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Background and Objectives: The microvascular circulation plays an important role in bone health. This study examines whether albuminuria, a marker of renal microvascular disease, is associated with incident hip and pelvic fractures., Design, Setting, Participants, & Measurements: This study reanalyzed data from the Ongoing Telmisartan Alone and in combination with Ramipril Global End Point Trial/Telmisartan Randomized Assessment Study in Angiotensin-Converting Enzyme Intolerant Subjects with Cardiovascular Disease trials, which examined the impact of renin angiotensin system blockade on cardiovascular outcomes (n=28,601). Albuminuria was defined as an albumin-to-creatinine ratio≥30 mg/g (n=4597). Cox proportional hazards models were used to determine the association of albuminuria with fracture risk adjusted for known risk factors for fractures, estimated GFR, and rapid decline in estimated GFR (≥5%/yr)., Results: There were 276 hip and pelvic fractures during a mean of 4.6 years of follow-up. Participants with baseline albuminuria had a significantly increased risk of fracture compared with participants without albuminuria (unadjusted hazard ratio=1.62 [1.22, 2.15], P<0.001; adjusted hazard ratio=1.36 [1.01, 1.84], P=0.05). A dose-dependent relationship was observed, with macroalbuminuria having a large fracture risk (unadjusted hazard ratio=2.01 [1.21, 3.35], P=0.007; adjusted hazard ratio=1.71 [1.007, 2.91], P=0.05) and microalbuminuria associating with borderline or no statistical significance (unadjusted hazard ratio=1.52 [1.10, 2.09], P=0.01; adjusted hazard ratio=1.28 [0.92, 1.78], P=0.15). Estimated GFR was not a predictor of fracture in any model, but rapid loss of estimated GFR over the first 2 years of follow-up predicted subsequent fracture (adjusted hazard ratio=1.47 [1.05, 2.04], P=0.02)., Conclusions: Albuminuria, especially macroalbuminuria, and rapid decline of estimated GFR predict hip and pelvic fractures. These findings support a theoretical model of a relationship between underlying causes of microalbuminuria and bone disease.

Background: A recent clinical trial showed harmful renal effects with the combined use of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin-II receptor blockers (ARB) in people with diabetes or vascular disease. We examined the benefits and risks of these agents in people with albuminuria and one or more cardiovascular risk factors., Methods: MEDLINE, EMBASE and Renal Health Library were searched for trials comparing ACEI, ARB or their combination with placebo or with one another in people with albuminuria and one or more cardiovascular risk factor., Results: Eighty-five trials (21,708 patients) were included. There was no significant reduction in the risk of all-cause mortality or fatal cardiac-cerebrovascular outcomes with ACEI versus placebo, ARB versus placebo, ACEI versus ARB or with combined therapy with ACEI + ARB versus monotherapy. There was a significant reduction in the risk of nonfatal cardiovascular events with ACEI versus placebo but not with ARB versus placebo, ACEI versus ARB or with combined therapy with ACEI + ARB versus monotherapy. Development of end-stage kidney disease and progression of microalbuminuria to macroalbuminuria were reduced significantly with ACEI versus placebo and ARB versus placebo but not with combined therapy with ACEI + ARB versus monotherapy., Conclusions: ACEI and ARB exert independent renal and nonfatal cardiovascular benefits while their effects on mortality and fatal cardiovascular disease are uncertain. There is a lack of evidence to support the use of combination therapy. A comparative clinical trial with ACE, ARB and its combination in people with albuminuria and a cardiovascular risk factor is warranted.

