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Background Older adults at a higher risk of adverse outcomes and mortality if they get infected with Severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2). These undesired outcomes are because ageing is associated with other conditions like multimorbidity, frailty and disability. This paper describes the impact of frailty on coronavirus disease 2019 (COVID-19) management and outcomes. We also try to point out the role of inflamm-ageing, immunosenescence and reduced microbiota diversity in developing a severe form of COVID-19 and a different response to COVID-19 vaccination among older frail adults. Additionally, we attempt to highlight the impact of frailty on intensive care unit (ICU) outcomes, and hence, the rationale behind using frailty as an exclusion criterion for critical care admission. Similarly, the importance of using a time-saving, validated, sensitive, and user-friendly tool for frailty screening in an acute setting as COVID-19 triage. We performed a narrative review. Publications from 1990 to March 2021 were identified by searching the electronic databases MEDLINE, CINAHL and SCOPUS. Based on this search, we have found that in older frail adults, many mechanisms contribute to the severity of COVID-19, particularly cytokine storm; those mechanisms include lower immunological capacity and status of ongoing chronic inflammation and reduced gut microbiota diversity. Higher degrees of frailty were associated with poor outcomes and higher mortality rates during and after ICU admission. Also, the response to COVID-19 vaccination among frail older adults might differ from the general population regarding effectiveness and side effects. Researches also had shown that there are many tools for identifying frailty in an acute setting that could be used in COVID-19 triage, and before ICU admission, the clinical frailty scale (CFS) was the most recommended tool. Conclusion Older frail adults have a pre-existing immunopathological base that puts them at a higher risk of undesired outcomes and mortality due to COVID-19 and poor response to COVID-19 vaccination. Also, their admission in ICU should depend on their degree of frailty rather than their chronological age, which is better to be screened using the CFS.

For more than 6 decades, many patients with advanced chronic kidney disease (CKD) have undergone surgical parathyroidectomy (sPTX) for severe secondary hyperparathyroidism (SHPT) mainly based historical clinical practice patterns, but not on evidence of outcome.We aimed in this meta-analysis to evaluate the benefits and harms of sPTX in patients with SHPT. We searched MEDLINE (inception to October 2016), EMBASE and Cochrane Library (through Issue 10 of 12, October 2016) and website clinicaltrials.gov (October 2016) without language restriction. Eligible studies evaluated patients reduced glomerular filtration rate (GFR), below 60 mL/min/1.73 m2 (CKD 3-5 stages) with hyperparathyroidism who underwent sPTX. Reviewers working independently and in duplicate extracted data and assessed the risk of bias. The final analysis included 15 cohort studies, comprising 24,048 participants. Compared with standard treatment, sPTX significantly decreased all-cause mortality (RR 0.74 [95% CI, 0.66 to 0.83]) in End Stage Kidney Disease (ESKD) patients with biochemical and / or clinical evidence of SHPT. sPTX was also associated with decreased cardiovascular mortality (RR 0.59 [95% CI, 0.46 to 0.76]) in 6 observational studies that included almost 10,000 patients. The available evidence, mostly observational, is at moderate risk of bias, and limited by indirect comparisons and inconsistency in reporting for some outcomes (eg. short term adverse events, including documented voice change or episodes of severe hypocalcaemia needing admission or long-term adverse events, including undetectable PTH levels, risk of fractures etc.). Taken together, the results of this meta-analysis would suggest a clinically significant beneficial effect of sPTX on all-cause and cardiovascular mortality in CKD patients with SHPT. However, given the observational nature of the included studies, the case for a properly conducted, independent randomised controlled trial comparing surgery with medical therapy and featuring many different outcomes from mortality to quality of life (QoL) is now very strong.

Complement system inhibitors are emerging as promising therapies in nephrology, particularly for diseases where complement dysregulation is central to pathogenesis. This review summarizes the role of complement activation in kidney diseases and current evidence supporting complement-targeted treatments. As the complement system can be involved in the pathogenesis of different diseases to varying degrees, several research works have been conducted. These research efforts aim, firstly, to understand the mechanisms and role of complement cascade components in the most prevalent nephrological diseases and, secondly, to explore the potential of complement system inhibitors in these conditions and their possible clinical applications. Clinical trials demonstrate that complement inhibitors are most effective in conditions with significant complement involvement, such as C3 glomerulopathy (C3G), atypical hemolytic uremic syndrome (aHUS), and immune complex membranoproliferative glomerulonephritis (IC-MPGN). These agents show variable benefits in diseases with partial complement activation, including lupus nephritis and ANCA-associated vasculitis, while their role in disorders like diabetic nephropathy and focal–segmental glomerulosclerosis remains limited. Complement inhibition offers a targeted strategy to prevent disease progression and improve outcomes in selected nephrological disorders.

