Long-Term Outcome of Steroid-Resistant Nephrotic Syndrome in Children.

We investigated the value of genetic, histopathologic, and early treatment response information in prognosing long-term renal outcome in children with primary steroid-resistant nephrotic syndrome. From the PodoNet Registry, we obtained longitudinal clinical information for 1354 patients (disease onset at >3 months and <20 years of age): 612 had documented responsiveness to intensified immunosuppression (IIS), 1155 had kidney biopsy results, and 212 had an established genetic diagnosis. We assessed risk factors for ESRD using multivariate Cox regression models. Complete and partial remission of proteinuria within 12 months of disease onset occurred in 24.5% and 16.5% of children, respectively, with the highest remission rates achieved with calcineurin inhibitor-based protocols. Ten-year ESRD-free survival rates were 43%, 94%, and 72% in children with IIS resistance, complete remission, and partial remission, respectively; 27% in children with a genetic diagnosis; and 79% and 52% in children with histopathologic findings of minimal change glomerulopathy and FSGS, respectively. Five-year ESRD-free survival rate was 21% for diffuse mesangial sclerosis. IIS responsiveness, presence of a genetic diagnosis, and FSGS or diffuse mesangial sclerosis on initial biopsy as well as age, serum albumin concentration, and CKD stage at onset affected ESRD risk. Our findings suggest that responsiveness to initial IIS and detection of a hereditary podocytopathy are prognostic indicators of favorable and poor long-term outcome, respectively, in children with steroid-resistant nephrotic syndrome. Children with multidrug-resistant sporadic disease show better renal survival than those with genetic disease. Furthermore, histopathologic findings may retain prognostic relevance when a genetic diagnosis is established.

Two-dimensional (2D), three-dimensional static (3D) and real-time (4D) contrast enhanced voiding urosonography (ceVUS) versus voiding cystourethrography (VCUG) in children with vesicoureteral reflux.

BACKGROUND: Two-dimensional (2DUS) contrast enhanced voiding urosonography has been used in the diagnosis and treatment monitoring of the vesicoureteral reflux in children for over 15 years. The opportunity of performing this examination with the use of three-dimensional static (3DUS) and real-time (4DUS) techniques opens up new diagnostic horizons. OBJECTIVE: To analyze if 3DUS/4DUS bring additional information leading to an increased detection rate or change in the grading of reflux compared to 2DUS and voiding cystouretrography. MATERIAL AND METHODS: We evaluated 69 patients (mean 4.1 years) who underwent 2DUS/3DUS/4DUS contrast enhanced voiding urosonography (ceVUS) and voiding cystourethrography (VCUG) for the diagnosis and grading of vesicoureteral reflux. RESULTS: 2DUS and 3DUS/4DUS urosonography diagnosed 10 more refluxes (7.25%) than cystourethrography and in 3 refluxes (2.17%) detected a higher grade. In 9 refluxes (6.52%) 3DUS/4DUS urosonography and cystourethrography diagnosed a higher grade than 2DUS. There was a statistically significant difference between cystourethrography and 3DUS/4DUS urosonography when the number of detected refluxes and differences in grading were compared. 4DUS enabled a better visualization of reflux than 3DUS. CONCLUSIONS: 3DUS/4DUS techniques bring additional information leading to a change in reflux grading compared to 2DUS and a detect higher number of refluxes compared to cystourethrography.

Genotype-phenotype associations in WT1 glomerulopathy.

WT1 mutations cause a wide spectrum of renal and extrarenal manifestations. Here we evaluated disease prevalence, phenotype spectrum, and genotype-phenotype correlations of 61 patients with WT1-related steroid-resistant nephrotic syndrome relative to 700 WT1-negative patients, all with steroid-resistant nephrotic syndrome. WT1 patients more frequently presented with chronic kidney disease and hypertension at diagnosis and exhibited more rapid disease progression. Focal segmental glomerulosclerosis was equally prevalent in both cohorts, but diffuse mesangial sclerosis was largely specific for WT1 disease and was present in 34% of cases. Sex reversal and/or urogenital abnormalities (52%), Wilms tumor (38%), and gonadoblastoma (5%) were almost exclusive to WT1 disease. Missense substitutions affecting DNA-binding residues were associated with diffuse mesangial sclerosis (74%), early steroid-resistant nephrotic syndrome onset, and rapid progression to ESRD. Truncating mutations conferred the highest Wilms tumor risk (78%) but typically late-onset steroid-resistant nephrotic syndrome. Intronic (KTS) mutations were most likely to present as isolated steroid-resistant nephrotic syndrome (37%) with a median onset at an age of 4.5 years, focal segmental glomerulosclerosis on biopsy, and slow progression (median ESRD age 13.6 years). Thus, there is a wide range of expressivity, solid genotype-phenotype associations, and a high risk and significance of extrarenal complications in WT1-associated nephropathy. We suggest that all children with steroid-resistant nephrotic syndrome undergo WT1 gene screening.

