Renal coloboma syndrome/dominant optic atrophy with severe retinal atrophy and de novo digenic mutations in PAX2 and OPA1.

Renal coloboma syndrome (RCS) and dominant optic atrophy are mainly caused by heterozygous mutations in PAX2 and OPA1, respectively. We describe a patient with digenic mutations in PAX2 and OPA1. A female infant was born without perinatal abnormalities. Magnetic resonance imaging at 4 months of age showed bilateral microphthalmia and optic nerve hypoplasia. Appropriate body size was present at 2 years of age, and mental development was favorable. Color fundus photography revealed severe retinal atrophy in both eyes. Electroretinography showed slight responses in the right eye, but no responses in the left eye, suggesting a high risk of blindness. Urinalysis results were normal, creatinine-based estimated glomerular filtration rate was 63.5 mL/min/1.73 m2, and ultrasonography showed bilateral hypoplastic kidneys. Whole exome sequencing revealed de novo frameshift mutations in PAX2 and OPA1. Both variants were classified as pathogenic (PVS1, PS2, PM2) based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). Genetic testing for ocular diseases should be considered for patients with suspected RCS and a high risk of total blindness.

Relationship between the serum creatinine concentrations of preterm neonates within 24 h of birth and their mothers before delivery.

BACKGROUND: Neonatal serum creatinine (n-sCr) concentrations during the first few days of life have been reported to correlate with the maternal serum Cr (m-sCr) concentrations. We aimed to derive a regression equation to describe the relationship between n-sCr within 24 h of birth in preterm neonates and m-sCr before delivery, and to perform multiple regression analysis to identify factors related to n-sCr and the difference between n-sCr and m-sCr. METHODS: We recruited preterm neonates who were treated at the University of the Ryukyus Hospital between March 2012 and October 2022. Patients with underlying diseases or conditions that might affect hemodynamics were excluded, as were patients whose n-sCr and m-sCr were not measured in pairs. A total of 278 cases were included in the analysis. RESULTS: The median (interquartile range) gestational age, birth weight, n-sCr, and m-sCr were 33.9 weeks (32.0-35.1 weeks), 1901 g (1579-2284 g), 0.55 mg/dL (0.48-0.64 mg/dL), and 0.47 mg/dL (0.42-0.57 mg/dL), respectively. The regression equation derived was n-sCr = 0.092 + 0.970 × m-sCr (R2 = 0.768, p < 0.001). The multiple regression analysis showed that m-sCr was the most potent influencer of n-sCr, and the ratio of placental weight to birth weight (PW/BW ratio) was the most potent influencer of the difference between n-sCr and m-sCr. CONCLUSIONS: We have obtained an approximate equation of n-sCr = 0.1 + m-sCr for preterm neonates. In addition, the high PW/BW ration may reduce the difference between n-sCr and m-sCr.

Protocol for the nationwide registry of patients with polycystic kidney disease: japanese national registry of PKD (JRP).

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD) are major genetic polycystic kidney diseases that can progress to end-stage kidney disease (ESKD). Longitudinal data on the clinical characteristics associated with clinical outcomes in polycystic kidney disease (PKD), including the development of ESKD and cardiovascular disease (CVD) are lacking in Japan. To address this unmet need the authors are establishing a novel, web-based, Nationwide Cohort Registry Study-the Japanese Registry of PKD (JRP). METHODS: The JRP is a prospective cohort study for ADPKD (aim to recruit n = 1000 patients), and both a retrospective and prospective study for ARPKD (aim to recruit n = 100). In the prospective registry, patients will be followed-up for 10 years every 6 months and 12 months for patients with ADPKD and ARPKD, respectively. Data collection will be recorded on Research Electronic Data Capture (REDCap) starting on April 1, 2024, with recruitment ending on March 31, 2029. (jRCT 1030230618). RESULTS: Data to be collected include: baseline data, demographics, diagnostic and genetic information, radiological and laboratory findings, and therapeutic interventions. During follow-up, clinical events such as development of ESKD, hospitalization, occurrence of extra kidney complications including CVD events, and death will be recorded, as well as patient-reported health-related quality of life for patients with ADPKD. CONCLUSIONS: The JRP is the first nationwide registry study for patients with ADPKD and ARPKD in Japan, providing researchers with opportunities to advance knowledge and treatments for ADPKD and ARPKD, and to inform disease management and future clinical practice.

Role of Iron in Children With Immunoglobulin A Nephropathy and Macrohematuria-Induced Acute Kidney Injury.

Introduction: The role of iron in, and the prognosis of, pediatric Immunoglobulin A nephropathy (IgAN) with macrohematuria (MH)-induced acute kidney injury (AKI) (MH-AKI) have not been evaluated. Thirty percent of adults with MH-AKI, and especially those who are older, show progression to chronic kidney disease. Methods: We evaluated the immunohistopathologic characteristics of renal biopsy samples from pediatric patients with MH-AKI IgAN and controls, using Berlin Blue to identify iron, CD163 (a hemoglobin-scavenging receptor), and CD68 (a total macrophage marker), then compared the findings against the clinical characteristics of the patients. Results: We enrolled 44 children as follows: 19 with IgAN but no MH or AKI; 5 with IgAN and MH but no AKI (MH(+)AKI(-) IgAN); 11 with MH-AKI IgAN; and 9 with no IgAN, MH, or AKI, according to a renal biopsy. Berlin Blue staining was detected predominantly at the injured tubulointerstitium, and the areas of staining in children with MH(+)AKI(-) and MH-AKI IgAN were significantly more extensive. The areas of Berlin Blue and CD163 staining did not perfectly match; however, areas of Berlin Blue were surrounded by immunopositivity for CD163. No children with MH-AKI IgAN showed decreased renal function at their last visit. Conclusion: Children with IgAN and MH, with or without AKI, showed considerable iron deposition in their renal tubules. CD163-positive cells might scavenge hemoglobin in patients with MH-AKI IgAN, but not their roles as macrophages. The renal prognosis of pediatric MH-AKI IgAN is good.