The degree of albuminuria predicts cardiovascular and renal outcomes, but it is not known whether changes in albuminuria also predict similar outcomes. In two multicenter, multinational, prospective observational studies, a central laboratory measured albuminuria in 23,480 patients with vascular disease or high-risk diabetes. We quantified the association between a greater than or equal to twofold change in albuminuria in spot urine from baseline to 2 years and the incidence of cardiovascular and renal outcomes and all-cause mortality during the subsequent 32 months. A greater than or equal to twofold increase in albuminuria from baseline to 2 years, observed in 28%, associated with nearly 50% higher mortality (HR 1.48; 95% CI 1.32 to 1.66), and a greater than or equal to twofold decrease in albuminuria, observed in 21%, associated with 15% lower mortality (HR 0.85; 95% CI 0.74 to 0.98) compared with those with lesser changes in albuminuria, after adjustment for baseline albuminuria, BP, and other potential confounders. Increases in albuminuria also significantly associated with cardiovascular death, composite cardiovascular outcomes (cardiovascular death, myocardial infarction, stroke, and hospitalization for heart failure), and renal outcomes including dialysis or doubling of serum creatinine (adjusted HR 1.40; 95% CI 1.11 to 1.78). In conclusion, in patients with vascular disease, changes in albuminuria predict mortality and cardiovascular and renal outcomes, independent of baseline albuminuria. This suggests that monitoring albuminuria is a useful strategy to help predict cardiovascular risk., (Copyright © 2011 by the American Society of Nephrology)

Screening for chronic kidney disease is recommended in people at high risk, but data on the independent and combined associations of estimated glomerular filtration rate (eGFR) and albuminuria with all-cause and cardiovascular mortality are limited. To clarify this, we performed a collaborative meta-analysis of 10 cohorts with 266,975 patients selected because of increased risk for chronic kidney disease, defined as a history of hypertension, diabetes, or cardiovascular disease. Risk for all-cause mortality was not associated with eGFR between 60-105 ml/min per 1.73 m², but increased at lower levels. Hazard ratios at eGFRs of 60, 45, and 15 ml/min per 1.73 m² were 1.03, 1.38 and 3.11, respectively, compared to an eGFR of 95, after adjustment for albuminuria and cardiovascular risk factors. Log albuminuria was linearly associated with log risk for all-cause mortality without thresholds. Adjusted hazard ratios at albumin-to-creatinine ratios of 10, 30 and 300 mg/g were 1.08, 1.38, and 2.16, respectively compared to a ratio of five. Albuminuria and eGFR were multiplicatively associated with all-cause mortality, without evidence for interaction. Similar associations were observed for cardiovascular mortality. Findings in cohorts with dipstick data were generally comparable to those in cohorts measuring albumin-to-creatinine ratios. Thus, lower eGFR and higher albuminuria are risk factors for all-cause and cardiovascular mortality in high-risk populations, independent of each other and of cardiovascular risk factors.

Background: Glomerular filtration rate and albuminuria are risk factors for cardiovascular disease and markers of renal function., Objective: To examine the contribution of estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio beyond that of traditional cardiovascular risk factors to classification of patient risk for cardiovascular and renal outcomes., Design: Prospective cohort study that pooled all patients of ONTARGET (ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial) and TRANSCEND (Telmisartan Randomized Assessment Study in Angiotensin-Converting-Enzyme-Inhibitor Intolerant Subjects with Cardiovascular Disease)., Patients: 27,620 patients older than 55 years with documented cardiovascular disease, who were followed for a mean of 4.6 years., Measurements: Baseline eGFR, urinary albumin-creatinine ratio, and cardiovascular risk factors. Outcomes were all-cause mortality; a composite of cardiovascular death, myocardial infarction, stroke, and hospitalization for heart failure; long-term dialysis; and a composite of long-term dialysis and doubling of serum creatinine level., Results: Lower eGFRs and higher urinary albumin-creatinine ratios were associated with the primary cardiovascular composite outcome (for example, an adjusted hazard ratio of 2.53 [95% CI, 1.61 to 3.99] for an eGFR <30 mL/min per 1.73 m(2) and a very high urinary albumin-creatinine ratio). However, adding information about eGFR and urinary albumin-creatinine ratio to the risk reclassification analyses led to no meaningful decrease in the proportion of patients assigned to the intermediate-risk category (31% without vs. 32% with renal information). In contrast, eGFR and urinary albumin-creatinine ratio were strongly associated with risk for long-term dialysis and greatly improved both model calibration and risk stratification capacity when added to traditional cardiovascular risk factors (65% assigned to intermediate-risk categories without renal information vs. 18% with renal information)., Limitation: Creatinine levels were not standardized., Conclusion: In patients with high vascular risk, eGFR and urinary albumin-creatinine ratio add little to traditional cardiovascular risk factors for stratifying cardiovascular risk but greatly improve risk stratification for renal outcomes., Primary Funding Source: Boehringer Ingelheim, Population Health Research Institute, and the European Commission.

