Factors associated with lipoprotein(a) in chronic kidney disease.

BACKGROUND: It is unclear whether lipoprotein(a) (Lp[a]) levels in patients with chronic kidney disease (CKD) are elevated as a result of reduced glomerular filtration rate (GFR) or other factors associated with CKD. The goal of this study is to describe the association of Lp(a) level with GFR in the context of apoprotein(a) (apo[a]) isoform size, race, and other kidney disease-related factors, such as proteinuria, serum albumin level, C-reactive protein (CRP) level, and serum lipid levels. METHODS: Lp(a) and apo(a) isoforms were measured in serum samples obtained at baseline from 804 participants in the Modification of Diet in Renal Disease study (GFR range, 13 to 55 mL/min/1.73 m2). The cross-sectional association between Lp(a) level and GFR, apo(a) isoform size, race, and other variables was analyzed in univariate and multivariate linear regression. RESULTS: Median Lp(a) level was greater in blacks than whites (97.5 versus 28.1 nmol/L; P < 0.001). Those with a low-molecular-weight apo(a) isoform size had greater Lp(a) levels than those with a high-molecular-weight apo(a) isoform size (57.5 versus 21.3 nmol/L; P < 0.001). Lp(a) level was not associated with GFR. Low-molecular-weight apo(a), black race, and greater levels of proteinuria, CRP, and triglycerides were independently associated with greater Lp(a) levels. CONCLUSION: In this population with CKD stages 3 to 4, GFR was not associated with Lp(a) level, whereas other factors related to CKD, such as proteinuria, CRP level, and triglyceride level, as well as genetic factors such as apo(a) isoform size and race, were associated with Lp(a) level.

Design and statistical aspects of the African American Study of Kidney Disease and Hypertension (AASK).

The African American Study of Kidney Disease and Hypertension (AASK) is a multicenter randomized clinical trial designed to test the effectiveness of three anti-hypertensive drug regimens and two levels of BP control on the progression of hypertensive kidney disease. Participants include African-American men and women aged 18 to 70 yr who have hypertensive kidney disease and GFR between 20 and 65 ml/min per 1.73 m(2). The three anti-hypertensive drug regimens include an angiotensin converting enzyme inhibitor (ramipril), a dihydropyridine calcium channel blocker (amlodipine) or a beta-blocker (metoprolol) as initial therapy. The BP control levels are a lower goal (mean arterial pressure,

Serum C-reactive protein and leptin as predictors of kidney disease progression in the Modification of Diet in Renal Disease Study.

BACKGROUND: In vitro and in vivo data suggest that markers of inflammation and nutritional status may be risk factors for the progression of chronic kidney disease. METHODS: We investigated whether higher levels of C-reactive protein (CRP) and leptin were risk factors for progression of chronic kidney disease in the Modification of Diet in Renal Disease (MDRD) Study. Frozen samples were assayed for high sensitivity C-reactive protein (CRP) or leptin in 804 patients. CRP and leptin were then evaluated as risk factors for glomerular filtration rate (GFR) decline using univariate and multivariable analyses. RESULTS: At baseline, the mean (median) CRP in Study A (GFR between 25 and 55 mL/min/1.73 m2) and Study B (GFR between 13 and 24 mL/min/1.73 m2) were 0.48 (0.25) and 0.46 (0.20) mg/dL, respectively, while the mean (median) leptin in Study A and Study B were 15.2 (9.80) and 15.1 (7.80) ng/mL, respectively. Mean follow-up time was 2.2 years. The mean GFR decline was -4.33 and -3.65 mL/min/year in Study A and B, respectively. There was no significant association between the rate of GFR decline with the level of CRP or leptin in multivariable analysis in Study A [0.08 (-0.14, 0.30) mL/min/year slower GFR decline per twofold increase in CRP level; and 0.14 (-0.13, 0.40) mL/min/year slower GFR decline per twofold increase in leptin level], or in multivariable analysis in Study B [-0.05 (-0.28, 0.18) mL/min/year faster GFR decline per twofold increase in CRP level; and -0.12 (-0.42, 0.19) mL/min/year faster GFR decline per twofold increase in leptin level]. CONCLUSIONS: Higher serum levels of CRP and leptin are not independent risk factors for progression of non-diabetic kidney disease.

Homocysteine, cysteine, and B vitamins as predictors of kidney disease progression.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Higher tHcy or cysteine levels and lower folate, PLP, and vitamin B12 levels are not independent risk factors for progression of nondiabetic kidney disease.

Cross-sectional study of health-related quality of life in African Americans with chronic renal insufficiency: the African American Study of Kidney Disease and Hypertension Trial.

We measured health-related quality of life (HRQL) by using the Medical Outcomes Study 36-Item Short-Form (SF-36) in a cross-sectional study of 1,094 African American men and women with mild to moderate chronic renal insufficiency (mean glomerular filtration rate, 45.7 mL/min/1.73 m2) caused by hypertension before randomization onto the African American Study of Kidney Disease and Hypertension (AASK) Trial. Scales contributing to physical health and a summary measure, the Physical Component Summary (PCS) score (mean, 43.4 +/- 10.9 [SD]), were significantly lower than scales relating to mental health and the Mental Component Summary (MCS) score (51.3 +/- 10.3). All scales (except Role-Physical) and the PCS and MCS were significantly higher in men (44.3 +/- 10.9 and 51.8 +/- 10.0, respectively) than women (41.9 +/- 10.8 and 50.5 +/- 10.6, respectively). In multivariate analysis, employment status, education level, household income, body mass index, comorbid medical conditions, years of hypertension, number of antihypertensive drugs prescribed, exercise status, and male sex were significant independent predictors of PCS. Fewer factors predicted MCS and included employment status, marital status, current smoking, age, comorbid medical conditions, and male sex. In the entire AASK cohort, mean scores for individual scales, except Mental Health, and the PCS were lower, but the mean MCS score was slightly higher than values for the US general population. Values for individual scales of the SF-36 and the PCS were substantially higher among AASK participants compared with African-American hemodialysis patients. Six of the eight scales were lower in the AASK cohort compared with groups of racially mixed and exclusively African-American hypertensive subjects. We conclude that physical aspects of quality of life are substantially reduced compared with mental components among AASK participants, and a number of demographic and clinical characteristics significantly impact on HRQL.