Chronic subclinical volume overload occurs very frequently and may be ubiquitous in hemodialysis (HD) patients receiving the standard thrice-weekly treatment. It is directly associated with hypertension, increased arterial stiffness, left ventricular hipertrophy, heart failure, and eventually, higher mortality and morbidity. We aimed to assess for the first time if the relationship between bioimpedance assessed overhydration and survival is maintained when adjustments for echocardiographic parameters are considered. A prospective cohort trial was conducted to investigate the impact of overhydration on all cause mortality and cardiovascular events (CVE), by using a previously reported cut-off value for overhydration and also investigating a new cut-off value derived from our analysis of this specific cohort. The body composition of 221 HD patients from a single center was assessed at baseline using bioimpedance. In 157 patients supplemental echocardiography was performed (echocardiography subgroup). Comparative survival analysis was performed using two cut-off points for relative fluid overload (RFO): 15% and 17.4% (a value determined by statistical analysis to have the best predictive value for mortality in our cohort). In the entire study population, patients considered overhydrated (using both cut-offs) had a significant increased risk for all-cause mortality in both univariate (HR = 2.12, 95%CI = 1.30-3.47 for RFO>15% and HR = 2.86, 95%CI = 1.72-4.78 for RFO>17.4%, respectively) and multivariate (HR = 1.87, 95%CI = 1.12-3.13 for RFO>15% and HR = 2.72, 95%CI = 1.60-4.63 for RFO>17.4%, respectively) Cox survival analysis. In the echocardiography subgroup, only the 17.4% cut-off remained associated with the outcome after adjustment for different echocardiographic parameters in the multivariate survival analysis. The number of CVE was significantly higher in overhydrated patients in both univariate (HR = 2.46, 95%CI = 1.56-3.87 for RFO >15% and HR = 3.67, 95%CI = 2.29-5.89 for RFO >17.4%) and multivariate (HR = 2.31, 95%CI = 1.42-3.77 for RFO >15% and HR = 4.17, 95%CI = 2.48-7.02 for RFO >17.4%) Cox regression analysis. The study shows that the hydration status is associated with the mortality risk in a HD population, independently of cardiac morphology and function. We also describe and propose a new cut-off for RFO, in order to better define the relationship between overhydration and mortality risk. Further studies are needed to properly validate this new cut-off in other HD populations.

Type 2 diabetes mellitus (T2DM) is associated with increased risk of cardiovascular disease and nephropathy—now the leading cause of end-stage renal disease and dialysis in Europe and the United States. Inflammation and oxidative stress play a pivotal role in the development of diabetic complications. Silymarin, an herbal drug with antioxidant and anti-inflammatory properties, may improve glycemic control and prevent the progression of the complications. In a systematic review and meta-analysis including five randomized controlled trials and 270 patients, routine silymarin administration determines a significant reduction in fasting blood glucose levels (−26.86 mg/dL; 95% CI −35.42–18.30) and HbA1c levels (−1.07; 95% CI −1.73–0.40) and has no effect on lipid profile. Benefits for silymarin on proteinuria and CKD progressions are reported in only one small study and are uncertain. However, being aware of the low quality of the available evidence and elevated heterogeneity of these studies, no recommendation can be made and further studies are needed.

