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Constantinos J. Stefanidis

Head of Pediatric Nephrology
"P. & A. Kyriakou" Children's Hospital
Thivon and Levadias Str, Goudi, 115 27
Athens, Greece

stefanid@hol.gr

Journal articles

2011
Spyridon Megremis, Andromachi Mitsioni, Irene Fylaktou, Sofia Kitsiou Tzeli, Filadelfia Komianou, Constantinos J Stefanidis, Emmanuel Kanavakis, Joanne Traeger-Synodinos (2011)  Broad and unexpected phenotypic expression in Greek children with steroid-resistant nephrotic syndrome due to mutations in the Wilms' tumor 1 (WT1) gene.   Eur J Pediatr 170: 12. 1529-1534 Dec  
Abstract: Mutations in the Wilms' tumor suppressor gene 1 (WT1), most commonly within exons 8 or 9 or intron 9, are found in cases with the overlapping conditions of Denys-Drash and Frasier syndromes, as well as in patients with steroid-resistant nephrotic syndrome (SRNS). This study investigated the presence of WT1 gene mutations in cases with childhood SRNS, along with an evaluation of their clinical outcome. Twenty-seven Greek children with sporadic (19 cases) and familial (8 cases) SRNS were tested. Four phenotypically female patients with sporadic SRNS were found to carry de novo WT1 mutations, including two cases with p.R394W, and one case each with p.R366H, or n.1228+5G>A. Karyotype analysis found 46XX in three cases, but 46XY in one. No phenotype-genotype correlations were apparent in the WT1 gene positive cases since their clinical presentation varied broadly. Interestingly, one patient with a pathological WT1 nucleotide variation responded fully to combined therapy with cyclosporine A and corticosteroids. This study further illustrates that investigation of WT1 gene mutations is clinically useful to support definitive diagnosis in children presenting with SRNS in order to direct the most appropriate clinical management.
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Sandrine Leroy, François Bouissou, Anna Fernandez-Lopez, Metin K Gurgoze, Kyriaki Karavanaki, Tim Ulinski, Silvia Bressan, Geogios Vaos, Pierre Leblond, Yvon Coulais, Carlos Luaces Cubells, A Denizmen Aygun, Constantinos J Stefanidis, Albert Bensman, Liviana DaDalt, Stefanos Gardikis, Sandra Bigot, Dominique Gendrel, Gérard Bréart, Martin Chalumeau (2011)  Prediction of high-grade vesicoureteral reflux after pediatric urinary tract infection: external validation study of procalcitonin-based decision rule.   PLoS One 6: 12. 12  
Abstract: Predicting vesico-ureteral reflux (VUR) ≥3 at the time of the first urinary tract infection (UTI) would make it possible to restrict cystography to high-risk children. We previously derived the following clinical decision rule for that purpose: cystography should be performed in cases with ureteral dilation and a serum procalcitonin level ≥0.17 ng/mL, or without ureteral dilatation when the serum procalcitonin level ≥0.63 ng/mL. The rule yielded a 86% sensitivity with a 46% specificity. We aimed to test its reproducibility.
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Costas Tsioufis, Anastasia Mazaraki, Kyriakos Dimitriadis, Costas J Stefanidis, Christodoulos Stefanadis (2011)  Microalbuminuria in the paediatric age: current knowledge and emerging questions.   Acta Paediatr 100: 9. 1180-1184 Sep  
Abstract: The prevalence of microalbuminuria (MA) in children and adolescents differs from the one in adults, and it is estimated to be about 5.7-7.3% in boys and 12.7-15.1% in girls. The percentage is greater in smaller age group, whereas a positive association is found between albumin excretion rate and pubertal development stage in nondiabetic subjects. The data so far suggest that impairment of glucose metabolism, obesity-related proatherosclerotic pathways and the impact of haemodynamic load constitute major determinants of albuminuria development in the early years of life. In everyday practice if persistent MA is present at a young age, especially in the setting of diabetes, further investigation of cardiovascular risk factors, a more careful follow-up and dietary/lifestyle interventions are needed. CONCLUSION: Although the significance of MA in paediatric essential hypertension has yet to be determined, its role in diabetic children and adolescents is established and albuminuria assessment has been utilized as a screening test for the presence of diabetes-related kidney disease.
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Wesley N Hayes, Alan R Watson, Nichola Callaghan, Elizabeth Wright, Constantinos J Stefanidis (2011)  Vascular access: choice and complications in European paediatric haemodialysis units.   Pediatr Nephrol Dec  
Abstract: BACKGROUND: European and U.S. guidelines emphasise that permanent vascular access in the form of arteriovenous fistulae (AVF) or grafts (AVG) are preferable to central venous catheters (CVC) in paediatric patients on long-term haemodialysis. We report vascular access choice and complication rates in 13 European paediatric nephrology units. METHODS: A survey of units participating in the European Pediatric Dialysis Working Group requesting data on type of vascular access, routine care and complications in patients on chronic haemodialysis between March 2010 and February 2011. RESULTS: Information was complied on 111 patients in 13 participating centres with a median age of 14 (range 0.25-20.2) years. Central venous catheters were used in 67 of 111 (60%) patients, with 42 patients (38%) having an AVF and two patients (2%) having an AVG. Choice of vascular access was significantly related to patient age, with patients with AVF/AVG having a median age of 16 years compared to 12 years for patients with CVCs (p < 0.001). Routine CVC exit site care and catheter lock solution use differed between centres. CVC infections requiring intravenous antibiotics were reported at a rate of 1.9 and exit site infections at a rate of 1.8 episodes/1000 catheter days. Overall infective complications necessitating CVC change occurred at a rate of 0.9 episodes/1000 catheter days. No infective complications were reported in patients with AVF/AVG access. The rate of CVC infections requiring intravenous antibiotics was significantly lower in patients in whom CVC exit sites were cleaned weekly as opposed to every dialysis session (relative risk with every session cleaning vs. weekly cleaning 2.58, 95% confidence interval 1.17-5.69). Catheter malfunction (inadequate blood flow) was a more prevalent complication necessitating 22.4 thrombolytic interventions/1000 catheter days and 2.1 CVC changes/1000 catheter days. CONCLUSIONS: Central venous catheters remain the predominant choice of vascular access in Europe despite problems of malfunction and infection. AVF/AVG were predominantly used in adolescents without reported complications. More regular exit site cleaning may predispose to CVC infection, but this observation requires prospective evaluation.
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Constantinos J Stefanidis, Uwe Querfeld (2011)  The podocyte as a target: cyclosporin A in the management of the nephrotic syndrome caused by WT1 mutations.   Eur J Pediatr 170: 11. 1377-1383 Nov  
Abstract: Children with steroid-resistant nephrotic syndrome secondary to WT1-associated glomerulopathies (WT1-GP) were considered unresponsive to cyclosporin A (CsA). This assumption is challenged by the findings of recent studies. The patients of these studies had different types of WT1 mutations and varying clinical presentations. However, all of them were of young age and the favourable response to CsA might be the result of treatment at an early stage of the disease. The additional administration of angiotensin-converting enzyme inhibitors may have contributed to the positive outcome. We review recent data on the role of WT1 in the development of WT1-GP and discuss putative therapeutic targets explaining the therapeutic effect of CsA.