2D/3D/4D contrast-enhanced voiding urosonography in the diagnosis and monitoring of treatment of vesicoureteral reflux in children - can it replace voiding cystourethrography?

INTRODUCTION: Vesicoureteral reflux appears in 20-50% of pediatric patients with recurrent urinary tract infections. The most common method of diagnosing this disease is voiding cystourethrography. However, contemporary pediatric radiology does not favor this method due to exposure to X-radiation. AIM: The aim of this study was to assess the usefulness of 2D/3D/4D contrast-enhanced voiding urosonography in the diagnosis and treatment monitoring of vesicoureteral reflux in children and the possibility of using contrast-enhanced voiding urosonography to replace voiding cystourethrography. MATERIAL AND METHODS: Voiding cystourethrography and contrast-enhanced voiding urosonography were conducted in 80 pediatric patients in order to assess sensitivity, specificity, positive and negative predictive values as well as the number of vesicoureteral refluxes detected by each of the two methods. The second stage of the study involved performing voiding urosonography in an extended protocol in 58 children in order to determine the usefulness of three-dimensional (3D/4D) examinations in the assessment of vesicoureteral reflux and the ability to assess the urethra. RESULTS: The concordance between the two methods was 86.95%. The sensitivity of voiding urosonography was 84.51%, specificity - 90.99%, positive predictive value - 85.71% and negative predictive value - 90.17%. A 3D/4D assessment of the urinary bladder and transperineal 2D morphological assessment of the urethra were possible in all patients (100%). Assessment of the urethra during micturition with the use of 2D/3D/4D techniques was possible in all patients in whom voiding was elicited (95.83%), and 3D/4D assessment of vesicoureteral reflux was possible in all patients with reflux (100%). Although the application of 3D/4D techniques allowed accurate specification of the grade of reflux in all cases (100%), it appeared particularly useful in differentiating between grades II and III (70.97%). CONCLUSIONS: Contrast-enhanced voiding urosonography allows the diagnosis and monitoring of treatment of vesicoureteral reflux in pediatric patients as well as assessment of the urethra in both girls and boys. The method is characterized by high sensitivity and specificity. Moreover, it is safe, relatively inexpensive and can replace voiding cystourethrography.

Anaemia treatment in chronically dialysed children: a multicentre nationwide observational study.

OBJECTIVE: Erythropoiesis-stimulating agents (ESAs) are applied as a standard therapy in children with anaemia in chronic kidney disease. The aim of this study was to describe the efficacy and details of ESA treatment in a population of dialysed children in Poland. MATERIAL AND METHODS: The study had a prospective observational design and was performed in 12 dialysis centres. The study group comprised 117 dialysed children with a mean age at enrolment of 165.33 (97.18-196.45) months. RESULTS: Dialysed children were treated mostly with epoietin beta and darbepoietin. The mean dose of ESA was 99 (68-147) U/kg/week with a significant difference between patients on peritoneal dialysis [83 (54-115)] and haemodialysis [134 (103-186)] (p < 0.0001). The mean haemoglobin of all the time-point tests during 6 months was 10.91 ± 1.18 g/dl. The efficacy of anaemia treatment was unsatisfactory in 52% of subjects. In multivariate analysis, initial haemoglobin level <10 g/l, any infection, younger age at first dialysis, malnutrition and inadequate ESA dosage remained significant predictors of anaemia. CONCLUSIONS: The study revealed that anaemia treatment in Polish children is unsatisfactory. Late commencement of the treatment, inadequate dosing, malnutrition and infections could constitute risk factors for therapy failure.

[Treatment of first incidences of urolithiasis in children]. / Leczenie pierwszych epizodów kamicy ukladu moczowego u dzieci w materiale wlasnym.

Unlike adults urolithiasis in children is a rare disease. For this reason medical treatment in this age group is still a serious therapeutic challenge. The aim of the study was to analyze the results of the applied treatment in the first incidences of urinary stones disease. A group of 143 patients aged 1.5 to 17 years was enrolled in this study. Spontaneous stone passage was obtained in case of 65 patients, which amounts to 63% of patients, who received conservative treatment. 17% were qualified to the ESWL treatment, 5.6% underwent the URS procedure, and in 2.8% of patients open surgery was performed. In 29% of cases stones were left for further observation. Conservative therapy was effective in the majority of children with small urinary stones. Preferred treatment in remaining patients were minimally invasive urological procedures.

