Genetic background and clinicopathologic features of adult-onset nephronophthisis

Abstract Introduction Recently, nephronophthisis is considered to be a monogenic cause of end stage renal disease in adults. However, adult-onset nephronophthisis is difficult to accurately diagnose and has not been reported in a cohort study. In this study, we assessed the genetic background and clinicopathologic features of adult nephronophthisis. Methods We investigated 18 sporadic adult patients who were suspected as nephronophthisis by renal biopsy. We analyzed 69 genes that cause hereditary cystic kidney disease, and compared clinicopathologic findings between patients with and without pathogenic mutations in nephronophthisis-causing genes. Results Seven of 18 patients had pathogenic nephronophthisis-causing mutations in NPHP1, NPHP3, NPHP4, or CEP164. Compared with patients without pathogenic mutations, those with pathogenic mutations were significantly younger but did not significantly differ in the classic nephronophthisis pathologic findings, such as tubular cyst. On the other hand, the number of tubules with thick tubular basement membrane (TBM) duplication, which was defined as >10-μm thickness, was significantly higher in patients with genetically proven adult nephronophthisis than in those without pathogenic mutations. Alpha smooth muscle actin positive myofibroblasts were detected inside thick TBM duplication. Conclusions In adult patients with nephronophthisis, thick TBM duplication was the specific finding. Our analysis also suggested that older patients tended to have no pathogenic mutations, even when they were suspected to have nephronophthisis by renal biopsy. These findings could be the novel clinical clue for the diagnosis of nephronophthisis in adult patients.