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Christina D Liakou, Varvara Askiti, Andromachi Mitsioni, Constantinos J Stefanidis, Maria C Theodoridou, Vana I Spoulou (2011)  Safety, immunogenicity and kinetics of immune response to 7-valent pneumococcal conjugate vaccine in children with idiopathic nephrotic syndrome.   Vaccine 29: 40. 6834-6837 Sep  
Abstract: Safety, immunogenicity and kinetics of 7-valent pneumococcal-conjugate vaccine (PCV7) immune response were evaluated in 33 children with idiopathic nephrotic syndrome (INS) and 16 controls. PCV7 was not associated with increased risk of relapse (RR=0.80, p=0.61). Serotype (PS)-specific antibodies increased in all subjects at 1 month (p<0.01) with inferior immunogenicity for 3/7 PS in patients on immunomodulators (p<0.02). Most patients retained protective antibodies at 12-14 months although at lower levels for 4/7 PS (p<0.08). Different PS kinetics in INS suggests antibody monitoring and revaccination when necessary for protection from pneumococcal infections.
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Ekaterini Siomou, Anna Challa, Nikoleta Printza, Vasileios Giapros, Fotini Petropoulou, Andromachi Mitsioni, Fotios Papachristou, Constantinos J Stefanidis (2011)  Serum osteoprotegerin, RANKL and fibroblast growth factor-23 in children with chronic kidney disease.   Pediatr Nephrol 26: 7. 1105-1114 Jul  
Abstract: Osteoprotegerin (OPG), receptor activator of the nuclear factor κB ligand (RANKL) and fibroblast growth factor-23 (FGF-23) play a central role in renal osteodystrophy. We evaluated OPG/RANKL and FGF-23 levels in 51 children with chronic kidney disease (CKD) [n = 26 stage 3 or 4 (CKD3-4) and n = 25 stage 5 (CKD5)] and 61 controls. Any possible association with intact parathyroid hormone (iPTH) and bone turnover markers was also investigated. The OPG levels were lower in the CKD3-4 group (p < 0.001) and higher in the CKD5 group (p < 0.01) than in the controls, while RANKL levels did not differ. The FGF-23 levels were higher in both patient groups (p < 0.0001), while the levels of phosphate and iPTH were higher only in the CKD5 group (p < 0.0001). There were independent positive correlations between OPG and RANKL (β = 0.297, p < 0.01) and FGF-23 (β = 0.352, p < 0.05) and a negative correlation with the bone resorption marker TRAP5b (β = -0.519, p < 0.001). OPG was positively correlated with iPTH (R = 0.391, p < 0.01). An independent positive correlation between FGF-23 and phosphate (β = 0.368, p < 0.05) or iPTH (β = 0.812, p < 0.0001) was noted. In conclusion, we found that higher OPG levels in patients with CKD stage 5 correlated with the levels of RANKL, FGF-23, iPTH, and TRAP5b. These findings may reflect a compensatory mechanism to the negative balance of bone turnover. High FGF-23 levels in early CKD stages may indicate the need for intervention to manage serum phosphate (Pi) levels.
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2010
Jutta Gellermann, Constantinos J Stefanidis, Andromachi Mitsioni, Uwe Querfeld (2010)  Successful treatment of steroid-resistant nephrotic syndrome associated with WT1 mutations.   Pediatr Nephrol Feb  
Abstract: The Wilms' tumor suppressor gene 1 (WT1) encodes a transcription factor involved in kidney and gonadal development. WT1 is also a key regulator of podocyte functions and mutations have been found in a small percentage of children with isolated or syndromal steroid-resistant nephrotic syndrome. It is commonly assumed that the nephrotic syndrome (NS) in patients with WT1 mutations is unresponsive to therapy and characterized by rapid progression to end-stage renal disease. We report long-term observations in 3 children with focal-segmental glomerulosclerosis associated with WT1 mutations and NS (2 cases) or nephrotic range proteinuria (1 case). All patients showed a favorable response to an intensified therapy consisting of cyclosporin A (CyA) in combination with induction therapy with intravenous and oral prednisone. Treatment with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers was added to the regimen at various times. As shown both by the short-term response and during long-term follow-up, this treatment resulted in clinical remission of the NS and/or significant reduction of proteinuria, while normal renal function could be maintained over many years. Thus, glomerular diseases in selected patients with mutations in genes regulating renal development and podocyte function may respond to combination therapy with CyA and corticosteroids.
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Jerome C Lane, Bradley A Warady, Reinhard Feneberg, Nancy L Majkowski, Alan R Watson, Michel Fischbach, Hee Gyung Kang, Klaus E Bonzel, Eva Simkova, Constantinos J Stefanidis, Günter Klaus, Steven R Alexander, Mesiha Ekim, Ilmay Bilge, Franz Schaefer (2010)  Relapsing Peritonitis in Children Who Undergo Chronic Peritoneal Dialysis: A Prospective Study of the International Pediatric Peritonitis Registry.   Clin J Am Soc Nephrol Apr  
Abstract: BACKGROUND AND OBJECTIVES: The International Pediatric Peritonitis Registry (IPPR) was established to collect prospective data regarding peritoneal dialysis (PD)-associated peritonitis in children. In this report, we present the IPPR results that pertain to relapsing peritonitis (RP). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was an online, prospective entry into the IPPR of data that pertain to peritonitis cases by participating centers. RESULTS: Of 490 episodes of nonfungal peritonitis, 52 (11%) were followed by a relapse. There was no significant difference between RP and non-RP in distribution of causative organisms and antibiotic sensitivities. Initial empiric therapy-ceftazidime with either first-generation cephalosporin or glycopeptide (vancomycin or teicoplanin)-was not associated with relapse. Switching to monotherapy with a first-generation cephalosporin on the basis of culture results was associated with higher relapse rate (23%) than other final antibiotic therapies (0 to 9%). Culture-negative RP was less likely to have a satisfactory early treatment response than non-RP (82 versus 98%). Young age, single-cuff catheter, downward-pointing exit site, and chronic systemic antibiotic prophylaxis were additional independent risk factors for RP in the multivariate analysis. Compared with non-RP, RP was associated with a lower rate of full functional recovery (73 versus 91%), higher ultrafiltration problems (14 versus 2%), and higher rate of permanent PD discontinuation (17 versus 7%). CONCLUSIONS: This is the largest multicenter, prospective study to date to examine RP in children. In addition, this is the first report in the literature to examine specifically the relationship of postempiric antibiotic treatment regimens to the subsequent risk for relapse.
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Constantinos J Stefanidis (2010)  Preventing catheter-related infections in children undergoing hemodialysis.   Expert Rev Anti Infect Ther 8: 11. 1239-1249 Nov  
Abstract: The increased use of tunneled cuffed catheters in children on chronic hemodialysis is the result of their relative ease of insertion, pain-free dialysis and immediate use. The disadvantage of their use is that they are associated with catheter-related bacteremia (CRB), which in turn is related with increased morbidity, access loss and occasionally metastatic infections and even death. A CRB might be difficult to diagnose and is often associated with a previous history of CRB, exit-site infection, low serum albumin and long duration of catheter use. There is evidence that the use of arteriovenous fistulae is associated with lower infection rates. The implementation of effective strategies for the prevention of CRBs include the adoption of policies for improving arteriovenous fistula rates, appropriate surgical catheter insertion and optimal nursing care of the exit site, and a safe connection technique. Recently, the effectiveness of antimicrobial catheter solutions for preventing CRB has been documented in a number of randomized clinical trials. In addition, the application of antibiotic ointments at the exit sites of tunneled cuffed catheters might be significant for the reduction of Staphylococcus-related CRB. The upside is that education-based programs combining specific preventive measures can significantly reduce CRBs.
