Introduction: Nephronophthisis (NPH) is an inherited renal disease caused by abnormal function of the primary cilia. End-stage renal failure at a relatively young age, requiring renal replacement therapy. Early detection is difficult because urinalysis rarely shows abnormalities. About 15-20% of NPH have extrarenal manifestations. There are few reports on outcomes after renal replacement therapy for NPH. The purpose of this study is to evaluate the etiology of detection, genetic mutations, complications, management of renal failure, and outcomes of NPH, a rare renal disease.
Subjects and Methods: A retrospective study of 14 patients with NPH who underwent renal transplantation at our center from 2009 to 2024 was conducted using medical records. Trends in renal function and height were evaluated at 3-4 months, 1 year, 3 years, 5 years, and 10 years after renal transplantation. Height was evaluated excluding cases with skeletal abnormalities.
Results: There were 203 renal transplant cases under 20 years of age with NPH in 6.9% of cases. There were 9 boys, with a median observation period of 5.9 years. Genetic testing was performed in 10 cases and genetic abnormalities were identified in 8 cases: 5 NPH related gene mutations and 3 other cases. Median age at diagnosis was 0.8 years (IQR 0 months-11.4 years). The most common reason for detection was extrarenal symptoms (n=5), followed by school physical examinations, incidental examinations, and others (3 cases each). The main complications were visual impairment and skeletal abnormalities in 5 cases each and psychomotor retardation in 4 cases (duplicates). Dialysis therapy was administered to 9 patients. Median age at  induction and median duration of dialysis were 7.0 years and 1.9 years, respectively. The median age at the time of renal transplantation was 8.8 years, and there were 10 living donor renal transplants, of which 5 were preemptive. Median renal function (Cr-eGFR: mL/min/1.73m2) was 87.6 at 3-4 months (n=14), 90.6 at 1 year (n=12), 72.5 at 3 years (n=10), 70.0 at 5 years (n=6), and 75.1 at 10 years (n=2) after transplant. Two patients, however, had graft loss due to chronic rejection caused by non-adherence. The median height SDS was -2.0 SD before transplantation (n=7) and after transplantation: 3-4 months (n=8) -2.0 SD, 1 year (n=8) -1.2 SD, 3 years (n=6) -1.9 SD, 5 years (n=4) -2.0 SD and 10 years (n=2) -1.2 SD.
Conclusion: The age of diagnosis was low because extrarenal symptoms accounted for 35.7% of the causes of detection. Hence, extrarenal symptoms were shown to be informative for early detection of NPH. Among the cases for which genetic testing was performed, 62.5% had NPH-related gene mutations. Transplant renal function was well generally maintained. On the other hand, important for growth gain is the improvement of the height SDS at the time of transplantation.