Derivation and validation of a clinical index for prediction of rapid progression of kidney dysfunction.

BACKGROUND: Chronic kidney disease is common among the elderly, and these patients are at risk of progressive kidney dysfunction. AIM: To develop an index to predict rapid progression of kidney dysfunction. DESIGN: Community-based cohort divided into derivation (n = 6789) and validation (n = 3395) subsets. METHODS: We identified 10 184 subjects aged >/=66 years from computerized laboratory data. Prescription drug data was used to define disease categories and medication exposure, and an index for predicting rapid progression of kidney dysfunction (> or =25% decline in glomerular filtration rate over a 2-year period) was obtained from a logistic regression model in the derivation cohort. The risk score for each subject was calculated by summing the component variables together, which were subsequently categorized into five risk classes. RESULTS: Five predictors of rapid progression were identified: age >75 years, cardiac disease, diabetes mellitus, gout, and use of anti-emetic medications. Rates of rapid progression for risk classes I through V were 8.6%, 10.9%, 13.9%, 15.6%, and 24.1%, respectively, for the derivation cohort, and 8.4%, 11.6%, 15.5%, 17.3%, 21.9%, respectively, for the validation cohort. The risk index distinguished between low and high risk of rapid progression, with a 2.5-fold greater risk for the highest, compared to the lowest, risk decile. DISCUSSION: Readily available clinical data can be used to identify most elderly at risk of rapid progression of kidney dysfunction. This simple index could help clinicians to identify patients at risk, and implement strategies to slow the progression of kidney dysfunction.

Progression of kidney dysfunction in the community-dwelling elderly.

Despite the high prevalence of chronic kidney disease among the elderly, few studies have described their loss of kidney function. We sought to determine the progression of kidney dysfunction among a community-based cohort of elderly subjects. The cohort included 10 184 subjects 66 years of age or older, who had one or more outpatient serum creatinine measurements during each of two time periods: 1 July to 31 December 2001 and 1 July to 31 December 2003. A mixed effects model, including covariates for age, gender, diabetes mellitus, and comorbidity, was used to determine the rate of decline in estimated glomerular filtration rate (eGFR, in ml/min/1.73 m2) per year over a median follow-up of 2.0 years. Subjects with diabetes mellitus had the greatest decline in eGFR of 2.1 (95% CI 1.8-2.5) and 2.7 (95% CI 2.3-3.1) ml/min/1.73 m2 per year in women and men, respectively. The rate of decline for women and men without diabetes mellitus was 0.8 (95% CI 0.6-1.0) and 1.4 (95% CI 1.2-1.6) ml/min/1.73 m2 per year. Subjects with a study mean eGFR<30 ml/min/1.73 m2, both those with and without diabetes mellitus, experienced the greatest decline in eGFR. In conclusion, we found that the majority of elderly subjects have no or minimal progression of kidney disease over 2 years. Strategies aimed at slowing progression of kidney disease should consider underlying risk factors for progression and the negligible loss of kidney function that occurs in the majority of older adults.

Contrast-induced nephropathy: epidemiology and prevention.

Contrast-induced nephropathy (CIN) is a leading cause of iatrogenic acute kidney failure. Periprocedural CIN results in a greater risk of requiring renal replacement therapy, prolonged hospitalization, excessive health care costs, potential long term kidney impairment and mortality. Identified risk factors for CIN include premorbid chronic kidney disease, diabetes mellitus, congestive heart failure, critical illness and volume of administered contrast media. Prophylactic interventions for the prevention of CIN remain controversial and uncertain. In this review we critically appraise the evidence for prevention of CIN. In general, every attempt should be made to correct underlying volume depletion, discontinue potential nephrotoxins, reverse any acute kidney dysfunction or when not possible, consider delay of procedure or an alternative modality for imaging. A minimum volume of contrast media should be employed, including going left ventriculogram and performing staged procedures if applicable. There are few interventions with quality evidence for reducing the incidence of CIN. procedure hydration and the use of nonionic iso-osmolar contrast media have consistently demonstrated efficacy. For patients at high risk, there is evidence to suggest benefit with N-acetylcysteine. Clinical studies with adenosine antagonists are encouraging; however, further confirmatory trials are required. Based on the available studies, there is inadequate evidence for the routine use of hemofiltration, atrial natriuretic peptides, calcium channel blockers, or prostaglandins. There is no evidence to support prophylaxis with diuretic therapy, forced diuresis, low dose dopamine, fenoldopam, captopril, or endothelin receptor antagonists. Despite recent advances in the epidemiology, pathophysiology and natural history of CIN, few effective prophylactic or therapeutic interventions have conclusively demonstrated evidence for a reduction in CIN incidence and no therapy has proven efficacious once CIN is established.

