Abstract: BACKGROUND: Cardiovascular diseases resulting from atherosclerotic complications are major causes of death in hemodialysis (HD) patients. Adiponectin (ADPN) is a recently discovered adipocyte-derived protein that appears to have protective role against atherosclerosis. HD patients have an excess accumulation of intra-abdominal fat mass in association with an atherogenic serum lipid profile despite low body mass index; however, the role of intra-abdominal fat mass in the progress of atherosclerosis remains to be clarified. METHODS: We evaluated visceral (VFA) and subcutaneous fat areas (SFA) by computed tomography and measured the plasma ADPN in 47 HD patients. We also examined the relationship between visceral fat accumulation and plasma ADPN levels and clinical parameters related to atherosclerosis. RESULTS: Plasma ADPN was 29.0 +/- 12.5 microg/ml in HD patients (mean +/- SD), two-fold higher than that in control subjects (14.0 +/- 9.1 microg/ml). Plasma ADPN correlated significantly and negatively with visceral fat area (VFA) (r = -0.49, p < 0.001) and subcutaneous fat area (SFA) (r = -0.42, p < 0.01) in HD patients. Plasma ADPN also correlated significantly and positively with HDL-cholesterol (r = 0.45, p < 0.005) and significantly and negatively with atherosclerotic index (AI, r = -0.39, p < 0.01) and triglycerides (r = -0.32, p < 0.05) in HD patients. Multiple stepwise regression analysis identified VFA as a significant independent predictor of plasma ADPN concentration in HD patients. CONCLUSION: Our findings indicate that visceral fat is a major determinant of plasma ADPN level, suggesting that visceral fat accumulation might be closely associated with the progression of atherosclerotic vascular disease in HD patients.
Abstract: BACKGROUND: Homocysteine (Hcy) and asymmetric dimethylarginine (ADMA) recently were recognized as potential risk factors for atherosclerosis in the general population, and the metabolism of each of these substances seems to be closely related. This study investigates the association between these substances and whether elevated serum Hcy and ADMA levels are related to high risk for atherosclerosis and cardiovascular events in maintenance hemodialysis (HD) patients. METHODS: A study was made of 197 HD patients (132 men, 65 women; mean age, 56.9 +/- 8.6 years) for the correlation between plasma total Hcy (tHcy) and ADMA concentrations and the association of these substances with atherosclerotic indices of cervical intima-media thickness, plaque diameter, aortic calcification index, and aortic elongation. Cardiovascular events were followed up for 5 years in these patients. RESULTS: Mean plasma tHcy (37.3 +/- 25.8 micromol/L) and ADMA (0.77 +/- 0.16 micromol/L) levels were significantly greater in HD patients than in healthy subjects. Plasma tHcy level did not correlate with plasma ADMA level (r = -0.1; P = not significant). Although ADMA level was associated significantly with atherosclerotic indices from a simple regression analysis, this association was less from multiple regression analysis. When patients were classified into 3 groups according to ADMA level, cardiovascular events during 5 years were significantly greater in the group with the highest ADMA levels than in the other groups, confirmed by using a Cox proportional hazard model. However, no association was found between tHcy levels and atherosclerotic indices or cardiovascular events. CONCLUSION: ADMA level emerged as a potential risk factor for cardiovascular events that might be mediated in part by atherosclerosis in HD patients. Conversely, neither high nor low plasma tHcy levels were associated with atherosclerotic indices and cardiovascular events. This result for our HD patients does not fulfill the terms of traditional epidemiology and paradoxical reverse epidemiology of Hcy.
Abstract: BACKGROUND: In the general population, aging induces changes in body composition, such as sarcopenia or a relative increase in visceral fat, but it remains unclear if similar changes occur in elderly haemodialysis (HD) patients. METHODS: Age-related changes in muscle and fat mass and fat distribution in the thigh and abdomen were cross-sectionally investigated in Japanese HD patients. The thigh muscle area (TMA), thigh intermuscular fat area (IMFA), thigh subcutaneous fat area (TSFA), abdominal muscle area (AMA), abdominal visceral fat area (AVFA) and abdominal subcutaneous fat area (ASFA) were measured by computed tomography in 134 non-diabetic patients between 21 and 82 years on HD. AMA, AVFA and ASFA were also measured in 70 age-matched controls. RESULTS: Muscle mass, fat mass and fat distribution differed significantly with age in both HD patients and controls, without significant differences in BMI. In both male and female HD patients, TMA and AMA showed significant negative correlations with age. All measures of subcutaneous fat-including TSFA, ASFA and the triceps skinfold thickness, were inversely associated with age in the female patients. In contrast, both IMFA and AVFA showed significant positive correlations with age in both male and female patients. The increase in the AVFA/ASFA ratio with age suggests progression of visceral fat accumulation in the elderly HD patients. Controls showed similar relationships between age and muscle mass and visceral fat accumulation. CONCLUSIONS: We found an association between age and decrease in muscle mass as well as increase in visceral and intermuscular fat in non-diabetic HD patients. Such changes may be associated with the metabolic abnormalities and increased mortality in elderly HD patients.
