Sema Akman

Spectrum of Steroid-Resistant and Congenital Nephrotic Syndrome in Children: The PodoNet Registry Cohort

BACKGROUND AND OBJECTIVES Steroid-resistant nephrotic syndrome is a rare kidney disease involving either immune-mediated or genetic alterations of podocyte structure and function. The rare nature, heterogeneity, and slow evolution of the disorder are major obstacles to systematic genotype-phenotype, intervention, and outcome studies, hampering the development of evidence-based diagnostic and therapeutic concepts. To overcome these limitations, the PodoNet Consortium has created an international registry for congenital nephrotic syndrome and childhood-onset steroid-resistant nephrotic syndrome. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Since August of 2009, clinical, biochemical, genetic, and histopathologic information was collected both retrospectively and prospectively from 1655 patients with childhood-onset steroid-resistant nephrotic syndrome, congenital nephrotic syndrome, or persistent subnephrotic proteinuria of likely genetic origin at 67 centers in 21 countries through an online portal. RESULTS Steroid-resistant nephrotic syndrome manifested in the first 5 years of life in 64% of the patients. Congenital nephrotic syndrome accounted for 6% of all patients. Extrarenal abnormalities were reported in 17% of patients. The most common histopathologic diagnoses were FSGS (56%), minimal change nephropathy (21%), and mesangioproliferative GN (12%). Mutation screening was performed in 1174 patients, and a genetic disease cause was identified in 23.6% of the screened patients. Among 14 genes with reported mutations, abnormalities in NPHS2 (n=138), WT1 (n=48), and NPHS1 (n=41) were most commonly identified. The proportion of patients with a genetic disease cause decreased with increasing manifestation age: from 66% in congenital nephrotic syndrome to 15%-16% in schoolchildren and adolescents. Among various intensified immunosuppressive therapy protocols, calcineurin inhibitors and rituximab yielded consistently high response rates, with 40%-45% of patients achieving complete remission. Confirmation of a genetic diagnosis but not the histopathologic disease type was strongly predictive of intensified immunosuppressive therapy responsiveness. Post-transplant disease recurrence was noted in 25.8% of patients without compared with 4.5% (n=4) of patients with a genetic diagnosis. CONCLUSIONS The PodoNet cohort may serve as a source of reference for future clinical and genetic research in this rare but significant kidney disease.

Renal function after hematopoietic stem cell transplantation in children

The aim of this study was to assess glomerular and tubular renal function after HSCT in children in a prospective trial.

Mercury intoxication resulting from school barometers in three unrelated adolescents

Three adolescents with severe hypertension due to mercury intoxication are presented. Two of them had skin rash, signs and symptoms of central nervous system involvement, peripheral neuropathy and mild-to-moderate proteinuria in addition to hypertension. All three patients had a history of exposure to mercury, the source being broken barometers taken from school laboratories 2–4 months previously. Urine and blood mercury levels were consistent with mercury intoxication. The patients were treated with chelation therapy. One of them died; the others recovered over a period of 1–4 months. Conclusion:mercury intoxication should be considered in any child with signs and symptoms of hypertension, skin rash, peripheral neuropathy and behavioural changes. The parents and school administrators, as well as paediatricians, should be aware of the potential risks of mercury and should be encouraged to avoid mercury-containing devices in schools and households.

Impact of peritoneal transport characteristics on cardiac function in Paediatric peritoneal dialysis patients: a Turkish Pediatric Peritoneal Dialysis Study Group (TUPEPD) report

