Progression of kidney disease in type 2 diabetes – beyond blood pressure control: an observational study

BACKGROUND: The risk factors for progression of chronic kidney disease (CKD) in type 2 diabetes mellitus (DM) have not been fully elucidated. Although uncontrolled blood pressure (BP) is known to be deleterious, other factors may become more important once BP is treated. METHODS: All patients seen in the outpatient clinics of our hospital between January 1993 and September 2002 with type 2 DM and clinical evidence of CKD were evaluated. Progression of kidney disease was evaluated by rate of decline of glomerular filtration rate (GFR) as estimated from the simplified MDRD formula. Variables associated with progression in univariate analyses were examined by multivariate analysis to determine the factors independently associated with kidney disease progression. RESULTS: 343 patients (mean age 69 years; all male; 77% Caucasian) were studied. Mean BP, glycated hemoglobin, and serum cholesterol during the study period were 138/72 mmHg, 8.1%, and 4.8 mmol/L, respectively. Mean decline of GFR was 4.5 ml min-1 1.73 m(2)-1 yr-1 (range -14 to +32). Low initial serum albumin (p < 0.001), black race (p < 0.001), and degree of proteinuria (p = 0.002), but not blood pressure, glycated hemoglobin, or serum cholesterol, were independently associated with progression. CONCLUSION: In a cohort of diabetic patients with CKD in whom mean BP was < 140/80 mmHg, the potentially remediable factors hypoalbuminemia and proteinuria but not blood pressure were independently associated with progression of kidney disease. Further understanding of the relationship between these factors and kidney disease progression may lead to beneficial therapies in such patients

The correlates of urinary albumin to creatinine ratio (ACR) in a high risk Australian Aboriginal community

Background: Albuminuria marks renal disease and cardiovascular risk. It was estimated to contribute 75% of the risk of all-cause natural death in one Aboriginal group. The urine albumin/creatinine ratio (ACR) is commonly used as an index of albuminuria. This study aims to examine the associations between demographic factors, anthropometric index, blood pressure, lipid-protein measurements and other biomarkers and albuminuria in a cross-sectional study in a high-risk Australian Aboriginal population. The models will be evaluated for albuminuria at or above the microalbuminuria threshold, and at or above the "overt albuminuria" threshold with the potential to distinguish associations they have in common and those that differ

Microalbuminuria and C-reactive protein: Similar messengers of cardiovascular risk?

C-reactive protein (CRP) and urinary albumin excretion are both determinants of cardiovascular risk. The first is closely related to systemic and vascular low-grade inflammation, the latter is considered to be a marker of endothelial dysfunction. Because of these properties, one might presume them to be closely interrelated. In this article, we review the available evidence concerning the relationships of CRP and urinary albumin excretion, with each other and with other cardiovascular risk markers might be present in the cardiovascular risk estimation formula of the near future. The reasons that this formula might or should CRP and urinary albumin and the metabolic syndrome are discussed

C-reactive protein is associated with renal function abnormalities in a non-diabetic population

C-reactive protein is associated with renal function abnormalities in a non-diabetic population.BackgroundC-reactive protein (CRP) has recently been introduced in cardiovascular medicine as a predictor of myocardial infarction, stroke and peripheral artery disease in different populations. We hypothesized that elevated CRP levels are associated with renal function abnormalities.MethodsTo test this hypothesis, we studied the relationship between CRP levels and renal function loss measured as diminished creatinine clearance in a large non-diabetic population (7317 subjects). In addition, the associations and confounding effects of established renal risk factors that could explain the association between CRP and diminished renal filtration were studied. Also, the association of CRP with early alterations in renal function, such as those evidenced by a relatively high glomerular filtration (“hyperfiltration”), was examined. CRP levels were divided in quartiles. Subjects with CRP levels within the first quartile were defined as the reference group. Diminished renal filtration and hyperfiltration were defined as a creatinine clearance below or exceeding two times the prediction interval of the age- and sex-related reference group.ResultsElevated CRP levels were positively associated with cardiovascular and renal risk factors: age, body mass index, blood pressure, serum cholesterol level, smoking, plasma glucose level and elevated urinary albumin excretion. Elevated CRP was positively associated with diminished filtration (OR 1.8; 95% CI 1.2 to 2.6). In multivariate analyses, CRP was independently associated with a diminished filtration (OR 1.9; 95% CI 1.3 to 2.9). Interestingly, CRP also was associated with hyperfiltration (highest quartile, OR 1.7; 95% CI 1.2 to 2.5). However, body mass index accounted for most of the relationship between CRP and hyperfiltration.ConclusionsAs in cardiovascular disease, CRP appears to be a risk marker for renal function loss. The mechanism of this relationship remains to be clarified. However, the association between CRP, body weight, and a relatively elevated creatinine clearance is a hypothesis-generating finding, suggesting that early inflammatory processes related to high body fat may predispose the kidney to glomerular hyperfiltration-related renal function loss

C-reactive protein and microalbuminuria differ in their associations with various domains of vascular disease

C-reactive protein (CRP) and microalbuminuria (MA) have been identified as risk markers for cardiovascular disease (CVD). We questioned whether CRP and MA are similar markers of vascular disease in different regions of the vascular tree like the heart, kidneys and extremities or if they differ in their relationships with these vascular beds. Baseline levels of CRP and urinary albumin were measured in 6669 non-diabetic participants in the Prevention of Renal and Vascular ENdstage Disease (PREVEND) study, a Dutch cohort derived from the general population. We defined three domains of vascular disease; coronary heart disease (myocardial infarction or infarct pattern on the ECG), renal insufficiency (creatinine clearance <60 ml min(-1)) and peripheral artery disease (ankle brachial index <0.9 or lower limb revascularisation). The prevalence of an elevated CRP (27.7 vs. 17.9%) and MA (17.5 vs. 10.4%) were increased in subjects with vascular disease as compared with subjects without CVD. The prevalence of an elevated CRP was equal in subjects with either coronary heart disease, renal insufficiency or peripheral artery disease (28.4 vs. 29.5 vs. 26.0%, NS), whereas MA was most prevalent in subjects with coronary heart disease (22.5 vs. 12.8 vs. 14.9%, P <0.05). Using multivariate analyses, CRP was independently associated with all three domains of vascular disease, whereas MA was independently associated with coronary heart disease only. In addition, we found synergistic contributions of an elevated CRP and older age to the risk of vascular disease in all three domains. Thus, CRP and MA are risk markers for vascular disease, each showing a different risk profiling for different vascular beds. (C) 2003 Elsevier Ireland Ltd. All rights reserved

C-reactive protein modifies the relationship between blood pressure and microalbuminuria

C-reactive protein (CRP) and microalbuminuria reflect intimately related components of the atherosclerotic disease process. Epidemiological studies found only modest associations between CRP and microalbuminuria. Blood pressure, one of the components of the metabolic syndrome in the general population, is the main determinant of microalbuminuria in diabetes and hypertension. We questioned whether CRP modifies the relationship of blood pressure and other cardiovascular risk factors with microalbuminuria in a cross-sectional study in 8592 inhabitants from Groningen, The Netherlands. The crude data showed an increase in the prevalence of microalbuminuria with increasing CRP quartiles (4.8, 9.6, 14.5, and 18.6%,