Background: Cardiovascular disease (CVD) is common in kidney transplant recipients (KTRs). The level of kidney function (glomerular filtration rate [GFR]) estimated from serum creatinine has been shown to be independently associated with CVD outcomes in a wide range of populations, including KTRs. In other populations, CVD outcomes are more strongly associated with the alternative filtration markers serum cystatin C and beta-2-microglobulin (B2M) than creatinine, but this has not been evaluated in KTRs.
Methods: We performed a case-cohort study of participants of the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) Trial, a randomized, double blind clinical trial of homocysteine lowering with B vitamins in KTRs. Study participants were enrolled from 2002-07 from centers in the US, Canada & Brazil; we studied a 15% random subcohort of eligible baseline participants (N=508; mean age 52 years, 38% women) and all additional eligible adjudicated CVD (CVD death, myocardial infarction, resuscitated sudden death, stroke, N=211) and all-cause mortality (N=314) events that occurred through June 2009. Filtration markers measured at baseline were expressed as estimated GFR using established CKD-EPI equations (eGFRcr, eGFRcys & eGFRB2M). Associations of eGFRcr, eGFRcys & eGFRB2M with CVD and mortality were evaluated with weighted Cox proportional hazard regression to account for the case-cohort design.
Results: In multivariable adjusted models eGFRcr was not significantly associated with CVD or all-cause mortality. In contrast, both lower eGFRcys and eGFRB2M were associated with increased risk of CVD and all-cause mortality (Figure). Findings were similar when eGFR was treated as a continuous variable.
Conclusion: Similar to non-transplant cohorts, cystatin C and B2M have stronger risk associations for CVD and all-cause mortality compared to creatinine in KTRs. These findings likely reflect differences in their non-GFR determinants; future work is needed to evaluate non-GFR determinants in KTRs.