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Albuminuria and kidney function independently predict cardiovascular and renal outcomes in diabetes.

ABSTRACT: There are limited data regarding whether albuminuria and reduced estimated GFR (eGFR) are separate and independent risk factors for cardiovascular and renal events among individuals with type 2 diabetes. The Action in Diabetes and Vascular disease: preterAx and diamicroN-MR Controlled Evaluation (ADVANCE) study examined the effects of routine BP lowering on adverse outcomes in type 2 diabetes. We investigated the effects of urinary albumin-to-creatinine ratio (UACR) and eGFR on the risk for cardiovascular and renal events in 10,640 patients with available data. During an average 4.3-yr follow-up, 938 (8.8%) patients experienced a cardiovascular event and 107 (1.0%) experienced a renal event. The multivariable-adjusted hazard ratio for cardiovascular events was 2.48 (95% confidence interval 1.74 to 3.52) for every 10-fold increase in baseline UACR and 2.20 (95% confidence interval 1.09 to 4.43) for every halving of baseline eGFR, after adjustment for regression dilution. There was no evidence of interaction between the effects of higher UACR and lower eGFR. Patients with both UACR >300 mg/g and eGFR <60 ml/min per 1.73 m(2) at baseline had a 3.2-fold higher risk for cardiovascular events and a 22.2-fold higher risk for renal events, compared with patients with neither of these risk factors. In conclusion, high albuminuria and low eGFR are independent risk factors for cardiovascular and renal events among patients with type 2 diabetes.

SUBMITTER: Ninomiya T

PROVIDER: S-EPMC2723977 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature

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Albuminuria and kidney function independently predict cardiovascular and renal outcomes in diabetes.

Ninomiya Toshiharu T Perkovic Vlado V de Galan Bastiaan E BE Zoungas Sophia S Pillai Avinesh A Jardine Meg M Patel Anushka A Cass Alan A Neal Bruce B Poulter Neil N Mogensen Carl-Erik CE Cooper Mark M Marre Michel M Williams Bryan B Hamet Pavel P Mancia Giuseppe G Woodward Mark M Macmahon Stephen S Chalmers John J

Journal of the American Society of Nephrology : JASN 20090514 8

There are limited data regarding whether albuminuria and reduced estimated GFR (eGFR) are separate and independent risk factors for cardiovascular and renal events among individuals with type 2 diabetes. The Action in Diabetes and Vascular disease: preterAx and diamicroN-MR Controlled Evaluation (ADVANCE) study examined the effects of routine BP lowering on adverse outcomes in type 2 diabetes. We investigated the effects of urinary albumin-to-creatinine ratio (UACR) and eGFR on the risk for card ...[more]

PMID: 19443635

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Project description:Background and objectivesIn trials of people with type 2 diabetes, albuminuria reduction with renin-angiotensin system inhibitors is associated with lower risks of cardiovascular events and CKD progression. We tested whether progression or remission of microalbuminuria is associated with cardiovascular and renal risk in a well characterized cohort of type 1 diabetes.Design, setting, participants, & measurementsWe studied 1441 participants in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications study. Albumin excretion rate (AER) was quantified annually or biennially for up to 30 years. For each participant, albuminuria status was defined over time as normoalbuminuria (AER continuously <30 mg/d), sustained microalbuminuria (AER, 30-299 mg/d on two consecutive visits), macroalbuminuria (AER≥300 mg/d), or remitted microalbuminuria (transition from sustained microalbuminuria to AER<30 mg/d on two consecutive visits). We tested associations of time-updated albuminuria status with adjudicated clinical cardiovascular events, the development of reduced GFR (<60 ml/min per 1.73 m2 on two consecutive visits), and subclinical cardiovascular disease.ResultsAt least one cardiovascular event occurred in 184 participants, and 98 participants developed reduced eGFR. Compared with normoalbuminuria, sustained microalbuminuria, remitted microalbuminuria, and macroalbuminuria were each associated with higher risk of cardiovascular events (adjusted hazard ratios [HRs] and 95% confidence intervals [95% CIs]: 1.79 [1.13 to 2.85], 2.62 [1.68 to 4.07], and 2.65 [1.68 to 4.19], respectively) and reduced eGFR (adjusted HRs [95% CIs], 5.26 [2.43 to 11.41], 4.36 [1.80 to 10.57], and 54.35 [30.79 to 95.94], respectively). Compared with sustained microalbuminuria, remission to normoalbuminuria was not associated with reduced risk of cardiovascular events (adjusted HR, 1.33; 95% CI, 0.68 to 2.59) or reduced eGFR (adjusted HR, 1.75; 95% CI, 0.56 to 5.49). Compared with normoalbuminuria, sustained microalbuminuria, remitted microalbuminuria, and macroalbuminuria were associated with greater carotid intima-media thickness, and macroalbuminuria was associated with a greater degree of coronary artery calcification.ConclusionsIn type 1 diabetes, microalbuminuria and macroalbuminuria are associated with higher risks of cardiovascular disease and reduced eGFR, but achieving a remission of established microalbuminuria to normoalbuminuria does not appear to improve outcomes.