Abstract: Dietary salt intake modulates the renin-angiotensin system (RAS); however, little is known about the effect of salt intake on the progression of glomerulonephritis. We investigated the glomerular expression of TGF-beta1 type I (TbetaRI) and II (TbetaRII) TGF-beta receptors and RAS components in rats with antithymocyte serum (ATS) nephritis on normal (NSI)-, low (LSI)-, and high-salt intake (HSI) and on HSI rats receiving candesartan cilexetil (CC) and LSI rats receiving PD-123319. Glomerular lesions were less severe in rats on LSI and aggravated in those on HSI compared with those on NSI. Intrarenal renin and glomerular ANG II levels were significantly higher in LSI and lower in HSI rats. In ATS nephritis, HSI increased glomerular TbetaRI, TbetaRII, and ANG II type 1 receptor (AT1R), and decreased glomerular ANG II type 2 receptor (AT2R), whereas LSI decreased glomerular TGF-beta1 and TbetaRI and increased glomerular AT2R. CC ameliorated glomerular lesions, reduced glomerular TGF-beta1 and TbetaRII, and increased glomerular AT2R. PD-123319 aggravated glomerular lesions and increased glomerular TGF-beta1 and TbetaRII. Our results suggest that dietary salt intake influences progression of ATS nephritis by modulating glomerular TGF-beta1 and TbetaR expression resulting, at least in part, from altered glomerular AT1R and AT2R expression.
Abstract: BACKGROUND/AIMS: While a low-protein diet (LPD) has been reported to increase blood pressure, the mechanism for its increase has not yet been clarified. We investigated the factors involved in the development of hypertension induced by LPD in rats with post-cyclosporine (CsA) nephropathy, and determined the appropriate composition for LPD that is to be utilized for renal research. METHODS: The rats were divided into 4 groups, each group being fed either a normal-protein diet (NPD), LPD with a low sucrose content as the main component of carbohydrate, LPD with a high-sucrose content, or LPD with low sucrose plus 2% L-arginine (Arg) for 12 weeks, and the blood pressure, urinary nitric oxide (NO) metabolite (NOx) excretion, renal NO-generating capacity and renal Arg content were compared among these groups. CsA was administered for the first 5 weeks to all groups. RESULTS: The blood pressure was significantly higher in the high-sucrose LPD rats than in the NPD and the low-sucrose LPD rats. The supplement of Arg significantly decreased the blood pressure in the low-sucrose LPD rats. Urinary NOx, renal NO-generating capacity and the renal Arg content were significantly lower in the low-sucrose LPD rats than in the NPD rats. Arg supplementation to the LPD rats returned these values to the level of the NPD rats. CONCLUSION: The increase in blood pressure by LPD was associated with the higher amount of sucrose contained in LPD and the decrease in NO generation caused by the Arg depletion in rats with post-CsA nephropathy. For animal experiments we recommend that sucrose should not be used in LPD to balance the energy intake between LPD and NPD, and that a small amount of Arg be supplemented to LPD.
Abstract: BACKGROUND: There is controversy about whether the dietary protein requirement of 1.2 g/kg/d for hemodialysis (HD) patients, in the nutritional guidelines recommended by the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (NKF-KDOQI), is reasonable. METHODS: A cross-sectional study was conducted in 129 stable HD patients without diabetes (84 men, 45 women) to investigate the association between the protein equivalent of nitrogen appearance normalized by ideal body weight (nPNAibw), an index of protein intake, and skeletal muscle mass or other metabolic consequences. Patients were divided into 5 groups according to nPNAibw index. Midthigh muscle area (TMA), midthigh subcutaneous fat area (TSFA), abdominal muscle area (AMA), abdominal subcutaneous fat area (ASFA), and visceral fat area (AVFA) were measured using computed tomography, and various nutritional parameters were compared among these groups. RESULTS: TMA and AMA values increased with increasing dietary protein intake from less than 0.7 g/kg/d to 0.9-1.1 g/kg/d and showed a plateau at greater than 0.9 to 1.1 g/kg/d of dietary protein intake. Conversely, fat mass, including TSFA, ASFA, and AVFA, and serum potassium concentration increased with graded protein intake, and no plateau was formed. Patients with nPNAibw greater than 1.3 g/kg/d satisfied the criterion of visceral obesity. Although serum prealbumin levels showed a trend similar to that of muscle mass, there was no significant difference in serum albumin levels among the study groups. CONCLUSION: Optimal dietary protein requirement for patients undergoing maintenance HD in a stable condition appears to be less than the level recommended by the NKF-KDOQI nutritional guidelines.
