies have demonstrated that cyclosporine increases statin drug levels, presumably via competitive inhibition of cytochrome P450 3A4.
Abstract: BACKGROUND: Limited data exist on the safety and efficacy of bariatric surgery (BS) in patients with kidney failure. METHODS: We examined Medicare billing claims within USRDS registry data (1991-2004) to identify BS cases among renal allograft candidates and recipients. RESULTS: Of 188 BS cases, 72 were performed pre-listing, 29 on the waitlist, and 87 post-transplant. Roux-en-Y gastric bypass was the most common procedure. Thirty-day mortality after BS performed on the waitlist and post-transplant was 3.5%, and one transplant recipient lost their graft within 30 days after BS. BMI data were available for a subset and suggested median excess body weight loss of 31%-61%. Comparison to published clinical trials of BS in populations without kidney disease indicates comparable weight loss but higher post-BS mortality in the USRDS sample. CONCLUSIONS: Given the substantial contributions of obesity to excess morbidity and mortality, BS warrants prospective study as a strategy for improving outcomes before and after kidney transplantation.
Abstract: Many studies relating flow cytometery crossmatch (FCXM) results to kidney transplant outcomes have examined risk in the first 3 to 12 months. We used Organ Procurement and Transplant Network registry data for 66,594 kidney transplants from 1995 to 2007 to investigate associations of T-cell positive (T+) and T-cell negative/B-cell positive (T(-)B+) FCXM with graft failure risk early (years 0-1) and late (years >1-5) after transplant. Compared with transplants with T-cell negative/B-cell negative (T(-)B(-)) FCXM, living-donor transplants performed after T+ FCXM had significantly higher adjusted, relative risks of both early (adjusted hazards ratio [aHR] 1.71, p < 0.0001) and late (aHR 1.36, p = 0.017) graft loss. T(-)B+ FCXM was associated with approximately 40% higher relative risk of graft loss in the late period only. Patterns were similar for deceased-donor transplants. The risks of positive FCXM persist beyond the peritransplant period for years after transplant. Damage by memory effector cells may explain the long-term risks associated with positive FCXM.
Abstract: Whether to include additional comorbidities beyond diabetes in future kidney allocation schemes is controversial. We investigated the predictive ability of multiple pretransplant comorbidities for graft and patient survival. We included first-kidney transplant deceased donor recipients if Medicare was the primary payer for at least one year pretransplant. We extracted pretransplant comorbidities from Medicare claims with the Clinical Classifications Software (CCS), Charlson and Elixhauser comorbidities and used Cox regressions for graft loss, death with function (DWF) and death. Four models were compared: (1) Organ Procurement Transplant Network (OPTN) recipient and donor factors, (2) OPTN + CCS, (3) OPTN + Charlson and (4) OPTN + Elixhauser. Patients were censored at 9 years or loss to follow-up. Predictive performance was evaluated with the c-statistic. We examined 25 270 transplants between 1995 and 2002. For graft loss, the predictive value of all models was statistically and practically similar (Model 1: 0.61 [0.60 0.62], Model 2: 0.63 [0.62 0.64], Models 3 and 4: 0.62 [0.61 0.63]). For DWF and death, performance improved to 0.70 and was slightly better with the CCS. Pretransplant comorbidities derived from administrative claims did not identify factors not collected on OPTN that had a significant impact on graft outcome predictions. This has important implications for the revisions to the kidney allocation scheme.
Abstract: OBJECTIVE: To quantify the incremental survival benefit of the pancreas allograft in simultaneous pancreas-kidney (SPK) transplant recipients. RESEARCH DESIGN AND METHODS: Data from the national transplant database from 2000 to 2007 were analyzed. SPK recipients who had functioning allografts to 1-year post transplant (n = 3,304) were compared with those who had failure of the renal (n = 233) or pancreatic (n = 112) graft. The main outcome was a projection of 10 life-years of patient survival beyond the first transplant anniversary. RESULTS: Recipients with function of both organs accrued 9.4 life-years following transplantation. Projected survival in patients with kidney failure was reduced to 2.5 life-years. Pancreas failure reduced predicted survival to 8 life-years. Renal allograft failure impacts life expectancy significantly (adjusted hazard ratio [aHR] 12.13). However, pancreas allograft failure was also associated with reduced survival (aHR 2.62). CONCLUSIONS: Although the majority of the survival benefit of SPK transplant is due to the renal transplant, pancreas allograft function does contribute to patient survival.
Abstract: BACKGROUND AND OBJECTIVES: Renal transplantation is increasingly performed in elderly patients, and the incidence of benign prostatic hyperplasia (BPH) increases with age. Anuric males on dialysis may have occult BPH and not develop obstructive symptoms until urine flow is restored after transplantation. If left untreated, BPH poses a risk for numerous complications, including acute urinary retention (AUR), recurrent urinary tract infections (UTI), and renal failure. The authors hypothesized that incident BPH after renal transplantation would adversely affect allograft survival. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Medicare claims for BPH, AUR, UTI, and prostate resection procedures (transurethral resection of the prostate; TURP) were assessed in a retrospective cohort of 23,622 adult male Medicare primary renal transplant recipients in the United States Renal Data System database who received transplants from 1 January 2000 to 31 July 2005 and followed through 31 December 2005. RESULTS: The 3-yr incidence of BPH post-transplant was 9.7%. The incidences of AUR, UTI, and TURP after BPH diagnosis (up to 3 yr posttransplant) were 10.3%, 6.5%, and 7.3% respectively, and each was significantly associated with BPH. Cox regression analysis showed that recipient age per year, later year of transplant, and dialysis vintage were associated with incident BPH. Using Cox nonproportional hazards regression, BPH was significantly associated with renal allograft loss (including death). CONCLUSIONS: BPH is common in males after renal transplant and is independently associated with AUR, UTI, and graft loss. It is unknown whether treatment of BPH, either medical or surgical, attenuates these risks.
Abstract: BACKGROUND: Risk of new-onset diabetes after transplant (NODAT) is well characterized for adults but much less understood in pediatric transplant. This study examines the incidence and risk factors of NODAT in pediatric renal transplant patients. METHODS: The incidence of NODAT over the first 3 years after transplant was examined with the United States Renal Data System data for primary renal transplant recipients (ages 0-21 years, transplanted between 1995 and 2004) with Medicare primary. Patients had no evidence of diabetes before transplant. We estimated the cumulative incidence rate and used Cox proportional hazards regression to identify the risk factors for NODAT. Propensity scores were calculated for immunosuppression choice to adjust for potential confounding factors. RESULTS: Two thousand one hundred sixty-eight recipients with valid immunosuppression records and without pretransplant evidence of diabetes were included. Unadjusted, cumulative NODAT incidence at 3 years posttransplant was 7.1%. Significant factors for increased risk of NODAT included cytomegalovirus D+/R- serostatus (adjusted hazard ratio [aHR]=1.60), age 13 to 18 years (aHR=2.18), age 19 to 21 years (aHR=2.60), body mass index more than or equal to 30 kg/m (aHR=2.17), and use of tacrolimus (aHR=1.51). We failed to find any significant relationships between NODAT and graft failure or death. CONCLUSIONS: Although the incidence of NODAT among patients aged 0 to 21 years is lower than that for adult patients, it is higher than suggested by earlier research and may represent an increase over time. The lack of association between NODAT and graft or failure death has important implications for posttransplant care. A clearer understanding of risk factors can help guide posttransplant monitoring and clinical decision making.
Abstract: We describe factors associated with immunosuppression compliance after kidney transplantation and examine relationships between compliance with allograft outcomes and costs. Medicare claims for immunosuppression in 15 525 renal transplant recipients with at least 1 year of graft function were used to calculate compliance as medication possession ratio. Compliance was categorized by quartiles as poor, fair, good and excellent. We modeled adjusted associations of clinical factors with the likelihood of persistent compliance by multiple logistic regressions (aOR), and estimated associations of compliance with subsequent graft and patient survival with Cox proportional hazards (aHR). Adolescent recipients aged 19-24 years were more likely to be persistently noncompliant compared to patients aged 24-44 years (aOR 1.49 [1.06-2.10]). Poor (aHR 1.80 [1.52-2.13]) and fair (aHR 1.63[1.37-1.93]) compliant recipients were associated with increased risks of allograft loss compared to the excellent compliant recipients. Persistent low compliance was associated with a $12 840 increase in individual 3-year medical costs. Immunosuppression medication possession ratios indicative of less than the highest quartile of compliance predicted increased risk of graft loss and elevated costs. These findings suggest that interventions to improve medication compliance among kidney transplant recipients should emphasize the benefits of maximal compliance, rather than discourage low compliance.
