Five-year outcome of children with idiopathic nephrotic syndrome: the NEPHROVIR population-based cohort study.

BACKGROUND: The optimal therapeutic regimen for children at onset of idiopathic nephrotic syndrome (INS) is still under debate. A better knowledge of the disease's course is necessary to design more appropriate and/or personalized treatment protocols. METHODS: We report the 5-year outcome of patients included from December 2007 to May 2010 in the prospective multicentric and multiethnic population-based NEPHROVIR study. Patients were treated at onset according to the French steroid protocol (3990 mg/m2, 18 weeks). Data were collected at 5 years or last follow-up. RESULTS: Out of the 188 children with nephrotic syndrome (121 boys, 67 girls; median age 4.1 years), 174 (93%) were steroid-sensitive. Six percent of steroid-sensitive patients required intravenous steroid pulses to get into remission. Relapse-free rate for steroid-sensitive patients was 21% (36/174) at last follow-up (median 72 months). A first relapse occurred in138 steroid sensitive patients (79%) with a median time of 8.3 months (IQ 3.4-11.3). Out of the 138 relapsers, 43 were frequent relapsers. Age at onset below 4 years was the only predictive factor of relapse, while gender, ethnicity, and delay to first remission were not. At 96 months of follow-up, 83% of frequent relapsers were still under steroids and/or immunosuppressive drugs. CONCLUSIONS: The treatment of the first flare deserves major improvements in order to reduce the prevalence of relapsers and the subsequent long-lasting exposure to steroids and immunosuppression.

Escherichia coli virulence patterns may help to predict vesicoureteral reflux in paediatric urinary tract infections.

AIM: Ultrasound and biological tools are used to predict high-grade vesicoureteral reflux, but other markers are needed to better select patients who need voiding cystography. Our aim was to determine whether studying Escherichia coli virulence factors would help to predict vesicoureteral reflux in patients with their first acute pyelonephritis. METHODS: We included children presenting with E. coli-related acute pyelonephritis or cystitis. Vesicoureteral reflux was assessed by voiding cystography. Virulence factors were identified by multiplex polymerase chain reaction. Statistical analysis was performed using logistic regression and the mean c-statistic test. RESULTS: We included 198 patients: 30 with cystitis and 168 with acute pyelonephritis, including 46 with vesicoureteral reflux. High-grade reflux was associated with acute pyelonephritis caused by the E. coli lacking virulence factors papGII (82% versus 47%, p < 0.001) or papC (85% versus 53%, p < 0.001) or belonging to phylogenetic group A or B1. When we added genetic data (lack of papGII, fyuA and phylogenetic groups) to classical predictors of vesicoureteral reflux (ultrasound examination, gender, age), the ability to predict high-grade reflux increased, with the c-statistic rising from 0.88 to 0.93. CONCLUSION: Bacterial virulence factors and clinical factors helped to predict high-grade reflux and may help to avoid unnecessary voiding cystographies.

Vesicoureteral reflux in children with urinary tract infection: comparison of diagnostic accuracy of renal US criteria.

PURPOSE: To directly compare various renal ultrasonography (US) criteria for vesicoureteral reflux (VUR) with voiding cystography, the reference method, for diagnostic accuracy in helping to determine an intermediate strategy of screening children who require cystography. MATERIALS AND METHODS: Institutional review board approval and parental consent were obtained for this prospective hospital-based cohort study involving children with urinary tract infections (UTIs). Renal length, ureteral dilatation, pelvic dilatation, and corticomedullary differentiation were analyzed and compared. One hundred seventeen patients (median age, 0.8 year; age range, 0.0-13.9 years) were included: 46 (39%) boys (median age, 0.3 year; age range, 0.5-13.9 years) and 71 girls (median age, 1.2 years; age range, 0.0-11.5 years). A two-level logistic regression model was used to analyze data, and diagnostic accuracy calculations were performed. RESULTS: Thirty-two (27%) children had all-grade VUR, and eight (7%) had VUR of grade 3 or higher. Only ureteral dilatation was significantly related to all-grade VUR (odds ratio [OR], 7.5; 95% confidence interval [CI]: 1.0, 58.2; P = .05), with 25% sensitivity (95% CI: 15%, 39%) and 88% specificity (95% CI: 83%, 92%). Ureteral, pelvic, and urinary tract dilatations were significantly associated with VUR of grade 3 or higher, with ORs of 20.2 (95% CI: 3.5, 118.2; P = .001), 13.7 (95% CI: 4.1, 46.0; P < .001), and 20.0 (95% CI: 4.4, 90.1; P < .001), respectively. The best compromise between sensitivity and specificity was achieved by using the ureteral dilatation criterion, which had 73% sensitivity (95% CI: 43%, 90%) and 88% specificity (95% CI: 84%, 92%) for high-grade VUR. CONCLUSION: Ureteral dilatation may yield the best accuracy for the US-based diagnosis of both all-grade and high-grade VUR. This US criterion, perhaps in combination with other predictors, might find a place in an evidence-based selective strategy for limiting cystography in children with UTIs.

Acute renal cortical necrosis due to acquired antiprotein S antibodies.

Although varicella is a common disease of childhood, renal complications are quite rare. We report here the interesting case of a-22 month-old boy exhibiting renal cortical necrosis related to an acquired protein S deficiency following varicella. Ten days after the vesicle eruption appearance, he presented with ecchymosed heels, oligoanuric kidney failure, anemia [hemoglobin (Hb) 78 g/L], schizocytosis (2.5%), but normal platelet count. Kidney sonography and magnetic resonance imaging evoked renal cortical necrosis. All together, these features suggested acquired protein S deficiency secondary to varicella. Strikingly, it was confirmed by a dramatic decrease in protein S plasma activity and a huge increase in immunoglobulin (Ig)G antibodies against protein S in the plasma. Anticoagulation therapy in addition with plasmapheresis and steroid pulses allowed a dramatic decrease in the antibodies against protein S and recovery of normal protein S activity. Undelayed diagnosis and treatment did not avoid kidney insufficiency but prevented life-threatening complications. In the light of this case report, protein S deficiency due to antibody inhibition should be carefully monitored anytime in the context of varicella when kidney insufficiency or necrosis occurs.

Ocular involvement in hemolytic uremic syndrome due to factor H deficiency--are there therapeutic consequences?

Factor H deficiency is responsible for thrombotic microangiopathy (TMA) via uncontrolled activation of the alternative pathway of the complement system. Ocular TMA has never been reported in patients with factor H abnormalities. A male patient with congenital homozygote factor H deficiency reached end-stage renal disease at the age of 10 years. Hemodialysis was uneventful for 3 years, when, suddenly, unilateral ocular pain and blurred vision occurred while he had febrile pharyngitis. Ophthalmologic examination found vitreous bleeding, elevated ocular pressure, choroidal hemorrhage (ultrasound biomicroscopy) and retinal ischemia (fluorescein angiography). C-reactive protein concentration was increased, while haptoglobin levels remained normal. We suspected that TMA due to factor H deficiency was responsible for the ocular manifestations and immediately initiated daily plasma exchanges (PEs) with fresh frozen plasma (FFP) for 10 days followed by three sessions per week. Factor H serum level increased from 6% to 82%, and C3 level normalized. Progressively, ocular pain decreased, and visual acuity and ophthalmologic findings showed improvement. When there is permanent activation of the alternative pathway in patients with end-stage renal disease (ESRD), the search for secondary targets might be of interest. In nephrectomized patients, no biological parameter can predict isolated ocular TMA. Early ophthalmologic investigation and substitution of factor H via FFP may avoid irreversible damage.