Pediatric Nephrology最新文献

Background: Limited research exists regarding the genetic profile, clinical characteristics, and outcomes of refractory rickets in children from India.

Methods: Patients with refractory rickets aged ≤ 18 years were enrolled. Data regarding clinical features, etiology, genotype-phenotype correlation, and estimated glomerular filtration rate (eGFR) were recorded.

Results: Seventy-two patients with refractory rickets (non-nutritional, with normal kidney function at presentation) from 65 families attending the pediatric nephrology clinic from 2005-2024 were included. Median (IQR) age at first presentation was 2 (1, 4) years. Clinical features included failure-to-thrive (49 [68.1%]), polyuria (37 [51.4%]), nephrocalcinosis (33 [45.8%]), fractures (10 [13.9%]), and hypokalemic paralysis (4 [5.6%]). Major etiologies included distal renal tubular acidosis (dRTA) [34(47.2%)], hereditary hypophosphatemic rickets (11 [15.3%]), cystinosis (9 [12.5%]), Lowe syndrome (3 [4.2%]), vitamin D-dependent rickets (4 [5.5%]), and Fanconi-Bickel syndrome (3 [4.2%]). Next-generation sequencing identified 61 variants among 71 children tested (85.9%), of which 56 variants (among 55 children) were pathogenic (P)/likely-pathogenic (LP) (77.5% diagnostic-yield). P/LP variants included SLC4A1 (n = 14), CTNS (n = 9), PHEX (n = 8), WDR72 (n = 5), OCRL (n = 2), SLC2A2 (n = 3), ATP6V0A4 (n = 4), VDR (n = 3), CLDN16 (n = 2), ATP6V1B1 (n = 1), SLC12A1 (n = 1), CLCN5 (n = 1), SLC34A3 (n = 1), ATP7B (n = 1), and KCNJ1 (n = 1). Fifteen novel P/LP variants and five novel variants-of-uncertain-significance (VUS) were identified. c.2573C > A in exon 19 among SLC4A1-dRTA (n = 14) was a recurrent mutation. Five patients with cystinosis, two patients with SLC4A1-dRTA, two with WDR72-dRTA, and two with Bartter syndrome showed progression to CKD stage 2 or greater during follow-up.

Conclusions: dRTA, X-linked hypophosphatemic rickets, and cystinosis were common causes of refractory rickets. The c.2573C > A variant in exon 19 was a recurrent mutation in SLC4A1-dRTA.

Background: The application of international recommendations for paediatric maintenance haemodialysis (HD) could be strengthened by national laws or written recommendations. Our aim was therefore to describe the national rules governing paediatric maintenance HD in European countries.

Methods: A national representative, approved by the president of each paediatric nephrology society, was contacted in all 42 European countries to complete two online questionnaires.

Results: Answers were received from 36 countries. The population served by HD centres varies from 83,000 to 1,197,000 residents below 18 years of age and the estimated mean number of children on HD per centre from 0.2 to 13.5. The lowest age at which a child can be dialysed in an adult centre varies from 0 to 18 years. Laws or written national recommendations specifying: this age, the need for a paediatrician as part of medical team in mixed adult-paediatric centres, the minimum number of doctors per centre and the number of patients per nurse or nurse's aide required during sessions exist in only 25, 22, 22, 44 and 8% of the countries, respectively. Similarly, dietitians, social workers, school service, psychologists and play specialists/youth workers are required by law or written national recommendations in 36, 28, 36, 31 and 14% of countries, respectively.

Conclusion: Laws or written national recommendations for paediatric maintenance HD are rare in European countries and very heterogeneous when they exist. This calls for discussion among paediatric and adult nephrologists and health authorities on the organisation of safe and effective paediatric HD practices.

Proliferative Glomerulonephritis with Monoclonal IgG Deposits (PGNMID) is a glomerular disease characterized by membranoproliferative and mesangioproliferative lesions, with granular capillary wall monoclonal IgG positivity and immunoglobulin light chain restriction. Most commonly a disease of older adults, we present the case of an 18-year-old patient who developed de novo PGNMID in a kidney allograft three years after kidney transplantation. There was minimal proteinuria and no serum paraproteinemia was detected, so the patient was managed conservatively. To our knowledge, this is the youngest reported case of de novo PGNMID occurring in a kidney allograft and highlights the importance of considering PGNMID as a possible etiology of de novo glomerular disease in adolescent and young adult patients.

