The GenoDiabMar Registry: A Collaborative Research Platform of Type 2 Diabetes Patients.

The GenoDiabMar registry is a prospective study that aims to provide data on demographic, biochemical, and clinical changes in type 2 diabetic (T2D) patients attending real medical outpatient consultations. This registry is also used to find new biomarkers related to the micro- and macrovascular complications of T2D, with a particular focus on diabetic nephropathy. With this purpose, longitudinal serum and urine samples, DNA banking, and data on 227 metabolomics profiles, 77 immunoglobulin G glycomics traits, and other emerging biomarkers were recorded in this cohort. In this study, we show a detailed longitudinal description of the clinical and analytical parameters of this registry, with a special focus on the progress of renal function and cardiovascular events. The main objective is to analyze whether there are differential risk factors for renal function deterioration between sexes, as well as to analyze cardiovascular events and mortality in this population. In total, 650 patients with a median age of 69 (14) with different grades of chronic kidney disease­G1−G2 (eGFR > 90−60 mL/min/1.73 m2) 50.3%, G3 (eGFR; 59−30 mL/min/1.73 m2) 31.4%, G4 (eGFR; 29−15 mL/min/1.73 m2) 10.8%, and G5 (eGFR < 15 mL/min/1.73 m2) 7.5%­were followed up for 4.7 (0.65) years. Regardless of albuminuria, women lost 0.93 (0.40−1.46) fewer glomerular filtration units per year than men. A total of 17% of the participants experienced rapid deterioration of renal function, 75.2% of whom were men, with differential risk factors between sexes­severe macroalbuminuria > 300 mg/g for men OR [IQ] 2.40 [1.29:4.44] and concomitant peripheral vascular disease 3.32 [1.10:9.57] for women. Overall mortality of 23% was detected (38% of which was due to cardiovascular etiology). We showed that kidney function declined faster in men, with different risk factors compared to women. Patients with T2D and kidney involvement have very high mortality and an important cardiovascular burden. This cohort is proposed as a great tool for scientific collaboration for studies, whether they are focused on T2D, or whether they are interested in comparing differential markers between diabetic and non-diabetic populations.

Circulating metabolic biomarkers of renal function in diabetic and non-diabetic populations.

Using targeted NMR spectroscopy of 227 fasting serum metabolic traits, we searched for novel metabolic signatures of renal function in 926 type 2 diabetics (T2D) and 4838 non-diabetic individuals from four independent cohorts. We furthermore investigated longitudinal changes of metabolic measures and renal function and associations with other T2D microvascular complications. 142 traits correlated with glomerular filtration rate (eGFR) after adjusting for confounders and multiple testing: 59 in diabetics, 109 in non-diabetics with 26 overlapping. The amino acids glycine and phenylalanine and the energy metabolites citrate and glycerol were negatively associated with eGFR in all the cohorts, while alanine, valine and pyruvate depicted opposite association in diabetics (positive) and non-diabetics (negative). Moreover, in all cohorts, the triglyceride content of different lipoprotein subclasses showed a negative association with eGFR, while cholesterol, cholesterol esters (CE), and phospholipids in HDL were associated with better renal function. In contrast, phospholipids and CEs in LDL showed positive associations with eGFR only in T2D, while phospholipid content in HDL was positively associated with eGFR both cross-sectionally and longitudinally only in non-diabetics. In conclusion, we provide a wide list of kidney function-associated metabolic traits and identified novel metabolic differences between diabetic and non-diabetic kidney disease.

The renin-angiotensin-aldosterone system blockade in patients with advanced diabetic kidney disease. / Bloqueo del sistema renina-angiotensina-aldosterona en pacientes con enfermedad renal diabética avanzada.

BACKGROUND AND OBJECTIVES: Diabetic kidney disease is the leading cause of end-stage chronic kidney disease. The renin-angiotensin-aldosterone system (RAAS) blockade has been shown to slow the progression of diabetic kidney disease. Our objectives were: to study the percentage of patients with diabetic kidney disease treated with RAAS blockade, to determine its renal function, safety profile and assess whether its administration is associated with increased progression of CKD after 3 years of follow-up. MATERIALS AND METHODS: Retrospective study. 197 diabetic kidney disease patients were included and divided into three groups according to the treatment: patients who had never received RAAS blockade (non-RAAS blockade), patients who at some point had received RAAS blockade (inconstant-RAAS blockade) and patients who received RAAS blockade (constant-RAAS blockade). Clinical characteristics and analytical variables such as renal function, electrolytes, glycosylated haemoglobin and glomerular filtration rate according to chronic kidney disease -EPI and MDRD formulas were assessed. We also studied their clinical course (baseline, 1 and 3 years follow-up) in terms of treatment group, survival, risk factors and renal prognosis. RESULTS: Non-RAAS blockade patients had worse renal function and older age (p<0.05) at baseline compared to RAAS blockade patients. Patients who received RAAS blockade were not found to have greater toxicity or chronic kidney disease progression and no differences in renal prognosis were identified. Mortality was higher in non-RAAS blockade patients, older patients and patients with worse renal function (p<0.05). In the multivariate analysis, older age and worse renal function were risk factors for mortality. CONCLUSIONS: Treatment with RAAS blockade is more common in diabetic kidney disease patients with eGFR≥30ml/min/1.73m2. In our study, there were no differences in the evolution of renal function between the three groups. Older age and worse renal function were associated with higher mortality in patients who did not receive RAAS blockade.

Diabetic nephropathy is an independent factor associated to severe subclinical atheromatous disease.

BACKGROUND: Atheromatous disease (AD) is a risk factor for death in renal patients. Traditional CV risk factors do not predict the presence of AD in this population. The aim of this study is to analyze whether the etiology of the primary renal disease influences in the risk of having silent AD. STUDY DESIGN: Observational cross-sectional study in chronic kidney disease patients without previous cardiovascular events. SETTINGS AND PARTICIPANTS: 2436 CKD subjects without any previous CV event included in the prospective Spanish multicenter NEFRONA study. Patients were classified according to primary renal disease: diabetic nephropathy (n = 347), vascular nephropathy (n = 476), systemic/glomerular disease (n = 447), tubulointerstitial and drug toxicity nephropathy (n = 320), polycystic kidney disease (n = 238), non-filiated nephropathy (n = 406) and other causes (n = 202). PREDICTORS: B-mode and Doppler ultrasonography analysis of the carotid arteries were performed to measure intima media thickness (IMT) and the presence of plaques. Clinical and laboratory parameters related to CV risk were also determined. OUTCOMES: AD was scored according with the ultrasonography findings and the ankle-brachial index into two large groups: absence or incipient AD and severe AD. RESULTS: In multivariate regression analysis, older age (OR 1.09/year [1.088-1.108]), smoking habit (OR 2.10 [1.61-2.74]), male gender (OR 1.33 [1.09-1.64]), grade-5D of CKD (OR 2.19 [1.74-2.74]), and diabetic nephropathy (OR 2.59 [1.93-3.48]) are independent risk factors for severe AD. The prevalence of silent AD was highest for diabetic nephropathy with grade-5D of CKD (82.2%) and lowest with stages 2-3 CKD systemic/glomerular disease (36.6%). LIMITATIONS: Observational study with the potential for confounding. CONCLUSION: In CKD patients without any CV event in the background clinical history, diabetic nephropathy as primary renal disease is the most significant factor associated to severe silent AD. Furthermore, this difference was independent of other conventional risk factors for atherosclerosis and CV events.