Homocysteine, cysteine, and B vitamins as predictors of kidney disease progression.
ABSTRACT Pathological similarities between atherosclerosis and glomerulosclerosis suggest that risk factors for the two processes may be similar. Elevated total homocysteine (tHcy) levels and low B vitamin levels are risk factors for atherosclerosis, but have not been evaluated sufficiently as risk factors for the progression of kidney disease.
Frozen samples from the Modification of Diet in Renal Disease Study were assayed for serum tHcy, cysteine, pyridoxal 5-phosphate (PLP), folate, and vitamin B12 levels in 804 participants. These factors were evaluated in both continuous and categorical analyses as risk factors for glomerular filtration rate (GFR) decline by using univariate and multivariable analyses.
At baseline, mean tHcy levels in study A (GFR, 25 to 55 mL/min/1.73 m2) and study B (GFR, 13 to 24 mL/min/1.73 m2) were 16.9 micromol/L (median, 15.6 micromol/L) and 23.0 micromol/L (median, 20.5 micromol/L), respectively. Mean follow-up was 2.2 years. Mean GFR declines were -4.35 and -3.65 mL/min/y in studies A and B, respectively. There was no significant association between change in GFR with baseline level of tHcy in univariate (-0.26 mL/min/y per 1-SD unit increase in tHcy level; 95% confidence interval [CI], -0.67 to 0.15) or multivariable (-0.18 mL/min/y per 1-SD unit increase in tHcy level; 95% CI, -0.53 to 0.17) analysis in study A or univariate (0.07 mL/min/y per 1-SD unit increase in tHcy level; 95% CI, -0.36 to 0.51) or multivariable (0.24 mL/min/y per 1-SD unit increase in tHcy level; 95% CI, -0.16 to 0.64) analysis in study B. Similarly, higher cysteine levels and lower B vitamin levels were not associated with faster rates of GFR decline in multivariable analysis in either study.
Higher tHcy or cysteine levels and lower folate, PLP, and vitamin B12 levels are not independent risk factors for progression of nondiabetic kidney disease.
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ABSTRACT: A low serum bicarbonate level is prevalent in chronic kidney disease (CKD); however, its relationship to long-term outcomes is unclear. Cohort study. The Modification of Diet in Renal Disease (MDRD) Study examined the effects of dietary protein restriction and blood pressure control on progression of kidney disease. This analysis includes 942 screened but non-randomized individuals and 839 randomized participants with baseline serum bicarbonate measurements with stage 2-4 CKD. Serum bicarbonate level categorized into quartiles. Kidney failure, all-cause mortality, and a composite outcome of mortality and kidney failure. Local laboratories at each participating site measured bicarbonate in fasting serum samples. Kidney failure outcomes were obtained from the US Renal Data System, and mortality data, from the National Death Index. Mean glomerular filtration rate (GFR) was 39 ± 21 (SD) mL/min/1.73 m(2) and serum bicarbonate level was 23.3 ± 3.8 mEq/L. Kidney failure rates were 72%, 64%, 50%, and 41%; mortality rates were 31%, 25%, 21%, and 25%, and rates of the composite outcome were 78%, 71%, 58%, and 54% in bicarbonate quartiles 1, 2, 3, and 4, respectively. In analyses adjusted for demographic and cardiovascular disease factors, serum albumin level, proteinuria, and cause of kidney disease, compared with quartile 4, quartile 1 was associated with a 2.22 HR (95% CI, 1.83-2.68) of kidney failure; 1.39 HR (95% CI, 1.07-1.18) of all-cause mortality; and 1.36 HR (95% CI, 1.15-1.62) of the composite outcome. These associations were rendered nonsignificant with adjustment for GFR (kidney failure HR, 1.05 [95% CI, 0.87-1.28]; all-cause mortality HR, 0.99 [95% CI, 0.75-1.13]; composite HR, 1.04 [95% CI, 0.87-1.24]). Single baseline measurement of serum bicarbonate. Low serum bicarbonate level was associated with increased risk of long-term outcomes in nondiabetic patients with CKD. However, this risk is not independent of baseline GFR. Clinical trials are necessary to evaluate whether bicarbonate supplementation slows the progression of CKD.American Journal of Kidney Diseases 11/2010; 56(5):907-14. · 5.29 Impact Factor
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ABSTRACT: Increasing experimental evidence, including recently developed animal models, supports a role for homocysteine in the development of chronic kidney disease (CKD). However, relatively few clinical/epidemiological studies have examined this hypothesis in humans. We examined the relationship between plasma homocysteine level and CKD in a population-based study of older Australians. Community-based study (1992-1994) among 2,609 individuals (58.6% women), aged 49-98 years, free of clinical cardiovascular disease in the Blue Mountains region, west of Sydney, Australia. The main outcome-of-interest was CKD (n = 461), defined as estimated glomerular filtration rate of <60 ml/min/1.73 m(2). Higher plasma homocysteine levels were positively associated with CKD, independent of smoking, body mass index, diabetes mellitus, hypertension, cholesterol levels, and other confounders. The multivariable odds ratio (OR; 95% confidence intervals, CI) comparing quartile 4 of plasma homocysteine (>14 micromol/l) to quartile 1 (< or =9 micromol/l) was 10.44 (6.99-15.60), p-trend <0.0001. This association persisted in both men and women separately. The results were also consistent in subgroup analyses by categories of diabetes mellitus and hypertension. Higher plasma homocysteine levels are associated with CKD in a community-based sample of older Australians. This association appeared to be independent of diabetes mellitus and hypertension.Kidney and Blood Pressure Research 02/2008; 31(1):55-62. · 1.60 Impact Factor
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ABSTRACT: Hyperhomocysteinemia is thought to be an independent risk factor for cardiovascular disease, but the association between renal dysfunction and homocysteine may not have been fully taken into account. We performed a meta-analysis of studies that report correlations between glomerular filtration rate (GFR) and homocysteine plasma levels. Using a prespecified research strategy, we identified 41 studies involving 26,617 participants that reported Pearson or Spearman correlation coefficients for the association between 1/GFR and homocysteine. The summary correlation coefficients with 95% CI were obtained by pooling the logarithmic Z values derived from the individual trial correlation coefficients. Subgroup analysis was performed to compare results for measured GFR using clearance methods and various estimates of GFR. The pooled correlation coefficient between homocysteine and 1/GFR was 0.37 (CI 0.32-0.40, p < 0.0001). The correlation coefficient based on various estimates of GFR was 0.33 (CI 0.29-0.38, p < 0.0001), and for measured GFR it was 0.45 (CI 0.39-0.51, p < 0.0001). The correlation coefficient was higher when GFR was measured using clearance methods compared with various estimates GFR (1.36 [CI 1.13-1.65], p = 0.0014). Homocysteine plasma levels significantly depend on renal function. This correlation is even more robust when GFR is measured using clearance methods. Therefore, in order to assess whether homocysteine is an independent cardiovascular risk factor, accurate adjustments for renal dysfunction are essential.Kidney and Blood Pressure Research 02/2008; 31(4):259-67. · 1.60 Impact Factor