Abstract: We report a woman with lupus nephritis complicated with lupus peritonitis and cytomegalovirus (CMV) colitis. Diagnosis of lupus peritonitis was made by abdominal computed tomography scan, colonoscopy, and ascitic fluid analysis. Steroid and cyclophosphamide therapy resulted in the improvement of severe lupus nephritis and peritonitis. Thereafter, she developed multiple colonic ulcers as diagnosed by colonoscopy and positive CMV antigenemia assay. Treatment with ganciclovir resulted in the disappearance of colonic lesions. The low cluster of differentiation (CD)4+ lymphocyte count (41/mm3) suggested that the cell-mediated immunity of this patient was comparable to that seen in patients with acquired immunodeficiency syndrome (AIDS).
Abstract: BACKGROUND: Muscle wasting is highly prevalent in long-term hemodialysis (HD) patients. Although inflammatory indices have been associated with malnutrition in these patients, the role of inflammation in muscle wasting has not yet been determined. METHODS: The relationship between the inflammatory mediators C-reactive protein (CRP) and interleukin-6 (IL-6) and the muscle mass indices thigh muscle area (TMA), measured by computed tomography, and creatinine (Cr) production, estimated by the Cr kinetic model (Cr-CKM), were investigated in 188 HD patients. RESULTS: Serum IL-6 level (7.3 +/- 7.8 pg/mL) was significantly elevated in HD patients, whereas mean serum CRP level (4.8 +/- 7.5 mg/L) remained within the normal range. Similar to serum albumin, muscle mass indices had significantly negative correlations with both serum IL-6 and CRP levels (TMA/dry weight [DW] versus log IL-6, r = -0.28; P < 0.01; TMA/DW versus log CRP, r = -0.38; P < 0.001; Cr-CKM versus log IL-6, r = -0.31; P < 0.01; Cr-CKM versus log CRP, r = -0.24; P < 0.01). Although muscle mass indices also were associated with both age and sex, a multiple regression analysis confirmed that these inflammatory indices were significantly associated with muscle mass in HD patients. CONCLUSION: Data indicate that muscle wasting is associated closely with inflammatory indices in long-term HD patients. It may be important to clarify the mechanism for the increasing inflammatory status and suppress the inflammatory response in these patients to improve their malnutrition and recover muscle mass.
Abstract: Increases in transforming growth factor-beta (TGF-beta) expression and extracellular matrix accumulation are transient in acute self-limited mesangial proliferative glomerulonephritis induced by a single injection of anti-thymocyte serum (ATS), while these increases persist following repeated injections that produce chronic progressive sclerosing glomerulonephritis with tubulointerstitial lesions. However, little is known about the expression of TGF-beta receptors (TbetaRs) in cells involved in the proliferative and sclerosing renal lesions. A study of protein and mRNA expression for type I (TbetaRI), type II (TbetaRII), and type III (TbetaRIII) TbetaR in both forms of nephritis was therefore carried out by immunohistochemistry and in situ hybridization. Inhibition of cell proliferation and stimulation of matrix production by TGF-beta1 were assessed in isolated glomeruli using [(3)H]thymidine incorporation and [(3)H]proline metabolic labelling, respectively. In acute self-limited nephritis, expression of TbetaRI, TbetaRII, and TbetaRIII increased in the glomerular and Bowman's capsular epithelial cells comprising the glomerular tuft adhesions to Bowman's capsules. However, TbetaRII expression was not prominent in proliferating mesangial cells. Glomeruli isolated from rats with acute self-limited nephritis at day 7, when mesangial cell proliferation was maximal, were partially resistant to the mitoinhibitory effects of TGF-beta1. In contrast, expression of all three TbetaRs was elevated in glomerular and tubulointerstitial lesions in chronic progressive nephritis, and glomeruli isolated from rats with chronic progressive nephritis 7 days after the second ATS injection were sensitive to TGF-beta1. These data suggest that distinct cellular responses to TGF-beta1 resulting from differential expression of TbetaR underlie the difference between acute self-limited mesangial proliferative and chronic progressive sclerosing ATS nephritis in the development of proliferative and sclerotic renal lesions.
