Nephrology

ABSTRACTBackground: Nephrotic syndrome is one of the most common kidney diseases in childhood. About 20% of children are steroid-resistant NS (SRNS) which progress to end-stage renal disease (ESRD). More than 53 genes are associated with SRNS which represent the genetic heterogeneity of SRNS. This study was aimed to screen disease causing mutations within NPHS1 and NPHS2 and evaluate new potential variants in other genes.Method: In first phase of study, 25 patients with SRNS were analyzed for NPHS1 (exon 2, 26) and all exons of NPHS2 genes by Sanger sequencing. In the second phase, whole exome sequencing was performed on 10 patients with no mutations in NPHS1 and NPHS2.Result: WES analysis revealed a novel mutation in FAT1 (c.10570C>A; Q3524K). We identified 4 pathogenic mutations, located in exon 4 and 5 of NPHS2 gene in 20% of patients (V180M, P118L, R168C and Leu156Phe). Also our study has contributed to the descriptions of previously known pathogenic mutations across WT1 (R20...

Objective: Several factors have been identified as predictive of future renal function in children with posterior urethral valves (PUV). Our aim was to analyse upper and lower urinary tract outcome in patients with PUV, and determine any factors from the period of early management that were predictive of future renal function. Methods: The charts of 67 boys (mean age 2.4 years) diagnosed with PUV were reviewed. The most common presenting symptom was dribbling in 43.2% and UTI in 28.3%. Twenty-three (34.8%) patients developed end-stage renal disease aged 1e15 years. The mean time of renal survival was calculated as 7.8 (SEM Z 0.73) years. Results: Incontinence in patients over 5 years old, lower urinary tract dysfunction, serum creatinine level in first year or at the time of diagnosis, and presence of vesicoureteral reflux and high-grade bilateral reflux were significant risk factors for occurrence of renal failure in the future. Lower tract dysfunction was seen in 58.6% of patients. Postnatal diagnosis and presence of high-grade reflux were significant risk factors for the future occurrence of lower urinary tract dysfunction. Conclusion: It is important to recognize that PUV have consequences not only during childhood or before treatment, but also during or after the treatment period. Long-term assessment and follow-up of upper and lower urinary tract functions after valve ablation is necessary.

Mutations of the anion exchanger 1 (AE1) gene encoding the kidney anion exchanger 1 can result in autosomal dominant or autosomal recessive form of distal renal tubular acidosis (DRTA). This study aimed to report deletion mutations of the AE1 and its impact on Iranian children with DRTA. Twelve children with DRTA referred to Ali Asghar Children Hospital were investigated for all AE1 gene exons through polymerase chain reaction amplification, DNA sequencing, and bioinformatics analysis. Eleven of 12 patients (91.7%) showed an alteration in AE1 gene with a real hot spot in its exons 11 or 15. Homozygote and heterozygote deletions were confirmed in exon 15 in 5 (41.7%) and 3 (25.0%), respectively. Two patients (16.7%) showed homozygote deletions in exon 11 of AE1 gene, and 1 patient (8.3%) showed point mutation in exon 11. The 3-dimensional structures of the native and these mutant kidney AE1 proteins were determined by the multitemplate method using the Phyre and Hidden Markov Model a...

A b s t r a c t: Urodynamic study (UDS) is a serial of clinical tests, like uroflowmetry, filling cystometry, pressure-flow studies and assessment of urethral closure pressure. These tests include urethral pressure profilometry and also measurement of the leak-point pressure of lower urinary system. UDS is one of the essential clinical studies in children complaining of voiding dysfunction, neurogenic bladder, urine incontinence, enuresis and another lower urinary tract symptom. The aim of proper bladder management in these patients is to maintain the lower urinary tract to have good capacity, low pressure, preventing infection and incontinence. Long term goal is preventing any undue damage to the upper urinary tracts and intact kidneys function. This review article of pediatric urodynamic study provides a classified diagnostic approach to bladder dysfunctions in children.

