BackgroundWe present a rare early presentation of a ADCK4-related glomerulopathy. This case is of interest as potentially treatable if genetic results are timely obtained.Case presentationWe report the case of a 5-year-old boy who was identified with significant proteinuria by a urinary routine screening program for school children. Physical examination revealed dysplastic ears and abnormal folded pinna. Albumin level was 41 g/L (39–53 g/L), and urine proteins/creatinine ratio was 2.6 g/g. Renal ultrasound showed enlarged kidneys and perimedullary hyperechogenicity. Treatment by angiotensin-converting-enzyme inhibitor was not beneficial. Renal biopsy showed signs of focal segmental glomerulosclerosis. After 4 years of follow-up, he developed a clinical nephrotic syndrome and no response to prednisone and other immunosuppressive agents was obtained. Within 6 months, he was in end-stage-renal-failure (ESRF) and hemodialysis was started. He was transplanted at 10 years with his mother’s kidney. Genes known to be responsible in steroid-resistant nephrotic syndromes were tested. Our patient is compound heterozygous for two mutations in the aarF domain-containing-kinase 4 (ADCK4) gene. ADCK4 gene is one of the genes involved in coenzyme Q10 (CoQ10) biosynthesis, is located in chromosome 19q13.2 and expressed in podocytes. ADCK4 mutations show a largely renal-limited phenotype. The nephropathy usually presents during adolescence, fast evolves towards ESRF, and may be treatable by CoQ10 supplementation if started early in the disease. Our patient presented nephrotic range proteinuria at 5 years, and he reached ESRF at 10 years.ConclusionADCK4-related glomerulopathy is an important novel and potentially treatable cause of isolated nephropathy not only in adolescents, but also in children in their first decade of life. Discovery of important proteinuria in an asymptomatic child should prompt early genetic investigations.

Kidney transplantation (KT) is often delayed in small children because of fear of postoperative complications. We report early- and long-term outcomes in children transplanted at ≤15 kg in the two largest Belgian pediatric transplant centers. Outcomes before (period 1) and since the introduction of basiliximab and mycophenolate-mofetil in 2000 (period 2) were compared. Seventy-two KTs were realized between 1978 and 2016: 38 in period 1 and 34 in period 2. Organs came from deceased donors in 48 (67%) cases. Surgical complications occurred in 25 KTs (35%) with no significant difference between the two periods. At least one acute rejection (AR) occurred in 24 (33%) KTs with significantly less patients experiencing AR during period 2: 53% and 12% in period 1 and, period 2 respectively (P < 0.001). Graft survival free of AR improved significantly in period 2 compared with period 1: 97% vs. 50% at 1 year; 87% vs. 50% at 10 years post-KT (P = 0.003). Graft survival tended to increase over time (period 1: 74% and 63% at 1 and 5 years; period 2: 94% and 86% at 1 and 5 years; P = 0.07), as well as patient survival. Kidney transplantation in children ≤15 kg remains a challenging procedure with 35% of surgical complications. However, outcomes improved and are nowadays excellent in terms of prevention of AR, patient and graft survival.

Background: Primary hyperoxaluria type 1 (PH1) is a rare genetic disease caused by hepatic overproduction of oxalate, ultimately responsible for kidney stones, kidney failure and systemic oxalosis. Lumasiran, is a liver-directed RNA interference therapeutic agent. It has been shown to reduce hepatic oxalate production by targeting glycolate oxidase, and to dramatically reduce oxalate excretion.Care Report: We present the case of a teenager patient affected by PH1, who entered in the lumasiran compassionate use program. The patient had a rapid and sustained decrease in urinary oxalate/creatinine ratio, with a mean reduction after lumasiran administration of about 70%. During the 18 months long follow-up, urinary oxalate remained low, reaching nearly normal values. Plasma oxalate also decreased dramatically. Normal levels were reached immediately after the first dose and remained consistently low thereafter. During the same follow-up period, eGFR remained stable at about 60 ml/min/1.73 m2, but no new kidney stones were observed. Existing kidney stones did not increase in size. The patient did not suffer renal colic events and did not require further urological interventions.Conclusion: In our severely affected PH1 patient, lumasiran proved to be very effective in rapidly and consistently reducing plasma oxalate and urinary excretion to normal and near-normal levels, respectively. In the 18 months long follow-up post-lumasiran, the eGFR remained stable and the patient showed clinical improvements. As far as we know, this report covers the longest observation period after initiation of this novel RNAi therapy.