Abstract: BACKGROUND: Carpal tunnel syndrome (CTS) is one of the major problems of long-term hemodialysis (HD), but sometimes difficult to distinguish from uremic or diabetic neuropathy by clinical symptoms. PATIENTS AND METHODS: To evaluate the diagnosis of CTS more precisely, we examined the ultrasonographic alterations of the carpal tunnel and tendons of 90 wrists from 45 patients undergoing HD for more than 5 years. We measured the thickness of the palmar radiocarpal ligament (PRL), corresponding to the posterior wall of the carpal tunnel (CT), and the width of the CT, and compared those values with sensory (SCV), motor conduction velocity (MCV) of the median nerve and clinical symptoms. In addition, we longitudinally measured CT and PRL in the same patients for 5 years, and compared ultrasonographic changes and clinical parameters. RESULTS: A linear positive relationship was found between HD duration and PRL thickness (r = 0.43, p < 0.01) or CT width (r = 0.53, p < 0.01). CT diameter was negatively correlated with MCV (r = -0.30, p < 0.01) and SCV (r = -0.33, p < 0.04). PRL thickness was also inversely correlated with MCV (r = -0.44, p < 0.01) and SCV (r = -0.46, p < 0.01) of the median nerve, respectively. The wrists with clinical CTS and/or previous CTS surgery had significantly greater CT and PRL values compared to patients without CTS (CT: 6.1 0.2vs. 8.0+/-0.3 mm,p<0.01;PRL: 1.9+/-0.1 vs. 3.6 +/- 0.2 mm, p < 0.01). There was a significant increase in CT width from 6.2 +/- 0.2 to 7.1 +/- 0.2 mm (p < 0.01) and PRL thickness from 2.4 +/- 0.2 to 2.8 +/- 0.2 mm (p <0.01) during the 5-year observation, respectively. PRL thickness was constantly increased at the rate of 0.4 mm during the study. However, no significant association was found between the 5-year increases in CT and PRL distance and age, gender, the prevalence of diabetes, or laboratory parameters such as blood beta2-microglobulin, pentosidine and Kt/V(urea). CONCLUSION: Our data suggest that echographic evaluation of the wrist tissue thickness was useful to assess the progression of CTS. Serial measurements of the wrist by echography may be helpful to clarify the advance of subclinical CTS in patients receiving long-term HD.
Abstract: BACKGROUND: While hyperhomocysteinemia is associated with an increased risk of atherosclerosis and the related cardiovascular diseases, the effect of hyperhomocysteinemia on the kidney has not been clearly demonstrated. The purpose of this study was to investigate whether long-term hyperhomocysteinemia develops atherosclerotic lesions in the kidney. METHODS: The effects of various dietary combinations, including folate deficiency, choline deficiency and methionine loading, on the plasma homocysteine concentration, renal function and renal histopathology were examined for 12 weeks in male weanling Fisher rats. RESULTS: Folate deficiency, choline deficiency and methionine loading synergistically induced hyperhomocysteinemia up to 69.7 +/- 23.1 micromol/L (control, 11.6 +/- 3.9 micromol/L, P < 0.01) without any change in blood pressure. Creatinine clearance was negatively correlated with the plasma homocysteine concentration (r = -0.55, P < 0.01). Arterial and arteriolar wall thickening, and focal tubulointerstitial fibrosis were found in the kidneys of the hyperhomocysteinemic rat. The lesions of tubulointerstitial fibrosis appeared striped or wedge-shaped at the subcapsular cortex of the kidney. In addition, the expression of vascular endothelial growth factor, an indicator of hypoxia, was increased in the adjacent more intact area of the cortex. These findings suggest that the renal tubulointerstitial lesions were likely to be mediated by severe ischemia due to regional circulatory disturbance. Folate supplementation diminished these vascular and tubulointerstitial changes. CONCLUSION: These results indicate that diet-induced chronic hyperhomocysteinemia could induce vascular remodeling and tubulointerstitial injury in the kidney, and that these changes were ameliorated by folate supplementation.
Abstract: We report our experience with a 62-year-old Japanese man with cholesterol crystal embolism after angiographic procedures performed because of intermittent claudication. In addition to progressive renal failure and nephrotic-range proteinuria, cutaneous ischemia, consisting of livedo reticularis in the lower limbs and digital necrosis at the tip of the right toe, and fundoscopic findings showing several white spots in the branches of retinal artery were also observed. Progressive renal failure and nephrotic-range proteinuria were halted just after treatment with simvastatin. Thus, simvastatin can exert a beneficial therapeutic effect on renal cholesterol embolism.
Abstract: Acute renal failure (ARF) is a well-documented but infrequent complication in patients treated with low-molecular weight dextran (LMWD). We herein report 3 cases of oliguric ARF following the administration of dextran-40. One case developed ARF totally after 1.200 g of LMWD administration. In contrast, two cases having increased serum creatinine developed oliguria despite the acceptable therapeutic doses (totally 450 and 650 g). Contrast media was also co-administered in these patients. Plasma exchange (PE), double filtration plasmapheresis (DFPP), or continuous hemodiafiltration (CHDF) but not hemodialysis (HD) reduced circulating dextran concentrations by 35-44% during a single session. All patients completely recovered from ARF by 14-32 days after the treatment. Our cases suggested that radiocontrast could predispose to the development of LMWD-induced ARF especially in patients having pre-existing renal dysfunction. In addition, PE, DFPP and CHDF afforded a beneficial effect for removing accumulated LMWD from the circulation.