Introduction: Atypical hemolytic uremic syndrome (HUS) is accompanied by a poor prognosis and high mortality rate. We investigated the predictive value of severity of renal involvement, as evaluated by pathologic examination, for long-term outcome of atypical HUS. Materials and methods: Kidney biopsies of 29 children diagnosed with atypical HUS between 1992 and 2005 were reviewed. The severity of glomerular, vascular (arteriolar and arterial), interstitial, and tubular involvement were determined. Scores of renal involvement were determined by re-evaluating kidney specimens. The outcome measures were death, chronic kidney disease (CKD), hypertension, and proteinuria. Results: After a mean of 3.7 years of follow-up, 24.1% of the patients had normal kidney function and blood pressure, 24.1% showed proteinuria, and 41.4% had CKD, and 10.3% had unknown prognosis. Overall, 24.1% of the patients died due to emergent hypertension with or without CKD. The existence of arteriolar and arterial thrombosis attributed to severe CKD (risk ratio, 3.67; 95% confidence interval, 1.63 to 8.2). Presence of thrombosis in the vessels, and thickening of the arterial medial and intimal layers had brought about a significantly higher mortality rate. Chronic kidney disease was more frequent in the children with vascular scores higher than 0.14 and a final score of more than 0.2. Conclusions: The severity of renal pathological involvement, especially the degree of vascular damage, is a good predictor of long-term outcome of patient with atypical HUS.

Introduction: Some evidence suggest an increase in the prevalence of focal segmental glomerular sclerosis (FSGS) in children. To date, there has been no study of the outcome in children with FSGS and its frequency over several decades in Iran. We aimed to report the changing trend of FSGS incidence and its outcome in a sample of Iranian children. Materials and methods: Between 1982 and 2008, all 716 kidney biopsies performed in children referred to Ali Asghar Children Hospital were recorded and confirmed cases with FSGS lesions were further evaluated. Baseline and clinical characteristics of all FSGS patients were assessed and the therapies and outcomes were reviewed. Results: The incidence rate of FSGS was 10.1% between 1982 and 1990, which was significantly increased to as high as 20.5% after the year 2000 (P = .001). Among 64 children with FSGS, 20 progressed to end-stage renal disease with a mean survival time of 11.45 years (standard error of mean, 1.34 years). Kidney survival rates were 90.4%, 69%, and 47% at 1, 5 and 10 years of follow-up. Conclusions: Our study demonstrates an increasing trend in FSGS incidence in Iranian children. However, kidney survival rates of our patients were similar to those reported by others in different countries.

Paraneoplastic syndromes result from secretion of hormones, peptides or cytokines by tumor or immune cross-reactivity between malignant and normal tissues. These conditions are rare in children, but when the clinical presentation of patients with a tumor is unusual, these syndromes should be emphasized. Extrarenal tumors with renin-secretion are rare in children. They may be related to paraneoplastic syndromes. We report a 22-month-old infant with hepatoblastoma presented with severe hypertension and related neurologic symptoms due to high plasma renin activity. To the best of our knowledge, this is the second report of renin producing hepatoblastoma in the literature. However, due to lack of laboratory facilities such as immunohistochemical study or polyclonal antibody for human renin activity, we could not prove the secretion of renin just by tumor tissue cells, but this potentiality is very likely. Other intensive investigations did not show any other origin for rennin secretion or hypertension in this patient.

Introduction: Congenital nephrotic syndrome (CNS), an uncommon form of kidney disease, presents during the first year of life and is a diagnostic and therapeutic challenge for the pediatricians as well as pediatric nephrologists. Our study is the first study of Iranian children with CNS in two pediatric nephrology centers in Tehran, Iran. Materials and methods: We reviewed medical charts of 30 infants diagnosed with CNS from 1990 to 2005. Results: There were 15 boys and 15 girls with CNS (mean age, 1.7 months). The presentation of the disease was nephrotic syndrome in 96.6% of the patients. Eighty percent of the patients presented within 3 months of life and 16 in the neonatal period. The Finnish type of CNS was seen in 43.3% and diffuse mesangial sclerosis in 50%. Preterm labor and low birth weight was seen in 20%. A family history of nephrotic syndrome in infancy was noted for 8 children (26.7%). Numerous complications of nephrotic syndrome occurred in 73.3%. Seventy percent of the patients had 27 episodes of infections. Sepsis was seen in 43.3% of the children, of which 61.5% were caused by gram-negative bacteria and 38.6% were caused by Staphylococcus aureus. Thrombotic complications and hypertension developed in 6.6% and 23.3% of the patients, respectively. The mortality rate of patients was 86.6%. Conclusions: Diffuse mesangial sclerosis is an important cause of CNS. The outcome of our patients was poor and most of our patients died before reaching the age of 5 years old.