BACKGROUND The peritoneal equilibration test (PET) is recommended in paediatric peritoneal dialysis (PD) patients to assist prescription management. Despite contradictory reports, high transporter status is associated with reduced survival rate in adults. Since cardiac disease is one of the main causes of mortality in paediatric PD patients, we aimed to evaluate whether transport features have any effect on biochemical data and cardiac function in this group. METHODS One hundred and ten PD patients (13 +/- 5 years, PD vintage: 31 +/- 27 months) were enrolled into the study. Four-hour dialysate/plasma creatinine ratio was used for differentiating PET groups. Thirty-eight patients were high transporters, 29 were high-average transporters and 43 were low-average/low transporters. Echocardiography was performed in all subjects. RESULTS Age, PD vintage, dialysate glucose concentration, ultrafiltration volume, urine volume and blood pressure levels were similar in all PET groups. No biochemical or echocardiographic data (ejection fraction, fractional shortening, left ventricular mass index, myocardial performance index, power Doppler E/tissue Doppler E ratio reflecting diastolic function) were different among PET groups except lower albumin (P = 0.025) levels in high transporters and higher high-sensitivity C-reactive protein (P = 0.026) levels in high and high-average transporters compared to other transport groups. CONCLUSIONS Cardiac structural and functional abnormalities are highly prevalent among paediatric PD patients. Transport rates did not have a significant effect on biochemical parameters or cardiac structural/functional parameters. It might be suggested that being a high transporter does not provide a disadvantage in terms of atherogenic tendency and cardiac disease in paediatric PD patients. Oligoanuria, anaemia and hypertension were independent predictors of cardiac disease.

Evaluation of reproductive functions in male adolescents following renal transplantation

Abstract:  The aim of this study was to analyze the semen variables and hormone profiles in kidney transplanted male adolescents. Eight post‐pubertal male patients who underwent successful renal tx during the peripubertal period and who had ESRD during childhood were enrolled in the study. Patients who underwent tx before 14 yr old (group I) and patients who underwent tx after 14 yr old (group II) were evaluated separately. Semen was collected and analyzed. Serum levels of LH, FSH, and testosterone were measured and found to be normal in all patients except one. The mean age at the diagnosis of CKD was six yr and 13 yr in groups I and II, respectively. The mean age at the time of tx was 12 yr in the first and 17.8 yr in the second group. The patients in group I had received prednisone, cyclosporine A and azathioprine with a longer duration of time compared with patients in group II. Sperm counts (15.5 ± 15.7 vs. 82.3 ± 64.2 millions/mL) and sperm motilities (37.8 ± 30.9 vs. 57.8 ± 22.1%) were lower in group I than group II. Only one patient in group II had normal sperm parameters and azospermia was observed in one patient from group I. We conclude that the earlier onset and the longer duration of uremia, the more impairment of reproductive function. Also, it seems that duration of exposure to corticosteroids or cyclosporine combined with azathioprine contribute to sperm dysfunction in peripubertal transplanted boys.

Can serum cystatin C reflect the glomerular filtration rate accurately in pediatric patients under chemotherapeutic treatment? A comparative study with Tc-99m DTPA two-plasma sample method.

ObjectiveIt was assessed whether cystatin C (cysC) could be used as a marker of glomerular filtration rate (GFR) by considering the technetium-99m diethylenetriamine penta-acetate (Tc-99m DTPA)-two blood sample method (GFRTc-99m DTPA) as the reference in pediatric patients under chemotherapeutic treatment. MethodsThe chemotherapy group (CG) consisted of 31 patients (21 females, 10 males median age: 8.2 years; range: 2–16 years) who had been planned to receive allogenic hematopoietic stem cell transplantation. All patients in the CG received conditioning regimen (includes chemotherapy protocol) before hematopoietic stem cell transplantation. In addition, 21 patients (14 females, seven males median age: 9.5 years; range: 4–16 years) without any chemotherapy (nonchemotherapy group: nCG) were also prospectively investigated. Serum cysC, serum creatinine, GFRTc-99m DTPA, and GFR with a cysC-based formula (GFRcysC) were analyzed. Tubular function was also assessed. ResultsAlthough we found good correlation between GFRTc-99m DTPA and cysC (r = −0.78), GFRTc-99m DTPA and GFRcysC (r = 0.91), cysC and creatinine (r = 0.91) in nCG, the same correlations were poor in CG (r = −0.42, r = 0.43, r = 0.46, respectively). Tubular function was impaired after chemotherapy. Bias±1.96 SD values were −6±15.7 and −3±54.8 ml/min/1.73 m2 in nCG and CG, respectively. Precision was also better in nCG (10 ml/min/1.73 m2) than in CG (27.6 ml/min/1.73 m2). ConclusionSerum cysC and GFRcysC cannot reflect GFR accurately in pediatric patients under chemotherapeutic treatment. Tubular cell damage induced by chemotherapeutics could be a responsible factor through the impairment of tubular absorption and metabolism of cysC.

