Phenotypic spectrum and antialbuminuric response to angiotensin converting enzyme inhibitor and angiotensin receptor blocker therapy in pediatric Dent disease.

Background: To characterize the phenotypic spectrum and assess the antialbuminuric response to angiotensin converting enzyme (ACE) inhibitor and/or angiotensin receptor blocker (ARB) therapy in a cohort of children with Dent disease. Methods: The patients' clinical findings, renal biopsy results, genetic and follow-up data were analyzed retrospectively. Mutations in CLCN5 or OCRL were detected by next-generation sequencing or Sanger sequencing. Results: Of 31 Dent disease boys, 24 carried CLCN5 and 7 carried OCRL mutations. Low molecular weight proteinuria and albuminuria were detected in all cases. Nephrotic-range proteinuria and severe albuminuria were identified in 52% and 62% of cases, respectively; by 7 years of age, 6 patients had hematuria and nephrotic-range proteinuria, and 7 patients had hematuria and moderate to severe albuminuria. In addition to disease-related renal features, patients with Dent-1 disease also presented with congenital cataract (1/9) and developmental delay (2/7). Seventeen of 31 patients underwent renal biopsy. Glomerular changes included mild glomerular lesions, mesangial proliferative glomerulonephritis and focal segmental glomerular sclerosis. Thirteen of the 31 patients had follow-up records and received ACE inhibitor and/or ARB treatment for more than 3 months. After a median 1.7 (range 0.3-8.5) years of treatment, a reduction in the urinary microalbumin-to-creatinine ratio was observed in 54% of children. Conclusions: Hematuria with nephrotic-range proteinuria or moderate to severe albuminuria was common in Dent disease patients. Extrarenal manifestations were observed in Dent-1 patients, which extends the phenotypic spectrum. In addition, ACE inhibitors and ARBs are well tolerated, and they are partially effective in controlling albuminuria.