[Malformations of urinary system in our series of children--treatment approaches]. / Wady ukladu moczowego w materiale wlasnym--postepowanie terapeutyczne.

The purpose of the study was to analyze treatment approaches in children with malformations of urinary system. The retrospective study comprised 557 children (196 boys and 361 girls) aged 1-18 years with malformations of urinary system hospitalized in 2000-2007 in the Department of Pediatric Nephrology, University Children's Hospital, Lublin. Primary and secondary vesicoureteral reflux (269 children), ureteral obstruction (102 children), urethral obstruction (91 children) and renal duplication (83 children) were the most common malformations observed. In 26 children, multiple urinary system malformations were diagnosed. 332 children required surgery including 113 with vesicoureteral reflux. However, in the majority of children with vesicoureteral reflux, on an average 18-month pharmacologic treatment resulted in complete recovery.

[The diagnosis of familial hypomagnesemia with hypercalciuria and nephrocalcinosis in a girl with acute lymphoblastic leukemia--case report]. / Rozpoznanie rodzinnej hipomagnezemii z hiperkalciuria i nefrokalcynoza u dziewczynki chorej na ostra bialaczke limfoblastyczna--opis przypadku.

Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare autosomal recessive tubulopathy resulting from mutation in the gene encoding paracelin 1. The main symptoms of FHHNC include excessive urinary calcium and magnesium excretion, nephrocalcinosis, and chronic renal failure. We present 16-year old girl in whom symptoms of FHHNC were accidentally recognized during therapy of acute lymphoblastic leukemia. In our patient, some symptoms of FHHNC were initially taken for the adverse effects of cytostatic therapy that delayed an adequate diagnosis. To the best of our knowledge, this is the first report of FHHNC associated with acute lymphoblastic leukemia. However, in our opinion this association is accidental.

Acute renal failure due to bilateral xanthine urolithiasis in a boy with Lesch-Nyhan syndrome.

Lesch-Nyhan syndrome is a very rare X-linked recessive disorder caused by mutation in the gene encoding enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT). A complete deficiency of HPRT leads to severe purine overproduction and to uric acid renal lithiasis as a consequence. This may be effectively prevented by administration of allopurinol; however, its overdosage may result in xanthinuria and xanthine urolithiasis. We report on a 9-year-old boy with Lesch-Nyhan syndrome who developed acute renal failure due to bilateral staghorn xanthine urolithiasis resulting from long-term treatment with excessive doses of allopurinol. To the best of our knowledge, the presented case is the first one in the literature.

Urinary excretion of N-acetyl-beta-D-glucosaminidase and alpha1-microglobulin in children with proliferative blood diseases.

The purpose of the study was to estimate the urinary excretion of NAG and alpha-1M among children who suffer from proliferative blood diseases. The group of the examined children included those who went through a viral hepatitis (VH) and who are or were treated by means of cytostatic drugs. The study comprised 73 children aged from 4 to 18 (average 11.7+/-3.5. There were 70 children with the diagnosis of leukemia and 3 with the diagnosis of non-Hodgkin lymphoma. The examined group was divided according to the stage of treatment of a basic disease. Group I--22 children who are treated currently or whose treatment has been completed recently. Group II--51 children whose treatment was completed over two years ago. In group II there were 4 subgroups distinguished depending on positive antigenemia HBs and the presence of HCV antibodies. There were no clinical or biochemical features of damage of renal function observed among any of the children. The testing group consisted of 70 healthy children who were selected regarding age and sex. The urinary excretion of NAG and alpha-1M was estimated in the second morning portion of urine and it was presented as NAG/creatinine and alpha-1M/creatinine ratio. The results of the research underwent the statistical analysis by means of a t-Student test. It was stated that the urinary excretion of NAG and alpha-1M was higher among children who currently are or were treated by means of cytostatics drugs. It was also stated that the urinary excretion of NAG was higher among the children who went through viral hepatitis C in comparison with HBs antigen carriers. Similarly, the urinary excretion of alpha-1M was higher among children with positive markers of viral hepatitis B and C markers in comparison with a group of HBs antigen carriers.

Urinary iodine excretion in inhabitants of rural region living in the Lublin Province.

Iodine is the element necessary for the human organism to function properly. Iodine is essential especially for the synthesis of thyroid hormones that regulate the cellular metabolism of the whole organism. The purpose of the work was to estimate the concentration of iodine in urine among the inhabitants of a typical agricultural region as a simple method of detecting deficiency of iodine in the human organism. The biggest iodine excretion was observed in a group above 40 years of age. The amount of the excretion of iodine together with urine was similar among men and women up to 40 years old. Monitoring of iodine concentration in urine is a sensitive marker of iodine deficiency in the human organism.