Abstract: BACKGROUND: Retrospective comparison of treatment-related kidney transplant outcomes may be facilitated by multivariable statistical adjustments and case-matching. METHODS: We studied Organ Procurement and Transplantation Network registry data for kidney transplants in 2001 to 2005 managed with thymoglobulin, basiliximab, or no antibody induction and discharge maintenance immunosuppression regimens of tacrolimus and mycophenolate mofetil. The primary outcome was the 6 month, Food and Drug Administration-approved composite endpoint of rejection, graft failure, or death. Outcomes according to induction exposure were compared using logistic regression analysis, exposure likelihood matching, and outcome risk score matching. RESULTS: All statistical approaches demonstrated lower rates of the 6-month triple endpoint with thymoglobulin compared with basiliximab when steroids were present, with approximately 22% adjusted, relative reduction by logistic regression analysis and 3% absolute reductions by matching approaches. When steroids were absent, risk reduction among thymoglobulin versus basiliximab-treated patients was of larger magnitude but borderline statistical significance. Triple endpoint incidence was lower with both induction regimens compared with no induction across methods. Estimated sample sizes necessary to detect the observed differences between induction types in the presence of steroids in a prospective trial ranged from 1600 to nearly 7000 patients. CONCLUSIONS: Consistency across statistical approaches suggests superiority of thymoglobulin compared with basiliximab or no antibody induction therapy for 6-month kidney transplant outcomes in the modern immunosuppression era. As the sample sizes necessary to power a prospective superiority trial are likely prohibitive, studies such as these provide clinically relevant information that may not be otherwise attainable.
Abstract: BACKGROUND AND OBJECTIVES: Billing claims are increasingly examined beyond administrative functions as outcomes measures in observational research. Few studies have described the performance of billing claims as surrogate measures of clinical events among kidney transplant recipients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We investigated the sensitivity of Medicare billing claims for clinically verified cardiovascular diagnoses (five categories) and procedures (four categories) in a novel database linking Medicare claims to electronic medical records of one transplant program. Cardiovascular events identified in medical records for 571 Medicare-insured transplant recipients in 1991 through 2002 served as reference measures. RESULTS: Within a claims-ascertainment period spanning +/-30 d of clinically recorded dates, aggregate sensitivity of single claims was higher for case definitions incorporating Medicare Parts A and B for diagnoses and procedures (90.9%) compared with either Part A (82.3%) or Part B (84.6%) alone. Perfect capture of the four procedures was possible within +/-30 d or with short claims window expansion, but sensitivity for the diagnoses trended lower with all study algorithms (91.2% with window up to +/-90 d). Requirement for additional confirmatory diagnosis claims did not appreciably reduce sensitivity. Sensitivity patterns were similar in the early compared with late periods of the study. CONCLUSIONS: Combined use of Medicare Parts A and B billing claims composes a sensitive measure of cardiovascular events after kidney transplant. Further research is needed to define algorithms that maximize specificity as well as sensitivity of claims from Medicare and other insurers as research measures in this population.
Abstract: Methods of crossmatch testing prior to kidney transplantation are not standardized and there are limited large-scale data on the use and outcomes implications of crossmatch modality. Data describing the most sensitive crossmatch modality for crossmatch-negative kidney transplants were drawn from the Organ Procurement and Transplant Network Registry. Within the cohort transplanted in 1999-2005, we identified patient and transplant characteristics predictive of each testing modality by multivariate logistic regression. We assessed associations of crossmatch modality with rejection risk by logistic regression and with graft survival by Cox's hazards analysis. Among 230,995 transplants, use of flow cytometry with T-and B-lymphocytes (T&B FC) increased progressively in 1987-2005. Among the recent transplants performed in 1999-2005 (n=64,320), negative T&B FC crossmatch was associated with 15% lower relative risk of first-year acute rejection (adjusted HR 0.85, 95% CI 0.80-0.89) compared to negative T-antihuman-globulin and B-National Institutes of Health/Wash (T AHG &B) crossmatch. Five-year graft survival after transplant with negative T&B FC (82.6%) was modestly better than after negative T AHG &B (81.4%, P= 0.008) or T AHG crossmatch (81.1%, P 0.0001), but on adjusted analysis was significantly different only among recipients from deceased donors and patients aged > 60 years. Many subgroups for whom negative T&B FC crossmatch predicted lower rejection risk (Caucasians, deceased donor recipients, re-transplants) were not more likely to be crossmatched by this method. We conclude that current practice patterns have not aligned utilization of T&B FC crossmatch with associated benefits. Prospective evaluation of the relationship of crossmatch modality with outcomes is warranted.
Abstract: BACKGROUND AND OBJECTIVES: Racial disparities in provision of healthcare are widespread in the United States but have not been specifically assessed in provision of chronic kidney disease (CKD) care. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a retrospective cohort study of the clinical database used in a Department of Defense (DOD) medical system. Beneficiaries studied were DOD-eligible beneficiaries with CKD stage 3 (n = 7729) and 4 (n = 589) using the modified Modification of Diet in Renal Disease (MDRD)-estimated GFR formula but requiring manual correction for Black race. Compliance with selected Kidney Disease Outcomes Quality Initiative (KDOQI) CKD recommended targets (monitoring of recommended laboratory data, prescription of recommended medications, and referral to nephrology) was assessed over a 12-mo period, stratified by CKD stage. Logistic regression analysis was used to assess whether race (White, Black, or other) was independently associated with provider compliance with targets, adjusted for demographic factors and burden of comorbid conditions. RESULTS: Among the targets, only monitoring of LDL cholesterol was significantly less common among Blacks. For all other measures, compliance was either not significantly different or significantly higher for Black compared with White beneficiaries. However, patients categorized as "Other" race were in general less likely to achieve targets than Whites, and at stage 3 CKD significantly less likely to achieve targets for monitoring of phosphorous, hemoglobin, and vitamin D. CONCLUSIONS: In the DOD health system, provider compliance with selected CKD stage 3 and 4 targets was not significantly lower for Black beneficiaries than for Whites, with the exception of LDL cholesterol monitoring. Patients classified as Other race were generally less likely to achieve targets than Whites, in some patients significantly so.
Abstract: BACKGROUND: The cardiac implications of obesity in kidney transplant recipients are not well-described. METHODS: We examined associations of body mass index (BMI) at transplant with posttransplant cardiac risk among 1102 renal allograft recipients at a single center in 1991 to 2004. Cumulative posttransplant incidences of congestive heart failure (CHF), atrial fibrillation (AF), myocardial infarction, and a composite of these cardiac diagnoses were estimated by the Kaplan-Meier method. Bivariate (hazards ratio) and covariate (adjusted hazards ratio) relationships of BMI increments with cardiac risk were modeled by Cox's regression. We also systematically reviewed the literature on BMI and cardiac events after transplant. RESULTS: In the local data, 5-year cumulative incidence of any cardiac diagnosis rose from 8.67% to 29.35% across the lowest to highest BMI quartiles (P=0.02), driven primarily by increases in CHF and AF. In contrast, the rate of myocardial infarction did not differ by BMI quartile (P=0.56). Each 5 U BMI increase predicted 25% higher risk of the cardiac composite (hazards ratio 1.25, 95% CI 1.07-1.47, P=0.005), a relationship that persisted with significance after covariate adjustment (adjusted hazards ratio 1.19, 95% CI 1.00-1.43, P=0.049). BMI independently predicted cardiac risk in subcohorts with pretransplant heart disease and with nondiabetic renal failure. Data from 26 original articles support BMI as a risk factor for posttransplant CHF and AF, whereas findings for coronary/ischemic outcomes are inconsistent and predominantly negative. CONCLUSIONS: High BMI at transplant predicts increased cardiac risk, especially of CHF and AF. Further research should examine whether obesity treatment modifies cardiac risk after kidney transplantation.
