关键词: 肾单位肾痨, 成人发病, 囊性肾脏病, 基因型, 表型

Abstract: Objective:To investigate genotypic and phenotypic characteristics of adult⁃onset nephronophthisis (NPHP) patients. Methods:We retrospectively reviewed medical records of adult⁃onset NPHP patients treated at the National Clinical Research Center for Kidney Diseases between January 2016 and September 2025. Clinicopathological features, genetic results, and prognosis were analyzed. Results:29 patients were included (18 males,11 females),with median onset age of 24 (19,34) years. Most presented with elevated serum creatinine on routine testing or uremic symptoms. Median eGFR at diagnosis was 31 (15,53) ml/(min·1.73 m²); median proteinuria was 0.43 (0.22,0.66) g/24h. Anemia and hypertension prevalences were 62% and 38%,respectively. Renal cysts were present in 58%. Among 11 patients biopsied,all showed chronic tubulointerstitial damage. Genetic testing identified 6 pathogenic genes:NPHP1 (21 cases),NPHP3(2),NPHP4(3),and one case each of NPHP6(CEP290),NPHP14(ZNF423),and NPHP16(ANKS6). Isolated kidney disease occurred in 22 patients (76%);7(24%) had systemic involvement (3 central nervous system,3 ocular,1 skeletal). Of these,6 carried NPHP1 mutations and 1 carried an NPHP6 mutation. During follow⁃up,17 patients (59%) progressed to ESKD at median age 22 (19,40) years. Homozygous whole⁃exon deletion of NPHP1 led to significantly faster progression to ESKD versus other mutations. Conclusion:NPHP is a hereditary tubulointerstitial kidney disease. Adult⁃onset NPHP is characterized by an insidious onset and mild urinary abnormalities,but typically presents with early renal impairment. Some patients show systemic involvement. NPHP1 is the most common pathogenic gene,with homozygous whole⁃exon deletion predicting worse outcomes.

Key words: nephronophthisis, adult?onset, renal cystic disease, phenotype, genotype