Chronic kidney disease more than doubles mortality risk in patients with type 2 diabetes, researchers found.
In an analysis of nearly two dozen randomized controlled trials involving diabetic patients, the highest mortality rates were observed in those trials that required the inclusion of patients with renal disease, according to Marc Pfeffer, MD, PhD, of Brigham and Women's Hospital in Boston, and colleagues.
Trials that selected for patients with elevated serum creatinine or impaired estimated glomerular filtration rate (eGFR) had mortality rates of 5.9 to 8.2 per 100 patient-years, whereas the rest of the trials had rates no higher than 3.3, the researchers reported online in the Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease.
"Risk stratification by evidence of kidney disease, determined by renal function or proteinuria, should be emphasized in diabetic subjects, given its major impact on morbidity and mortality," they wrote.
Pfeffer and colleagues examined 22 randomized trials of at least 1,000 patients with type 2 diabetes and a follow-up duration of at least one year, looking for relationships between specific inclusion and exclusion criteria and all-cause mortality. They excluded trials that selected patients with acute coronary syndromes or end-stage renal disease.
The trials included a total of 91,742 patients, of whom 7.5% died.
After intervention and control arms were combined, mortality rates among the trials ranged widely, from 0.28 to 8.24 per 100 patient-years.
Six trials had a mortality rate of less than 1 per 100 patient-years, 10 had a rate of 1 to less than 2, and three each had rates of 2 to less than 4 and 4 to less than 10.
On average, patients in the trials with the highest mortality rates -- versus those in trials with the lowest rates -- were older (64.2 versus 59), had a longer diabetes duration (15.2 versus 7.2 years), and had a higher systolic blood pressure (145 mm Hg versus 136 mm Hg), serum creatinine (1.8 versus 0.9 mg/dL), and proteinuria prevalence (100% versus 9%).
Both the average LDL cholesterol level and prevalence of current smoking decreased across the increasing mortality categories.
"While the lower prevalence of smoking is probably related to the inclusion criteria, reports from cohorts of chronic kidney disease and heart failure demonstrated that lower cholesterol correlates with higher mortality -- what is described as 'reverse epidemiology' in other populations of patients with advanced disease," the authors wrote.
Selection for hypertension was common across trials in all four of the mortality categories, ranging from 69% to 97% of patients. Hypertension was not a strong predictor of mortality, but rates were lowest in primary prevention trials and those in which hypertension was the only additional inclusion criterion.
Mortality rates were higher in trials selecting for prior cardiovascular disease compared with those for which cardiovascular disease was simply permitted but not required (2.0 to 2.5 versus 0.9 to 2.0 per 100 patient-years).
The highest rates, however, occurred in the three trials that required the presence of chronic kidney disease -- defined as either elevated serum creatinine or eGFR less than 60 mL/min/1.73 m2 with or without the presence of proteinuria.
The authors acknowledged that the study was limited by the lack of individual patient data, of information on the effects of medications and therapeutic interventions during the trials, and of information on the effects of the randomized treatment arms and their relationships with mortality.
Pfeffer
reported links with Amgen, Novartis, sanofi-aventis, Anthera,
Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Cerenis,
Eleven Biotherapeutics, GlaxoSmithKline, Hamilton Health Sciences, Karo
Bio, Roche, Salutria, Servier, and the University of Oxford. He is a
co-inventor on a patent that Brigham and Women's Hospital has for the
use of inhibitors of the renin-angiotensin system in selected survivors
of myocardial infarction.
A co-author reported a link with sanofi-aventis.
From the American Heart Association:A co-author reported a link with sanofi-aventis.
Primary source: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
Source reference:
Pfeffer M, et al "Mortality rates in trials of subjects with type 2 diabetes" JAHA 2012.
Source reference:
Pfeffer M, et al "Mortality rates in trials of subjects with type 2 diabetes" JAHA 2012.
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