Proteinuria reduction and progression to renal failure in patients with type 2 diabetes mellitus and overt nephropathy.
ABSTRACT Little is known of the effects of blood pressure reduction by specific classes of antihypertensive drugs on the association between proteinuria reduction and progression of kidney insufficiency and development of end-stage kidney disease in patients with overt diabetic nephropathy in type 2 diabetes mellitus.
Associations between baseline proteinuria and proteinuria reduction by either irbesartan, amlodipine, or control for similar decrements in blood pressure and the cumulative incidence of renal end points were examined using the Kaplan-Meier method in patients enrolled in the Irbesartan Diabetic Nephropathy Trial.
Risk for kidney failure doubled for each doubling of baseline proteinuria level (hazard ratio, 2.04; 95% confidence interval, 1.87 to 2.22; P < 0.001). For each halving of proteinuria level between baseline and 12 months with treatment, risk for kidney failure was reduced by more than half (hazard ratio, 0.44; 95% confidence interval, 0.40 to 0.49; P < 0.001). For the same proportional change in proteinuria, the reduction in risk for kidney failure was significantly greater for irbesartan compared with amlodipine ( P = 0.048), but not control ( P = 0.245). Proteinuria reduction in the first 12 months of therapy with irbesartan is associated with 36% of the total renoprotective effect observed.
Baseline proteinuria is an important risk factor for kidney failure and provides a means to identify patients at greatest risk. Halving proteinuria halves the kidney risk. Proteinuria reduction using an angiotensin receptor-blocking agent, such as irbesartan, should be regarded as an important therapeutic goal in renoprotective strategies.
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ABSTRACT: Cardiovascular disease (CVD) is very common in patients with chronic kidney disease (CKD) and is by far the leading cause of morbidity and mortality in dialysis patients . The National Health And Nutrition Epidemiology Survey (NHANES III) estimated that 11% of adults in the United States have CKD . World-wide, 5-10% of the world's population may also have CKD, a staggering 300-600 million people . Of the major outcomes of CKD, progression to ESRD has attracted the most attention. However, the development of CVD is more serious since only a small fraction of patients with CKD progress to ESRD and requires renal replacement therapy such as dialysis or renal transplantation. The majority of patients, particularly those with an estimated glomerular filtration rate (eGFR) of <60 ml/min, usually die from heart disease before they reach ESRD [4,5]. This was clearly shown by Keith et al  who analyzed outcomes of 27,998 patients with evidence of CKD and found that the 5-year mortality rates for CKD stages 2, 3, and 4 were 19.5, 24.3, and 45.7% respectively; while the percentages of patients with these stages who progressed to ESRD were much lower at 1.1%, 1.3%, and 19.9%. Similarly, CVD is very common in dialysis patients and accounts for almost 50% of deaths, a rate that is 20 to 30 fold higher than age, gender and race matched controls . The risk of CVD is even higher in children and young adults with ESRD in whom the mortality rate from CVD is almost 100 times greater than in the general population. Thus, CKD clearly represents a major public heath problem. Evidence for the increased prevalence of CVD in CKD was derived from both prospective and retrospective community-based epidemiologic studies. Weiner et al pooled data from four community-based longitudinal studies to assess whether CKD was an independent risk factor for cardiovascular events . They concluded that CKD is an independent risk factor for the composite outcome of all-cause mortality and CVD. In another study, it was shown that a decrease in eGFR by 5 mL/min/1.73m 2 was associated with a 26% increase in cardiovascular death . Even mild reduction of renal function is associated with significant increase in cardiovascular morbidity and mortality in a post-myocardial infarction population [Figure 1] .
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ABSTRACT: Introduction. The presence of aortic arch calcification (AoAC) and cardiomegaly on chest radiography has been demonstrated as important risk factors for cardiovascular mortality in patients with chronic kidney disease (CKD). However, the interrelationship among AoAC, cardiomegaly, and renal function progression remains unclear. The aim of this study is to assess whether AoAC and cardiomegaly are independently associated with the renal function progression in patients with stages 3-5 CKD. Methods. We retrospectively determined AoAC and cardiomegaly by chest X-ray in 237 patients, followed up for at least three years without entering dialysis and classified into 4 groups according to the presence or absence of AoAC and cardiomegaly. The change in renal function was measured by the slope of estimated glomerular filtration rate (eGFR). Results. Of the 237 patients, the rate of eGFR decline was significantly higher in the group with coexistence of AoAC and cardiomegaly than any other groups. Baseline AoAC and proteinuria were independently associated with eGFR decline. AoAC were independently determined by age, eGFR slope, and cardiomegaly. Conclusions. The coexistence of AoAC and cardiomegaly is associated with faster eGFR decline. AoAC is an independent determinant of renal outcomes in patients with CKD stages 3-5.BioMed Research International 01/2015; 2015:131263. DOI:10.1155/2015/131263 · 2.71 Impact Factor
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ABSTRACT: The use of renin-angiotensin system (RAS) inhibitors, such angiotensin converting enzyme inhibitors/angiotensin-II receptor blockers, to slow progression of chronic kidney disease (CKD) in a large group dominated by elderly people in the real world is not supported by available evidence. Large-scale clinical trials had many faults, among them a lack of focus on the elderly. However, it would be difficult to conduct clinical trials of a similar scale in elderly CKD patients. Besides, progression of kidney disease is often slow in elderly persons, and the vast majority of older adults with CKD will die before reaching end stage renal disease. Moreover, since it is not clear that progression of kidney disease, and even of proteinuric diabetic nephropathy, is not inhibited through the use of RAS inhibitors, the most patient-centric goal of therapy for many elderly individuals should be individualized.