Abstract: Mycophenolate mofetil (MMF) use may be associated with progressive multifocal leukoencephalopathy (PML). We conducted a retrospective cohort study of 32,757 renal transplant recipients using the United States Renal Data System kidney transplant files for the incidence, prognosis, and clinical features associated with PML occurring after kidney transplant. Subjects were transplanted from January 1, 2000 to July 31, 2004 and followed through December 31, 2004. The incidence density of PML in MMF users was 14.4 cases/100,000 person-years at risk versus 0 for non-MMF users (P=0.11) by log rank test. Factors significantly associated with PML were BK virus infection (22.2% vs. 1.1%), pretransplant transfusion (75% vs. 34%), panel reactive antibody more than 20% (56% vs. 14%), and use of antirejection medications in the first year (33% vs. 9.2%), all P less than 0.05. PML is rare in the renal transplant population. There was no significant association between PML and MMF, but MMF use in this cohort is too high to accurately assess an association.
Abstract: Beginning January 1, 2000, Medicare extended coverage of immunosuppression medications from 3 years to lifetime based on age >65 years or disability. Using United States Renal Data System (USRDS) data for Medicare-insured recipients of kidney transplants between July 1995 and December 2000, we identified four cohorts of Medicare-insured kidney transplant recipients. Patients in cohort 1 were individuals who were both eligible and received lifetime coverage. Patients in cohort 2 would have been eligible, but their 3-year coverage expired before lifetime coverage was available. Patients in cohort 3 were ineligible for lifetime coverage because of youth or lack of disability. Patients in cohort 4 were transplanted between 1995 and 1996 and were ineligible for lifetime coverage. Incomes were categorized by ZIP code median household income from census data. Lifetime extension of Medicare immunosuppression was associated with improved allograft survival among low-income transplant recipients in the sense that the previously existing income-related disparities in graft survival in cohort 2 were not apparent in cohort 1. Ineligible individuals served as a control group; the income-related disparities in graft survival observed in the early cohort 4 persisted in more recent cohort 3. Multivariate proportional hazards models confirmed these findings. Future work should evaluate the cost effectiveness of these coverage increases, as well as that of benefits extensions to broader patient groups.
Abstract: Pulsatile machine perfusion (PMP) has been shown to reduce delayed graft function (DGF) in expanded criteria donor (ECD) kidneys. Here, we investigate whether there is a cost benefit associated with PMP utilization in ECD kidney transplants. We analyzed United States Renal Data System (USRDS) data describing Medicare-insured ECD kidney transplant recipients in 1995-2004 (N = 5840). We examined total Medicare payments for transplant hospitalization and annually for 3 years posttransplant according to PMP utilization. After adjusting for other recipient, donor and transplant factors, PMP utilization was associated with a $2130 reduction (p = 0.007) in hospitalization costs. PMP utilization was also associated with lower DGF risk (p < 0.0001). PMP utilization did not predict differences in rejection, graft survival, patient survival, or costs at 1, 2 and 3 years posttransplant. PMP utilization is correlated with lower costs for the transplant hospitalization, which is likely due to the associated reduction in DGF among recipients of PMP kidneys. However, there is no difference in long-term Medicare costs for ECD recipients by PMP utilization. A prospective trial is necessary as it will help determine if the associations seen here are due to PMP utilization and not differences in the population studied.
Abstract: BACKGROUND: Clinical practice guidelines for management of chronic kidney disease (CKD) have been developed within the Kidney Disease Outcomes Quality Initiative (K/DOQI). Adherence patterns may identify focus areas for quality improvement. METHODS: We retrospectively studied contemporary CKD care patterns within a private health system in the United States, and systematically reviewed literature of reported practices internationally. Five hundred and nineteen patients with moderate CKD (estimated GFR 30-59 ml/min) using healthcare benefits in 2002-2005 were identified from administrative insurance records. Thirty-three relevant publications in 2000-2006 describing care in 77,588 CKD patients were reviewed. Baseline demographic traits and provider specialty were considered as correlates of delivered care. Testing consistent with K/DOQI guidelines and prevalence of angiotensin converting enzyme inhibitor/angiotensin receptor blocker (ACEi/ARB) medication prescriptions were ascertained from billing claims. Care descriptions in the literature sample were based on medical charts, electronic records and/or claims. RESULTS: KDOQI-consistent measurements of parathyroid hormone (7.1 vs. 0.6%, P = 0.0002), phosphorus (38.2 vs. 1.9%, P < 0.0001) and quantified urinary protein (23.8 vs. 9.4%, P = 0.008) were more common among CKD patients with versus without nephrology referral in the administrative data. Nephrology referral correlated with increased likelihood of testing for parathyroid hormone and phosphorus after adjustment for baseline patient factors. Use of ACEi/ARB medications was more common among patients with nephrology contact (50.0 vs. 30.0%; P = 0.008) but appeared largely driven by higher comorbidity burden. The literature review demonstrated similar practice patterns. CONCLUSIONS: Delivery of CKD care may be monitored by administrative data. There is opportunity for improvement in CKD guideline adherence in practice.
Abstract: BACKGROUND: Gastrointestinal complications after kidney transplantation are associated with inferior graft outcomes. We examined the incidence, risk factors, and outcomes of posttransplantation diarrhea. STUDY DESIGN: Historic cohort study. SETTING & PARTICIPANTS: We examined first kidney transplant recipients in the United States from 1995 to 2002, with follow-up through December 2002. Recipients of multiple organs were excluded. We limited our study population to Medicare beneficiaries. PREDICTORS: Recipient, donor, and transplant characteristics were ascertained by means of US Renal Data System database inquiry. OUTCOMES: Incidence of diarrhea, graft loss, and death after transplantation. First episodes of diarrhea after transplantation were ascertained by using International Classification of Disease, Ninth Revision, Clinical Modification codes using Medicare billing data. Cause of diarrhea was classified as infectious or not and according to specific cause. Graft loss and death were ascertained from the date of the first diarrhea episode. RESULTS: We enrolled 41,442 patients. Mean follow-up was 758 +/- 399 days. We observed 7,103 diarrhea cases and 8,104 graft losses (4,201 deaths). The 3-year cumulative incidence of diarrhea was 22%, with 18% diagnosed as noninfectious diarrhea with an unspecified cause. Using multivariate Cox proportional hazards analysis, factors associated with increased risk of unspecified noninfectious diarrhea were female sex (hazard ratio [HR], 1.40; 95% confidence interval, 1.33 to 1.48), type 1 diabetes (HR, 1.20; 95% confidence interval, 1.06 to 1.37), and regimens containing tacrolimus and mycophenolate mofetil (HR, 1.37; 95% confidence interval, 1.28 to 1.46). Unspecified noninfectious diarrhea was associated with increased risk of graft failure (HR, 2.13; 95% confidence interval, 1.98 to 2.28) and patient death (HR, 2.04; 95% confidence interval, 1.85 to 2.24). LIMITATIONS: Use of claims data to ascertain patient characteristics and events; inability to make causal inference based on retrospective designs. CONCLUSIONS: Regimens containing tacrolimus and mycophenolate mofetil were associated with increased risk of noninfectious diarrhea. Episodes of noninfectious diarrhea doubled the hazard of graft loss and patient death.
Abstract: BACKGROUND: Proximal or "downhill" esophageal varices are a rare complication of superior vena caval (SVC) obstruction. Few reports describe downhill varices in dialysis patients with catheter-related SVC occlusion. METHODS: We studied a case of downhill esophageal varices in a dialysis patient from our center and reviewed the published literature on presentation, evaluation and treatment in other dialysis patients (MEDLINE database search). RESULTS: Including our current case, we identified eight reports of dialysis patients with downhill varices. All cases were recognized after presentation with gastrointestinal bleeding, in contrast to low reported bleeding rates of downhill varices in non-dialysis patients. Localized edema and superficial venous engorgement (signs of SVC occlusion) were each observed in four of eight patients. The duration of hemodialysis dependence ranged from 2.5 to 23 years, and dialysis access history included multiple central venous catheters when described (seven cases). Central venous imaging by direct, magnetic resonance or computerized tomographic venography documented SVC stenosis in all cases. Management included percutaneous transluminal angioplasty of the SVC with or without stenting in five of eight patients, three of whom developed restenosis during observation. Successful surgical venous bypass was performed in one patient after failed percutaneous venoplasty. Varices were treated with band ligation in four of eight cases without reported complications. CONCLUSIONS: Although rare, downhill esophageal varices should be considered in the differential diagnosis of upper gastrointestinal hemorrhage in dialysis patients exposed to central venous catheters. Diagnosis should prompt radiographic evaluation of SVC patency. Treatment requires timely and coordinated care by specialists in endovascular interventions and gastrointestinal endoscopy.
