Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Effect of Anaerobic Digestate on the Fatty Acid Profile and Biodiesel Properties of Chlorella sorokiniana Grown Heterotrophically

The growth kinetics and the lipid and protein content of the microalgal species Chlorella sorokiniana (CS) grown heterotrophically in growth media containing glycerol and increasing amounts of anaerobic digestate (AD) equal to 0%, 15%, 30%, and 50% was studied. The effect of the AD on the fatty acid (FA) distribution of the bio-oil extracted from the CS, as well as on the fatty acid methyl ester (FAME) properties such as the saponification number (SN), the iodine value (IV), the cetane number (CN), and the higher heating value (HHV) was also estimated. The percentage of AD in the growth medium affects the rate of carbon uptake. The maximum carbon uptake rate occurs at about 30% AD. Protein and lipid content ranged from 32.3&ndash;38.4% and 18.1&ndash;23.1%, respectively. Fatty acid distribution ranged from C10 to C26. In all AD percentages the predominant fatty acids were the medium chain FA C16 to C18 constituting up to about 89% of the total FA at 0% AD and 15% AD and up to about 54% of the total FA at 30% AD and 50% AD. With respect to unsaturation, monounsaturated FA (MUFA) were predominant, up to 56%, while significant percentages, up to about 38%, of saturated FA (SFA) were also produced. The SN, IV, CN, and HHV ranged from 198.5&ndash;208.3 mg KOH/g FA, 74.5&ndash;93.1 g I/100 g FAME, 52.7&ndash;56.1, and 39.7&ndash;40.0 MJ/kg, respectively. The results showed that with increasing AD percentage, the CN values tend to increase, while decrease in IV leads to biofuel with better ignition quality

Effect of Anaerobic Digestate on the Fatty Acid Profile and Biodiesel Properties of <i>Chlorella sorokiniana</i> Grown Heterotrophically

The growth kinetics and the lipid and protein content of the microalgal species Chlorella sorokiniana (CS) grown heterotrophically in growth media containing glycerol and increasing amounts of anaerobic digestate (AD) equal to 0%, 15%, 30%, and 50% was studied. The effect of the AD on the fatty acid (FA) distribution of the bio-oil extracted from the CS, as well as on the fatty acid methyl ester (FAME) properties such as the saponification number (SN), the iodine value (IV), the cetane number (CN), and the higher heating value (HHV) was also estimated. The percentage of AD in the growth medium affects the rate of carbon uptake. The maximum carbon uptake rate occurs at about 30% AD. Protein and lipid content ranged from 32.3–38.4% and 18.1–23.1%, respectively. Fatty acid distribution ranged from C10 to C26. In all AD percentages the predominant fatty acids were the medium chain FA C16 to C18 constituting up to about 89% of the total FA at 0% AD and 15% AD and up to about 54% of the total FA at 30% AD and 50% AD. With respect to unsaturation, monounsaturated FA (MUFA) were predominant, up to 56%, while significant percentages, up to about 38%, of saturated FA (SFA) were also produced. The SN, IV, CN, and HHV ranged from 198.5–208.3 mg KOH/g FA, 74.5–93.1 g I/100 g FAME, 52.7–56.1, and 39.7–40.0 MJ/kg, respectively. The results showed that with increasing AD percentage, the CN values tend to increase, while decrease in IV leads to biofuel with better ignition quality

Histology and Immunohistochemistry of Radial Arteries Are Suggestive of an Interaction between Calcification and Early Atherosclerotic Lesions in Chronic Kidney Disease

Background and Objectives: recent studies suggest an implication of immune mechanisms in atherosclerotic disease. In this paper, the interaction between inflammation, calcification, and atherosclerosis on the vessel walls of patients with chronic kidney disease (CKD) is described and evaluated. Materials and Methods: patients with stage V CKD, either on pre-dialysis (group A) or on hemodialysis (HD) for at least 2 years (group B), in whom a radiocephalic arteriovenous fistula (RCAVF) was created, were included in the study. The control group included healthy volunteers who received radial artery surgery after an accident. The expressions of inflammatory cells, myofibroblasts, and vascular calcification regulators on the vascular wall were estimated, and, moreover, morphometric analysis was performed. Results: the expressions of CD68(+) cells, matrix carboxyglutamic acid proteins (MGPs), the receptor activator of nuclear factor-kB (RANK) and RANK ligand (RANKL), and osteoprotegerin (OPG), were significantly increased in CKD patients compared to the controls p = 0.02; p = 0.006; p = 0.01; and p = 0.006, respectively. In morphometric analysis, the I/M and L/I ratios had significant differences between CKD patients and the controls 0.3534 ± 0.20 vs. 0.1520 ± 0.865, p = 0.003, and 2.1709 ± 1.568 vs. 4.9958 ± 3.2975, p = 0.03, respectively. The independent variables correlated with the degree of vascular calcification were the intensity of CD34(+), aSMA(+) cells, and OPG, R2 = 0.76, p &lt; 0.0001, and, with intima-media thickness (IMT), the severity of RANKL expression R2 = 0.3, p &lt; 0.0001. Conclusion: atherosclerosis and vascular calcification in CKD seem to be strongly regulated by an immunological and inflammatory activation on the vascular wall

Effects of mineralocorticoid receptor antagonists in proteinuric kidney disease: A systematic review and meta-analysis of randomized controlled trials

