Temporal changes of proteinuria after kidney transplantation: association with cardiovascular morbidity and mortality

Background: Proteinuria is common in kidney transplant recipients and has been established as a risk factor for graft-loss and mortality. In the general population, proteinuria has also been tied to a higher risk of cardiovascular disease. There is limited data exploring the association between changes in proteinuria over time and cardiovascular disease in kidney transplant recipients. Methods: In this retrospective cohort study we evaluated proteinuria as a time-varying covariate using urine dipstick protein values at 6 month intervals post-transplant. The primary outcome was the occurrence a major cardiovascular event (MACE). Univariate and multivariate time varying Cox model was used. Results: 579 patients were included in the final cohort. 120 episodes of MACE were documented in 98 patients. Time varying proteinuria was associated with MACE by univariate and multivariate analysis (HR 2.63, 95% CI 1.76–3.93, p < 0.001) and (HR 2.33, 95% CI 1.53–3.54, p < 0.001). Reduction of proteinuria to normal was associated with reduced risk of MACE compared with active proteinuria (HR 0.44, 95% CI 0.28–0.69, p < 0.001) and (HR 0.47, 95% CI 0.3–0.76, p = 0.002) for univariate and multivariate analyses. Exposure to proteinuria for more than 1 year was significantly associated with an increased risk of MACE for univariate and multivariate analysis (HR 2.33, 95% CI 1.48–3.68, p < 0.001) and (HR 2.18, 95% CI 1.37–3.45, p = 0.002) respectively, in comparison to exposure of less than 1 year. Conclusion: These findings may suggest that we should consider applying clinical interventions that are known to reduce cardiovascular morbidity in these patients.