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Olivia Boyer, Geneviève Benoit, Olivier Gribouval, Fabien Nevo, Audrey Pawtowski, Ilmay Bilge, Zelal Bircan, Georges Deschênes, Lisa M Guay-Woodford, Michelle Hall, Marie-Alice Macher, Kenza Soulami, Constantinos J Stefanidis, Robert Weiss, Chantal Loirat, Marie-Claire Gubler, Corinne Antignac (2010)  Mutational analysis of the PLCE1 gene in steroid resistant nephrotic syndrome.   J Med Genet 47: 7. 445-452 Jul  
Abstract: BACKGROUND: Mutations in the PLCE1 gene encoding phospholipase C epsilon 1 (PLCepsilon1) have been recently described in patients with early onset nephrotic syndrome (NS) and diffuse mesangial sclerosis (DMS). In addition, two cases of PLCE1 mutations associated with focal segmental glomerulosclerosis (FSGS) and later NS onset have been reported. METHOD: In order to better assess the spectrum of phenotypes associated with PLCE1 mutations, mutational analysis was performed in a worldwide cohort of 139 patients (95 familial cases belonging to 68 families and 44 sporadic cases) with steroid resistant NS presenting at a median age of 23.0 months (range 0-373). RESULTS: Homozygous or compound heterozygous mutations were identified in 33% (8/24) of DMS cases. PLCE1 mutations were found in 8% (6/78) of FSGS cases without NPHS2 mutations. Nine were novel mutations. No clear genotype-phenotype correlation was observed, with either truncating or missense mutations detected in both DMS and FSGS, and leading to a similar renal evolution. Surprisingly, three unaffected and unrelated individuals were also found to carry the homozygous mutations identified in their respective families. CONCLUSION: PLCE1 is a major gene of DMS and is mutated in a non-negligible proportion of FSGS cases without NPHS2 mutations. Although additional variants in 19 candidate genes (16 other PLC genes, BRAF,IQGAP1 and NPHS1) were not identified, it is speculated that other modifier genes or environmental factors may play a role in the renal phenotype variability observed in individuals bearing PLCE1 mutations. This observation needs to be considered in the genetic counselling offered to patients.
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2009
Constantinos J Stefanidis (2009)  Prevention of catheter-related bacteremia in children on hemodialysis: time for action.   Pediatr Nephrol 24: 11. 2087-2095 Nov  
Abstract: This editorial commentary discusses the strategies for prevention of catheter-related bacteremia (CRB) in children on hemodialysis, which is associated with high morbidity and the increase of hospital cost. There is evidence that the use of arteriovenous fistulae in children on hemodialysis is associated with lower infection rates. Therefore, the use of catheters in these patients should be decreased by improving arteriovenous fistulae use rates or by increasing peritoneal dialysis patient recruitment. However, despite the wide adoption of such policies, hemodialysis catheters are still being used in a significant number of cases. For these patients, implementation of effective strategies for preventing contamination of the catheter hub should be a priority. The appropriate recording and evaluation of CRB rates are important for assessing preventive policies. In addition, the successful management of a CRB is essential for preventing recurrence of bacteremia. Recently it was documented in a number of randomized clinical trials that antimicrobial lock solutions were effective for preventing CRB. It is suggested that the use of antimicrobial locks should be considered in children who are at high risk of developing CRB, with caution for their long-term use, because of the possibility of bacterial resistance. Now is the time for action, and all preventive steps should be performed simultaneously to minimize the risk of CRB.
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George S Stergiou, Nikos Karpettas, Anastasios Kapoyiannis, Constantinos J Stefanidis, Andriani Vazeou (2009)  Home blood pressure monitoring in children and adolescents: a systematic review.   J Hypertens 27: 10. 1941-1947 Oct  
Abstract: OBJECTIVE: As in the adults, in children and adolescents with elevated blood pressure (BP), the conventional office BP measurements might lead to incorrect diagnosis. Therefore, out-of-office BP measurements are often needed. Several studies have demonstrated the value of ambulatory BP (ABP) monitoring in pediatric hypertension, whereas home BP (HBP) monitoring has only recently been evaluated. METHODS: A systematic review of the evidence on HBP monitoring in children and adolescents has been performed (Medline/PubMed, Embase and Cochrane Library). RESULTS: A total of 27 studies (19 original study reports, two surveys, three guidelines documents, two reviews and one letter) were identified. These data suggest that by using electronic arm devices, reliable HBP readings are obtained. Unfortunately, very few electronic devices have been successfully validated in children. The reproducibility of HBP in children appears to be superior to office and similar to ABP measurements. Three-day-HBP monitoring with duplicate morning and evening measurements is the minimum schedule required, yet 6-7-day monitoring is recommended. HBP in children and adolescents is lower than daytime ABP, whereas no such difference exists in the adults. A school-based study in 778 children and adolescents provided the first HBP normalcy data. HBP has similar diagnostic value in children as in the adults and appears to be a reliable alternative to ABP monitoring in the detection of white-coat hypertension. CONCLUSION: HBP monitoring appears to have considerable potential in pediatric hypertension. More research is needed on the clinical application of this method in children and adolescents.
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Spyridon Megremis, Andromachi Mitsioni, Artemis G Mitsioni, Irene Fylaktou, Sofia Kitsiou-Tzelli, Constantinos J Stefanidis, Emmanuel Kanavakis, Joanne Traeger-Synodinos (2009)  Nucleotide variations in the NPHS2 gene in Greek children with steroid-resistant nephrotic syndrome.   Genet Test Mol Biomarkers 13: 2. 249-256 Apr  
Abstract: Mutations in the NPHS2 gene, encoding podocin, are a major cause of autosomal-recessive steroid-resistant nephrotic syndrome (SRNS) in childhood, accounting for up to 30% of sporadic and 20-40% of familial cases. Among 22 Greek children with a clinical diagnosis of SRNS, mutation analysis was performed in all eight NPHS2 gene exons, using denaturing gradient gel electrophoresis and DNA sequencing. The frequency of all nucleotide variations found in patients was also evaluated in 100 unrelated samples (18-30 years) with no known history of nephrotic disease. Three pathogenic genotypes (R138Q/R138Q, R229Q/A295T, and R168H/R168H) accounted for 3/14 (21%) of sporadic patients; the A295T mutation in exon 8 (c.883G>A) is novel and predicted in silico to be pathogenic. Among the familial cases, a single patient was heterozygous for R229Q. Several known polymorphisms were found, including the in cis variants IVS3-46C>T plus IVS3-21C>T, IVS7+7A>G A and exonic variants S96S (c.288C>T), A318A (c.954T>C), and L346L (c.1038A>G), with allele frequencies comparable to those in other populations. A novel substitution (IVS3-17C>T) was found in two related patients, but in no controls. In conclusion, podocin mutations do not appear to be a major cause of SRNS in Greek children, although the study cohort was small. However, NPHS2 gene analysis could still be considered in Greek SRNS patients to support appropriate management. The present study also contributes potentially useful observations for the clinical management of SRNS patients.
