Chronic kidney disease in the type 2 diabetic patients: prevalence and associated variables in a random sample of 2642 patients of a Mediterranean area

Background: Kidney disease is associated with an increased total mortality and cardiovascular morbimortality in the general population and in patients with Type 2 diabetes. The aim of this study is to determine the prevalence of kidney disease and different types of renal disease in patients with type 2 diabetes (T2DM). Methods: Cross-sectional study in a random sample of 2,642 T2DM patients cared for in primary care during 2007. Studied variables: demographic and clinical characteristics, pharmacological treatments and T2DM complications (diabetic foot, retinopathy, coronary heart disease and stroke). Variables of renal function were defined as follows: 1) Microalbuminuria: albumin excretion rate & 30 mg/g or 3.5 mg/mmol, 2) Macroalbuminuria: albumin excretion rate & 300 mg/g or 35 mg/mmol, 3) Kidney disease (KD): glomerular filtration rate according to Modification of Diet in Renal Disease < 60 ml/min/1.73 m2 and/or the presence of albuminuria, 4) Renal impairment (RI): glomerular filtration rate < 60 ml/min/1.73 m2, 5) Nonalbuminuric RI: glomerular filtration rate < 60 ml/min/1.73 m2 without albuminuria and, 5) Diabetic nephropathy (DN): macroalbuminuria or microalbuminuria plus diabetic retinopathy. Results: The prevalence of different types of renal disease in patients was: 34.1% KD, 22.9% RI, 19.5% albuminuria and 16.4% diabetic nephropathy (DN). The prevalence of albuminuria without RI (13.5%) and nonalbuminuric RI (14.7%) was similar. After adjusting per age, BMI, cholesterol, blood pressure and macrovascular disease, RI was significantly associated with the female gender (OR 2.20; CI 95% 1.86-2.59), microvascular disease (OR 2.14; CI 95% 1.8-2.54) and insulin treatment (OR 1.82; CI 95% 1.39-2.38), and inversely associated with HbA1c (OR 0.85 for every 1% increase; CI 95% 0.80-0.91). Albuminuria without RI was inversely associated with the female gender (OR 0.27; CI 95% 0.21-0.35), duration of diabetes (OR 0.94 per year; CI 95% 0.91-0.97) and directly associated with HbA1c (OR 1.19 for every 1% increase; CI 95% 1.09-1.3). Conclusions: One-third of the sample population in this study has KD. The presence or absence of albuminuria identifies two subgroups with different characteristics related to gender, the duration of diabetes and metabolic status of the patient. It is important to determine both albuminuria and GFR estimation to diagnose KD

Defective sarcoplasmic reticulum-mitochondria calcium exchange in aged mouse myocardium

Mitochondrial alterations are critically involved in increased vulnerability to disease during aging. We investigated the contribution of mitochondria-sarcoplasmic reticulum (SR) communication in cardiomyocyte functional alterations during aging. Heart function (echocardiography) and ATP/phosphocreatine (NMR spectroscopy) were preserved in hearts from old mice (420 months) with respect to young mice (5-6 months). Mitochondrial membrane potential and resting O-2 consumption were similar in mitochondria from young and old hearts. However, maximal ADP-stimulated O-2 consumption was specifically reduced in interfibrillar mitochondria from aged hearts. Second generation proteomics disclosed an increased mitochondrial protein oxidation in advanced age. Because energy production and oxidative status are regulated by mitochondrial Ca2+, we investigated the effect of age on mitochondrial Ca2+ uptake. Although no age-dependent differences were found in Ca2+ uptake kinetics in isolated mitochondria, mitochondrial Ca2+ uptake secondary to SR Ca2+ release was significantly reduced in cardiomyocytes from old hearts, and this effect was associated with decreased NAD(P)H regeneration and increased mitochondrial ROS upon increased contractile activity. Immunofluorescence and proximity ligation assay identified the defective communication between mitochondrial voltage-dependent anion channel and SR ryanodine receptor (RyR) in cardiomyocytes from aged hearts associated with altered Ca2+ handling. Age-dependent alterations in SR Ca2+ transfer to mitochondria and in Ca2+ handling could be reproduced in cardiomyoctes from young hearts after interorganelle disruption with colchicine, at concentrations that had no effect in aged cardiomyocytes or isolated mitochondria. Thus, defective SR-mitochondria communication underlies inefficient interorganelle Ca2+ exchange that contributes to energy demand/supply mistmach and oxidative stress in the aged heart.The authors are grateful to Angeles Rojas for her excellent technical work. Supported by the Spanish Ministry of Science (SAF2008-03067, BIO2012-37926 and ProteoRed-PT13/0001/0017) and the Instituto de Salud Carlos III (RETICS-RECAVA RD12/0042/0021, RD12/0042/0056 and FIS-PI12-/00788). The CNIC is supported by the Spanish Ministry of Economy and Competitiveness and the Pro-CNIC Foundation.S