Abstract: BACKGROUND AND OBJECTIVES: Accurate assessment of the use of immunosuppressive medications is vital for observational analyses that are widely used in transplantation research. This study assessed the accuracy of three potential sources of maintenance immunosuppression data. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This study investigated the agreement of immunosuppression information in directly linked electronic medical records for Medicare beneficiaries who received a kidney transplant at one center in 1998 through 2001, Organ Procurement and Transplantation Network (OPTN) survey data, and Medicare pharmacy claims. Pair-wise, interdata concordance (kappa) and percentage agreement statistics were used to compare immunosuppression regimens reported at discharge, and at 6 mo and 1 yr after transplantation in each data source. RESULTS: Among 181 eligible participants, agreement between data sources for nonsteroid immunosuppression increased with time after transplantation. By 1-yr, concordance was excellent for calcineurin inhibitors and mycophenolate mofetil (kappa = 0.79 to 1.00), and very good for azathioprine (kappa = 0.73 to 0.85). Similarly, percentage agreement at 1 yr was 94.9 to 100% for calcineurin inhibitors, 91.1 to 95.7% for mycophenolate mofetil, and 87.5 to 92.8% for azathioprine. Widening the comparison time window resolved 33.6% of cases with discordant indications of calcineurin inhibitor and/or antimetabolite use in claims compared with other data sources. CONCLUSIONS: This analysis supports the accuracy of the three sources of data for description of nonsteroid immunosuppression after kidney transplantation. Given the current strategic focus on reducing collection of data, use of alternative measures of immunosuppression exposure is appropriate and will assume greater importance.
Abstract: BACKGROUND AND OBJECTIVES: This study examined the risks, predictors, and mortality implications of cerebrovascular disease events after kidney transplantation in a national cohort. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This analysis used United States Renal Data System registry data to study retrospectively Medicare-insured kidney transplant candidates (n = 51,504), recipients (n = 29,614), and recipients with allograft failure (n = 2954) in 1995 through 2002. New-onset cerebrovascular disease events including ischemic stroke, hemorrhagic stroke, and transient ischemic attacks were ascertained from billing records, and participants were followed until Medicare-end or December 31, 2002. Multivariable survival analysis was used to compare cerebrovascular disease event incidence and risk profiles among the study samples. RESULTS: The cumulative, 3-yr incidence of de novo cerebrovascular disease events after transplantation was 6.8% and was lower than adjusted 3-yr estimates of 11.8% on the waiting list and 11.2% after graft loss. In time-dependent regression, transplantation predicted a 34% reduction in subsequent, overall cerebrovascular disease events risk compared with remaining on the waiting list, whereas risk for cerebrovascular disease events increased >150% after graft failure. Similar relationships with transplantation and graft loss were observed for each type of cerebrovascular disease event. Smoking was a potentially preventable correlate of posttransplantation cerebrovascular disease events. Women were not protected. All forms of cerebrovascular disease event diagnoses after transplantation predicted increased mortality. CONCLUSIONS: Along with known benefits for cardiac complications, transplantation with sustained graft function seems to reduce risk for vascular disease events involving the cerebral circulation.
Abstract: BACKGROUND AND OBJECTIVES: Evaluation for ischemic heart disease (IHD) is a nonstandardized practice before kidney transplantation. We retrospectively studied pretransplant cardiac evaluation (CE) practices in a national sample of renal allograft recipients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The USRDS data for Medicare beneficiaries transplanted in 1991 to 2004 with Part A&B benefits from dialysis initiation through transplantation were examined. Clinical traits defining "high" expected IHD risk were defined as diabetes, prior IHD, or > or = 2 other coronary risk factors. Pretransplant CE were identified by billing claims for noninvasive stress tests and angiography. Patients were quantified with claims for coronary revascularization procedures between CE and transplant. Post-transplant acute myocardial infarction (AMI) events were abstracted from claims and death records. RESULTS: Among 27,786 eligible patients, 46.3% underwent CE before transplantation. Overall, 9.5% who received CE also received pretransplant revascularization, but only 0.3% of lower-risk patients undergoing CE had revascularization. The adjusted odds of transplant without CE increased sharply with younger age and shorter dialysis duration. Increased likelihood of transplant without CE also correlated with black race, female sex, and certain geographic regions. Among patients transplanted without CE, 3-yr incidence of post-transplant AMI was 3% in lower-risk and 10% in high-risk groups, and varied by individual traits within these groups. Among lower-risk patients transplanted without CE, blacks were higher risk for AMI than whites (adjusted hazards ratio 1.47, 95% CI 1.11-1.93). CONCLUSIONS: Observed practices demonstrate infrequent use of pretransplant revascularization after CE but also raise concern for socio-demographic barriers to evaluation access.
Abstract: The flow cytometry crossmatch (FXCM) is an increasingly common method for pre-transplant crossmatching. We examined FCXM use in a national sample of kidney transplants, characterizing target cell utilization, results patterns, and associated graft outcomes. We queried Organ Procurement and Transplant Network Registry to identify kidney transplants performed in 1995-2007 with prospective FCXM testing for IgG antibodies against T-cells, B-cells or undifferentiated lymphocytes. FCXM was categorized according to target utilization and target-specific results. We modeled associations of FCXM testing-results patterns with risk of five-year graft loss and with projected graft survival by multivariable survival analysis. Sixty-five percent of the deceased donor transplants were performed with negative T-cell and B-cell FCXM, 16% with negative T-cell/unmeasured B-cell FCXM, 9% with negative undifferentiated lymphocyte FCXM, and < 0.5% with negative B-cell/unmeasured T-cell FCXM. Test results for at least one target were positive in 7.6% of transplants, most commonly in the form of B-cell positive/T-cell negative. Allograft survival was most favorable when both T-cell and B-cell FCXM targets were included and yielded negative results. Notably, B-cell positive/T-cell negative FCXM predicted elevated graft loss risk, with approximately 16% and 32% relative risk increases for deceased and living donor grafts, respectively, compared to negative T-cell and B-cell FCXM. Negative FCXM results with undifferentiated targets alone also predicted inferior graft survival. These data support the importance of using differentiated B-cell and T-cell targets for FCXM. Transplants that proceeded with positive FCXM experienced decrements in long-term graft survival - the decision to accept such risk must be individualized.
Abstract: BACKGROUND: Gastrointestinal complications are common in patients who undergo kidney transplantation and may affect posttransplant outcomes. We examined the incidence and predictors of gastroesophageal reflux disease (GERD) and dyspepsia and their associations with graft survival and mortality after transplant. METHODS: We examined United States Renal Data System data and Medicare billing claims to identify diagnoses of dyspepsia and GERD among Medicare beneficiaries transplanted in 1995-2002 (n=42,257). Among GERD cases, we identified patients with reflux esophagitis (RE). We determined independent predictors of upper gastrointestinal complications and modeled these conditions as time-dependent outcomes predictors with Cox regression. RESULTS: The 3-year cumulative incidences of GERD, RE, and dyspepsia were 20%, 5%, and 6%, respectively. Overall, 23% of transplant recipients received a diagnosis of at least one of these complications by 3 years after transplant. Female gender and a pretransplant upper gastrointestinal disease diagnosis predicted posttransplant gastrointestinal complications. Older age, obesity, Caucasian, and African-American race were associated to increased risk of developing GERD. Patients diagnosed with any of the examined upper gastrointestinal complications experienced an increased risk of graft-failure (hazard ratio 1.58; 95% confidence interval 1.48-1.69) and death (hazard ratio 1.61; 95% confidence interval 1.46-1.77). CONCLUSIONS: Upper gastrointestinal complications are relatively common after kidney transplantation and are associated with a significantly increased risk of graft loss and death. Further research is needed to elucidate mechanisms underlying the observed adverse prognoses conferred by diagnosis of upper gastrointestinal complications after kidney transplant.