Uric acid and cardiovascular disease: a renal-cardiac relationship?

Elevated serum uric acid is a frequent finding in patients with kidney disease and cardiovascular disease. Intrarenal ischaemia, induced by hypertension, increased sympathetic nervous system activity, and hyperinsulinaemia have all been implicated in reduced renal clearance of urate. This frequently results in elevated serum uric acid levels. The association of hyperuricaemia with cardiovascular disease remains controversial. Current evidence suggests that serum uric acid may provide additional prognostic information in patients with essential hypertension. However, there has been no test of the hypothesis that a reduction in serum uric acid would prevent cardiovascular disease. Furthermore, a critical review of the current literature does not support a causal role of serum uric acid in the development of cardiovascular disease. Serum uric acid probably reflects and integrates different risk factors and their possible interactions.

Proteinuria as a risk factor for cardiovascular disease and mortality in older people: a prospective study.

BACKGROUND: The prognostic significance of proteinuria in older people is not well defined. We examined the associations between proteinuria and incident coronary heart disease, cardiovascular mortality, and all-cause mortality in older people. SUBJECTS AND METHODS: Casual dipstick proteinuria was determined in 1,045 men (mean [+/- SD] age 68 +/- 7 years) and 1,541 women (mean age 69 +/- 7 years) attending the 15th biennial examination of the Framingham Heart Study. Participants were divided by grade of proteinuria: none (85.3%), trace (10.2%), and greater-than-trace (4.5%). Cox proportional hazards analyses were used to determine the relations of baseline proteinuria to the specified outcomes, adjusting for other risk factors, including serum creatinine level. RESULTS: During 17 years of follow-up, there were 455 coronary heart disease events, 412 cardiovascular disease deaths, and 1,214 deaths. In men, baseline proteinuria was associated with all-cause mortality (hazards ratio [HR] = 1.3, 95% confidence interval [CI] 1.0 to 1.7 for trace proteinuria; HR = 1.3, 95% CI 1.0 to 1.8 for greater-than-trace proteinuria; P for trend = 0.02). In women, trace proteinuria was associated with cardiovascular disease death (HR = 1. 6, 95% CI 1.1 to 2.4), and all-cause mortality (HR = 1.4, 95% CI 1.1 to 1.7). CONCLUSION: Proteinuria is a significant, although relatively weak, risk factor for all-cause mortality in men and women, and for cardiovascular disease mortality in women.

Cardiovascular disease and mortality in a community-based cohort with mild renal insufficiency.