Project description:BACKGROUND:Canagliflozin is approved for glucose lowering in type 2 diabetes and confers cardiovascular and renal benefits. We sought to assess whether it had benefits in people with chronic kidney disease, including those with an estimated glomerular filtration rate (eGFR) between 30 and 45 mL/min/1.73 m2 in whom the drug is not currently approved for use. METHODS:The CANVAS Program randomized 10 142 participants with type 2 diabetes and eGFR >30 mL/min/1.73 m2 to canagliflozin or placebo. The primary outcome was a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke, with other cardiovascular, renal, and safety outcomes. This secondary analysis describes outcomes in participants with and without chronic kidney disease, defined as eGFR <60 and ?60 mL/min/1.73 m2, and according to baseline kidney function (eGFR <45, 45 to <60, 60 to <90, and ?90 mL/min/1.73 m2). RESULTS:At baseline, 2039 (20.1%) participants had an eGFR <60 mL/min/1.73 m2, 71.6% of whom had a history of cardiovascular disease. The effect of canagliflozin on the primary outcome was similar in people with chronic kidney disease (hazard ratio, 0.70; 95% CI, 0.55-0.90) and those with preserved kidney function (hazard ratio, 0.92; 95% CI, 0.79-1.07; P heterogeneity = 0.08). Relative effects on most cardiovascular and renal outcomes were similar across eGFR subgroups, with possible heterogeneity suggested only for the outcome of fatal/nonfatal stroke ( P heterogeneity = 0.01), as were results for almost all safety outcomes. CONCLUSIONS:The effects of canagliflozin on cardiovascular and renal outcomes were not modified by baseline level of kidney function in people with type 2 diabetes and a history or high risk of cardiovascular disease down to eGFR levels of 30 mL/min/1.73 m2. Reassessing current limitations on the use of canagliflozin in chronic kidney disease may allow additional individuals to benefit from this therapy. CLINICAL TRIAL REGISTRATION:URL: https://www.clinicaltrials.gov . Unique identifiers: NCT01032629, NCT01989754.

Project description:Aims/hypothesisIn previous work, we reported the HR for the risk (95% CI) of the secondary kidney composite endpoint (time to first event of doubling of serum creatinine from baseline, renal dialysis/transplant or renal death) with ertugliflozin compared with placebo as 0.81 (0.63, 1.04). The effect of ertugliflozin on exploratory kidney-related outcomes was evaluated using data from the eValuation of ERTugliflozin effIcacy and Safety CardioVascular outcomes (VERTIS CV) trial (NCT01986881).MethodsIndividuals with type 2 diabetes mellitus and established atherosclerotic CVD were randomised to receive ertugliflozin 5 mg or 15 mg (observations from both doses were pooled), or matching placebo, added on to existing treatment. The kidney composite outcome in VERTIS CV (reported previously) was time to first event of doubling of serum creatinine from baseline, renal dialysis/transplant or renal death. The pre-specified exploratory composite outcome replaced doubling of serum creatinine with sustained 40% decrease from baseline in eGFR. In addition, the impact of ertugliflozin on urinary albumin/creatinine ratio (UACR) and eGFR over time was assessed.ResultsA total of 8246 individuals were randomised and followed for a mean of 3.5 years. The exploratory kidney composite outcome of sustained 40% reduction from baseline in eGFR, chronic kidney dialysis/transplant or renal death occurred at a lower event rate (events per 1000 person-years) in the ertugliflozin group than with the placebo group (6.0 vs 9.0); the HR (95% CI) was 0.66 (0.50, 0.88). At 60 months, in the ertugliflozin group, placebo-corrected changes from baseline (95% CIs) in UACR and eGFR were -16.2% (-23.9, -7.6) and 2.6 ml min-1 [1.73 m]-2 (1.5, 3.6), respectively. Ertugliflozin was associated with a consistent decrease in UACR and attenuation of eGFR decline across subgroups, with a suggested larger effect observed in the macroalbuminuria and Kidney Disease: Improving Global Outcomes in Chronic Kidney Disease (KDIGO CKD) high/very high-risk subgroups.Conclusions/interpretationAmong individuals with type 2 diabetes and atherosclerotic CVD, ertugliflozin reduced the risk for the pre-specified exploratory composite renal endpoint and was associated with preservation of eGFR and reduced UACR.Trial registrationClinicalTrials.gov NCT01986881.

