Transplantation for infantile nephronophthisis with loss-of-function mutation in NPHP3: Lesson from a case

The choice of KT only or CLKT for infantile NPHP with mild liver fibrosis is understudied. A 5-year-old girl was transferred to our center for KT due to ESRD. Her primary disease was infantile NPHP with compound heterozygous NPHP3 mutations: c.458A>C(p.Q153P)/missense mutation and c.2032A>T(p. K678X)/nonsense mutation. The patient had elevated liver enzymes and biopsy-proven liver fibrosis. As liver synthesis was acceptable, only KT was performed. However, liver fibrosis progressed at 1.5 years after transplantation, manifested with portal hypertension and hypersplenism. Common causes for portal hypertension were excluded, and the progression was attributed to NPHP. AMR attacked allograft at about 2 years post-transplant. To solve both the liver and the kidney problems, CLKT was performed. Her liver and kidney function recovered initially, but she unfortunately died of pneumonia and subsequent intracranial hemorrhage two weeks later. Nonsense mutation in NPHP3 gene may be correlated with rapid progression of liver disease in infantile NPHP. More studies are required to determine the role of CLKT in these cases; however, combined transplantation may improve long-term graft and patient survival.