Harika Alpay

Etiology of chronic renal failure in Turkish children

The etiology of chronic renal failure (CRF) was studied in 459 Turkish children (205 girls, 254 boys) for the period January 1979-December 1993. Their mean age at onset of CRF was 9.5±4.2 years (range 1–16 years); CRF was defined as a glomerular filtration rate (GFR) below 50 ml/min per 1.73 m2 for at least 6 months. When a GFR determination was not available, the serum creatinine concentration was used: greater than 1 mg/dl for children aged 1–3 years, greater than 1.5 mg/dl for those 3–10 years and greater than 2 mg/dl for those 10–16 years. Primary renal disorders were as follows: reflux nephropathy 32.4% glomerular diseases 22.2%, hereditary renal disorders 11.4%, amyloidosis 10.6%, urinary stones 8% and other renal disorders 15.4%. Twenty-three cases of reflux nephropathy (15.4%) were associated with neural tube defects (NTD) and 20 (13.4%) were caused by infravesical obstruction. CRF caused vesicoureteral reflux associated with NTD and amyloidosis are more frequent in our series compared with west European and Nordic countries.

Comparison of direct radionuclide cystography and voiding cystourethrography in detecting vesicoureteral reflux.

Background: Fluoroscopic voiding cystourethrography (VCUG) is a widely used imaging test for the diagnosis of vesicoureteral reflux (VUR). However, high gonadal radiation and intermittent imaging are the main disadvantages of VCUG. Direct radionuclide cystography (DRC) has been advocated for the detection of VUR with increased sensitivity and low radiation doses, however, having the disadvantage of providing less anatomical details for urethral evaluation. In this study, DRC has been compared with standard fluoroscopic VCUG for detection of VUR.

The efficacy of Tc99m dimercaptosuccinic acid (Tc-DMSA) scintigraphy and ultrasonography in detecting renal scars in children with primary vesicoureteral reflux (VUR).

Introduction: Pyelonephritis-induced renal scarring in children is a major predisposing factor for proteinuria, hypertension, and ultimate renal failure. The aim of this study was to investigate and compare the efficacy of Tc99m dimercaptosuccinic acid (Tc-DMSA) renal scintigraphy and renal ultrasonography (USG) in detecting renal scars in children with primary vesicoureteral reflux (VUR). Materials and methods: Tc-DMSA scan and USG studies were done in 62 children who were admitted to our clinic between 1997 and 2003 because of documented urinary tract infection (UTI) and diagnosed with primary VUR. Renal scarring detection rates of Tc-DMSA scan and USG were compared according to reflux grades. Results: In the whole group, renal scars were detected by Tc-DMSA scan and USG in 55% and 38% of refluxing units, respectively. Detection rates of Tc-DMSA and USG according to reflux grades were as follows: 47% and 29 % in low-grade VUR (grades 1 and 2), 46 % and 25% in mid-grade VUR (grade 3), 76% and 65% in high-grade VUR (grades 4 and 5), respectively. Conclusion: USG was found to be an inappropriate study in the detection of renal parenchymal scars, irrespective of the reflux grade. In this study, Tc-DMSA scan detected scars in 35% of kidneys reported to be normal on USG.

Henoch-Schönlein nephritis: a nationwide study.

Background/Aim: The aim of this retrospective study was to evaluate the presentation, clinical and pathological manifestations and outcome of the Henoch-Schönlein purpura (HSP) nephritis in children. Methods: Clinical and laboratory data of 443 children with HSP nephritis aged between 3 and 16 years from 16 pediatric nephrology reference centers were analyzed retrospectively. The biopsy findings were graded according to the classification developed by the International Study of Kidney Disease in Children (ISKDC). Results: Renal biopsy was performed in 179 of the patients with HSP nephritis. The most common presenting clinical finding in patients who were biopsied was nephrotic range proteinuria (25%) which was followed by nephritic-nephrotic syndrome (23.5%). The biopsy findings according to the ISKDC were as follows: class I: 8.3%; II: 44.1%; III: 36.3%; IV: 6.7%; V: 3.3%; VI: 1.1%. All of the patients who developed end-stage renal disease had nephritic-nephrotic syndrome at presentation. Of 443 patients, 87.2% had a favorable outcome and 12.8% had an unfavorable outcome. The overall percentage of children who developed end-stage renal disease at follow-up was 1.1%. Logistic regression analysis did not show any association of initial symptoms and histology with outcome. Conclusion: In the presented cohort, the presence of crescents in the first biopsy or presenting clinical findings did not seem to predict the outcome of HSP nephritis in children. We conclude that children with HSP nephritis even with isolated microscopic hematuria and/or mild proteinuria should be followed closely.

Varicella vaccination in children with steroid-sensitive nephrotic syndrome.

