Elevated serum homocysteine is a predictor of accelerated decline in renal function and chronic kidney disease: A historical prospective study.

Objective: To estimate the effect of elevated serum homocysteine level on renal function decline and on the incidence of chronic kidney disease (CKD) in the general population.

Methods: A historical prospective study on 3602 subjects attending a screening center in Israel between the years 2000 and 2012. Only subjects with normal estimated glomerular filtration rate (eGFR) and without proteinuria were included. Subjects were divided to two groups according to mean total serum homocysteine level (≤ 15, >15μmol/l). Linear mixed effect model was used to estimate the annual eGRF decline in respect to homocysteine group. Cox proportional hazards models were used to estimate hazard ratios for CKD in the normal compared to the elevated homocysteine group.

Results: Annual eGFR decline was 25% higher in subjects with elevated versus normal mean homocysteine level (0.90 ± 0.16 ml/min/1.37 m(2) vs. 0.72 ± 0.14 ml/min/1.37 m(2), p<0.001). In a median follow up of 7.75 years, 38 subjects developed CKD (1.05%). Elevated mean homocysteine level was highly associated with developing CKD (HR 4.85, 95% CI 2.48-9.49, p<0.001). In a multivariate analysis which adjusted for age, baseline kidney function, HDL cholesterol, BMI, vitamin B12 and folic acid levels, these relationships remained substantially unchanged.

Conclusions: Elevated mean serum homocysteine level is associated with an accelerated decline in renal function in both men and women, and is an independent risk factor for the development of CKD in the general population. Further prospective randomized clinical trials are needed to clarify whether the reduction in serum homocysteine concentrations will result in an improved renal prognosis.