How may Doppler indices help in the differentiation of obstructive from nonobstructive hydronephrosis?

BACKGROUND: We assess the potency of different Doppler indices in the differentiation of obstructive and nonobstructive hydronephrosis. MATERIALS AND METHODS: In this study, infants and children who were referred for the evaluation of unilateral hydronephrosis were enrolled. Ultrasonography for the assessment of the degree of hydronephrosis and a voiding cystourethrogram for the exclusion of vesicoureteral reflux was performed. Then, Doppler ultrasonography was done for both kidneys of each patient using four classic Doppler indices as well as the difference (delta) of each index between to kidneys. Diuretic renography with 99 mTc-ethylene dicysteine (99 mTc-EC) was performed for each patient. RESULTS: Thirty-nine patients met the inclusion criteria. After diuretic renography, 29 (74.35%) patients had shown a nonobstructive pattern, and ten (25.65%) patients had a partial (intermediate) or complete obstruction. Using receiver operating characteristic (ROC) curve, none of the classic indices of Doppler duplex (i.e., resistive index [RI], resistance index, end diastolic velocity, and peak systolic velocity) had the ability to make a difference between obstructive and nonobstructive hydronephrosis. However, by calculating the difference (delta) of these indices between two kidneys of each patient, delta RI could differentiate the nonobstructive condition, significantly (P = 0.006). A cutoff value of 0.055 has 60% sensitivity and 82.8% specificity. The area under the ROC curve for delta RI is 0.795 (standard error: 0.086, 95% confidence interval [CI]: 0.626, 0.964). Furthermore, RI ratio between two kidneys of each patient could differentiate the nonobstructive condition, significantly (P = 0.012). A cutoff point of 1.075 has 70% sensitivity and 82.8% specificity. The area under the ROC curve for RI ratio was 0.769 (standard error: 0.104, 95% CI: 0.565, 0.973). CONCLUSION: This study shows that RI ratio and delta RI with a high specificity could differentiate nonobstructive hydronephrosis and therefore it is a promising way to use especially in the follow-up of children with hydronephrosis.

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.

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.