Lower serum 25-hydroxyvitamin D levels are associated with impaired glomerular filtration rate in type 2 diabetes patients

Background: 25-Hydroxyvitamin D [25(OH)D] deficiency has been implicated as a possible risk factor for the onset and progression of diabetes kidney disease (DKD). The aim of this study was to evaluate the interaction between levels of 25(OH)D and DKD in type 2 diabetes mellitus (DM) patients. Methods: Cross-sectional design, outpatient type 2 DM. Glomerular filtration rate (GFR) was measured by 51Cr-EDTA and estimated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), urinary albumin excretion (UAE) by immunoturbidimetry, and 25(OH)D by chemiluminescence. Receiver operating characteristic (ROC) curve analysis and generalized linear model (Poisson robust regression estimator) were used to assess the interaction between 25(OH)D levels and renal function. Results: A total of 114 type 2 DM patients aged 60±10years, 49 males (43%), DM duration 22±10years, with GFR>60ml/min/1.73m2 were evaluated. Patients with GFRs 60–90 (n=50) had significantly lower 25(OH)D levels than individuals with GFRs>90ml/min/1.73m2 (n=64), respectively 40±20 versus 48±20nmol/l, p=0.027. This difference was more pronounced for older individuals (39±20 versus 54±23nmol/l, respectively), and Poisson robust regression disclosed that lower 25(OH)D [Poisson regression (PR)=0.989, confidence interval (CI): 0.978– 0.999, p=0.034], and advanced age (PR=1.050, CI: 1.007–1.096, p=0.023) were significantly associated with the lower GFR category, adjusted for seasons. ROC curve analysis showed that the cutoff point of 25(OH)D of 41nmol/l was associated with lower GFR [area under the curve (AUC)=0.694, p=0.009]. CKD-EPI estimated GFR (eGFR) was not associated with 25(OH)D in any analysis. There was no difference in 25(OH)D levels between patients with elevated UAE as compared with normoalbuminuric ones (44±21 versus 46±19nmol/l, p=0.587). Conclusion: Lower levels of 25(OH)D are associated with decreased GFR in patients with type 2 DM, especially in older patients, with no evidence of interaction with UAE levels

Update in diagnosis and management of primary aldosteronism

Primary aldosteronism (PA) is a group of disorders in which aldosterone is excessively produced. These disorders can lead to hypertension, hypokalemia, hypervolemia and metabolic alkalosis. The prevalence of PA ranges from 5% to 12% around the globe, and the most common causes are adrenal adenoma and adrenal hyperplasia. The importance of PA recognition arises from the fact that it can have a remarkably adverse cardiovascular and renal impact, which can even result in death. The aldosterone-to-renin ratio (ARR) is the election test for screening PA, and one of the confirmatory tests, such as oral sodium loading (OSL) or saline infusion test (SIT), is in general necessary to confirm the diagnosis. The distinction between adrenal hyperplasia (AH) or aldosterone-producing adenoma (APA) is essential to select the appropriate treatment. Therefore, in order to identify the subtype of PA, imaging exams such as computed tomography or magnetic ressonance imaging, and/or invasive investigation such as adrenal catheterization must be performed. According to the subtype of PA, optimal treatment – surgical for APA or pharmacological for AH, with drugs like spironolactone and amiloride – must be offered

The A allele of the rs1990760 polymorphism in the IFIH1 gene is associated with protection for arterial hypertension in type 1 diabetic patients and with expression of this gene in human mononuclear cells

Background: The rs1990760 polymorphism of interferon induced with helicase C domain 1 (IFIH1) has been associated with type 1 diabetes mellitus (T1DM). Here, we investigated whether this polymorphism is associated with T1DM or its clinical characteristics in a Brazilian population, and if IFIH1 gene expression in mononuclear cells from T1DM patients differs according to the genotypes of this polymorphism. A meta-analysis was also conducted to evaluate if the rs1990760 polymorphism is associated with T1DM. Methods: Frequencies of the rs1990760 polymorphism were analyzed in 527 T1DM patients and in 517 healthy subjects. IFIH1 gene expressions according to genotypes were measured in a sub-sample of 26 T1DM patients by quantitative realtime PCR. Results: Our data show the association of the A allele with risk to T1DM under a dominant model of inheritance [odds ratio (OR) = 1.421, P = 0.037], adjusting for ethnicity. The meta-analysis revealed significant association between the rs199760A allele and risk for T1DM for all analyzed inheritance models. Surprisingly, T1DM patients carrying the A allele showed lower levels of systolic (P = 0.001) and diastolic (P = 1610210) blood pressures as compared to G/G carriers. Furthermore, the A/A genotype seems to be associated with protection to arterial hypertension (AH) after adjustment for covariates (OR = 0.339, P = 0.019). IFIH1 gene expression in mononuclear cells from 26 T1DM patients did not differ among genotypes (P = 0.274). Nevertheless, IFIH1 gene expression was increased in mononuclear cells from T1DM patients with AH as compared with T1DM patients without AH [6.7 (1.7–2.0) vs. 1.8 (1.3–7.1) arbitrary units; P = 0.036]. The association with blood pressures and AH was not observed in patients with type 2 diabetes mellitus. Conclusions: Our results indicate that the rs1990760 polymorphism is associated with T1DM. Interestingly, the rs1990760 A allele seems to be associated with protection for AH in T1DM patients. Further studies are needed to confirm the association with AH

Urinary peptidomics and bioinformatics for the detection of diabetic kidney disease

The aim of this study was to establish a peptidomic profle based on LC-MS/MS and random forest (RF) algorithm to distinguish the urinary peptidomic scenario of type 2 diabetes mellitus (T2DM) patients with diferent stages of diabetic kidney disease (DKD). Urine from 60 T2DM patients was collected: 22 normal (stage A1), 18 moderately increased (stage A2) and 20 severely increased (stage A3) albuminuria. A total of 1080 naturally occurring peptides were detected, which resulted in the identifcation of a total of 100 proteins, irrespective of the patients’ renal status. The classifcation accuracy showed that the most severe DKD (A3) presented a distinct urinary peptidomic pattern. Estimates for peptide importance assessed during RF model training included multiple fragments of collagen and alpha-1 antitrypsin, previously associated to DKD. Proteasix tool predicted 48 proteases potentially involved in the generation of the 60 most important peptides identifed in the urine of DM patients, including metallopeptidases, cathepsins, and calpains. Collectively, our study lightened some biomarkers possibly involved in the pathogenic mechanisms of DKD, suggesting that peptidomics is a valuable tool for identifying the molecular mechanisms underpinning the disease and thus novel therapeutic targets