UNLABELLED: Cardiovascular disease and mortality in a community-based cohort with mild renal insufficiency. BACKGROUND: Little is known about the prevalence of cardiovascular disease (CVD) and associated risk factors in individuals with mild renal insufficiency (RI). Furthermore, the long-term outcomes associated with mild RI in the community have not been described. METHODS: Serum creatinine (SCr) was measured in 6233 adult participants of the Framingham Heart Study (mean age 54 years, 54% women). Mild RI was defined as SCr 136 to 265 micromol/liter (1.5 to 3.0 mg/dl) in men and 120 to 265 micromol/liter (1.4 to 3.0 mg/dl) in women. The lower limits for mild RI were defined by the sex-specific 95th percentile SCr values in a healthy subgroup of our sample. The upper limit for mild RI was chosen to exclude those subjects with more advanced renal failure. Cox proportional hazards analyses were used to determine the relationship of baseline RI to CVD and all-cause mortality. RESULTS: At baseline, 8.7% of men (N = 246) and 8.0% of women (N = 270) had mild RI. Nineteen percent of the subjects with mild RI had prevalent CVD. During 15 years of follow-up, there were 1000 CVD events and 1406 deaths. In women, mild RI was not associated with increased risk for CVD events [hazards ratio (HR) 1.04, 95% CI, 0.79 to 1.37] or all-cause mortality (HR 1.08, 95% CI, 0.87 to 1.34). In men, mild RI showed no significant associations with CVD events (HR 1.17, 95% CI, 0.88 to 1.57), but it was associated with all-cause mortality in age-adjusted (HR 1.42, 95% CI, 1.12 to 1.79) and multivariable adjusted (HR 1.31, 95% CI, 1.02 to 1.67) analyses. CONCLUSION: Mild RI in the community is common and is associated with a high prevalence of CVD. The association of RI with risk for adverse outcomes is strongly related to coexisting CVD and CVD risk factors.

Prevalence and correlates of elevated serum creatinine levels: the Framingham Heart Study.

BACKGROUND: Elevated serum creatinine (SCr) levels are a predictor of end-stage renal disease, but little is known about the prevalence of elevated SCr levels and their correlates in the community. METHODS: In this cross-sectional, community-based sample, SCr levels were measured in 6233 adults (mean age, 54 years; 54% women) who composed the "broad sample" of this investigation. A subset, consisting of 3241 individuals who were free of known renal disease, cardiovascular disease, hypertension, and diabetes, constituted the healthy reference sample. In this latter sample, sex-specific 95th percentiles for SCr levels (men, 136 micromol/L [1.5 mg/dL]; women, 120 micromol/L [1.4 mg/dL]) were labeled cutpoints. These cutpoints were applied to the broad sample in a logistic regression model to identify prevalence and correlates of elevated SCr levels. RESULTS: The prevalence of elevated SCr levels was 8.9% in men and 8.0% in women. Logistic regression in men identified age, treatment for hypertension (odds ratio [OR], 1.75; 95% confidence interval [CI], 1.27-2.42), and body mass index (OR, 1.08; 95% CI, 1.01-1.15) as correlates of elevated SCr levels. Additionally, men with diabetes who were receiving antihypertensive medication were more likely to have raised SCr values (OR, 2.94; 95% CI, 1.60-5.39). In women, age, use of cardiac medications (OR, 1.58; 95% CI, 1.10-2.96), and treatment for hypertension (OR, 1.42; 95% CI, 1.07-1.87) were associated with elevated SCr levels. CONCLUSIONS: Elevated SCr levels are common in the community and are strongly associated with older age, treatment for hypertension, and diabetes. Longitudinal studies are warranted to determine the clinical outcomes of individuals with elevated levels of SCr and to examine factors related to the progression of renal disease in the community.

Serum uric acid and risk for cardiovascular disease and death: the Framingham Heart Study.