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Ioanna Bouba, Ekaterini Siomou, Constantinos J Stefanidis, Anastasia Emmanouilidou, Anna Galidi, Elissavet Hatzi, Sofia Markoula, Andromachi Mitsioni, Antigoni Siamopoulou, Ioannis Georgiou (2009)  Absence of mutations in the HOXA11 and HOXD11 genes in children with congenital renal malformations.   Pediatr Nephrol 24: 8. 1569-1572 Aug  
Abstract: Experimental studies have shown that homeobox genes are essential for the development of the kidney and urinary tract. Hoxa11/Hoxd11 double mutant mice demonstrate renal agenesis or hypoplasia. Since, to our knowledge, these genes have never been examined for alterations in humans with congenital anomalies of the kidney and urinary tract (CAKUT), we investigated whether mutations of HOXA11/HOXD11 genes are associated with non-syndromal congenital renal parenchymal malformations. DNA samples from 26 unrelated children with unilateral renal agenesis (URA), 20 with renal hypodysplasia (RHD) and 13 with multicystic dysplastic kidney (MCDK) were included in the study. Exons 1 and 2 of the HOXA11/HOXD11 genes were amplified individually by polymerase chain reaction (PCR) using 12 unique oligonucleotide primers. Single-strand conformation polymorphism (SSCP) analysis of overlapping polymerase chain reaction products was performed. SSCP analysis revealed no variant band shifts in the samples of the amplified segments of the 59 patients, suggesting lack of either mutation or polymorphisms. Our findings do not support the hypothesis that mutations in the HOXA11/HOXD11 coding regions are involved in the pathogenesis of human non-syndromal congenital renal parenchymal malformations. Further studies are necessary, since other genes known to affect nephrogenesis, as well as genetic and environmental factors, may be involved.
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George S Stergiou, Christina Alamara, Antonis Drakatos, Constantinos J Stefanidis, Adriani Vazeou (2009)  Prediction of albuminuria by different blood pressure measurement methods in type 1 diabetes: a pilot study.   Hypertens Res 32: 8. 680-684 Aug  
Abstract: In type 1 diabetes, the risk of nephropathy is strongly influenced by the level of blood pressure (BP). Ambulatory BP (ABP) monitoring has revealed an association between disturbed nocturnal BP drop and albuminuria and suggested a role of BP in microalbuminuria development. This study investigated the relationship between the urinary albumin excretion ratio (AER) and home BP (HBP) compared with ABP and clinical BP (CBP) measurements. A total of 50 adolescents and young adults with type 1 diabetes without hypertension or overt proteinuria (mean age 20+/-3.8 (s.d.) years, 21 male) had measurements of CBP (3 visits), HBP (6 days), 24-h ABP and AER (daytime and nighttime in the same 24 h with ABP monitoring). AER of 24 h was correlated with systolic 24-h (r=0.31), daytime (r=0.33) and nighttime ABP (r=0.36), without significant correlation with diastolic ABP, CBP or HBP (systolic or diastolic). Nighttime AER was correlated with 24-h (r=0.39/0.35, systolic/diastolic), daytime (r=0.36/0.32) and nighttime ABP (r=0.44/0.28). HBP was not associated with nighttime AER, but CBP was (diastolic BP only, r=0.41). No significant correlations were found between daytime AER and BP measurements. The nocturnal BP dip was not associated with any BP value. In non-dippers, nighttime AER showed strong correlations with ABP (24-h: r=0.45/0.42, systolic/diastolic; daytime: r=0.46/0.45; nighttime: r=0.49/0.35), HBP (r=0.34/0.31) and CBP (r=0.39/0.47). No such associations were found in dippers (r=0.05-0.10). These preliminary data suggest that in the early stage of diabetes-1, 24-h ABP monitoring seems to be the optimal method of revealing the association between BP and albuminuria, and cannot be replaced by HBP monitoring.
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2008
Meropi S Tzoufi, Polyxeni Sixlimiri, Iliada Nakou, Maria I Argyropoulou, Constantinos J Stefanidis, Antigone Siamopoulou-Mavridou (2008)  Blue rubber bleb nevus syndrome with simultaneous neurological and skeletal involvement.   Eur J Pediatr 167: 8. 897-901 Aug  
Abstract: Blue rubber bleb nevus syndrome (BRBNS) is a rare disorder characterized by venous malformations usually affecting the skin and the gastrointestinal tract. These skin haemangiomas are present at birth and deteriorate as the body grows, causing primarily cosmetic problems. The haemangiomas of the gastrointestinal tract may appear later in life and may bleed, causing chronic anaemia, or may present with severe complications such as rupture, intestinal torsion, and intussusception. Other organs may also be involved. This article describes a 13-year-old boy with multiple haemangiomas of the skin, the mucous membranes, and the gastrointestinal tract, which caused anaemia and ileoileic intussusception. In this patient, the nervous system was significantly affected with a haemangioma of the left occipital lobe, with complications of stroke. He also had multiple paravertebral heamangiomas, which caused pressure signs and symptoms. This boy suffered from complex partial and generalized seizures and cerebral palsy. Multiple skeletal anomalies were also present from birth. In the relevant literature, this is the first case of BRBNS with simultaneous neurological and skeletal involvement. Such cases should be recognized early, as they can lead to serious multiple health problems and handicaps.
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Ekaterini Siomou, Anastasios Serbis, Christos Salakos, Frederica Papadopoulou, Constantinos J Stefanidis, Antigoni Siamopoulou (2008)  Masked severe stenosing ureteritis: a rare complication of Henoch-Schönlein purpura.   Pediatr Nephrol 23: 5. 821-825 May  
Abstract: Henoch-Schönlein purpura (HSP)-associated stenosing ureteritis represents a rare complication of the disease, typically presenting with severe manifestations. This article reports on a 3.5-year-old boy with HSP and severe nephritis who developed a unilateral stenosing ureteritis with atypical manifestations, resulting in a nonfunctional kidney and consequent nephrectomy. The urinary tract ultrasound was normal in the first week of illness, and the diagnosis was made during follow-up 8 months after onset. The predominance of nephritic manifestations may have masked any signs of ureteritis, leading to the delay in diagnosis. To clarify the clinical spectrum of this complication, an extensive review of the literature was performed. We emphasize the necessity of repeated urinary tract ultrasound both early and later in the course of HSP, especially in cases with renal involvement, so that an early diagnosis of this complication can prevent a potentially serious renal outcome.
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2007
Kyriaki Karavanaki, Fotis Angelos Haliotis, Maria Sourani, Catherine Kariyiannis, Eugenia Hantzi, Levandia Zachariadou, Spyros Avlonitis, Ioannis Papassotiriou, Constantinos J Stefanidis (2007)  DMSA Scintigraphy in Febrile Urinary Tract Infections Could Be Omitted in Children With Low Procalcitonin Levels   Infect Dis Clin Pract 2007 15: 377-381  
Abstract: Purpose: The objective was to assess procalcitonin (PCT) as a marker of renal involvement in children with urinary tract infections (UTI). Methods: The study included 60 children with UTI, aged (median) 0.6 years (range, 0.1-9.5 years), admitted to a pediatric hospital. White blood cell count, C-reactive protein (CRP), and PCT levels were measured on admission and on the third treatment day, whereas renal involvement was assessed with dimercaptosuccinic acid (DMSA) scintigraphy within 7 days after admission and after 6 months. Results: During febrile UTI, PCT, and CRP levels increased in parallel with the severity of renal lesions in acute DMSA. During repeat DMSA, PCT levels were increased in the group with partially versus totally reversible renal lesions (5.3 [mu]g/L vs 3.0 [mu]g/L; P = 0.005). Procalcitonin and CRP had increased sensitivity (94% and 100%, respectively) and negative predictive values (97% and 100%, respectively), whereas PCT had higher specificity than CRP (100% vs 55%). Conclusions: Procalcitonin is a sensitive marker of the development, severity, and persistence of renal lesions in childhood UTI. Because of the high negative predictive values of PCT, we suggest that, in case of low PCT levels, the possibility of renal involvement is low, and DMSA could be omitted.