Project description:Background and objectivesDiabetes mellitus is associated with increased risk of cognitive impairment. This study examines whether microvascular disease, as measured by albuminuria and decline in estimated GFR (eGFR), is associated with cognitive decline during 3.3 years of follow-up in individuals with diabetes with a normal baseline eGFR (approximately 90 ml/min per 1.73 m(2)).Design, setting, participants, & measurementsParticipants were from the Action to Control Cardiovascular Risk in Diabetes Memory in Diabetes study (N=2977; mean age 62.5 ± 5.8 years; recruitment from August 2003 to December 2005, followed through June 2009), which examined the association of intensive versus standard glucose control on cognitive function. Participants underwent three neuropsychologic tests at baseline, 20 months, and 40 months. Tests included information processing speed, verbal memory, and executive function. Mixed-effects models were used to assess the association of albuminuria and eGFR on the percentage decline in each test.ResultsParticipants with albuminuria at baseline and follow-up (persistent albuminuria) (-5.8% [95% confidence interval (CI), -7.3 to -4.2]) and participants with albuminuria at follow-up but none at baseline (progressive albuminuria) (-4.1% [95% CI, -5.6 to -2.7]) had greater percentage declines on information processing speed than participants without albuminuria at baseline and at follow-up (no albuminuria) (-2.6% [95% CI, -3.4 to -1.9]) (P=0.001 and P=0.10, respectively). There were borderline percentage changes in the test of verbal memory (4.8% [95% CI, 2.4 to 7.1] and 4.7% [95% CI, 2.5 to 7.0] versus 7.1% [95% CI, 6.0 to 8.3]; P=0.11 and P=0.08, respectively). On logistic regression analysis, persistent albuminuria (odds ratio, 1.37 [95% CI, 1.09 to 1.72]) and progressive albuminuria (odds ratio, 1.25 [95% CI, 1.02 to 1.56]) were associated with a ≥ 5% decline in information processing speed scores but not with verbal memory or executive function performance. A 1 ml/min per 1.73 m(2) per year eGFR decline had a borderline association with decline in tests of cognitive function.ConclusionsPersistent albuminuria and progressive albuminuria are associated with a decline in cognitive function in relatively young individuals with diabetes with unimpaired eGFR. These findings do not rule out the possibility of other processes causing cognitive decline.

Project description:Aims/hypothesisBoth manifestations of kidney disease in diabetes, reduced eGFR (ml/min per 1.73 m2) and increased urinary albumin/creatinine ratio (UACR, mg/mmol), may increase the risk of specific CVD subtypes in adults with diabetes.MethodsWe assessed the prospective association between annually recorded measures of eGFR and UACR and the occurrence of myocardial infarction (MI), CHD, stroke, heart failure (HF) and cardiovascular mortality in 13,657 individuals with diabetes (53.6% male, age 62.3±12.1 years) from the Hoorn Diabetes Care System cohort, using data obtained between 1998 and 2018. Multivariate time-dependent Cox regression models adjusted for cardiovascular risk factors were used to estimate HRs and 95% CI. Associations of eGFR were adjusted for UACR values and vice versa. Effect modification by sex was investigated for all associations.ResultsAfter a mean follow-up period of 7 years, event rates per 1000 person-years were 3.08 for MI, 3.72 for CHD, 1.12 for HF, 0.84 for stroke and 6.25 for cardiovascular mortality. Mildly reduced eGFR (60-90 ml/min per 1.73 m2) and moderately to severely reduced eGFR (<59 ml/min per 1.73 m2) were associated with higher risks of MI (HR 1.52; 95% CI 1.10, 2.12 and HR 1.69; 95% CI 1.09, 2.64) and CHD (HR 1.67; 95% CI 1.23, 2.26 and HR 2.01; 95% CI 1.34, 3.02) compared with normal eGFR (>90 ml/min per 1.73 m2). Mildly reduced eGFR was associated with a higher risk of stroke (HR 2.53; 95% CI 1.27, 5.03). Moderately increased UACR (3-30 mg/mmol) and severely increased UACR (>30 mg/mmol) were prospectively associated with a higher cardiovascular mortality risk in men and women (HR 1.87; 95% CI 1.41, 2.47 and HR 2.78; 95% CI 1.78, 4.34) compared with normal UACR (<3 mg/mmol). Significant effect modification by sex was observed for the association between UACR and HF. Because there were a limited number of HF events within the category of UACR >30 mg/mmol, categories were combined into UACR <3.0 and >3.0 mg/mmol in the stratified analysis. Women but not men with UACR >3.0 mg/mmol had a significantly higher risk of HF compared with normal UACR (HR 2.79; 95% CI 1.47, 5.28).Conclusions/interpretationThis study showed differential and independent prospective associations between manifestations of early kidney damage in diabetes and several CVD subtypes, suggesting that regular monitoring of both kidney function measures may help to identify individuals at higher risk of specific cardiovascular events.

Dataset Information

Albuminuria and kidney function independently predict cardiovascular and renal outcomes in diabetes.

Publications

Albuminuria and kidney function independently predict cardiovascular and renal outcomes in diabetes.

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