Background: Reductions in albuminuria of more than 30% are considered a strong marker of delay of chronic kidney disease (CKD) progression. Single renin–angiotensin system (RAS) blockade represents the cornerstone of CKD treatment. However, as CKD progression still occurs, other nephroprotective options were explored; mineralocorticoid receptor antagonists (MRA) were tested with generally positive results. Methods: We conducted a systematic review and meta-analysis on the effects of MRAs on albuminuria/proteinuria, and adverse events, such as change in renal function and hyperkalemia incidence. A detailed search in electronic databases, clinical trial registries and grey literature was performed to retrieve randomized controlled trials (RCTs) in which administration of an MRA alone or on-top of ACEi/ARB was compared with placebo or active treatment. Results: Of the 45 initially identified reports, 31, with 2767 participants, were included in analysis of the primary outcome. The use of MRAs (alone or on top of RAS blockade) compared with placebo decreased urine albumin-to-creatinine ratio (UACR) by −24.55% (95% CI −29.57 to −19.53%), urine protein-to-creatinine ratio (UPCR) by −53.93% (95% CI −79% to −28.86%) and 24 h albumin excretion by −32.47% (95% CI −41.1 to −23.85%). MRAs also reduced UACR by −22.48% (95% CI −24.51 to −20.44%) compared with calcium-channel-blockers (CCBs), whereas no differences were found compared with a second ACEi/ARB or nonpotassium-sparing diuretics. Addition of an MRA was associated with change in estimated glomerular filtration rate (eGFR) of −2.38 ml/min per 1.73 m2 (95% CI −3.51 to −1.25), rise in potassium by 0.22 mEq/l (95% CI 0.16–0.28 mEq/l) and a 2.6-fold increase in hyperkalemia risk (RR 2.63, 95% CI 1.69–4.08) compared with placebo/active control. Conclusion: Use of MRAs alone or on top of RAS blockade confers important antiproteinuric effects in patients with CKD, with a slight increase in mean potassium levels.Sin financiación4.171 JCR (2019) Q1, 13/65 Peripheral Vascular Disease1.365 SJR (2019) Q1, 42/186 Physiology, 65/362 Cardiology and Cardiovascular Medicine, 21/139 Internal MedicineNo data IDR 2019UE

Histology and Immunohistochemistry of Radial Arteries Are Suggestive of an Interaction between Calcification and Early Atherosclerotic Lesions in Chronic Kidney Disease

Background and Objectives: recent studies suggest an implication of immune mechanisms in atherosclerotic disease. In this paper, the interaction between inflammation, calcification, and atherosclerosis on the vessel walls of patients with chronic kidney disease (CKD) is described and evaluated. Materials and Methods: patients with stage V CKD, either on pre-dialysis (group A) or on hemodialysis (HD) for at least 2 years (group B), in whom a radiocephalic arteriovenous fistula (RCAVF) was created, were included in the study. The control group included healthy volunteers who received radial artery surgery after an accident. The expressions of inflammatory cells, myofibroblasts, and vascular calcification regulators on the vascular wall were estimated, and, moreover, morphometric analysis was performed. Results: the expressions of CD68(+) cells, matrix carboxyglutamic acid proteins (MGPs), the receptor activator of nuclear factor-kB (RANK) and RANK ligand (RANKL), and osteoprotegerin (OPG), were significantly increased in CKD patients compared to the controls p = 0.02; p = 0.006; p = 0.01; and p = 0.006, respectively. In morphometric analysis, the I/M and L/I ratios had significant differences between CKD patients and the controls 0.3534 ± 0.20 vs. 0.1520 ± 0.865, p = 0.003, and 2.1709 ± 1.568 vs. 4.9958 ± 3.2975, p = 0.03, respectively. The independent variables correlated with the degree of vascular calcification were the intensity of CD34(+), aSMA(+) cells, and OPG, R2 = 0.76, p 2 = 0.3, p Conclusion: atherosclerosis and vascular calcification in CKD seem to be strongly regulated by an immunological and inflammatory activation on the vascular wall

Novel and Founder Pathogenic Variants in X-Linked Alport Syndrome Families in Greece

Alport syndrome (AS) is the most frequent monogenic inherited glomerulopathy and is also genetically and clinically heterogeneous. It is caused by semi-dominant pathogenic variants in the X-linked COL4A5 (NM_000495.5) gene or recessive variants in the COL4A3/COL4A4 (NM_000091.4/NM_000092.4) genes. The disease manifests in early childhood with persistent microhematuria and can progress to proteinuria and kidney failure in adolescence or early adulthood if left untreated. On biopsy, pathognomonic features include alternate thinning, thickening and lamellation of the glomerular basement membrane (GBM), in the presence of podocyte foot process effacement. Although previous studies indicate a prevalence of AS of about 1/50,000, a recent publication reported a predicted rate of pathogenic COL4A5 variants of 1/2320. We herewith present 98 patients (40 M/58 F) from 26 Greek families. We are selectively presenting the families segregating the X-linked form of AS with pathogenic variants in the COL4A5 gene. We found 21 different pathogenic variants, 12 novel: eight glycine and one proline substitutions in the collagenous domain, one cysteine substitution in the NC1 domain, two premature termination of translation codons, three splicing variants, one 5-bp insertion/frameshift variant, one indel-frameshift variant and four gross deletions. Notably, patients in six families we describe here and three families we reported previously, carried the COL4A5-p.G624D substitution, a founder defect encountered all over Europe which is hypomorphic with mostly milder symptomatology. Importantly, on several occasions, the correct genetic diagnosis reclassified patients as patients with AS, leading to termination of previous immunosuppressive/cyclosporine A therapy and a switch to angiotensin converting enzyme inhibitors (ACEi). With the understanding that all 98 patients span a wide range of ages from infancy to late adulthood, 15 patients (11 M/4 F) reached kidney failure and 11 (10 M/1 F) received a transplant. The prospects of avoiding lengthy diagnostic investigations and erroneous medications, and the advantage of delaying kidney failure with very early administration of renin-angiotensin-aldosterone system (RAAS) blockade, highlights the importance of timely documentation of AS by genetic diagnosis