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Background Cubilin is one of the receptor proteins responsible for reabsorption of albumin in proximal tubules and is encoded by the CUBN gene. We aimed to evaluate clinical and genetic characterization of six patients with proteinuria who had CUBN mutations. Methods Patients’ characteristics, serum creatinine, albumin, vitamin B12 levels, urine analysis, spot urine protein/creatinine, microalbumin/creatinine, beta-2 microglobulin/creatinine ratios, estimated glomerular fltration rates (eGFR), treatments, kidney biopsies, and genetic analyses were evaluated. Results Six patients (2 female, 4 male) with an incidental finding of proteinuria were evaluated. Mean admission age and follow-up time were 7.3 ± 2.9 and 6.5 ± 5.6 years, respectively. Serum albumin, creatinine, and eGFR were normal; urine analysis revealed no hematuria, and C3, C4, ANA, and anti-DNA were negative; kidney ultrasonography was normal for all patients. Urine protein/creatinine was 0.9± 0.3 mg/mg, and microalbumin was high in all patients. Serum vitamin B12 was low in two patients and normal in four. Kidney biopsy was performed in four patients, three demonstrated normal light microscopy, and there was one focal segmental glomerulosclerosis (FSGS). Genetic tests revealed four homozygous and two compound heterozygous mutations in the C-terminal part of cubilin. All patients had normal eGFR and still had non-nephrotic range proteinuria at last visit. Conclusions CUBN gene mutations should be considered in patients with isolated non-nephrotic range proteinuria and normal kidney function. Diagnosing these patients, who are thought to have a better prognosis, is important in terms of avoiding unnecessary treatment and predicting prognosis. CUBN gene mutations may also present as FSGS which extends the spectrum of renal manifestation of these patients.

Background: Nephrotic Syndrome (NS) is one of the most common renal diseases in children. Clinical response to corticosteroids is an important prognostic factor for long-term renal outcome. We aimed to evaluate the clinical parameters, histopathological findings and complications of NS patients and factors predicting steroid resistance in a single tertiary center. Methods: A hundred and sixty two children (57 girls, 105 boys) with NS followed between 1998 and 2018 in Department of Pediatric Nephrology were analyzed in a retrospective cohort. Secondary causes and infantile NS cases were excluded. Results: The median (IQR; range) age of the children at presentation and follow up time were 4.9(5.7; 0.1-16.8) and 5.5(5.4; 0.1-20.3) years, respectively. A hundred and thirty four (82.7%) patients were steroid-sensitive nephrotic syndrome (SSNS) and 28(17.3%) were steroid-resistant nephrotic syndrome (SRNS). Age at the first presentation was lower in SSNS group (p=0.002). Hypertension, macroscopic and microscopic hematuria were higher in SRNS group (pConclusion:The late onset is still an important sign for SRNS. Microscopic and macroscopic hematuria and hypertension may also give a hint for potential steroid resistance. We emphasize that FSGS is a biopsy finding that may reveal to different diagnosis in SRNS.

Background The accuracy of conventional urinalysis in diagnosing urinary tract infection (UTI) in children is limited, leading to unnecessary antibiotic exposure in a large fraction of patients. Urinary heat shock protein 70 (uHSP70) is a novel marker of acute urinary tract inflammation. We explored the added value of uHSP70 in discriminating UTI from other infections and conditions confused with UTI. Methods A total of 802 children from 37 pediatric centers in seven countries participated in the study. Patients diagnosed with UTI (n = 191), non-UTI infections (n = 178), contaminated urine samples (n = 50), asymptomatic bacteriuria (n = 26), and healthy controls (n = 75) were enrolled. Urine and serum levels of HSP70 were measured at presentation in all patients and after resolution of the infection in patients with confirmed UTI. Results Urinary (u)HSP70 was selectively elevated in children with UTI as compared to all other conditions (p < 0.0001). uHSP70 predicted UTI with 89% sensitivity and 82% specificity (AUC = 0.934). Among the 265 patients with suspected UTI, the uHSP70 > 48 ng/mL criterion identified the 172 children with subsequently confirmed UTI with 90% sensitivity and 82% specificity (AUC = 0.862), exceeding the individual diagnostic accuracy of leukocyturia, nitrite, and leukocyte esterase positivity. uHSP70 had completely normalized by the end of antibiotic therapy in the UTI patients. Serum HSP70 was not predictive. Conclusions Urine HSP70 is a novel non-invasive marker of UTI that improves the diagnostic accuracy of conventional urinalysis. We estimate that rapid urine HSP70 screening could spare empiric antibiotic administration in up to 80% of children with suspected UTI., Scientific Research Projects Coordination Unit of Istanbul University; European Society for Pediatric Nephrology (ESPN); Society for Children's Kidney Health; Istanbul Faculty of Medicine Foundation, UTILISE study was supported by Scientific Research Projects Coordination Unit of Istanbul University, by the European Society for Pediatric Nephrology (ESPN), by the Society for Children's Kidney Health, and by Istanbul Faculty of Medicine Foundation.