Abstract: We describe factors associated with poor compliance and dose reductions and examine the relative impact of compliance, dose reduction and discontinuation on graft outcome. Medicare claims for MMF in 7062 deceased donor renal recipients with at least 1 year of graft function were used to calculate compliance and dose reductions. Compliance was modeled using medication possession ratio to define quartiles for poor, low, medium and high compliance. The relative impact of compliance, dose reduction and discontinuation on graft outcome was assessed with Cox proportional hazards. Pediatric (Age 0-18, Odds ratio = 1.71, 95% CI 1.11-2.63, p = 0.014) and adolescent recipients (19-24, 1.57, 1.23-2.00, p < 0.001) were more likely poorly compliant compared to adults age 25-44. Poor compliance was also associated with physical limitations, hypertension, delayed graft function, rejection, infection and GI conditions. Poor (1.43, 1.11-1.84, p = 0.005) and low (1.46, 1.13-1.88, p = 0.004) compliance was associated with an increased hazard of graft loss as was >50% dose reduction (1.69, 1.15-2.50, p = 0.008) and discontinuation (8.34, 6.85-10.2, p < 0.001). Medication possession ratios lower than the 3-year mean were associated with an increased risk of graft loss. These results may indicate that interventions to improve compliance among kidney transplant recipients should strive for high rather than discourage low compliance.
Abstract: Risk for new-onset diabetes (NOD) after renal transplantation is higher with tacrolimus (Tac) than with cyclosporine (CsA), but the extent to which the diabetogenic effect of Tac is dosage dependent or steroid dependent remains uncertain. Patients who received a transplant between 1995 and 2002 were drawn from the United Network for Organ Sharing registry and prescription records and NOD diagnoses from Medicare claims, both provided by the United States Renal Data System. Patients were divided into six groups of steroid and Tac doses at 30 d after transplantation and referenced against CsA. Relative hazards of NOD with Cox proportional hazards regression were estimated incorporating propensity scores for Tac and nonimmunosuppressive factors related to NOD. A total of 8839 patients with valid immunosuppression records and without pretransplantation evidence of diabetes were included in the study. Unadjusted, cumulative, NOD incidence 1 yr after transplantation was 14.6% with CsA and 22.2% with Tac and at 3 yr after transplantation was 23.4% with CsA and 32.9% with Tac (P < 0.0001). Neither higher CsA nor higher steroid dosages were associated with NOD in CsA-treated patients. However, NOD hazard was significantly higher with Tac than with CsA in all six steroid/Tac dosing groups, including the cohort with the lowest dosages of Tac (dosage thresholds at 30 d after transplantation <0.12 mg/kg per d [mean 0.07 mg/kg per d] and steroids (<0.75 mg/kg per d; hazard ratio 1.28; 95% confidence interval 1.10 to 1.48; P = 0.0012). Whereas the incidence of NOD is greatest with high Tac dosages, the increased risk versus CsA is sustained with lower Tac dosages. Higher steroid dosages increase the early diabetogenic effect of Tac but not of CsA.
Abstract: BACKGROUND: Data are scarce regarding the incidence and risk factors for complications of new-onset diabetes mellitus (NODM) in renal transplant patients. METHODS: United States Renal Data System (USRDS) data from primary renal transplant recipients during 1995-2001 who developed NODM was used to examine diabetic complications over the first three years posttransplant. Prognostic models were used to evaluate patient characteristics and treatment choices associated with risk of each class of complications. Propensity scores for choice of calcineurin inhibitor were included in multivariate analyses. RESULTS: The analysis included 21,489 patients, of whom 4,105 developed NODM by 3 years posttransplant. One or more NODM complications developed in 2,393 patients (58.3% of all patients with NODM), comprising ketoacidosis (334, 8.1%), hyperosmolarity (131, 3.2%), renal complications (1,286, 31.3%), ophthalmic complications (340, 8.3%), neurological complications (665, 16.2%), peripheral circulatory disorders (170, 4.1%) and hypoglycemia/shock (301, 7.3%). Complications developed within a mean of 500 to 600 days from diagnosis of NODM. Multivariate analysis showed that increased recipient age, higher body mass index, African-American race, hepatitis C infection, hypertension as cause of end-stage renal disease, cold ischemia >or=30 hours, and use of tacrolimus each increased risk of complications. CONCLUSION: NODM is associated with similar complications to those seen in the general population, but these appear to develop at an accelerated rate. Obesity and use of tacrolimus are the only modifiable factors that appear to affect risk of NODM or its complications.
Abstract: The advent of improved immunosuppression and enhanced allograft outcomes has resulted in a growing number of patients taking expensive immunosuppression medications for the rest of their lives. Healthcare costs for the majority of transplantation procedures in the USA currently are covered by Medicare, but coverage ends for outpatient immunosuppression medications 36-44 months after transplantation. Two or three immunosuppressive agents typically are included in post-transplant regimens with a total annual cost that can exceed 13,000 dollars. This represents a significant financial burden for families no matter if they have adequate health insurance coverage because of co-payment obligations. Evidence suggests that some patients have reduced immunosuppression doses because of an inability to afford their medication, increasing the risk of graft failure. The purpose of this article was to review these and other issues pertaining to medical insurance coverage and transplantation, particularly for adolescent recipients as they transition to adulthood.
Abstract: Administrative claims data facilitate ascertainment of outcomes not collected by the transplant registry and provide the opportunity to examine prescribed doses of immunosuppressive medications. Here, we examine the impact of human leukocyte antigen (HLA) matching on traditional outcomes, rejection and survival, and use novel methods to examine immunosuppresion doses and complication rates. The central hypothesis tested in this analysis is that HLA-matched recipients receive lower doses of immunosuppression and have fewer posttransplant complications. We break from tradition by examining HLA matching in both living and deceased donor kidney transplants. As secondary aims, we compare the relative impact of class I and II mismatches and describe outcomes achieved with older donors. Medicare claims linked to the United States Renal Data System database for 23,443 kidney transplants were included in the study. A total of 15,793 transplants were DR mismatched (DRMM), 5,340 manifested no DR mismatches (NODRMM), and 2,310 manifested no ABDR mismatches (NOABDRMM). Patients with NOABDRMM experienced lower adjusted risk of rejection (0.66, 95% confidence interval 0.59-0.74, P < 0.001) and lower hazard of graft loss (0.69, 0.61-0.77, P < 0.001) and death (0.76, 0.63-0.92, P < 0.001) compared with those with DRMM. The hazard of cardiac and diabetic complications was similar between recipients of NOADRMM and DRMM transplants, but the hazard of diarrhea was significantly lower (0.82, 0.73-0.92, P < 0.001) in patients with NOABDRMM. The 6-month dose of mycophenolate mofetil was lower in patients with NOABDRMM. This study validates previous studies that indicated significantly lower risks of rejection, graft loss, and death among patients with 0 HLA-A,B,DR mismatches. Use of administrative claims revealed similar rates of cardiovascular complications. However, HLA-matched deceased donor recipients received lower dosages of mycophenolate mofetil and manifested a lower risk of developing posttransplant diarrhea.
Abstract: We investigated graft and patient survival implications of simultaneous pancreas kidney (SPK) transplant from old donors. Data describing patients with type 1 diabetes mellitus listed for an SPK transplant from 1994 to 2005 were drawn from Organ Procurement and Transplant Network registries. Allograft survival, patient survival and long-term survival expectations among SPK recipients from young (age <45 years) and old (age >/=45 years) donors were modeled by multivariate regression. We also examined predictors of reduced early access to young donor transplants. Of 16 496 eligible SPK candidates, 8850 patients (53.6%) received an SPK transplant and 776 (8.8%) of these transplants were from old donors. Reasonable 5-year, death-censored kidney (77.8 %) and pancreas (71.3%) survivals were achieved with old donors. SPK transplantation from both young and old donors predicted lower mortality compared to continued waiting. An additional expected wait of 1.5 years for a young donor equalized long-term survival expectations to that achieved with use of old donors. Early allocation of young donor transplants declined in the more recent era and varied by region, candidate age, blood type and sensitization. We conclude that old SPK donors should be considered for patients with decreased access to young donor transplants. Prospective evaluation of this practice is needed.