Tubulointerstitial nephritis and uveitis (TINU) is a rare syndrome with unknown pathogenesis. Data have shown a higher prevalence in female gender. We present a man with tubulointerstitial nephritis and uveitis syndrome and antitubular antibody. A 23-year-old man presented with a history of weight loss, nausea, and vomiting, and uveitis. His serum creatinine was 2.1mg/d with pyuria and proteinuria in urinalysis. Other laboratory and imaging studies were unremarkable. Kidney biopsy showed granulomatous interstitial nephritis. Normal renal tissue specimen treated with patient's serum showed focal cytoplasmic staining in cortical tubular cells. The patient received prednisolone for 1 month. Interstitial nephritis and uveitis were well controlled. There was no recurrence in 1-year follow-up. We suggest that tubulointerstitial nephritis and uveitis syndrome should be considered in differential diagnosis of patients with interstitial nephritis and uveitis. Antitubular antibody may be ...

Preeclampsia is a serious complication of pregnancy, which is the cause of 60 000 maternal deaths annually worldwide. In addition to the well-known maternal risk factors such as hypertension, diabetes mellitus, antiphospholipid antibody syndrome, obesity, aging, and multiple pregnancies, recent studies have identified the role of genetic and immunological factors in the pathogenesis of preeclampsia. In particular, imbalance between angiogenic and anti-angiogenic factors, anti-angiotensin II type 1 receptor antibodies and dysregulation of oxygen supplies can cause preeclampsia. A group of biomarkers have been introduced for diagnosis of preeclampsia. Chief among them is the ratio of soluble fms-like tyrosine kinase-1 to placental growth factor, which can be used in clinical practice. Recent studies have shown high specificity and sensitivity of these markers for early diagnosis of preeclampsia, which is critical for prevention of fetal and maternal complications.

Introduction. Our aim was to evaluate the frequency and risk factors of posttransplant diabetes mellitus (PTDM) at our kidney transplant center, and to compare graft and patient outcomes between the kidney recipients with and without PTDM. Materials and Methods. We studied 203 kidney transplant recipients with a negative history of diabetes mellitus before transplantation. We examined them for PTDM and made diagnosis on the basis of the American Diabetes Association criteria. Measurements of plasma glucose were carried out from 3 months to 24 months after transplantation. All data including recipient and donor demographics, cause of end-stage renal disease, cytomegalovirus and hepatitis C virus antibody tests, and patient and graft outcomes were assessed in relation to PTDM. Results. High fasting plasma glucose was seen in 24 (11.8%), 19 (9.4%), 16 (7.9%), and 13 (6.4%) patients at 3, 6, 12, and 24 posttransplant months, respectively. Moreover, impaired glucose tolerance was seen in 17 (8.4%), 16 (7.9%), 17 (8.4%), and 19 (9.4%) patients at the corresponding times, respectively. Accordingly, 39 patients (19.2%) were diagnosed to have PTDM. The mean age of the kidney recipients with PTDM was 46.5 ± 12.3 years as compared to 38.6 ± 13.4 years in nondiabetic kidney recipients (P = .02). The 5-year patient and graft survival rates were not significantly different between the kidney recipients with and without PTDM. Conclusions. This study showed that PTDM is a common metabolic disorder in our kidney transplant patients. We recommend a less diabetogenic immunosuppressive protocol, especially for our older recipients.

Introduction and aim. Occult hepatitis C infection (OHCI) is the presence of HCV-RNA in the liver or peripheral blood mononuclear cells (PBMC) accompanying with negative serologic results. The aim of this study was to evaluate the prevalence of OHCI among Iranian chronic hemodialysis (HD) patients. Material and methods. In this cross sectional study 200 chronic HD patients with negative HCV antibody enrolled the study. Blood sample of patients were obtained, followed by Polymerase Chain reaction (PCR) testing for detection of HCV RNA. Patients with positive serum HCV RNA were considered as manifest hepatitis C infection (MHCI). However, patients with negative serum HCV RNA underwent further tests on PBMCs for detection of OHCI. Results. Serum HCV RNA was positive in 2 (1%) patients whom considered as MHCI, and 6 (3.03%) patients had positive PBMC HCV RNA. Conclusion. In conclusion, chronic HD patients have been considered as a high risk group for hepatitis C infection. The results o...

