Work

Multifactorial Predictors of Renal Outcomes in Alport Syndrome: Integrating Genetic, Clinical, and Cystic Phenotypes

Year: 2026

Type: article

Abstract: Rationale & Objective: Alport syndrome is an inherited kidney disease with significant clinical heterogeneity. This study aims to explore risk factors affecting the prognosis and investigates the relationship between kidney cysts and clinical manifestations in Alport syndrome patients. Study Design A single-center retrospective cohort study. Setting & Participants: A total of 179 patients diagnosed with Alport syndrome in Peking University First Hospital. Predictors Clinical characteristics (renal manifestations and extrarenal features), genetic patterns, and the presence of kidney cysts. Outcomes Kidney failure with replacement therapy or chronic kidney disease stage 3b. Analytical Approach Kaplan-Meier survival analysis, Cox proportional hazards models, logistic regression models and linear mixed models. Results In this Chinese adult Alport syndrome cohort, we identified several prognostic risk factors, including baseline serum creatinine (HR=3.15 [95% CI 1.95-5.08]), proteinuria (HR=1.29 [95% CI 1.01-1.65]), earlier diagnostic age (HR=1.30 [95% CI 1.16-1.45]), male sex (HR=3.00 [95% CI 1.05-8.54]), eye and ear impairment (HR=19.49 [95% CI 2.52-150.67]), and inheritance mode (X-linked or autosomal recessive) (HR=5.46 [95% CI 1.47-20.30]). Notably, 33.5% of Alport syndrome patients presented with kidney cysts, compared to only 12.8% in the matched IgA nephropathy cohort (P <0.001). The presence of kidney cysts was associated with older age and faster eGFR decline, independent of inheritance patterns. In patients under 40 years old, those with kidney cysts exhibited significantly worse renal function (median eGFR 72 vs. 108 ml/min/1.73m 2 , P=0.002) and a nearly twofold faster decline in eGFR slope. Limitations Selection bias, absence of time-varying cyst observations, and limitations in generalizability. Conclusions Our study reveals that kidney cysts are associated with severe clinical manifestations in Alport syndrome, particularly in younger patients. This finding highlights the importance of monitoring kidney cysts in Alport syndrome patients and suggests their potential role as a prognostic indicator.

Source: Kidney Medicine

DOI: 10.1016/j.xkme.2026.101264