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Background: No study has compared cystatin C level, serum creatinine concentration, and estimated glomerular filtration rate (GFR) as risk factors for outcomes in chronic kidney disease (CKD), and none has compared measured GFR with CKD in any population. Objective: To compare cystatin C level with serum creatinine concentration and iothalamate GFR as risk factors for death and kidney failure. Design: Observational study using serum cystatin C assayed from baseline samples of the Modification of Diet in Renal Disease Study (1989-1993). Setting: 15 clinical centers in the United States that participated in the Modification of Diet in Renal Disease Study. Participants: 825 trial participants with stage 3 or 4 nondiabetic CKD who had measurements of serum cystatin C. Measurements: All-cause mortality, cardiovascular (CVD) mortality, and kidney failure until December 2000. Results: Mean cystatin C level, creatinine concentration, and GFR were 2.2 mg/L (SD, 0.7), 212.16 [micro]mol/L (SD, 88.4) (2.4 mg/dL [SD, 1.0]), and 33 mL/min per 1.73 [m.sup.2] (SD, 12), respectively. Median follow-up was 10 years. Twenty-five percent of patients (n = 203) died of any cause, 15% (n = 123) died of CVD, and 66% (n = 548) reached kidney failure. In multivariate-adjusted models, 1-SD decreases in 1/creatinine, GFR, and 1/cystatin C were associated with increased risks for all-cause mortality of 1.27 (95% Cl, 1.06 to 1.49), 1.27 (Cl, 1.08 to 1.49), and 1.41 (Cl, 1.18 to 1.67), respectively. For CVD mortality, the increased risks were 1.32 (Cl, 1.05 to 1.64), 1.28 (Cl, 1.04 to 1.59), and 1.64 (Cl, 1.28 to 2.08), respectively. For kidney failure, the increased risks were 2.81 (Cl, 2.48 to 3.18), 2.41 (Cl, 2.15 to 2.70), and 2.36 (Cl, 2.10 to 2.66), respectively. Limitation: The Modification of Diet in Renal Disease Study cohort may not be representative of all patients with nondiabetic CKD because participants were more likely to reach kidney failure than death in follow-up. Conclusion: The association of cystatin C level with all-cause and CVD mortality was as strong as or perhaps stronger than that of iothalamate GFR with these outcomes in stage 3 or 4 CKD.

Background Calcium supplementation has been shown to decrease the risk of recurrence of colorectal adenomas in randomized trials. However, the duration of this protective effect after cessation of active supplementation is not known. Methods In the Calcium Polyp Prevention Study, 930 subjects with a previous colorectal adenoma were randomly assigned from November 1988 through April 1992 to receive placebo or 1200 mg of elemental calcium daily for 4 years. The Calcium Follow-up Study was an observational phase of the trial that tracked adenoma occurrence for an average of 7 years after the end of randomized treatment and gathered information regarding the use of medications, vitamins, and supplements during that time. We obtained follow-up information for 822 subjects, 597 of whom underwent at least one colonoscopy after the end of study treatment and are included in this analysis. Generalized linear models were used to compute relative risks (RRs) and 95% confidence intervals (CIs) for the effect of randomized calcium treatment on risk of adenoma recurrence during the first 5 years after study treatment ended and during the subsequent 5 years. Statistical tests were two-sided. Results During the first 5 years after randomized treatment ended, subjects in the calcium group still had a substantially and statistically significantly lower risk of any adenoma than those in the placebo group (31.5% versus 43.2%; adjusted RR = 0.63, 95% CI = 0.46 to 0.87, P = .005) and a smaller and not statistically significant reduction in risk of advanced adenomas (adjusted RR = 0.85, 95% CI = 0.43 to 1.69, P = .65). However, the randomized treatment was not associated with the risk of any type of polyp during the next 5 years. The findings were broadly similar when the analysis was restricted to subjects who did not report use of any calcium supplements after the treatment phase of the trial ended. Conclusion The protective effect of calcium supplementation on risk of colorectal adenoma recurrence extends up to 5 years after cessation of active treatment, even in the absence of continued supplementation.

Background: In two large, randomized prevention trials, supplementation with [beta]-carotene increased the risk of lung cancer. Subjects in these studies were predominantly cigarette smokers, and the adverse effects were concentrated among those who also drank alcohol. Although [beta]-carotene supplementation appeared not to increase the risk of cancer generally, it is not clear if smoking and/or alcohol use alters the effect of [beta]-carotene on carcinogenesis at sites outside the lung. Methods: We studied the effect of [beta]-carotene supplementation on colorectal adenoma recurrence among subjects in a multicenter double-blind, placebo-controlled clinical trial of antioxidants for the prevention of colorectal adenomas. A total of 864 subjects who had had an adenoma removed and were polyp-free were randomly assigned (in a factorial design) to receive [beta]-carotene (25 mg or placebo) and/or vitamins C and E in combination (1000 mg and 400 mg, respectively, or placebo), and were followed with colonoscopy for adenoma recurrence 1 year and 4 years after the qualifying endoscopy. A total of 707 subjects had two follow-up examinations and provided smoking and alcohol use data. Adjusted multivariate risk ratios (RRs) and 95% confidence intervals (CIs) were used to assess the effects of [beta]-carotene on adenoma recurrence. Results: Among subjects who neither smoked cigarettes nor drank alcohol, [beta]-carotene was associated with a marked decrease in the risk of one or more recurrent adenomas (RR = 0.56, 95 % CI = 0.35 to 0.89), but [beta]-carotene supplementation conferred a modest increase in the risk of recurrence among those who smoked (RR = 1.36, 95% CI = 0.70 to 2.62) or drank (RR = 1.13, 95% CI = 0.89 to 1.43). For participants who smoked cigarettes and also drank more than one alcoholic drink per day, [beta]-carotene doubled the risk of adenoma recurrence (RR = 2.07, 95 % CI = 1.39 to 3.08; P for difference from nonsmoker/nondrinker RR < .001). Conclusion: Alcohol intake and cigarette smoking appear to modify the effect of [beta]-carotene supplementation on the risk of colorectal adenoma recurrence.