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

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 patients with Alport syndrome.

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 patients with Alport syndrome presented with kidney cysts, compared with only 12.8% in the matched IgA nephropathy cohort (P < 0.001). The presence of kidney cysts was associated with older age and faster estimated glomerular filtration rate (eGFR) decline, independent of inheritance patterns. In patients aged less than 40 years, those with kidney cysts exhibited significantly worse renal function (median eGFR, 72 vs 108 mL/min/1.73 m²; P = 0.002) and a nearly 2-fold 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 patients with Alport syndrome and suggests their potential role as a prognostic indicator.

Plain-Language Summary

Alport syndrome, an inherited kidney disease, varies widely in severity, but the risk factors affecting outcomes and the role of kidney cysts remain unclear. We analyzed the medical records of 179 patients with Alport syndrome and found that more urinary protein, younger age at diagnosis, male sex, eye/ear impairment, and specific genetic patterns increased risks. Kidney cysts were common in patients with Alport syndrome and were linked to faster kidney decline, especially in younger individuals. Those with kidney cysts had worse kidney function and faster disease progression. This work helps clinicians identify high-risk patients with Alport syndrome earlier and improve long-term kidney health.