Abstract We have studied serological and clinical response to live, attenuated varicella zoster virus (VZV) vaccine (Varilrix, SmithKline Beecham) in 20 patients with steroid-sensitive nephrotic syndrome (SSNS) in remission and 22 normal controls who had no history of varicella and no detectable antibody to VZV. Nephrotic patients included 15 boys and 5 girls, with a mean age of 4.7 years (range 2–11.4 years). The controls were healthy age-matched children (13 girls and 9 boys). Seventeen patients with SSNS (85%) and 19 healthy controls (86%) seroconverted 8 weeks after vaccination. One patient with SSNS had a relapse 20 days after vaccination, and 1 child in the control group had a rash. Two years after vaccination, antibodies to VZV were detected in 12 of 17 responders, 2 of 3 non-responders, and 13 of 22 controls. Within 2 years of vaccination, 3 of the vaccine responder children with SSNS had a mild varicella infection. Two responder and 1 non-responder nephrotic children and 9 controls were lost to long-term follow-up. Our results show that immunization with a single dose of VZV vaccine is safe and effective in children with SSNS in remission.

Contradictory supranormal function in hydronephrotic kidneys: fact or artifact on pediatric MAG-3 renal scans?

Objectives: Contradictory supranormal renal function (SRF) in unilateral hydronephrosis is a debatable subject resulting from the methodology of nuclear renography or the characteristics of the patient. In this study, we aimed to investigate the frequency and comparison of SRF with MAG-3 scans by 8 different technical analyses in pediatric hydronephrosis. Methods: We reviewed Tc-99m MAG-3 scans in 82 children with unilateral hydronephrosis (52 male, 30 female, mean age: 47.7 ± 64.5 months). Of 82, 34 also had Tc-99m DMSA scans. Data were reprocessed with 4 different regions of background activity (subrenal, perirenal C-type, perirenal ring, and lateral) at 2 different time intervals (1–2 and 2–3 minute), and 8 different estimates of MAG-3 differential renal function (DRF) were obtained in 67 patients. SRF was defined as DRF greater than 55% in the hydronephrotic kidney. Results: The routine processing protocol showed only 3 renal units with SRF, and all were on the right side (3.6%). After reprocessing, a total of 10 dilated kidneys had SRF in 1 or more of DRF estimates (5.2% of all estimations). These cases were significantly younger (8.1 ± 6.7 vs. 42.5 ± 52.5, P < 0.05) and had a larger renal area ratio (1.25 ± .24 vs. 1.07 ± .21, P < 0.05). There was no SRF with DMSA. In comparison between MAG-3 and DMSA DRF in 20 children who underwent both tests within 3 months, the best correlation was obtained when C-type correction was used for both agents at 2 time intervals (r: .86 and .84 for early and late time intervals, P < 0.00001, respectively). Conclusions: SRF in unilateral hydronephrosis is, at least, in part, technical in origin in this particular pediatric patient population with tubular immaturity (ie, physiological high background activity) and asymmetric kidney size.

The value of sacral skin lesions in predicting occult spinal dysraphism in children with voiding dysfunction and normal neurological examination

OBJECTIVE The role of magnetic resonance imaging (MRI) in detecting occult spinal dysraphism (OSD) in children with voiding dysfunction and a normal neurological examination is still under debate. The aim of this study was to assess the correlation of sacral skin lesions with OSD detected on MRI, in a population of children with resistant lower urinary tract symptoms (LUTS). PATIENTS AND METHODS A total of 114 children over 5 years of age with urinary tract infection (UTI) and/or LUTS and normal neurological examination were enrolled. All children underwent sacral neurological examination, urine analysis and cultures, renal/bladder ultrasound, voiding cystourethrogram and urodynamic examination. After a treatment period of 6 months, the patients were re-evaluated and spinal MRI was performed in 61 with ongoing LUTS or UTI. RESULTS Nineteen of 61 children (31%) had cutaneous stigmas. MRI detected spinal abnormality in 2/42 children with a normal sacral examination in comparison to 7/19 children with an abnormal sacral finding (Chi-squared test, P < 0.005). The sensitivity and specificity of an abnormal sacral finding in predicting MRI abnormality were 0.76 and 0.77, respectively. Urodynamic parameters did not predict an abnormal spinal MRI. CONCLUSIONS Abnormal sacral findings, but not urodynamic studies, are strong predictors of OSD. A normal sacral examination does not rule out OSD.

Schimke immunoosseous dysplasia: defining skeletal features

Schimke immunoosseous dysplasia (SIOD) is an autosomal recessive multisystem disorder characterized by prominent spondyloepiphyseal dysplasia, T cell deficiency, and focal segmental glomerulosclerosis. Biallelic mutations in swi/snf-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a-like 1 (SMARCAL1) are the only identified cause of SIOD, but approximately half of patients referred for molecular studies do not have detectable mutations in SMARCAL1. We hypothesized that skeletal features distinguish between those with or without SMARCAL1 mutations. Therefore, we analyzed the skeletal radiographs of 22 patients with and 11 without detectable SMARCAL1 mutations. We found that patients with SMARCAL1 mutations have a spondyloepiphyseal dysplasia (SED) essentially limited to the spine, pelvis, capital femoral epiphyses, and possibly the sella turcica, whereas the hands and other long bones are basically normal. Additionally, we found that several of the adolescent and young adult patients developed osteoporosis and coxarthrosis. Of the 11 patients without detectable SMARCAL1 mutations, seven had a SED indistinguishable from patients with SMARCAL1 mutations. We conclude therefore that SED is a feature of patients with SMARCAL1 mutations and that skeletal features do not distinguish who of those with SED have SMARCAL1 mutations.