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Constantinos J Stefanidis, Günter Klaus (2007)  Growth of prepubertal children on dialysis.   Pediatr Nephrol 22: 9. 1251-1259 Sep  
Abstract: Growth failure is a common and significant clinical problem for children on dialysis and often remains a major impediment to their rehabilitation. Early referral to a paediatric nephrology centre and appropriate management before the initiation of dialysis may significantly prevent growth deterioration. Growth in children on dialysis can be affected by nutritional, metabolic, and hormonal changes. Early diagnosis of malnutrition and aggressive management should be a priority. Gastrostomy feeding should be used when adequate oral intake to maintain normal height and weight velocity cannot be achieved. Active vitamin D metabolites should be used carefully, to prevent low-turnover bone disease. All children should have an adequate regimen of dialysis and an appropriate management of malnutrition, renal osteodystrophy, metabolic acidosis, salt wasting and anaemia, before recombinant human growth hormone (rhGH) administration is considered. The current challenge of reversing growth impairment in children on dialysis can only be achieved by optimization of their care.
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Sotiria D Mastroyianni, Anastasia Garoufi, Konstantinos Voudris, Angeliki Skardoutsou, Constantinos J Stefanidis, Efstathia Katsarou, Rebecca Gooding, Luba Kalaydjieva (2007)  Congenital cataracts facial dysmorphism neuropathy (CCFDN) syndrome: a rare cause of parainfectious rhabdomyolysis.   Eur J Pediatr 166: 7. 747-749 Jul  
Abstract: Congenital cataracts-facial dysmorphism-neuropathy syndrome (CCFDN, MIM: 604168), is a recently delineated neurogenetic disease causing recurrent episodes of rhabdomyolysis; prevention and early diagnosis of rhabdomyolysis should be part of the clinical management of the disease.
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Constantinos J Stefanidis, Ekaterini Siomou (2007)  Imaging strategies for vesicoureteral reflux diagnosis.   Pediatr Nephrol 22: 7. 937-947 Jul  
Abstract: The prevalence of vesicoureteral reflux (VUR), although reported to be low in the general population, is high in children with urinary tract infection (UTI), first degree relatives of patients with known VUR and children with antenatal hydronephrosis. In addition, it has been shown that VUR and UTIs are associated with renal scarring, predisposing to serious long-term complications, i.e., hypertension, chronic renal insufficiency and complications of pregnancy. Therefore, diagnostic imaging for the detection of VUR in the high-risk groups of children has been a standard practice. However, none of these associations has been validated with controlled studies, and recently the value of identifying VUR after a symptomatic UTI has been questioned. In addition, several studies have shown that renal damage may occur in the absence of VUR. On the other hand, some patients, mainly males, may have primary renal damage, associated with high-grade VUR, without UTI. Recently, increasing skepticism has been noted concerning how and for whom it is important to investigate for VUR. It has been suggested that the absence of renal lesions after the first UTI in children may rule out VUR of clinical significance and reinforces the redundancy of invasive diagnostic techniques. Therefore, the priority of imaging strategies should focus on early identification of renal lesions to prevent further deterioration.
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2006
G Klaus, A Watson, A Edefonti, M Fischbach, K Rönnholm, F Schaefer, E Simkova, C J Stefanidis, V Strazdins, J Vande Walle, C Schröder, A Zurowska, M Ekim (2006)  Prevention and treatment of renal osteodystrophy in children on chronic renal failure: European guidelines.   Pediatr Nephrol 21: 2. 151-159 Feb  
Abstract: Childhood renal osteodystrophy (ROD) is the consequence of disturbances of the calcium-regulating hormones vitamin D and parathyroid hormone (PTH) as well as of the somatotroph hormone axis associated with local modulation of bone and growth cartilage function. The resulting growth retardation and the potentially rapid onset of ROD in children are different from ROD in adults. The biochemical changes of ROD as well as its prevention and treatment affect calcium and phosphorus homeostasis and are directly associated with the development of cardiovascular disease in pediatric renal patients. The aims of the clinical and biochemical surveillance of pediatric patients with CRF or on dialysis are prevention of hyperphosphatemia, avoidance of hypercalcemia and keeping the calcium phosphorus product below 5 mmol(2)/l(2). The PTH levels should be within the normal range in chronic renal failure (CRF) and up to 2-3 times the upper limit of normal levels in dialysed children. Prevention of ROD is expected to result in improved growth and less vascular calcification.
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2005
Constantinos J Stefanidis (2005)  Growth and nutrition of children with chronic renal failure.   Turk J Pediatr 47 Suppl: 9-12  
Abstract: It has long been recognized that chronic renal failure (CRF) in children is associated with growth delay. Still In our days nevertheless, growth retardation remains today a major impediment to the full rehabilitation of children with CRF. The reduction of in height velocity frequently results in diminished final adult height. Available evidence suggests that growth retardation might be the result of late referral and/or suboptimal clinical care in children with CRF. Management of malnutrition, renal osteodystrophy, metabolic acidosis, salt wasting and anemia should be optimal before recombinant human growth hormone initiation.
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Jochen H H Ehrich, Anita Amina El Gendi, Alfred Drukker, Jan Janda, Constantinos Stefanidis, Kate Verrier-Jones, Jacqueline Collier, Manuel Katz (2005)  Demography of paediatric renal care in Europe: organization and delivery.   Nephrol Dial Transplant 20: 2. 297-305 Feb  
Abstract: BACKGROUND: Members of the European Society of Paediatric Nephrology (ESPN) initiated a study of the demography and policy of paediatric renal care among European countries at the end of the 20th century. METHODS: A questionnaire was mailed to the presidents of each of 43 national renal paediatric societies or working groups in Europe. Data on each country's population, income as reflected by its gross national product and infant mortality rate, were obtained from the United Nations. The paediatric health care systems were previously divided into three types: general practitioner care system, paediatric care system and combined care system (CCS). RESULTS: In 1998, 842 specialized paediatric nephrologists worked in hospitals in 42 European countries. The median number of paediatric nephrologists per million child population (pmcp) was 4.9 (range 0-15). The median number of children served per paediatric nephrologist was significantly higher in countries with the general practitioner care system than in those with the paediatric or combined care system (CCS), namely 370 747 vs 169 456 and 191 788, respectively. In addition to specially trained paediatric nephrologists, there were 1087 paediatricians with a part-time interest/activity in paediatric nephrology in hospitals in 34 European countries. Eastern European countries had significantly more general paediatricians with part-time nephrological activities than countries belonging to the European Union (EU), 16.7 vs 6.6 pmcp. In 1998, 92% of 42 European countries offered paediatric dialysis facilities for acute renal failure and 90% for chronic renal failure and 55% offered paediatric renal transplantation (RTx). Only 30% of Eastern European countries (central omitted) offered paediatric RTx vs 87% of EU countries. The availability of paediatric RTx was associated significantly with the countries' gross national product (r = 0.53, P<0.001). The median number of paediatric hospitals offering dialysis for childhood chronic renal failure was 1.5 pmcp (range 0-5.0) and the median number of paediatric hospitals offering paediatric RTx was 0.4 pmcp (range 0-3.5). Fewer children were on dialysis or were transplanted in Eastern European countries than in the EU. CONCLUSIONS: At the end of the 20th century, there was a marked variation in delivery of paediatric renal care within Europe. This was related to factors such as size of the population, geographical and political situation, the type of primary paediatric care system and economic situation. European countries were far from equal with regard to access of renal replacement therapy for children. Improvement of the economic situation is beyond the capabilities of paediatric nephrologists. However, in these days of world-wide globalization paediatricians in greater Europe should be able to achieve better cooperation and exchange of ideas and information which would be the first step towards equality of renal care for children.
