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 aldosteroneproducing 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 aim of this study was to establish a peptidomic profile based on LC-MS/MS and random forest (RF) algorithm to distinguish the urinary peptidomic scenario of type 2 diabetes mellitus (T2DM) patients with different 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 identification of a total of 100 proteins, irrespective of the patients' renal status. The classification 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 identified 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.Diabetic kidney disease (DKD) is the main cause of end-stage renal disease in the United States 1 . In Europe, a quarter of patients that start renal replacement therapy has diabetes mellitus as the primary renal diagnosis 2 . The presence of reduced kidney function in patients with type 2 diabetes (T2DM) predominantly accounts for the observed increase in mortality 3 . In Brazil, the crude diabetes death rate increased 90%, while that of kidney disease due to diabetes more than doubled from 1990 to 2015 4 .Diagnosis of DKD is based on the detection of elevated albuminuria and/or decreased glomerular filtration rate (GFR) 5 . The earliest putative diagnostic sign of diabetic renal damage is moderately elevated albuminuria 6,7 . However, substantial renal damage is already present at this stage. Furthermore, a non-albuminuric form of DKD, expressed by reduced GFR has been increasingly recognized, broadening the spectrum of the kidney involvement 8 . Reduced eGFR is generally estimated via creatinine-based equations 9 . Although demographic and clinical variables are included in the equation in an attempt to capture the variability in creatinine, the accuracy of equations is still disappointing 10,11 . Taken together, these evidence point that the current DKD clinical markers are nonspecific and late indicators of renal injury, suggesting the need for the search of early biomarkers, allowing interventions prior to established organ damage 12 . In addition, they can help the understanding of the pathogenesis of kidney disease and provide insight into novel therapeutic targets [13][14][15][16][17] .The number of proteins identified associated with DKD has constantly increased, but none of the proposed urinary biomarkers has been s...

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 ± 10 years, 49 males (43%), DM duration 22 ± 10 years, with GFR > 60 ml/min/1.73 m2 were evaluated. Patients with GFRs 60–90 ( n = 50) had significantly lower 25(OH)D levels than individuals with GFRs > 90 ml/min/1.73 m2 ( n = 64), respectively 40 ± 20 versus 48 ± 20 nmol/l, p = 0.027. This difference was more pronounced for older individuals (39 ± 20 versus 54 ± 23 nmol/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 41 nmol/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 ± 19 nmol/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.

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