Abstract: BACKGROUND: Transforming growth factor (TGF)-beta is a regulator of extracellular matrix accumulation. Both TGF-beta receptors, type I (TbetaRI) and type II (TbetaRII), may be required for signal transduction in the TGF-beta pathway. The aim of this study was to investigate the relationship between the TGF-beta pathways and glomerular basement membrane (GBM) accumulation in vivo. METHODS: We examined TbetaRI, II, and III protein expression on visceral glomerular epithelial cells (GEP) in relation to GBM alterations in passive Heymann nephritis (PHN), anti-GBM nephritis and anti-thymocyte serum (ATS) nephritis. Renal tissues were examined by pre-embedding immunoelectron microscopy 3, 7 and 14 days after induction of nephritis in rats. RESULTS: In normal control rats TbetaRI was not detected on GEP, TbetaRII expression was very occasionally found on GEP and TbetaRIII was seen in the cytoplasm of the GEP. TbetaRI, TbetaRII, and TbetaRIII were constitutively expressed on glomerular endothelial cells. By day 3 of anti-GBM nephritis and PHN, expression of TbetaRI, TbetaRII, and TbetaRIII was still similar to that of normal control rats, and GBM alterations in both models were not prominent except for deposit formation in PHN. From day 7 onwards, in both models, expression of TbetaRI and TbetaRII on GEP increased in association with GBM thickening. Expression of TbetaRIII in the cytoplasm of the GEP was increased, with occasional positive staining being seen on the urinary surface of the GEP from day 7 onwards. On the other hand, at day 3 of ATS nephritis, increased expression of TbetaRI and TbetaRII on GEP was noted, but from day 7 onwards, expression of TbetaR II on GEP dramatically decreased. Expression of TbetaRIII in the cytoplasm of the GEP also transiently increased at day 3. GBM thickening was not noted in ATS nephritis. CONCLUSIONS: The results suggest that persistent upregulation of expression of TbetaRI, TbetaRII and possibly TbetaRIII on GEP may contribute to GBM matrix accumulation in vivo.
Abstract: In this study, the authors evaluated the cerebral atrophy in 56 chronic hemodialyzed patients, who did not have clinical episodes or radiologic findings of cerebrovascular diseases, and 42 controls. Using computed tomography (CT) images, brain atrophy index (BAI), the proportion of subarachnoidal plus ventricular space in the cranial cavity, and ventricular area index (VAI), percent area of ventricle in the brain, were calculated. CT of the brain demonstrated an age-dependent increase in BAI in both hemodialyzed patients and controls. BAI and VAI were greater in hemodialyzed patients than healthy controls and the difference was significant at ages under 60 years in BAI and at ages less than 50 years in VAI. The atrophy of the frontal parts of the brain in patients on hemodialysis for 10 years or more was significantly greater than in patients dialyzed for less than 10 years. There was a significant negative correlation between BAI or VAI and hematocrit. These findings indicate that renal failure or hemodialysis itself might cause cerebral atrophy, and that the cerebral atrophy is more prominent in patients on hemodialysis for a long duration and with low hematocrit.
Abstract: BACKGROUND: We have previously reported that animals recovering from uranyl acetate (UA)-induced acute renal failure (ARF) were resistant to subsequent insult. Recent evidence suggests that apoptosis participates in tubular damage. We investigated the role of apoptosis in UA-induced ARF and attenuation of ARF in acquired resistance to UA in rats. METHODS: ARF was induced by an intravenous injection of UA (5 mg/kg) in rats. Rats of group 1 were injected with UA and followed for 28 days. Group 2 rats were injected with a second dose of UA (5 mg/kg) 14 days after the first injection and were followed for 14 days. All rats received an intraperitoneal injection of bromodeoxyuridine (BrdU) one hour before sacrifice. Using kidneys, histologic examination and immunohistochemical detection of proliferating cell nuclear antigen (PCNA), BrdU, Bcl-2, and Bax were performed. To detect apoptosis, electron microscopy, analysis of DNA fragmentation, and the TUNEL methods were adopted. RESULTS: UA increased the number of damaged renal tubules and serum creatinine, which peaked at 5 days in group 1, but both returned to baseline values by 14 days. Apoptosis was confirmed by electron microscopy and the "ladder" pattern of DNA fragments on gel electrophoresis. The number of apoptotic tubular cells evaluated by the TUNEL method showed two peaks at days 5 and 14 in group 1. The second peak of TUNEL-positive cells was preceded by an increased number of BrdU-positive nuclei, PCNA-positive nuclei, and total number of tubular epithelial cells. Renal damage after the second UA injection was markedly reduced. The peak number of apoptotic cells in group 2 was significantly less than that in group 1. CONCLUSIONS: Two peak levels of apoptotic cells occurred in UA-induced ARF. The first peak might play a role in UA-induced tubular damage, while the second one might represent the removal of excess regenerating cells during the recovery phase. Modulation of apoptotic cell death might be involved in the acquired resistance to rechallenge injury by UA.