Background: C3 glomerulopathy (C3G) is a rare kidney disease due to a dysregulation of the alternative complement pathway, orphan of specific treatment. Pegcetacoplan is an inhibitor of the third complement component C3, currently on a phase III registration protocol in C3G. Here we describe our experience with the off-label use of pegcetacoplan in pediatric patients with C3G.

Methods: This retrospective, observational study evaluated the efficacy and safety of pegcetacoplan in five pediatric patients, not eligible in the registration protocol, over a 12-week treatment period. The drug was given subcutaneously, twice a week for the first month, then weekly. The change in urinary protein-to-urinary creatinine ratio (mean of three samples) was the primary endpoint. We also evaluated the changes in serum C3, albumin, sC5-b9, creatinine, and urinary erythrocytes (number/µL).

Results: At baseline, median proteinuria/creatininuria ratio (mean of three samples) was 4.97 mg/mg (3.53-7.69), and after 12 weeks of treatment with pegcetacoplan, it decreased to less than 30% of baseline (p = 0.043) as did erythrocyturia (p = 0.043). C3 levels increased more than 600% of baseline (p = 0.043), whereas the levels of sC5-b9 decreased to normal range (p = 0.043). Three of four patients with impaired kidney function showed an improvement in eGFR. No adverse event was recorded.

Conclusions: In C3G patients, pegcetacoplan therapy improves clinical and laboratory features during a 12-week treatment. The present study, although small and with a limited follow-up, supports the use of complement-targeted therapy in C3G. Further studies with a larger number of patients and longer follow-up are needed.

Background: As voiding cystourethrography is invasive and exposes to radiation and urinary tract infection (UTI), identifying only high-grade reflux is important. We aimed to identify clinical, laboratory and imaging variables associated with high-grade primary reflux in children presenting with UTIs and/or urinary tract dilatation and develop a prediction model for severe reflux.

Methods: Data of children who underwent voiding cystourethrography due to UTI and/or urinary tract dilatation were retrospectively analyzed for demographic, clinical and imaging findings. Patients with severe (grades 4-5) reflux were compared with the rest for these parameters and a prediction model was developed for severe reflux.

Results: The study included 1044 patients (574 female). Severe reflux was present in 86 (8.2%) patients. Age < 2 years, male sex, non-E. coli uropathogens, UTD-P3 dilatation and multiple kidney scars on DMSA scintigraphy were associated with severe reflux. Using these variables a prediction model for severe reflux with a score ranging from 0-7 and accuracy rate of 93.4% was developed. A score ≥ 5 had sensitivity 44.2%, specificity 97.4%, PPV 60.3%, NPV 95.1% and OR 29.5 for severe reflux. Scores ≥ 5 and ≥ 4 catch 44% and 73% of severe reflux, while prevent invasive voiding cystourethrography in 94.0% and 83.6% of patients, respectively.

Conclusion: Age < 2 years, male sex, non-E. coli uropathogen growth, presence of UTD-P3 dilatation on ultrasonography and multiple scars on DMSA scintigraphy are risk factors for severe reflux. A scoring system based on these variables appears to be effective in predicting the presence of severe reflux and eliminating unnecessary voiding cystourethrography.

Homogentisic acid (HGA) accumulation in alkaptonuria (AKU) causes injuries in various organs including the kidney. We present a case of a 9-year-old girl initially diagnosed with AKU-related nephropathy due to proteinuria found in her urine analyses. Despite 1 month of ramipril treatment, the patient's proteinuria progressed, and as a result, kidney biopsy and nitisinone treatment were planned. In addition, we controlled her proteinuria with urine albumin measurement. After finding a normal urine albumin level in the 24-h urine sample, we realized that the patient was misdiagnosed with proteinuria because of HGA interference with urine protein level measurement using benzethonium. The patient's treatment for kidney injury was canceled. Urine albumin level was measured as normal 2 months later, confirming proteinuria was a false-positive test result. AKU-related nephropathy should be evaluated with urine albumin measurement instead of protein. In this way, the complication risk of unnecessary interventions and pharmacotherapies can be avoided.

Hepatopulmonary syndrome (HPS) is a life-threatening complication of chronic liver disease (CLD) that currently can be managed only by liver transplant. Though uncommon, some children with kidney disease have coexistent CLD and hence are at risk of developing HPS. Paediatric cases of HPS are rarely described in the nephrology literature. We present a patient with autosomal recessive polycystic kidney disease (ARPKD) and persistent hypoxaemia diagnosed as HPS and successfully managed with a liver transplant. We suggest that nephrologists caring for children with kidney and concomitant CLD consider routine screening for HPS with pulse oximetry.