Abstract: BACKGROUND: Mycophenolate mofetil (MMF) use in renal transplantation has steadily increased since 1995 because of its ability to lower the risks of rejection and chronic allograft nephropathy. However, significant gastrointestinal (GI) complications may lead to MMF dose reductions and discontinuations. Little is known of the association between MMF dose reductions and discontinuations following GI complications and graft survival. METHODS: Using the United States Renal Data System, we identified 3,675 adult recipients (age >or=18) with a diagnosed GI complication who were prescribed MMF at the time of first GI diagnosis and had Medicare as their primary insurer. MMF doses were ascertained from Medicare payment records. We estimated risk of graft loss associated with MMF dose adjustments after GI diagnosis: dosage unchanged (reference), reduced <50%, reduced >or=50%, and MMF discontinued. Patients were followed until graft loss, death, last recorded immunosuppression prescription, or 3 years posttransplant. RESULTS: Compared to those with no MMF dose reductions or discontinuations, the risk of graft failure increased with MMF doses reduction >or=50% (HR=2.36, 95% CI 1.23-4.54) and those with MMF discontinuation (2.72, CI 1.60-4.64). CONCLUSION: Renal transplant recipients who underwent MMF dose reduction or withdrawal following GI diagnosis are associated with increased risk of graft failure.
Abstract: The risk for and predictors of atrial fibrillation (AF) after kidney transplantation are not well described. Registry data that were collected by the United States Renal Data System were used to investigate retrospectively new-onset AF among adult first renal allograft recipients and transplant candidates who received a transplant or were wait-listed in 1995 to 2001 with Medicare as the primary payer. AF events were ascertained from billing records, and participants were followed until loss of Medicare coverage or December 31, 2001. Cox hazards analysis was used to identify independent correlates of posttransplantation AF (adjusted hazard ratio [AHR]; 95% confidence interval [CI]) and to examine AF as an outcomes predictor. Among 31,136 eligible transplant recipients, the cumulative incidence of new-onset AF was 3.6% (95% CI 3.4 to 3.8%) and 7.3% (95% CI 7.0 to 7.6%) at 12 and 36 mo and declined below the demographics-adjusted cumulative incidence on the waiting list by approximately 17 mo. Risk factors for posttransplantation AF included older recipient age, male gender, white race, renal failure from hypertension, and coronary artery disease. Extended pretransplantation dialysis duration, posttransplantation diabetes, and graft failure were identified as potentially modifiable correlates of AF. In separate analyses, AF independently predicted death (AHR 3.2; 95% CI 2.9 to 3.6) and death-censored graft loss (AHR 1.9; 95% CI 1.6 to 2.3). As the population of renal transplant recipients grows older, the incidence and prevalence of AF among these patients will likely increase. Appropriate risk stratification may identify transplant recipients who are in need of close monitoring for and management of this adverse cardiovascular event.
Abstract: BACKGROUND: Inflammatory markers predict cardiovascular risk and mortality in endstage renal disease. The relationship of chronic infections to inflammation and vascular disease events has not been reported among American dialysis patients. METHODS: We performed a cross-sectional and prospective study of a multiracial cohort of 97 chronic hemodialysis patients in California. Anti-Chlamydia pneumoniae IgA and IgG antibodies (Cp-IgA and Cp-IgG), anti-Helicobacter pylori antibodies (Hp-IgG), and highly sensitive C-reactive protein (hsCRP) levels were measured at enrollment. We ascertained the prevalence of atherosclerotic vascular (coronary artery, cerebrovascular, and peripheral vascular) disease (AVD) events, and observed participants for at least 1 year for incident events and mortality. We defined statistical significance as P < 0.01. RESULTS: Elevated hsCRP levels (77%) and seropositivity to C. pneumoniae were common (Cp-IgA, 49%; Cp-IgG, 64%), whereas the seroprevalence of Hp-IgG was relatively low (25%). The hsCRP levels did not vary with infection status. In bivariate analysis, Cp-IgA and Cp-IgG were each associated with approximately fourfold higher odds of prevalent AVD (P < 0.01). Although anti-chlamydial antibodies maintained nearly significant associations with AVD after covariate adjustment (P < 0.05), antibodies did not predict outcomes over the period of observation. However, hsCRP was a nearly significant independent predictor of prevalent AVD (P = 0.02) and of mortality during follow-up (P = 0.01). We did not detect an association of Hp-IgG with any study outcome. CONCLUSIONS: Our findings generalize a possible link between C. pneumoniae and prevalent atherosclerosis in American hemodialysis patients and confirm the importance of hsCRP as a prognostic indicator. Our work does not support H. pylori as an important mediator of cardiovascular risk in dialysis patients.
Abstract: The Organ Procurement and Transplantation Network (OPTN) collects intermittent survey data on immunosuppressive medication use that are studied frequently as research measures. Pharmacy billing claims may provide an accurate measure of immunosuppression use over time. Herein is characterized the agreement of Medicare pharmacy claims for immunosuppressive medications with OPTN reports. Data were drawn from the United States Renal Data System. Participants received a kidney transplant in 2000 to 2001 and had an OPTN record and a Medicare pharmacy claim for an immunosuppressive drug at transplant discharge and 6 mo and 1 yr after transplantation. The concordance (kappa) of the OPTN and claims (+/-30 d of survey) for indicated medication use was compared, and sensitivity, specificity, and predictive values for claims were computed, assuming OPTN as a "gold standard." Clinical trial participation and regimen changes were examined as explanations for discordance. A total of 4357 eligible subjects were identified. Concordance over observation ranged from excellent for calcineurin inhibitors (kappa > 0.86) to generally very good for adjunctive agents (kappa = 0.49 to 0.75) to poor for corticosteroids (kappa <0.15). Claims demonstrated high positive predictive values (> or =97%) but low negative predictive values (< or =13%) for OPTN-reported corticosteroid use. Regimen changes (28 to 75%) but not clinical trial participation (< or =21%) were identified frequently among cases with discordant indications of nonsteroid medication use. Close agreement of Medicare billing claims and the OPTN for indicated use of nonsteroid immunosuppressive medications supports both as useful measures of drug exposure. Low detection rates of OPTN-indicated corticosteroid use within claims require further examination.
Abstract: BACKGROUND: Whether the previously reported underutilization of standard-of-care medications in the management of patients with acute myocardial infarction (AMI) persists in more recent years or differs by ward of admission has not been reported. METHODS: We performed a retrospective cross-sectional study of patients hospitalized with a discharge diagnosis of incident AMI to a Department of Defense hospital (Walter Reed Army Medical Center, Washington, DC) from 2001 through 2004. Use of beta-blockers and aspirin at the time of discharge after AMI was assessed according to Modification of Diet in Renal Disease (MDRD) estimated glomerular filtration rate (eGFR) in milliliters per minute per 1.73 m2, stratified by admission to the coronary care unit (CCU) versus other wards. Adjusted odds ratios for discharge beta-blocker and aspirin therapy were calculated by using logistic regression. RESULTS: Among 431 patients, overall discharge use of beta-blockers was 86.8%, and aspirin, 86.8%, both significantly greater after CCU admission than admission to other wards (93%, aspirin use; 91.7%, beta-blocker use; P < 0.001 and P < 0.001). In logistic regression, CCU admission was the only independent factor associated with either beta-blocker or aspirin use; MDRD eGFR was not associated significantly with beta-blocker and aspirin use regardless of admission to the CCU or non-CCU. CONCLUSION: Future studies of disparities in use of standard-of-care medications after AMI according to renal function should account for the primary site of admission, particularly CCU versus others. In addition, legitimate contraindications to the use of beta-blockers and aspirin may be subtle, including appropriate end-of-life decisions.
Abstract: Understanding the additional life-years given to patients by deceased organ donors is necessary as substantial investments are being proposed to increase organ donation. Data were drawn from the Scientific Registry of Transplant Recipients. All patients placed on the wait-list as eligible to receive or receiving a deceased donor solid organ transplant between 1995 and 2002 were studied. The benefit of transplant was determined by the difference in the expected survival experiences of transplant recipients and candidates expecting transplant soon. An average organ donor provides 30.8 additional life-years distributed over an average 2.9 different solid organ transplant recipients, whereas utilization of all solid organs from a single donor provides 55.8 additional life-years spread over six organ transplant recipients. The relative contribution of the different organs to the overall life-year benefit is higher for liver, heart and kidney, and lowest for lung and pancreas. The life-year losses from unprocured and unused organs are comparable to suicide, congenital anomalies, homicide or perinatal conditions and half that of HIV. Approximately 250,000 additional life-years could be saved annually if consent for potential deceased donors could be increased to 100%. Therefore, increasing organ donation should be considered among our most important public health concerns.
