Albuminuria drives hyperlipidemia in patients with Alport syndrome

Hypercholesterolemia is a major driver of cardiovascular disease, a leading cause of premature mortality in patients with chronic kidney disease (CKD). Despite their typically young age, patients with Alport syndrome (AS), the second most prevalent genetic cause of CKD, may face a disproportionately high risk of hypercholesterolemia. This study investigates whether increased albuminuria precipitates hyperlipidemia in this population to a degree comparable with general CKD cohorts, while further delineating the risk factors underlying this development.

This was a multicenter, observational, non-interventional, and retrospective study.

Among 459 patients with AS, 59.3% had hypercholesterolemia and 58.5% had elevated low-density lipoprotein cholesterol (LDL-C). Despite lower eGFR and higher albuminuria, patients with lipid-lowering therapy (LLT) had significantly lower total cholesterol levels compared to the untreated patients (193.6 ± 55.2 mg/dL vs. 208.2 ± 51.0 mg/dL; p = 0.044). Similarly, LDL-C levels were significantly lower in the treatment group (111.6 ± 51 mg/dL, n = 59) compared to the untreated group (124.3 ± 40.2 mg/dL, n = 238; p = 0.041). Multivariable regression analysis adjusted for age, gender, BMI, eGFR, and LLT revealed that albuminuria was a significant independent determinant of total cholesterol (β=0.315; p < 0.001) and LDL-C levels (β=0.242; p < 0.001). Male gender was associated with significantly higher LDL-C and lower HDL-C levels. Conversely, eGFR and BMI were not significant predictors of cholesterol levels. This association was also observed in the pediatric cohort (n = 44), where albuminuria was the only independent predictor of cholesterol (β=0.728; p < 0.001).

Hypercholesterolemia is highly prevalent in young patients with AS and is primarily driven by the severity of albuminuria, rather than other risk factors such as obesity or eGFR decline. These findings highlight a critical gap in current guidelines, support the implementation of early lipid screening and suggest that risk-adapted management may be necessary to prevent long-term cardiovascular complications.