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2004
George S Stergiou, Christina V Alamara, Chrysa B Kalkana, Iraklis N Vaindirlis, Constantinos J Stefanidis, Catherine Dacou-Voutetakis, Theodore D Mountokalakis (2004)  Out-of-office blood pressure in children and adolescents: disparate findings by using home or ambulatory monitoring.   Am J Hypertens 17: 10. 869-875 Oct  
Abstract: BACKGROUND: The validity of home blood pressure (HBP) measurements in children has not been evaluated, although in clinical practice such measurements are being used. This study compares HBP, with clinic (CBP) and daytime ambulatory blood pressure (ABP) in children and adolescents. METHODS: Fifty-five children and adolescents aged 6 to 18 years were evaluated with CBP (three visits), HBP (6 days), and daytime ABP. Mean age was 12.3 +/- 2.9 (SD) years, 33 boys. According to the Task Force CBP criteria, 26 were hypertensives, 6 had high-normal BP (hypertensive group), and 23 were normotensives (normotensive group). RESULTS: In the hypertensive group, CBP was 130.8 +/- 7.6/72.5 +/- 8.1 mm Hg (systolic/diastolic), HBP 118.9 +/- 6.3/73.7 +/- 6.7, and ABP 130.8 +/- 8.1/75.5 +/- 8.3. In the normotensive group, CBP was 112.8 +/- 8/63.1 +/- 6.3, HBP 106.7 +/- 8.4/67.2 +/- 5.2, and ABP 123.9 +/- 7.2/72 +/- 4.3. Strong correlations (P < .001) were observed between CBP-HBP (r = 0.73/0.57, systolic/diastolic), CBP-ABP (r = 0.59/0.49), and HBP-ABP (r = 0.72/0.66). In normotensive subjects, ABP was higher than both CBP and HBP for systolic and diastolic BP (P < .001). Furthermore, systolic HBP was lower than CBP (P < .01), whereas the opposite was true for diastolic BP (P < .05). In hypertensive subjects systolic HBP was lower than both CBP and ABP (P < .001), whereas CBP did not differ from ABP. For diastolic BP no differences were found among measurement methods. CONCLUSIONS: These data suggest that, in contrast to adults in whom HBP is close to the levels of daytime ABP, in children and adolescents HBP appears to be significantly lower than daytime ABP. Until more data become available, caution is needed in the interpretation of HBP in children and adolescents.
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George S Stergiou, Christina V Alamara, Adriani Vazeou, Constantinos J Stefanidis (2004)  Office and out-of-office blood pressure measurement in children and adolescents.   Blood Press Monit 9: 6. 293-296 Dec  
Abstract: Office and out-of-office blood pressure measurements are being used for the diagnosis of hypertension in children and adolescents. The US National Heart, Lung, and Blood Institute have recently presented a new classification of blood pressure. On the basis of office measurements the 90th, 95th and 99th percentile for gender, age and height are used to classify children and adolescents as normotensive, pre-hypertensive and stage-1 or stage-2 hypertensive. Although auscultation using a standard mercury sphygmomanometer remains the recommended method, accumulating evidence suggests that ambulatory blood pressure monitoring is useful for the detection of white-coat hypertension and the prediction of target organ damage in children and adolescents. Studies have shown ambulatory blood pressure to be more reproducible than office measurements and normative tables for ambulatory measurements have been developed from cross-sectional studies in children and adolescents. In regard to home measurements in children, there are limited data from small trials showing lower blood pressure levels than daytime ambulatory blood pressure. In conclusion, ambulatory blood pressure monitoring is already finding a role as a supplementary source of information in children and adolescents, whereas at present home measurements should not be used for decision making in this population.
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2003
C J Stefanidis, A Mitsioni, M Bitsiori (2003)  A population-specific formula predicting creatinine excretion in children on chronic peritoneal dialysis.   Journal of the Balkan Cities Association of Nephrology, Dialysis, Transplantation and Artificial Organs 1: 2. 75-77  
Abstract: Introduction: The creatinine excretion (CrEx) is considered as a reliable index of lean body mass. The purpose of this study was to develop and test a formula to calculate predicted CrEx in children on chronic peritoneal dialysis (CPD). Materials and methods: Creatinine excretion data were measured in 145 24-hour urine and dialysate collections from 22 children on CPD (aged 7.0 +/- 4.3 years; male/female: 12/10). The CrEx ratio was calculated by dividing the patients measured CrEx (M CrEx) by the predicted CrEx (P CrEx). The formula predicting P CrEx was derived by surface area (SA in m2), height (Ht in cm) and serum creatinine (S.Cr in mg/dl) by linear regression. Results: There was a positive correlation (r=0.57, p<0.001) between M CrEx and P CrEx calculated by the equation: P CrEx (mg/kg/day) = (0.261 x S.Cr) + (0.047 x Ht) + 11. The positive and the negative predictive values of this equation were respectively 78% and 82%. The M CrEx was 17.5 +/- 2.8 mg/kg/day and CrEx ratio ranged from 0.67 to 1.36 (1.01 +/- 0.13). A significant positive correlation was found between P CrEx and percentage of ideal body weight. There was no correlation of CrEx ratio and age or height or surface area. Conclusions: An equation for the calculation of P CrEx was derived from data of routinely measured creatinine clearances. Using this formula CrEx ratio can be easily calculated and changes of lean body mass can be estimated. However this formula is population-specific and needs to be confirmed in other centers.