Abstract: BACKGROUND: We aim to describe the risk, predictors, and outcomes associated with de novo congestive heart failure (CHF) after kidney transplantation. METHODS: We used registry data from the US Renal Data System to retrospectively investigate de novo CHF in adult Medicare-insured transplant recipients and wait-listed candidates in 1995 to 2001. Heart failure was ascertained from inpatient and outpatient billing records, and participants were followed up until loss of Medicare or December 31, 2001. We used extended Cox hazards analysis to identify independent correlates of posttransplantation de novo CHF (adjusted hazard ratio [AHR], 95% confidence interval [CI]) and examine de novo CHF as a predictor of death and graft loss after transplantation. RESULTS: In 27,011 transplant recipients, cumulative incidences of de novo CHF were 10.2% (95% CI, 9.8 to 10.6) and 18.3% (95% CI, 17.8 to 18.9) at 12 and 36 months and decreased to less than the demographic-adjusted incidence on the waiting list beyond the early posttransplantation period. Risk factors for de novo CHF included older recipient age, female sex, unemployed status at transplantation, pretransplantation comorbidities (anemia, diabetes mellitus, myocardial infarction, angina, cardiac arrhythmia, and peripheral vascular disease), transplant from older donors, donor cardiovascular death, and delayed graft function. We identified pretransplantation obesity, smoking, and posttransplantation complications, including hypertension, anemia, new-onset diabetes, myocardial infarction, and graft failure, as potentially modifiable correlates of de novo CHF. In separate analyses, de novo CHF predicted death (AHR, 2.6; 95% CI, 2.4 to 2.9) and death-censored graft failure (AHR, 2.7; 95% CI, 2.4 to 3.0). CONCLUSION: Although associations may not reflect causality, identification of potentially mutable de novo CHF risk factors suggests targets for improving outcomes that should be evaluated prospectively.
Abstract: BACKGROUND: Avascular necrosis (AVN) after renal transplantation has been largely attributed to the use of corticosteroids. However, other risk factors such as microvascular thrombosis and hyperlipidemia have been well described and may be of increased importance in the era of early steroid cessation and avoidance. We hypothesized that maintenance immunosuppressive medications known to be associated with these risk factors for AVN would also be associated with a higher risk of AVN. METHODS: By using the U.S. Renal Data System database, we studied 27,772 primary patients on Medicare who received a solitary kidney transplant between January 1, 1996, and July 31, 2000. Cox proportional hazards regression models were used to calculate adjusted hazard ratios (AHRs) for patient- and transplant-related factors (including allograft rejection) with Medicare claims for AVN. The intensity and duration of corticosteroid use could not be assessed. RESULTS: Among patients who were prescribed sirolimus at discharge, 3.5% of patients who received the combination of sirolimus-cyclosporine A (CsA) demonstrated AVN, compared with 1.4% of patients who received the combination of sirolimus-tacrolimus (P=0.06 by chi). In Cox regression, CsA use (vs. tacrolimus) (AHR 1.36, 95% confidence interval, 1.09-1.71) was independently associated with an increased risk of AVN. Sirolimus use showed a trend toward significance (AHR 1.59, 95% confidence interval, 0.99-2.56), with no significant interaction with CsA. CONCLUSIONS: Compared with other maintenance immunosuppression, AVN was significantly more common after use of CsA prescribed at the time of discharge for renal transplantation. Whether this increased risk of AVN was directly attributable to hyperlipidemia, microvascular thrombosis, or differences in corticosteroid dosing could not be determined.
Abstract: PURPOSE: To describe practices for preventing venous thromboembolism in critically ill medical patients and to identify associations between prophylactic measures and survival. METHODS: We reviewed the records of all medical admissions to the intensive care units of a university hospital and an affiliated Veterans Affairs hospital over a 1-year period. We recorded patients' demographic characteristics, risk factors for venous thromboembolism, methods of prophylaxis, and in-hospital deaths. RESULTS: We identified 272 critically ill medical patients who received intensive care for at least 24 hours. Some form of prophylaxis was used in 205 patients (75%), including pharmacologic prophylaxis alone in 55 (20%), mechanical prophylaxis alone in 102 (38%), and both methods in 48 (18%). In-hospital mortality rates were 23% (24/103) for patients who received pharmacologic prophylaxis, and 36% (61/169) for those who received mechanical prophylaxis alone or no prophylaxis (P=.03). After adjusting for demographic characteristics, risk factors for thrombosis and severity of illness, the odds of death were 55% lower in patients who received pharmacologic prophylaxis (odds ratio [OR]=0.45; 95% confidence interval (CI): 0.22 to 0.93; P=.03). Similar results were obtained in propensity-adjusted and propensity-stratified analyses. Use of mechanical prophylaxis was not associated with survival (OR=0.88; 95% CI 0.44 to 1.77; P=.73). CONCLUSION: In this cohort of critically ill medical patients, pharmacologic but not mechanical thromboprophylaxis was associated with reduced risk of in-hospital death. This hypothesis must be tested in randomized trials.
Abstract: ICD-9-CM diagnoses for hospitalizations occurring during the first 6 post-transplant months were summarized into Clinical Classifications System (CCS) categories. Of the 28,900 patients examined, 54% had at least one hospitalization. There were 2.39 hospitalizations per patient-year at risk. The total Medicare inpatient costs were $339 million and mean length of stay was 8.3 days. The most common and costly CCS diagnosis was complications of a kidney transplant followed by infections, circulatory system disease, gastrointestinal disease and endocrine complications. The CCS is a useful tool to summarize the complexity of claims information in the USRDS and could prove useful in further claims research.
Abstract: The risk and predictors of post-kidney transplantation myocardial infarction (PTMI) are not well described. Registry data collected by the United States Renal Data System were used to investigate retrospectively PTMI among adult first renal allograft recipients who received a transplant in 1995 to 2000 and had Medicare as the primary payer. PTMI events were ascertained from billing and death records, and participants were followed for up to 3 yr after transplant or until the end of observation (December 31, 2000). Extended Cox's hazards analysis was used to identify independent clinical correlates of PTMI (hazard ratio [HR]) and to examine PTMI as an outcomes predictor. Among 35,847 eligible participants, the cumulative incidence of PTMI was 4.3% (95% confidence interval [CI], 4.1 to 4.5%), 5.6% (95% CI, 5.3 to 5.8%), and 11.1% (95% CI, 10.7 to 11.5%) at 6, 12, and 36 mo, respectively. Risk factors for PTMI included older recipient age, pretransplantation comorbidities (diabetes, angina, peripheral vascular disease, and MI), transplantation from older donors and deceased donors, and delayed graft function. Women, blacks, Hispanics, and employed recipients experienced reduced risk. The hazard of PTMI rose after a diagnosis of posttransplantation diabetes (HR, 1.60; 95% CI, 1.35 to 1.88) and markedly increased after graft failure (HR, 2.78; 95% CI, 2.41 to 3.19). In separate analyses, PTMI predicted death-censored graft failure (HR, 1.89; 95% CI, 1.63 to 2.20) and strongly predicted death in a manner that declined with time after PTMI. Risk factors for PTMI include potentially modifiable posttransplantation complications. Because PTMI in turn predicts graft failure and death, reducing the risk for PTMI may improve outcomes after kidney transplantation.
Abstract: BACKGROUND: Diabetic muscle infarction (DMI) is an unusual disorder of type 1 and type 2 diabetic patients with advanced microvascular damage including nephropathy. Few reports describe this complication among dialysis patients. METHODS: We studied four patients with terminal renal failure due to diabetic nephropathy who developed isolated skeletal muscle infarction at our institution between January 1998 and January 2003, and reviewed 15 additional cases of DMI reported among dialysis patients (Medline database search). RESULTS: Analysis of available data for all 19 cases revealed the following features: mean age at symptom onset of 46.4 years; average duration of renal replacement 25.7 months (range 36 h to 72 months); male predominance (2.2:1); higher prevalence of type 2 vs type 1 diabetes (2.2:1); and more common use of haemodialysis than peritoneal dialysis (2.6:1). One patient developed symptoms after being immobilized during surgery and initiating dialysis. Thigh involvement was frequent (17/19). Fever, leucocytosis and elevated serum creatine kinase levels were noted inconsistently, but were seen commonly with early evaluation after symptom onset. Erythrocyte-sedimentation rate and C-reactive protein levels were high when checked. All 16 instances of magnetic resonance imaging (MRI) demonstrated increased T2-weighted signal from affected muscles. Seven patients were managed without muscle biopsy. Histological features included myofibre necrosis (8/12), inflammatory infiltrates (8/12) and microvasculopathy (6/12). Symptoms resolved with conservative therapy, but patients were at high risk for subsequent infarctions of other muscles (14/19). CONCLUSIONS: DMI should be suspected in any diabetic dialysis patient who develops a painful, swollen muscle. A conservative MRI-based diagnostic approach may lead to satisfactory outcomes. The pathogenesis of the disorder is controversial, but the clinical sequence of one of our cases suggests precipitation by immobilization, direct pressure and/or haemoconcentration.
