Rationale & objective: Afamin is a vitamin E-binding glycoprotein primarily expressed in the liver and kidney. This study investigated whether serum afamin concentrations are associated with kidney function and incident kidney failure.

Study design: Prospective cohort study with 6.5 years follow-up.

Setting & participants: 5,041 White patients enrolled in the German Chronic Kidney Disease (GCKD) study with measured afamin concentrations and either an estimated glomerular filtration rate (eGFR) of 30-60mL/min/1.73m2 or an eGFR>60mL/min/1.73m2 with a urinary albumin-creatinine ratio (UACR) of≥300mg/g at study entry.

Exposure: Serum afamin concentrations (mg/L).

Outcome: Incident kidney failure (initiation of kidney replacement therapy or kidney-related death).

Analytical approach: Generalized linear regression and quantile regression models fit to investigate the association of afamin concentrations with eGFR and UACR. Adjusted Cox regression analysis to examine the association of afamin concentrations with incident kidney failure.

Results: The mean±SD afamin concentration at study entry was 73.2±17.6mg/L. Higher afamin concentrations were associated with better kidney function with a 2.60mL/min/1.73m2 higher eGFR (95% CI, 2.30-2.89) and a 5.97mg/g lower UACR (95% CI, 3.04-8.90) for each 10mg/L higher level of afamin concentration in adjusted analysis. During the follow-up period, each 10mg/L higher level of afamin concentration was associated with a 14% lower risk of kidney failure (HR, 0.86 [95%CI, 0.81-0.92], P<0.001).

Limitations: Residual confounding, and potential limited generalizability to non-White populations and people with mild stages of chronic kidney disease (CKD) or no CKD.

Conclusions: Higher serum afamin concentrations appear to be associated with a higher eGFR, less albuminuria, and a lower risk for future kidney failure in patients with CKD.