Urinary tract pathogens and their antimicrobial resistance patterns in Turkish children

Urinary tract infections (UTIs) are among the most common bacterial diseases in childhood affecting approximately 3–5% of girls and 1% of boys [1]. There is growing concern regarding the resistance of urinary pathogens to commonly used antibiotics because of the increasing number of therapeutic failures after empiric treatment [2]. To ensure appropriate treatment, knowledge of the organisms that cause UTI and their antibiotic susceptibility is mandatory [3]. They need to be constantly reevaluated to achieve maximal clinical response before the antibiotic susceptibility of the isolate is known. The aim of this study was to assess the susceptibility of urinary pathogens to commonly used antibiotics in Turkish children with community-acquired UTI. Children who were admitted with the first episode of UTI to the Pediatric Outpatient Clinic and consulted to the Pediatric Nephrology Department between 2001 and 2003 were included in the study prospectively. UTI was defined as the growth of a single pathogen of greater than 100,000 colony-forming units/ml by a properly collected urine specimen in children with febrile disease or urinary symptoms. Transurethral catheterisation was chosen for children who were not toilet trained (387 children, 75.4% of all cases) and clean midstream specimen collection was preferred for toilet trained children. Antimicrobial susceptibility of the isolates was tested by the automatized identification technique called VITEK (bioMerieux, France). Five hundred thirteen uncomplicated community-acquired UTIs were detected in children aged 0–16 years (mean age 3.0 years); 271 (52.8%) of the children were female. The isolated microorganisms were Escherichia coli in 277 (54.0%), Klebsiella spp. in 88 (17.2%), Proteus spp. in 62 (12.1%), Staphylococci spp. in 31 (6.0%), Pseudomonas spp. in 15 (2.9%), Enterococcus spp. in 15 (2.9%), Enterobacter spp. in 13 (2.5%), and others in 12 (2.4%). Gram-positive cocci were isolated in 48 (9.3%) of UTIs. No vancomycin-resistant Enterococcus spp. were isolated. The antibiotic resistance patterns of different gram-negative pathogens are shown in Table 1. A high proportion of the isolates were resistant to ampicillin (69%), amoxicillin/ clavulanate (44%), cefazolin (39%) and trimethoprim– sulfamethoxazole (TMP-SMX) (32%). The most effective drugs against all the isolates were found to be cefepime (99%), cefixime (99%), ceftriaxone (90%), nitrofurantoin (83%) and cefuroxime (79%). There was no antimicrobial resistance to ciprofloxacin and aminoglycosides except in one case. In our study nearly half of the pathogens were resistant to amoxicillin/clavulanate and one-third of them were resistant to TMP-SMX which shows that empiric treatment with TMP-SMX and amoxicillin/clavulanate is inadequate. The results showing 21% resistance to cefuroxime, 17% resistance to nitrofurantoin and 1% resistance to cefixim led us to recommend these drugs for common treatment of UTI in Turkish children. Parenteral treatment options for treatment are second and third generation cephalosporins and aminoglycosides. Our results showed that resistance rates for these drugs are tolerable. Only 10% of the microorganisms displayed resistance to ceftriaxone and none of them showed resistance to aminoglycosides.

Paraoxonase 1 192 and 55 polymorphisms in nephrotic children

Human paraoxonase 1 (PON1) is a serum enzyme related to high-density lipoprotein which has a major role in preventing oxidative modification of low-density lipoprotein. Due to its amino acid substitution PON1 has two genetic polymorphisms. These polymorphisms are characterized by the location of glutamine (A genotype) and arginine (B genotype) at position 192, and leucine (L genotype) and methionine (M genotype) at position 55. Hyperlipidemia and increased lipid oxidation in nephrotic syndrome may lead to glomerulosclerosis and progression of the glomerular disease. In this study we aimed to investigate PON1 192 and PON1 55 polymorphisms in children with focal segmental glomerulosclerosis (FSGS) and control subjects. The study included 25 children with biopsy-proven FSGS and 30 healthy controls. We demonstrated a statistically significant difference between FSGS patients and control subjects with respect to the distribution of the PON1 polymorphism. The AA genotype was less frequent and the AB+BB genotype was more frequent in FSGS patients than in controls (48 versus 73% for AA genotype and 52 versus 27% for AB+BB genotype, p<0.05). Distributions of PON1 55 genotypes of FSGS and control subjects were also statistically different (76 versus 43% for LL genotype and 24 versus 57% for LM+MM genotype, p<0.05) (case-control study, dominant model, Fisher’s exact test). The distributions of both genotypes in subgroups of FSGS (stable renal function versus declining renal function) were not statistically different. We conclude in this preliminary study that presence of B allele and/or L allele may be risk factors for the development of FSGS in children.