Abstract: The issue of whether recombinant human erythropoietin (rhEPO) increases thrombosis of arteriovenous (AV) fistulae used for hemodialysis remains unclear. Thrombosis often occurs at stenotic segments of fistulae where there is marked intimal hyperplasia and extracellular matrix accumulation. Increased expression of transforming growth factor-beta1 (TGF-beta1) has been shown to be involved in the development of atherosclerotic lesions by promoting intimal hyperplasia and extracellular matrix accumulation. To clarify the role of rhEPO in the development of stenosis of AV fistulae, this study examined expression of the erythropoietin receptor (EPO-R), TGF-beta1, plasminogen activator inhibitor type 1 (PAI-1), cellular fibronectin containing an extra domain A (EDA+), and TGF-beta1 mRNA, and assessed in situ rhEPO binding in tissue specimens from seven cutaneous veins and eight patent and seven stenosed portions of AV fistulae of patients undergoing dialysis. Prominent intimal hyperplasia was evident in the stenosed segments. Significant elevation in expression of EPO-R and TGF-beta1 was noted in patent AV fistulae compared to the cutaneous veins. Significant enhancement of EPO-R and TGF-beta expression was detected in the stenotic fistulae. Fibronectin EDA+ and PAI-1 expression was increased in intimal hyperplasia compared to patent fistulae and cutaneous veins. Elevated EPO-R expression was further confirmed by in situ binding of biotin-labeled rhEPO in stenosed tissue specimens. It is hypothesized that increased rhEPO binding due to elevated EPO-R expression contributes to the development of AV fistula stenosis caused by intimal hyperplasia and extracellular matrix accumulation in response to increased TGF-beta1 expression in patients receiving hemodialysis.
Abstract: We encountered a 53-year-old man associated with acute renal failure caused by Waldenström's macroglobulinemia and type I cryoglobulinemia. Treatment with prednisolone and cyclophosphamide induced a rapid recovery from acute renal failure. Renal histology revealed endocapillary proliferation and lobular formation with scattered subendothelial, amorphous and periodic acid-Schiff (PAS)-positive materials in the glomerular capillaries which were positive for IgM on immunofluorescence study. Although the exact mechanism for pathophysiology of acute renal failure remains unknown, treatment with prednisolone and cyclophosphamide could induce a rapid recovery from acute renal failure accompanied by Waldenström's macroglobulinemia and type I cryoglobulinemia.
Abstract: Sudden cardiopulmonary arrest due to a defective respiratory reflex is observed in diabetic patients. Impaired ventilatory response in diabetic patients to acute hypoxia or hypercapnia induced by the inhalation of an artificial gas has been reported. Little is known regarding the respiratory compensatory ability for mild to moderate metabolic acidosis due to renal failure in insulin-dependent diabetic subjects. Arterial blood pH, HCO3-, PaCO2 and PaO2 were measured in 13 insulin-dependent diabetic subjects with advanced nephropathy and in 33 non-diabetic subjects with end-stage renal failure. The diabetic group consisted of six predialysis patients and seven on regular hemodialysis (HD) and the non-diabetic group, ten predialysis patients and 23 on HD. Differences between measured partial arterial pressure of carbon dioxide (PaCO2) and predicted PaCO2 determined from HCO3- were examined. PaCO2 was significantly higher in the diabetic than in non-diabetic group (40.0 +/- 7.4 versus 31.1 +/- 5.1 mmHg, p < 0.05 in predialysis, 42.0 +/- 6.4 versus 36.0 +/- 2.6 mmHg, p < 0.05 in HD), though plasma pH was essentially the same for either. Differences in measured PaCO2 and predicted PaCO2 were significantly larger in the diabetic group than in non-diabetic group. Ventilatory response to uremic acidosis may thus be considered impaired in subjects with advanced diabetic nephropathy.
Abstract: Protein and mRNA expression of transforming growth factor-beta (TGF-beta) receptor type I (TbetaRI), type II (TbetaRII), and type III (TbetaRIII) were studied in serial sections of kidney samples obtained from patients with glomerulonephritis. In minimal change disease, weak expression of TbetaRI and TbetaRII was observed mainly in glomerular endothelial cells, peritubular capillaries, and interstitial arteriolar endothelial cells, whereas TbetaRIII expression was found mainly in the interstitium. Expression of all three TGF-beta receptors (TbetaR) was increased remarkably in glomerular and Bowman's capsular cells comprising the tuft adhesions to Bowman's capsules in glomerulonephritis with increased matrix accumulation, including IgA nephropathy, lupus nephritis, focal and segmental glomerulosclerosis, myeloperoxidase-antineutrophil cytoplasmic antibody-associated crescentic glomerulonephritis, and membranoproliferative glomerulonephritis. Increased expression of the three TbetaR was also seen in glomerular epithelial cells in the vicinity of glomerulosclerotic lesions, in crescent cells, and in some tubules and infiltrative mononuclear cells found in the periglomerular and tubulointerstitial lesions with increased matrix deposition. In contrast, no remarkable TbetaRII expression was noted in mesangial proliferative lesions in IgA nephropathy, lupus nephritis, and membranoproliferative glomerulonephritis. These data suggest that distinctive modulation of TbetaR expression may be involved in the development of adhesive, sclerotic, and proliferative renal lesions in human glomerulonephritis.
