Homocysteine and Its Determinants in Nondialyzed Chronic Kidney Disease Patients

Abstract

This cross-sectional study aimed to investigate the prevalence of hyperhomocysteinemia, the determinants of plasma total homocysteine concentrations, and the relationship of total homocysteine with nutritional parameters in a sample of patients with chronic kidney disease (CKD) and not yet on dialysis. The study was done with outpatients from the Nephrology Division of the Federal University of São Paulo and Oswaldo Ramos Foundation. Sixty-six patients with CKD (70% male; age 58.6±15.6 years [mean±standard deviation]) with moderate to severe renal impairment (creatinine clearance=29.8±14.3 mL/min [0.5±0.24 mL/sec]), clinically stable, and older than 18 years were included. A group of 20 healthy subjects from the clinic staff was also studied for reference values for plasma homocysteine, folate, and vitamin B-12 concentration. Fasting blood samples were collected to determine plasma total homocysteine, folate, vitamin B-12, and creatinine. To calculate creatinine clearance, a 24-hour urine collection sample was obtained. The assessment of nutritional status included anthropometric parameters. Pearson correlation, Mann-Whitney test, and multiple linear regression analysis were used for statistical analyses. The main results showed that the concentration of total homocysteine in the patients was significantly increased compared with the healthy subjects (3.4±1.7 vs 1.41±0.42 mg/L [25.4±12.2 vs 10.4±3.1 μmol/L]; P<0.001). Plasma folate and plasma vitamin B-12 were in the normal range and did not differ between patients and healthy individuals. A high prevalence of hyperhomocysteinemia (total homocysteine >1.89 mg/L [14 μmol/L]) was found in the patients (89%). Plasma total homocysteine did not correlate with any of the nutritional parameters studied and did not differ between patients in terms of whether they were using or not using folic acid supplementation (3.07±1.09 vs 3.55±1.78 mg/L [22.7±8.1 vs 26.3±13.2 μmol/L]; P=0.47), although plasma folate was significantly higher in the supplemented group (12.6±3.0 vs 8.0±3.6 ng/mL [28.5±6.8 nmol/L vs 18.1±8.2 nmol/L]; P<0.001). According to the multiple regression analysis, the determinants of total homocysteine were only plasma folate, plasma vitamin B-12, and creatinine clearance ( r 2 =0.20). In conclusion, a high prevalence of hyperhomocysteinemia was found in our sample of nondialyzed patients with CKD. The determinants of total homocysteine levels were plasma folate, plasma vitamin B-12, and creatinine clearance. No association between nutritional parameters and total homocysteine was observed.