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2002
Konstantinos A Voudris, Constantinos J Stefanidis, Eystathia Katsarou, Angeliki Skardoutsou, Eleni A Vagiakou (2002)  Seizures and haemolytic-uraemic syndrome   ARCH DIS CHILD 84: 5/434. 434  
Abstract: On their interesting paper, Eriksson et al. reported that children with haemolytic-uraemic syndrome (HUS) and seizures have a higher mortality or long term neurological sequelae.[1] In this paper, a significant number of patients had focal abnormalities. Severe sequelae occurred in six of the eight cases with partial or secondarily generalized seizures and four of the six cases with generalized seizures. There are only few reports to relate the presence of seizures in children with HUS and long-term neurological prognosis. It is of interest that in a previous study it was found that seizures do not predict death or significant central nervous system (CNS) sequelae.[2] The pathogenesis of CNS involvement in HUS is multifactorial and is usually secondary to metabolic abnormalities, such as uraemia, hyponatraemia, and hypocalcaemia, metabolic acidosis, changes in serum osmolality, anoxia, coagulopathy and/or thrombotic microangiopathy. The presence and the type of seizures and the outcome of patients depend mostly on the type of underlying disturbances. Metabolic abnormalities often cause generalized seizures and the prognosis is usually favorable.[2,3] Patients with structural damage of the brain documented by computed tomography scan or magnetic resonance imaging (MRI) studies usually have focal, recurrent or persisted seizures and their prognosis is usually unfavorable. It thus appears that brain imaging is a better predictor of outcome in these cases.[3] We have described four children (2 boys, 2 girls) with HUS and seizures, with late referral to our hospital.[4] Their age varied between 1 and 5 years (mean, 2.3 years). All 4 patients had prodromal gastrointestinal symptoms, with positive stool cultures in one patient (E coli O157:H7). The seizures occurred early in the illness (4-6 days from onset of gastrointestinal symptoms), and in all children, seizures were the clinical finding that led to the child’s hospitalization. At the time of seizures, all patients were normotensive, with elevated serum urea (160 -380 mg/dl) and hyponatraemia (111-119 mEq/L). No child had hypoglycemia, or hypocalcemia. The convulsions were brief, generalized tonic-clonic, and easily controlled with antiepileptic medication and correction of hyponatraemia. Lethargy was observed in all children. The electroencephalograms of all our patients revealed diffuse delta waves with no focality. No patient had focal neurological signs and MRI studies revealed nonspecific findings, which were probably due to the presence of metabolic abnormalities; however, focal findings or serious structural abnormalities such as infarcts, haemorrhage and/or significant cerebral edema were not found. All patients had a full recovery and, after 2.5-4 years (mean, 3.4 years), remained without neurological deficits or recurrent seizures. The findings of our patients suggest that there is a group of patients who, after the prodromal gastrointestinal illness, present with isolated, brief, generalized tonic-clonic seizures. The seizures of these children are easily controlled and probably related to metabolic abnormalities. Our impression is that the presence of this type of seizures in children with HUS does not usually imply an unfavorable prognosis. Earlier diagnosis and better fluid and electrolyte management might prevent these complications. References (1) Eriksson KJ, Boyd SG, Tasker RC. Acute neurology and neurophysiology of haemolytic-uraemic syndrome. Arch Dis Child 2001;84:434-5. (2) Bale JF, Brasher C, Siegler RL. CNS manifestations of the hemolytic- uremic syndrome. Relationship to metabolic alterations and prognosis. Am J Dis Child 1980;134:869-72. (3) Dhuna A, Pascual-Leone A, Talwar D, Torres F. EEG and seizures in children with hemolytic-uremic syndrome. Epilepsia 1992;33:482-6. (4) Voudris K, Stefanidis K, Katsarou E, et al. Early occurrence of seizures in children with haemolytic uraemic syndrome and nervous system involvement. [abstract] Eur J Paediatr Neurol 2001;5:A126.
Notes:
2001
2000
A I Mylonas, G B Massoulas, O Nicolatou, I A Dontas, L Nakopoulou, C J Stefanidis (2000)  Progress of ossification and epithelialization of wounds after simple or surgical extractions of teeth in rats with chronic renal failure: an experimental study.   Br J Oral Maxillofac Surg 38: 1. 35-43 Feb  
Abstract: Our aim was to investigate the progress of wound healing after simple and surgical removal of the first two molars of the right and left maxillary segments, respectively, in Wistar rats with experimentally induced moderate chronic renal failure (CRF). Sixty Wistar rats were divided into two groups of 30 rats each: experimental and control. CRF was induced in the experimental group by an intraperitoneal injection of cisplatin, 5 mg/kg body weight (BW) initially and then with two maintenance doses of 2.5 mg/kg BW at intervals of one month. The teeth were extracted one month after the last dose of cisplatin. The sockets and the kidneys of all the rats of both groups were evaluated. The mandibles of the 15 rats in the experimental group that developed moderate CRF, together with those of two controls, were evaluated for abnormalities that suggested renal osteodystrophy. The histopathological examination showed: (a) that there were no significant differences in the pattern of wound healing no matter how the tooth was extracted; (b) there were no specific abnormalities in the mandible to indicate of secondary hyperparathyroidism or renal osteodystrophy; and (c) the kidneys of the rats of the experimental group underwent histopathological changes that were significantly different from those in the controls (P < 0.001). Our results indicate that moderate CRF does not have any appreciable or significant modifying effect on wound healing after tooth extraction in Wistar rats.
Notes:
1998
1996
C J Stefanidis, A Papathanassiou, K Michelis, X Theodoridis, F Papachristou, J Sotiriou (1996)  Diabetes mellitus after therapy with recombinant human growth hormone (rhGH).   Br J Clin Pract Suppl 85: 66-67 Aug  
Abstract: An eight-year-old boy developed diabetes mellitus (DM) after kidney transplantation. This boy had previously been treated with recombinant human growth hormone (rhGH) for short stature due to chronic renal failure. An impaired glucose tolerance was documented after one year of rhGH treatment. An oral glucose tolerance test returned to normal six months after the discontinuation of rhGH. The boy was treated again with rhGH for seven months until his transplantation. A high fever with an enlargement of the parotid gland was noted and signs of acute rejection appeared two weeks post-transplantation. Two months after transplantation, overt DM had developed, and he was treated with insulin. The insulin dose was progressively decreased and was discontinued eight months after transplantation.
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C Stefanidis, D Siapera, A Papadopoulou, K Michelis (1996)  Body composition of children on CAPD.   Perit Dial Int 16 Suppl 1: S561-S566  
Abstract: Our objectives were to estimate the body composition of children on continuous ambulatory peritoneal dialysis (CAPD), assess the fat-free mass (FFM) by bioelectrical impedance (BIA) and skinfold anthropometry (SF), and determine the effect of various parameters of the nutritional status and adequacy of dialysis on body composition. The design was a noninterventional retrospective clinical trial. The percent of fat ranged from 10% to 25% (15 +/- 2), when it was calculated from SF, and was from 9% to 32% (18 +/- 2) when it was calculated from BIA. There was a significant correlation between the percent of fat calculated by SF and by BIA (r = 0.94, p < 0.0001 with limits of agreement 4.16 to 1.37 and -0.40 to -3.19). The water content of FFM ranged from 70%-79%(74 +/- 1). There was a weak but significant correlation (r = 0.64, p = 0.016) between protein catabolic rate (PCR) and KT/V (V = 60% of weight). This correlation became more significant (r = 0.83, p = 0.0007) when the V of KT/V was calculated from BIA. The prediction of body composition with the use of bioelectrical impedance is a simple and reliable technique. Serial measurements of BIA might be an important tool for the assessment of the nutritional intervention.
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C J Stefanidis (1996)  Is rhGH anabolic in patients undergoing peritoneal dialysis?   Br J Clin Pract Suppl 85: 44-46 Aug  
Abstract: The effect of rhGH treatment on protein metabolism was studied in nine prepubertal patients on CAPD. An improvement in nitrogen balance as evidenced by a falling of blood urea nitrogen and urea nitrogen appearance with a constant protein intake was noticed. The significant increase in serum creatinine and creatinine excretion with a constant weekly creatinine clearance and the increase in mid-arm muscle circumference were all indications of an improvement in lean body mass. In addition, there was an improvement in the pattern of plasma amino acids and an increase in serum albumin, possibly as a result of the improvement of protein metabolism.