Abstract: Contralateral uninephrectomy attenuates unilateral ischemic renal injury functionally and morphologically. In this study we investigated the effects of uninephrectomy on apoptotic renal cell death and tubular regeneration in ischemic acute renal failure (ARF) in rats. Unilateral ischemic injury was provoked by a 60-min left renal artery occlusion in right-nephrectomized (Nx) and sham-nephrectomized (sham-Nx) rats. Uninephrectomy attenuated tubular damage 48 h following the renal ischemia Apoptotic cells were found in renal tissue as early as 3 h after reperfusion and increased in number by 12 h. The "ladder" pattern of DNA fragments on agarose gel electrophoresis was also apparent in ischemic kidney. Uninephrectomy reduced apoptotic cells and DNA fragmentation. The expression of proliferating cell nuclear antigen (PCNA) could be seen 24 h after reperfusion and progressively increased thereafter PCNA expression in ischemic kidney was greater in Nx than sham-Nx rats at 24 h after renal reperfusion. These data suggest that uninephrectomy reduces apoptotic cells and DNA fragmentation and enhances PCNA expression. The reduced apoptotic cell death and enhanced cell regeneration may be importantly involved in the uninephrectomy-induced attenuation of ischemic acute renal failure in rats.
Abstract: Low-protein diets slow the progression of some renal diseases. We recently found that dietary restriction of L-arginine markedly ameliorates disease in antithymocyte serum-induced glomerulonephritis in the rat, suggesting that L-arginine may play a key role in the beneficial effects of low-protein diets. L-arginine is metabolized by nitric oxide synthases to nitric oxide and L-citrulline or by arginase to urea and L-ornithine. L-ornithine is a precursor for polyamines, which are required for cell proliferation and for proline, an essential component of collagen. In a time course of disease, we found that inducible nitric oxide synthase gene expression and nitric oxide production were increased very early. Arginase activity was significantly increased until 5 days of disease. Ornithine decarboxylase, the rate-limiting step for polyamine synthesis, was increased at 3 days coincident with the onset of cell proliferation. Gene expression of ornithine aminotransferase, a proline synthetic enzyme, was increased from day 1, paralleling increased collagen synthesis. Thus, the three pathways of L-arginine metabolism are upregulated in a manner consistent with their possible roles in the cell lysis, cell proliferation, and collagen deposition, which characterize this model of glomerulonephritis.
Abstract: A 66-year-old woman with chronic renal failure who had undergone hemodialysis for 15 years developed severe dilatation of the ascending and transverse colon. She had received right carpal tunnel release 5 years before this episode. The follow-up study of upper gastrointestinal series disclosed marked dilatation of the ascending and transverse colon with the retention of gastrografin persisted for 5 days, whereas colonic fiberscope showed no obstructive lesion. Pathologic study of biopsy specimens obtained from the colon demonstrated amyloid deposition. Avidin-biotin peroxidase complex method showed that these deposits strongly reacted with the antibody to human beta 2-microglobulin, but did not react with AA, lambda, and kappa antibodies. This case suggests that dialysis-related amyloidosis can cause intestinal pseudo-obstruction.
Abstract: The carpal tunnel syndrome (CTS) is the most frequent clinical symptom of dialysis-related amyloidosis. We examined CTS by ultrasound imaging and correlation between CTS and bone amyloidosis was sought. One hundred and forty-two wrists of 71 hemodialysis (HD) patients and 28 of 14 normal volunteers (group 1) were studied. Patients on HD were divided into 4 groups based on HD duration: Group 2, less than 5 years; group 3, 5-10 years; group 4, 10-15 years; and group 5, more than 15 years. The frequency of CTS increased gradually with HD duration: 0% in group 2, 35.3% in group 3, 36.4% in group 4 and 74.1% in group 5. The thickness of the palmar radiocarpal ligament (PRL), corresponding to the posterior wall of the carpal tunnel was significantly greater in groups 4 (p < 0.05), and 5 (p < 0.05) than in group 1 (2.25 +/- 1.30 and 3.11 +/- 1.02 in group 4 and 5 vs 1.15 +/- 0.34 mm in group 1); and the width of the carpal tunnel (CT) was significantly larger in group 5 than in group 1 (6.92 +/- 1.78 in group 5 vs 5.53 +/- 1.48 mm in group 1, p < 0.05). Wrists operated on for CTS had significantly increased PRL and CT compared to the control group and patients without CTS. Patients with CTS had wider PRL than the control and HD patients without CTS. Cystic radiolucent lesions (CRL) of carpal bones characteristic of bone amyloidosis were noted in 15 of 71 HD patients. The thickness of PRL and width of CT in HD patients with CRL exceeded those in patients without CRL. These data indicated that ultrasonographic findings of wrists were closely correlated with the degree of CTS and CRL. The usefulness of ultrasonographic evaluation of PRL thickness and CT width in the evaluation of dialysis-related amyloidosis should be evaluated.
