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

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.

[1]  B. Astor,et al.  Glomerular filtration rate, albuminuria, and risk of cardiovascular and all-cause mortality in the US population. , 2008, American journal of epidemiology.

[2]  S. Shankland,et al.  Proteinuria in diabetic kidney disease: a mechanistic viewpoint. , 2008, Kidney international.

[3]  M. Jardine,et al.  The Relationship between Proteinuria and Coronary Risk: A Systematic Review and Meta-Analysis , 2008, PLoS medicine.

[4]  M. Woodward,et al.  Systolic blood pressure, diabetes and the risk of cardiovascular diseases in the Asia–Pacific region , 2007, Journal of hypertension.

[5]  M. Woodward,et al.  Lowering blood pressure reduces renal events in type 2 diabetes. , 2009, Journal of the American Society of Nephrology : JASN.

[6]  Mark Woodward,et al.  Epidemiology: Study Design and Data Analysis , 1999 .

[7]  Anushka Patel,et al.  Effects of a fixed combination of perindopril and indapamide on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial): a randomised controlled trial , 2007, The Lancet.

[8]  R. Poveda,et al.  Goodpasture syndrome during the course of a Schönlein-Henoch purpura. , 2002, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[9]  A. Garg,et al.  Albuminuria and renal insufficiency prevalence guides population screening: results from the NHANES III. , 2003, Kidney international.

[10]  R. Klein,et al.  The risk of cardiovascular disease mortality associated with microalbuminuria and gross proteinuria in persons with older-onset diabetes mellitus. , 2000, Archives of internal medicine.

[11]  M. Woodward,et al.  The effects of diabetes on the risks of major cardiovascular diseases and death in the Asia-Pacific region. , 2003, Diabetes care.

[12]  M. Woodward,et al.  Lower target blood pressures are safe and effective for the prevention of recurrent stroke: the PROGRESS trial , 2006, Journal of hypertension.

[13]  F. Irie,et al.  The relationships of proteinuria, serum creatinine, glomerular filtration rate with cardiovascular disease mortality in Japanese general population. , 2006, Kidney international.

[14]  M. Thomas,et al.  Assessment and management of hypertension in patients with type 2 diabetes , 2009, Internal medicine journal.

[15]  C. Lawton.  Highlights of the 2003 Clinical Practice Guidelines for the prevention and management of diabetes in Canada. , 2004, CANNT journal = Journal ACITN.

[16]  Diederick Grobbee,et al.  Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. , 2008, The New England journal of medicine.

[17]  B. Brenner,et al.  Albuminuria, a Therapeutic Target for Cardiovascular Protection in Type 2 Diabetic Patients With Nephropathy , 2004, Circulation.

[18]  R. Garrick.  Association of Kidney Function and Albuminuria With Cardiovascular Mortality in Older vs Younger Individuals: The HUNT II Study , 2008 .

[19]  Robert M Califf,et al.  Relation between renal dysfunction and cardiovascular outcomes after myocardial infarction. , 2004, The New England journal of medicine.

[20]  J. Diamond,et al.  Analogous pathobiologic mechanisms in glomerulosclerosis and atherosclerosis. , 1991, Kidney international. Supplement.

[21]  R B D'Agostino,et al.  Comparison of baseline and repeated measure covariate techniques in the Framingham Heart Study. , 1988, Statistics in medicine.

[22]  N. Schneiderman,et al.  Cardiovascular responsivity to stress in adolescents with and without persistently elevated blood pressure , 2001, Journal of hypertension.

[23]  C. Anderson,et al.  Proteinuria and stroke: a meta-analysis of cohort studies. , 2009, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[24]  W. Kirch,et al.  The pharmacokinetic and metabolic profile of olmesartan medoxomil limits the risk of clinically relevant drug interaction , 2001, Journal of hypertension. Supplement : official journal of the International Society of Hypertension.

[25]  Po Box,et al.  Excess risk of fatal coronary heart disease associated with diabetes in men and women:meta-analysis of 37 prospective cohort studies , 2006 .

[26]  C. Stehouwer,et al.  Microalbuminuria and risk for cardiovascular disease: Analysis of potential mechanisms. , 2006, Journal of the American Society of Nephrology : JASN.

[27]  M. Mauer,et al.  Low glomerular filtration rate in normoalbuminuric type 1 diabetic patients: an indicator of more advanced glomerular lesions. , 2003, Diabetes.

[28]  Mark Woodward,et al.  Imputations of missing values in practice: results from imputations of serum cholesterol in 28 cohort studies. , 2004, American journal of epidemiology.

[29]  A G Babiker,et al.  Floating absolute risk: an alternative to relative risk in survival and case-control analysis avoiding an arbitrary reference group. , 1991, Statistics in medicine.

[30]  R. Bigazzi,et al.  Increased thickness of the carotid artery in patients with essential hypertension and microalbuminuria. , 1995, Journal of human hypertension.

[31]  J. Kirkpatrick.  Albuminuria and Risk of Cardiovascular Events , Death , and Heart Failure in Diabetic and Nondiabetic Individuals , 2002 .

[32]  A. Zanchetti,et al.  Definition of kidney dysfunction as a cardiovascular risk factor: use of urinary albumin excretion and estimated glomerular filtration rate. , 2008, Archives of internal medicine.

[33]  Charles E. McCulloch,et al.  Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. , 2004, The New England journal of medicine.

[34]  Bertram L Kasiske,et al.  Kidney disease as a risk factor for development of cardiovascular disease: a statement from the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention. , 2003, Hypertension.

[35]  D. de Zeeuw,et al.  Cardiovascular and renal outcome in subjects with K/DOQI stage 1-3 chronic kidney disease: the importance of urinary albumin excretion. , 2008, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[36]  M. Pfeffer,et al.  Proteinuria, impaired kidney function, and adverse outcomes in people with coronary disease: analysis of a previously conducted randomised trial , 2006, BMJ : British Medical Journal.

[37]  M. Nieminen,et al.  Reduction in Albuminuria Translates to Reduction in Cardiovascular Events in Hypertensive Patients: Losartan Intervention for Endpoint Reduction in Hypertension Study , 2005, Hypertension.

[38]  Simon Davies,et al.  Epidemiology: Study Design and Data Analysis (2nd ed.) , 2006 .

[39]  S. Yusuf,et al.  Albuminuria and risk of cardiovascular events, death, and heart failure in diabetic and nondiabetic individuals. , 2001, JAMA.

[40]  F. Ovalle.  10-Year Follow-up of Intensive Glucose Control in Type 2 Diabetes , 2009 .

[41]  C. Tsalamandris,et al.  Progressive Decline in Renal Function in Diabetic Patients With and Without Albuminuria , 1994, Diabetes.

[42]  D. Levy,et al.  Cross-classification of microalbuminuria and reduced glomerular filtration rate: associations between cardiovascular disease risk factors and clinical outcomes. , 2007, Archives of internal medicine.

[43]  Ethan M Balk,et al.  K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. , 2002, American journal of kidney diseases : the official journal of the National Kidney Foundation.