Abstract: Complications associated with use of donor hepatitis C-positive kidneys (DHCV+) have been attributed primarily to posttransplantation liver disease (as a result of hepatitis C disease). The role of posttransplantation diabetes has not been explored in this setting. With the use of the United States Renal Data System database, 28,942 Medicare KT recipients were studied from January 1, 1996, through July 31, 2000. Cox proportional hazards regression models were used to calculate adjusted hazard ratios (AHR) for the association of sero-pairs for HCV (D+/R-, D+/R+, D-/R+ and D-/R-) with Medicare claims for de novo posttransplantation HCV and posttransplantation diabetes. The peak risk for posttransplantation HCV was in the first 6 mo after transplantation. The incidence of posttransplantation HCV after transplantation was 9.1% in D+/R-, 6.3% in D+/R+, 2.4% in D-/R+, and 0.2% in D-/R-. The incidence of posttransplantation diabetes after transplantation also peaked early and was 43.8% in D+/R-, 46.6% in D+/R+, 32.3% in D-/R+, and 25.4% in D-/R-. Associations for both complications were significant in adjusted analysis (Cox regression). Both posttransplantation HCV (AHR, 3.36; 95% confidence interval, 2.44 to 4.61) and posttransplantation diabetes (AHR, 1.81; 95% confidence interval, 1.54 to 2.11) were independently associated with an increased risk of death, but posttransplantation diabetes accounted for more years of life lost, particularly among recipients of DHCV+ kidneys. Posttransplantation diabetes may contribute substantially to the increased risk of death associated with use of DHCV+ kidneys and accounts for more years of life lost than posttransplantation HCV. Because HCV infection acquired after transplantation is so difficult to treat, methods that have been shown to reduce viral transmission warrant renewed attention.
Abstract: Analysis of the USRDS kidney transplant registry disclosed that use of hepatitis C virus-positive donor (DHCV+) kidneys was an independent risk factor for patient death after kidney transplantation when compared to use of DHCV- kidneys, and that death in recipients of DCHV+ kidneys occurred earlier than previously reported. This increased risk of death was delayed for about 2 years, suggesting the development of an intermediate complication that resulted in a later increased risk of death. While liver disease early after transplant in these patients was rare, new-onset diabetes mellitus occurred early and commonly, suggesting this complication as a prominent mediator of mortality associated with transplantation with DHCV+ kidneys. Identification of new-onset diabetes mellitus may represent a new target of opportunity to improve outcomes associated with use of DHCV+ kidneys. Even under the current circumstances, use of DHCV+ kidneys was also independently associated with a survival experience that, although less favorable than associated with transplantation of DHCV- kidneys, was significantly better than remaining on the kidney transplant waiting list. Whether this survival advantage applies to all relevant subgroups could not be assessed and warrants further study. Our analyses suggest opportunities to improve survival and reduce morbidity after use of DHCV+ kidneys.
Abstract: Whether transplantation of deceased donor kidney allografts from donors with antibodies against hepatitis C virus (HCV) confers a survival advantage compared with remaining on the kidney transplant waiting list is not yet known. We studied 38,270 USRDS Medicare beneficiaries awaiting kidney transplantation who presented with end-stage renal disease from April 1, 1995 to July 31, 2000. Cox regression was used to compare the adjusted hazard ratios for death among recipients of kidneys from deceased donors, and donors with antibodies against hepatitis C (DHCV+), controlling for demographics and comorbidities. In comparison to staying on the waiting list, transplantation from DHCV+ was associated with improved survival among all patients (adjusted hazard ratio for death 0.76, 95% CI 0.60, 0.96). Of patients receiving DHCV+ kidneys, 52% were themselves hepatitis C antibody positive (HCV+), so outcomes associated with use of these grafts may have particular implications for HCV+ transplant candidates. Recommendations for use of DHCV+ kidneys may require analysis of data not currently collected from either dialysis or transplant patients. However, transplantation of DHCV+ kidneys is associated with improved patient survival compared to remaining wait-listed and dialysis dependent.
Abstract: BACKGROUND AND OBJECTIVES: HMG-CoA reductase inhibitor (statin) therapy reduces cardiovascular risk in the general population and may modulate rejection in solid organ transplant recipients. We assessed whether current clinical evidence supports the use of statins to improve cardiac and/or renal outcomes after kidney transplantation. METHODS: We performed a systematic review of randomized, controlled intervention trials of statins among renal allograft recipients. Clinical trials published between January 1, 1993 and January 1, 2004 were identified by systematic search of electronic databases. Eligible studies measured the impact of therapy on acute allograft rejection, surrogates of cardiovascular risk and/or cardiovascular morbidity and mortality. We abstracted descriptive summaries of trial design elements and primary effect estimates, and assessed trial quality with a standardized quality evaluation tool. RESULTS: Thirteen eligible trials were identified. Statin therapy was associated with less acute allograft rejection in two early studies but was ineffective in three subsequent, larger trials. Therapeutic benefit was also seen in six of seven small studies that evaluated cardiovascular risk surrogates. Statin use did not significantly alter the primary composite outcome in a single large cardiac events trial, but was associated with reductions in secondary end-points of cardiac death analysed alone or with myocardial infarction. Important design distinctions included statin preparation and dose, concomitant interventions, study power and randomization methods. Median total quality scores were 52 for the rejection trials, 41 for the studies of cardiovascular risk surrogates and 69 for the cardiac events trial, and showed a trend towards variation by outcome measure (P = 0.05). CONCLUSIONS: Heterogeneous study designs and methodological quality contribute to discrepant conclusions on the benefit of statin therapy to renal allograft recipients. Trial-based clinical evidence does not support the use of statins to lower acute rejection risk after kidney transplantation, but does indicate effectiveness for improvement in cardiovascular risk markers and possibly for reduction of clinical cardiac events.
Abstract: PURPOSE OF REVIEW: For several decades, dietary protein restriction has been considered as a strategy to slow renal disease progression. Recently, a National Kidney Foundation advisory board incorporated recommendations for supervised low-protein diets into guidelines for the care of non-dialyzed patients with chronic kidney failure. Despite this consensus statement, the clinical utility of dietary modification remains controversial. This article reviews new investigations of protein intake as a mediator of renal function and physiology published since 1 October 2002. RECENT FINDINGS: Population-level data indicate graded risk for progressive renal functional decline with increasing protein intake among women with mild renal insufficiency, and support a possible association of higher protein consumption with the risk of microalbuminuria in people with concomitant diabetes and hypertension. A link between the quantity of protein intake and the rate of renal deterioration is suggested by preliminary prospective studies among incident peritoneal dialysis patients, renal transplant recipients, and animal models of kidney disease. Varied renal consequences based on protein composition were reported in population-based studies, animal-model experiments, and animal studies of in-utero protein exposure. Clinical trial experience raises concern for the feasibility of dietary interventions in practice. SUMMARY: New research supports the view that high-protein diets accelerate renal disease progression, suggests differential consequences based on protein source, and explores risk among defined sub-populations. Topics for future exploration include the renal impact of high-protein weight-loss regimens, implications of dietary protein quantity and type across the stages of chronic kidney disease, and translation of animal studies of prenatal nutrition to humans.
Abstract: Only one of the two chromosomes in the asymmetric Caulobacter predivisional cell initiates replication in the progeny cells. Transcription from a strong promoter within the origin occurs uniquely from the replication-competent chromosome at the stalked pole of the predivisional cell. This regulated promoter has an unusual sequence organization, and transcription from this promoter is essential for regulated (cell type-specific) replication. Our analysis defines a new class of bacterial origins and suggests a coupling between transcription and replication that is consistent with the phylogenetic relationship of Caulobacter to the ancestral mitochondrion.