Abstract: We evaluated the correlation between histologic features and glomerular permselectivity based on fractional clearances of dextrans relative to inulin (FCsDex). The subjects consisted of 12 healthy volunteers, 18 patients with membranous nephropathy, and 20 patients with immunoglobulin A nephropathy. In membranous nephropathy, FCsDex measured with large dextrans (radii larger than 56 A) increased as the capillary lesion progressed. Histologic examination showed that glomerular capillary alteration was the factor most closely linked to changes in FCsDex in membranous nephropathy. Proteinuria (normalized to glomerular filtration rate) did not correlate with FCsDex. Increased FCsDex tended to normalize during prednisolone treatment in membranous nephropathy. In immunoglobulin A nephropathy, the impairment of glomerular size selectivity depended on the degree of mesangial sclerosis and tubulointerstitial injury. FCs of dextrans of 59 A were correlated with the mesangial sclerosis index (r = 0.573, p = 0.050) and the tubulointerstitial injury index (r = 0.707, p = 0.003). Proteinuria (again normalized to glomerular filtration rate) was significantly correlated with FCs of large dextrans in immunoglobulin A nephropathy (r = 0.668, p = 0.008). We conclude that glomerular size-selective barriers were impaired both in membranous nephropathy and immunoglobulin A nephropathy. However, the mechanisms of impaired size selectivity might differ, at least in part, between these nephropathies. The predominant factors responsible for the size-selective defect seemed to be glomerular capillary wall lesions in membranous nephropathy but mesangial sclerosis or tubulointerstitial damages (or both) in immunoglobulin A nephropathy.
Abstract: Acute renal insufficiency developed in four idiopathic nephrotic patients with minimal change or mild proliferative glomerulonephritis. The reduction in glomerular filtration rate (CInulin) was not in proportion to the renal plasma flow (CPAH) as evidenced by a low filtration fraction. Diuretic therapy failed to reverse renal insufficiency, and renal biopsy showed no evidence of interstitial nephritis, acute tubular necrosis or interstitial edema. Corticosteroid therapy induced a recovery of renal function with a decrease in proteinuria. These observations suggest that acute renal insufficiency in the idiopathic nephrotic syndrome might be caused by impaired glomerular permeability.
Abstract: A 27-year-old man, who had been on steroid therapy for 2 months for his nephrotic syndrome, suddenly developed intra-abdominal bile collection (biloma). He had no previous history of abdominal surgery, trauma, or any disease of the hepatobiliary system. The cause of the biloma formation was due, probably, to cholecystitis in the absence of calculi and a pinhole size perforation in the wall of gall bladder. It was assumed to be closely related to the high-dose steroid therapy over a prolonged period, which would likely suppress the repair process of the locally damaged biliary system.
Abstract: Acute aortic thrombosis associated with spinal cord infarction in a 47-year-old man with nephrotic syndrome is described. He was admitted to our hospital presenting with the nephrotic syndrome. Renal biopsy revealed mild mesangial proliferative glomerulonephritis. The urinary protein excretion rate transiently decreased after the start of treatment with prednisolone, but it increased again and was followed by the development of the signs and symptoms of spinal cord infarction, which was diagnosed by magnetic resonance signal abnormalities, and then symptoms of ischemia in the lower limbs. Digital subtraction angiography revealed an obstruction at the bifurcation of the abdominal aorta. Emergency thrombectomy was performed, and the arterial blood flow was reestablished. Laboratory data on the fibrinocoagulation system showed a hypercoagulable state. In this case, fibrinocoagulation abnormalities due to the nephrotic syndrome led to the hypercoagulable state, and dehydration might have triggered the thrombotic complication.
Abstract: Two cases of nephrotic syndrome during bucillamine treatment were encountered in 1989 in our hospital; both patients had suffered from rheumatoid arthritis for 2 years. They had received 200 mg bucillamine orally per day for 3-4 months before the onset of the nephrotic syndrome. Discontinuation of bucillamine led to complete remission of the nephrotic syndrome within 1 year. Bucillamine is a new therapeutic agent for rheumatoid arthritis developed in 1982 in Japan. Since 1985, 14 cases of nephrotic syndrome, including the two cases reported here have been reported. We review these cases and discuss the pathogenesis.