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1993
C Stefanidis, H Michelakaki, A Koulieri, K Michelis (1993)  Nutritional status and growth in children less than 12 kg treated with continuous ambulatory peritoneal dialysis.   Perit Dial Int 13 Suppl 2: S251-S253  
Abstract: Various parameters of nutritional status and growth in 13 children with weight less than 12 kg were estimated at the start of continuous ambulatory peritoneal dialysis (CAPD) and 1 year later. A significant improvement in weight, triceps skinfold, and serum albumin was noticed. Height and midarm muscle circumference did not change significantly. However, a significant improvement in height occurred in patients with initial abnormal height (<--2 SDS). There was no significant change in protein intake and urea nitrogen appearance (UNA) during the study period. A significant correlation between protein intake and UNA was noticed. All patients had normal serum insulinlike growth factor. In conclusion, there was no significant change in either height velocity or muscle mass despite the improvement in many nutritional parameters.
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1992
C J Stefanidis, A Koulieri, D Siapera, A Kapogiannis, A Mitsioni, K Michelis (1992)  Effect of the correction of anemia with recombinant human erythropoietin on growth of children treated with CAPD.   Adv Perit Dial 8: 460-463  
Abstract: Anemia correction with recombinant human erythropoietin (EPO) has been suggested to have a positive effect on nutritional status by improving appetite and protein metabolism. To assess this effect growth velocity and various parameters of nutritional status of 10 children on continuous ambulatory peritoneal dialysis (CAPD) were estimated at the start and one year after the correction of anemia. There was no significant improvement of growth velocity after EPO administration. Energy and protein intake, standard deviation scores of anthropometric measurements, BUN, serum creatinine, albumin, potassium, phosphorous and protein catabolic rate did not differ significantly before and after EPO administration. There was a significant correlation of protein intake and protein catabolic rate. Conclusion: There was no significant improvement of nutritional status and growth of children on CAPD treated with EPO, possibly because there was no evidence of malnutrition in most patients.
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1991
H V Kosmidis, D O Bouhoutsou, M C Varvoutsi, J Papadatos, C J Stefanidis, P Vlachos, A Scardoutsou, A Kostakis (1991)  Vincristine overdose: experience with 3 patients.   Pediatr Hematol Oncol 8: 2. 171-178 Apr/Jun  
Abstract: Vincristine overdose (7.5 mg/m2) was accidentally administered to 3 children with acute lymphoblastic leukemia. Treatment included double-volume exchange transfusion, phenobarbital administered prophylactically, and folinic acid rescue 18 mg every 3 hours for 16 doses. Vincristine levels were also assayed and showed a dramatic decline in postexchange levels in the 2 patients who survived and an almost unchanged value in the patient who succumbed. Early signs of toxicity in the 2 survivors were peripheral neuropathy (day 4), bone marrow toxicity (day 5), gastrointestinal toxicity (days 6 and 7), and hypertension (days 7 and 8). Marrow aplasia lasted for 4 and 10 days, peripheral neuropathy for 15 and 42 days, gastrointestinal toxicity for 3 and 5 days, and hypertension for 5 and 14 days. The 2 children were discharged on days 13 and 16 and cytostatic therapy was restarted on days 18 and 25. Both are alive without evidence of leukemia. The third patient developed liver and marrow toxicity on day 3 and died on day 9. Postmortem examination showed leukemia infiltration of the liver and spleen.
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1989
1985
1984
N J Papadoyannakis, C J Stefanidis, M McGeown (1984)  The effect of the correction of metabolic acidosis on nitrogen and potassium balance of patients with chronic renal failure.   Am J Clin Nutr 40: 3. 623-627 Sep  
Abstract: Nitrogen and potassium balance studies were conducted in six nondialyzed uremic patients. Each patient was investigated before and after supplementation with sodium bicarbonate and sodium chloride. Every period of the study lasted longer than 1 wk. Each patient had the same calorie and protein intake during the whole study. Urea nitrogen appearance was correlated with protein intake for the assessment of the compliance of patients with their diets. There was a significant decrease of blood urea nitrogen (p = 0.014) of 36% during bicarbonate supplementation and both metabolic balance studies improved significantly (p = 0.0005 and 0.0096). However, there was no significant improvement during sodium chloride administration indicating that the effect of bicarbonate was the result of the correction of metabolic acidosis and not of the expansion of the extracellular volume.
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1983
I K Hewitt, C Stefanidis, B J Reilly, S W Kooh, J W Balfe (1983)  Renal osteodystrophy in children undergoing continuous ambulatory peritoneal dialysis.   J Pediatr 103: 5. 729-734 Nov  
Abstract: Fifteen children undergoing continuous ambulatory peritoneal dialysis for 0.3 to 2.4 years were evaluated longitudinally for renal osteodystrophy. Immunoreactive parathyroid hormone, 25-OHD, total and ionized calcium, inorganic phosphate, and alkaline phosphatase levels were measured regularly. Skeletal radiographic studies were performed at the onset and conclusion of CAPD and at six-month intervals during therapy. All children received 1,25(OH)2D3 and aluminum hydroxide, and nine received supplemental calcium. Plasma 25-OHD concentrations were normal to elevated, and calcium increased steadily to high normal levels despite a trend to persistent hyperphosphatemia. The increased calcium levels suppressed parathyroid hormone overactivity in only one patient. At the onset of CAPD, nine patients had hyperparathyroid bone disease seen radiographically, three of whom also had rachitic lesions. At the end of CAPD, the hyperparathyroid lesions had improved in four patients, completely resolved in three, and deteriorated in two. Rachitic lesions had completely healed in two patients and improved in the third. However, among the six children without radiographically evident lesions at onset of CAPD, hyperparathyroid bone lesions developed in two and rachitic lesions in two others during CAPD. Although CAPD and appropriate therapy benefited most patients with renal osteodystrophy, the benefits were not uniform, and bone lesions deteriorated in some.
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C J Stefanidis, J W Balfe, G S Arbus, B E Hardy, B M Churchill, C P Rance (1983)  Renal transplantation in children treated with continuous ambulatory peritoneal dialysis   3: 5-8  
Abstract: Over the last three years 23 children, who were managed by CAPD at the Hospital for Sick Children, Toronto received a renal transplant. Their actuarial graft survival was similar to those of children on hemodialysis and to patients not dialyzed before transplantation. In addition, we analyzed the actuarial graft survival of 130 children treated before transplantation with peritoneal dialysis (IPD and CAPD), hemodialysis or no dialysis to determine the long-term effects of peritoneal dialysis. Again, we found no significant differences among the various groups.
Notes:
C J Stefanidis, I K Hewitt, J W Balfe (1983)  Growth in children receiving continuous ambulatory peritoneal dialysis.   J Pediatr 102: 5. 681-685 May  
Abstract: Linear growth of 17 children receiving CAPD was compared with growth in 18 patients receiving hemodialysis and 20 who had undergone transplantation, as well as with the previous growth in 11 of the 17 patients. Growth was normal in 10 receiving CAPD, fair in six others, and poor in only one. Growth velocity indexes in those receiving CAPD were significantly better than those of the group receiving hemodialysis (P less than 0.01) but did not differ significantly from those of children who had undergone kidney transplant. All patients grew significantly better after beginning CAPD than before (P less than 0.01). Appropriate management of renal osteodystrophy combined with adequate energy and protein intake were important factors in the growth of patients receiving CAPD.
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