Value of the urine strip test in the early diagnosis of bacterial peritonitis

Abstract Background : In an effort to detect the presence of leukocytes in the peritoneal dialysate fluid (PDF) a urine dipstick may be practical for the early detection of peritonitis in peritoneal dialysis patients.

IgG and IgG subclasses deficiency in children undergoing continuous ambulatory peritoneal dialysis and its provocative factors.

Background : Low levels of serum IgG or IgG subclasses may be responsible for the defective peritoneal defense and for peritonitis attacks in continuous ambulatory peritoneal dialysis (CAPD) children. Malnutrition, peritoneal loss or frequent peritonitis may lead to IgG or IgG subclasses deficiency.

Case of Bartter Syndrome Presenting With Hypokalemic Periodic Paralysis

Hypokalemic periodic paralysis can occur secondarily to excessive potassium loss. Thyrotoxicosis, diuretic ingestions, hyperaldosteronism, barium poisoning, Gitelman syndrome, and Bartter syndrome are among the disorders causing secondary hypokalemic periodic paralysis. Clinical presentation of Bartter syndrome with hypokalemic periodic paralysis is rare. A 12-year-old boy was admitted to our hospital because of transient paralysis. He had been suffering from transient weakness attacks for 2 years and had had a total of 10 attacks, lasting 1 to 3 days. He had growth retardation, polyuria, and polydipsia. Laboratory examinations revealed hypokalemic alkalosis, normomagnesemia, hypercalciuria, and hyperaldosteronism. The clinical and laboratory findings were in accordance with Bartter syndrome. He has been followed up for 6 months and has suffered no further paralytic attacks under indomethacin therapy. This case highlights the importance of blood pH measurement in patients with hypokalemic periodic paralysis; it might prevent misdiagnosis and mismanagement in such diseases. (J Child Neurol 2006;21:255—256; DOI 10.2310/7010.2006.00049).

Assessment of left ventricular function by tissue Doppler echocardiography in pediatric chronic kidney disease

Abstract Background: Cardiovascular (CV) disease remains the most common cause of mortality in chronic kidney disease (CKD). Methods: In this cross-sectional study, 43 pediatric patients with CKD were divided into two groups according to their estimated glomerular filtration rate (eGFR): groups 1 and 2 (eGR; 29–75 and 15–29 mL/min/1.73 m2, respectively). M – mode, conventional pulsed wave Doppler (cPWD) echocardiography and tissue Doppler imaging (TDI) were performed in all patients and 16 healthy controls. Maximal early (E wave) and late (A wave) diastolic flow velocities were assessed by cPWD. Using TDI, the early (E′) and late (A′) diastolic filling velocities were recorded. Early and late diastoles were evaluated using E′ values and E/E′ ratios, respectively. Results: Left ventricular hypertrophy (LVH) was determined in 19/43 (44.2%) patients. The E/E′ ratio was significantly higher in group 2 than in group 1 and controls. E/E′ was found to be positively correlated with left ventricular mass (LVM) index, and negatively with hemoglobin (Hb) levels. Low Hb levels were only independent predictor of E/E′ (p = 0.001, β: −0.470, 95% CI: −0.764; −0.196). E′ ratio was significantly lower in both patient groups compared to the controls. Conclusions: LVH and diastolic dysfunction are already present in early stages of CKD. Treatment of risk factors, such as anemia, is important to improve the clinical outcome.