BACKGROUND: Hyperuricemia is associated with risk for cardiovascular disease and death. However, the role of uric acid independent of established risk factors is uncertain. OBJECTIVE: To examine the relation of serum uric acid level to incident coronary heart disease, death from cardiovascular disease, and death from all causes. DESIGN: Community-based, prospective observational study. SETTING: Framingham, Massachusetts. PATIENTS: 6763 Framingham Heart Study participants (mean age, 47 years). MEASUREMENTS: Serum uricacid level at baseline (1971 to 1976); event rates per 1000 person-years by sex-specific uric acid quintile. RESULTS: During 117,376 person-years of follow-up, 617 coronary heart disease events, 429 cardiovascular disease deaths, and 1460 deaths from all causes occurred. In men, after adjustment for age, elevated serum uric acid level was not associated with increased risk for an adverse outcome. In women, after adjustment for age, uric acid level was predictive of coronary heart disease (P = 0.002), death from cardiovascular disease (P = 0.009), and death from all causes (P = 0.03). After additional adjustment for cardiovascular disease risk factors, uric acid level was no longer associated with coronary heart disease, death from cardiovascular disease, or death from all causes. In a stepwise Cox model, diuretic use was identified as the covariate responsible for rendering serum uric acid a statistically nonsignificant predictor of outcomes. CONCLUSIONS: These findings indicate that uric acid does not have a causal role in the development of coronary heart disease, death from cardiovascular disease, or death from all causes. Any apparent association with these outcomes is probably due to the association of uric acid level with other risk factors.

Epidemiology of cardiovascular disease in the United States.

A brief review of cardiovascular disease incidence and risk factors for coronary heart disease and cardiac failure is presented. The emphasis is placed on evidence from large scale prospective studies, and the pertinent US guidelines and recommendations for care are provided. Key risk factors are considered, including lipids, blood pressure, smoking, and diabetes mellitus. Additional information is also given concerning the role of vitamins, homocysteine metabolism, and left ventricular hypertrophy. This review focuses on commonly accepted risk factors that are of particular interest to health professionals.

Cardiovascular disease: risk factors, secular trends, and therapeutic guidelines.

A brief review of cardiovascular disease incidence and risk factors for coronary heart disease and cardiac failure is presented. Secular trends in cardiovascular disease risk factors, morbidity, and mortality are a major focus. Declines in cardiovascular disease mortality over the past 30 yr, a more modest decline in coronary heart disease, and an increase in cardiac failure are demonstrated. Emphasis is placed on evidence from large-scale, prospective, observational and interventional studies, and the pertinent U.S. guidelines and recommendations for care are provided. Consideration is given to the major risk factors, including lipids, blood pressure, smoking, and diabetes mellitus. Additional information is also given concerning the role of vitamins, homocysteine metabolism, and left ventricular hypertrophy. Although this review focuses on commonly accepted risk factors in the general population, where appropriate, specific information that is relevant to patients with chronic renal disease is provided.

Cardiac disease in diabetic end-stage renal disease.

Little is known about the epidemiology of cardiac disease in diabetic end-stage renal disease. We therefore prospectively followed a cohort of 433 patients who survived 6 months after the inception of dialysis therapy for an average of 41 months. Clinical and echocardiographic data were collected yearly. At baseline, diabetic patients (n = 116) had more echocardiographic concentric left ventricular hypertrophy (50 vs 38%, p = 0.04), clinically diagnosed ischaemic heart disease (32 vs 18%, p = 0.003) and cardiac failure (48 vs 24%, p < 0.00001) than non-diabetic patients (n = 317). After adjusting for age and sex, diabetic patients had similar rates of progression of echocardiographic disorders, and de novo cardiac failure, but higher rates of de novo clinically diagnosed ischaemic heart disease (RR 3.2, p = 0.0002), overall mortality (RR 2.3, p < 0.0001) and cardiovascular mortality (RR 2.6, p < 0.0001) than non-diabetic patients. Mortality was higher in diabetic patients following admission for clinically diagnosed ischaemic heart disease (RR 1.7, p = 0.05) and cardiac failure (RR 2.2, p = 0.0003). Among diabetic patients older age, left ventricular hypertrophy, smoking, clinically diagnosed ischaemic heart disease, cardiac failure and hypoalbuminaemia were independently associated with mortality. The excessive cardiac morbidity and mortality of diabetic patients seem to be mediated via ischaemic disease, rather than progression of cardiomyopathy while on dialysis therapy. Potentially remediable risk factors include smoking, left ventricular hypertrophy, and hypoalbuminaemia.