Brucellosis, a prevalent zoonosis disease in different countries, can involve the kidney during infection and also present in the complicated form in hemodialysis (HD), peritoneal dialysis (PD), and kidney transplant (Tx) patient. In spite of few reports of kidney involvements in the literature, this infection can imitate a wide range of glomerular disease from minimal change, membranous glomeropathy, focal and diffuse proliferative glomerular disease to rapidly progressive glomerulonephritis. Cryoglobulinemia, thrombotic microangiopathy, and ANCA-associated glomerular disease are vasculitis form of the disease. Tubulointerstitial involvement, electrolyte disorder, renal abscess, and pyelonephritis can present the same as other Gram-negative infections. Moreover, peritonitis in PD patient, spondyloarthropathy in HD, and severe infection in kidney Tx patients have been reported. Infection recurrence and infection from kidney donors are another dilemma in renal recipients. Brucellosis as a multifaced disease can mimic a wide range of presentations in nephrology. Clinicians should keep in mind the diverse pictures of the disease, especially when they practice in the endemic area.

INTRODUCTION Tuberculosis reactivation is one of significant complications after transplantation. Tuberculin skin test (TST) has been the major available screening test in end-stage renal disease patients, but it is associated with a low accuracy. Recently, an interferon-gamma release assay (IGRA) has been approved as a substitution test in diagnosis of Mycobacterium tuberculosis infection. This study aimed to compare the ability of the TST and IGRA in the diagnosis of latent tuberculosis in hemodialysis patients and investigate risk factors of having positive test results. MATERIALS AND METHODS Forty-seven hemodialysis patients underwent the IGRA and TST tests. Demographic data and blood samples were collected and chest radiography was done for all participants. RESULT Abnormal chest radiography was reported in 24% of the study group. The IGRA and TST were positive in 11 (23.4%) and 20 patients (43.5%), respectively. The agreement coefficient (kappa) between the IGRA and TST was 0....

INTRODUCTION Non-human leukocyte antigen antibodies are an independent risk factor for acute rejection in kidney transplant recipients. Among them, angiotensin II receptor type 1 (ART1) antibodies can induce various effects, but their clinical importance in kidney transplant recipients has not been properly explained. This study aimed to evaluate the effect of ART1 antibodies on allograft function and hypertension in stable kidney transplant recipients. MATERIALS AND METHODS Eighty-one kidney recipients from non- human leukocyte antigen antibodies-matched donors with stable allograft function were examined for estimated glomerular filtration rate (Chronic Kidney Disease-Epidemiology Collaboration formula) and ART1 antibodies (measured using an enzyme-linked immunosorbent assay method). The result was considered positive if the anti-ART1 level was greater than 17 U/mL. RESULTS The mean age of the participant was 51.1 ± 11.9 years with the mean time from transplantation was 83.5 ± 6.5...

Serum cystatin C is more sensitive for glomerular filtration rate (GFR) measurement, but it is not available for clinical use in all laboratories. Regarding the importance of accurate estimation of GFR in kidney transplant recipients, we compared cystatin C-based equations with creatinine-based formulas to estimate GFR as precisely and simply as possible in kidney transplant recipients. Materials and Methods. Seventy living donor kidney transplant recipients with stable kidney function were enrolled in our study. The patients' GFRs were estimated by 3 creatinine-based equations (the modification of diet in renal disease [MDRD], abbreviated MDRD, and Cockcroft-Gault) and 5 cystatin C-based equations (Filler, Le Bricon, Rule, Hoek, and Larsson), and the results were analyzed. Results. The mean age of the recipients was 38.7 ± 13.4 years. The mean GFRs were 67.1 ± 25.9 mL/min/1.73 m 2 , by the Cockcroft-Gault; 61.0 ± 17.7 mL/min/1.73 m 2 , by the abbreviated MDRD; and 60.0 ±18.6 mL/min/1.73 m 2 , by the MDRD formulas. Cystatin C-based GFR estimations were 43.6 ± 16.2 mL/min/1.73 m 2 , 44.0 ± 13.2 mL/min/1.73 m 2 , 33.8 ± 14.1 mL/min/1.73 m 2 , 35.6 ± 13.7 mL/min/1.73 m 2 , and 36.9 ± 13.6 mL/min/1.73 m 2 by the Filler, Le Bricon, Larsson, Rule, and Hoek equations, respectively. The estimates by creatinine-based and cystatin C-based equations were significantly different and the MDRD estimate was the closest to the cystatin C-based GFRs. Conclusions. Our findings revealed the MDRD equation could be provide a closer estimate of GFR to the cystatin C-based equations than other creatinine-based GFR calculations in kidney transplant recipients.