Background: Microvascular disease of the kidney (manifesting as albuminuria) and of the brain (manifesting as cognitive decline) may share a common pathogenesis. Gaining an understanding of the concomitant history of these 2 conditions may inform clinical practice and lead to novel prevention and treatment approaches., Methods: A total of 28 384 participants with vascular disease or diabetes mellitus were examined. At baseline and year 5, participants underwent a Mini-Mental State Examination (MMSE) and urine testing for albumin excretion. Multivariable logistic regression was used to determine the association between albumin excretion and MMSE score, cross-sectionally and prospectively, and whether angiotensin-converting enzyme inhibitor and/or angiotensin receptor blocker use modified the association., Results: Compared with participants with normoalbuminuria, those with microalbuminuria (odds ratio [OR], 1.26; 95% confidence interval [CI], 1.11-1.44]) and macroalbuminuria (1.49; 1.20-1.85) were more likely to have a reduced MMSE score (<24). On follow-up, participants with baseline albuminuria had increased odds of cognitive decline (decrease in MMSE score ≥3 points) compared with those with normoalbuminuria (microalbuminuria: OR, 1.22; 95% CI, 1.07-1.38; macroalbuminuria: 1.21; 0.94-1.55). Participants who developed new albuminuria had increased odds of cognitive decline during follow-up compared with those who remained normoalbuminuric (new microalbuminuria: OR, 1.30; 95% CI, 1.12-1.52; new macroalbuminuria: 1.77; 1.24-2.54). Participants with baseline macroalbuminuria treated with an angiotensin-converting enzyme inhibitor and/or angiotensin receptor blocker had lower odds of MMSE decline than participants treated with placebo., Conclusion: Factors that contribute to albuminuria may contribute to cognitive decline, supporting the notion that both conditions share a common microvascular pathogenesis. Trial Registration clinicaltrials.gov Identifier: NCT00153101.

This observational study examined the association between modifiable lifestyle and social factors on the incidence and progression of early chronic kidney disease (CKD) among those with type 2 diabetes. All 6972 people from the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) with diabetes but without macroalbuminuria were studied. CKD progression was defined as decline in GFR of more than 5% per year, progression to end-stage renal disease, microalbuminuria, or macroalbuminuria at 5.5 years. Lifestyle/social factors included tobacco and alcohol use, physical activity, stress, financial worries, the size of the social network and education. Adjustments were made for known risks such as age, diabetes duration, GFR, albuminuria, gender, body mass index, blood pressure, fasting plasma glucose, and angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers use. Competing risk of death was considered. At study end, 31% developed CKD and 15% had died. The social network score (SNS) was a significant independent risk factor of CKD and death, reducing the risk by 11 and 22% when comparing the third to the first tertile of the SNS (odds ratios of CKD 0.89 and death 0.78). Education showed a significant association with CKD but stress and financial worries did not. Those with moderate alcohol consumption had a significantly decreased CKD risk compared with nonusers. Regular physical activity significantly decreased the risk of CKD. Thus, lifestyle is a determinant of kidney health in people at high cardiovascular risk with diabetes. [ABSTRACT FROM AUTHOR]