This article explores the multifaceted role of micro-ribonucleic acids (RNAs) (miRNAs) as critical posttranscriptional regulators in renal physiology and disease, with a focus on their emerging significance in glomerulopathies. miRNAs, small endogenous noncoding RNAs, modulate gene expression by promoting messenger RNA degradation or inhibiting translation, thereby orchestrating essential cellular processes such as proliferation, differentiation, apoptosis, and stress responses. Recent advances have revealed that aberrant miRNA expression profiles are intricately linked to the pathogenesis and progression of various renal diseases, including acute kidney injury, chronic kidney disease, alloimmune injury in solid organ transplantation and glomerulonephritis. This review summarizes the pathogenic and protective roles of miRNAs in major glomerulopathies, discusses their potential as diagnostic and prognostic biomarkers, and outlines future directions for their integration into personalized therapeutic strategies. At the moment, it is not fully established whether some of these mechanisms are the primary pathogenic driver or a secondary response. Combining miRNAs with other molecular markers may further enhance diagnostic and predictive accuracy, facilitating clinical translation, while selective targeting of specific miRNAs at different stages of disease progression could offer promising therapeutic opportunities.

(1) Background: Cardiovascular disease represents the leading cause of morbidity and mortality in patients with autosomal dominant polycystic kidney disease (ADPKD), often developing early in the disease course, even in the presence of preserved renal function. We aimed to evaluate circulating heart-type fatty acid-binding protein (H-FABP) as a marker of subclinical cardiac involvement and cardiorenal interaction in ADPKD. (2) Methods: In this single-center observational study, 80 adult patients with ADPKD receiving tolvaptan therapy were evaluated using echocardiography, renal function parameters, and circulating H-FABP levels. Associations between H-FABP and echocardiographic indices of cardiac structure and function, as well as renal parameters, were assessed using linear regression models. In addition, a composite severity score integrating CKD stage and H-FABP levels was constructed to assess the combined cardiorenal burden. (3) Results: Higher H-FABP concentrations were significantly associated with echocardiographic markers suggestive of subclinical cardiac involvement, particularly parameters related to impaired myocardial relaxation, including lower E/A ratio and reduced tissue Doppler e' velocities. These associations remained significant after adjustment for renal function and relevant clinical covariates. In parallel, H-FABP levels were also associated with markers of renal disease severity, including lower baseline eGFR and greater total kidney volume. The composite severity score showed a graded association with echocardiographic parameters, with a progressive trend toward less favorable diastolic indices as risk categories increased. These findings suggest a potential complementary role for H-FABP in the integrated evaluation of cardiorenal involvement in ADPKD. Given the cross-sectional design and single-centre setting, these results should be considered hypothesis-generating and require prospective validation in larger, independent cohorts.

Background and Hypothesis: Mortality in hemodialysis (HD) remains high and is not fully explained by traditional risk factors. Biomarkers reflecting myocardial stress and fibrosis, together with measures of vascular stiffness, may provide additional prognostic information in this population. Methods: We conducted a retrospective study evaluating 173 HD patients who were clinically stable and asymptomatic at baseline over a follow-up period of over 10 years. Patients were classified into four groups based on median baseline values of NT-proBNP and galectin-3 (4234 pg/mL and 28.1 ng/mL, respectively). Primary outcomes were all-cause mortality and major adverse cardiovascular events (MACE). Pulse wave velocity (PWV) was evaluated as an additional prognostic marker. Results: During follow-up, 76.9% of patients died. Higher NT-proBNP levels were associated with increased all-cause mortality, irrespective of galectin-3 levels, with adjusted hazard ratios of 2.58 and 1.93 compared with the reference group (p < 0.05). Age and PWV were independently associated with mortality risk, corresponding to a 4% increase in risk per year of age and a 6% increase per 1 m/s increase in PWV. MACE occurred in 26.8% of patients and did not differ significantly between biomarker-defined groups. Conclusions: In this long-term HD cohort, elevated NT-proBNP and increased arterial stiffness were independently associated with higher all-cause mortality. These findings support the complementary prognostic value of markers of cardiac stress and vascular stiffness in chronic hemodialysis patients.

PurposeThe aim of this prospective cohort study was: to identify the association between different biomarkers [proprotein convertase subtilisin/kexin 9-PCSK9, lipoprotein(a)-Lp(a) and high‐sensitivity C‐reactive protein-hsCRP] and the cardiovascular events; to evaluate the relationship between the 3 biomarkers mentioned above and the renal outcomes that contributed to end-stage renal disease (ESRD).MethodsWe studied 110 patients with chronic kidney disease (CKD) stages 2 to 4. The identification of the new cardiovascular events and the renal outcomes were performed by clinical and paraclinical explorations.Results350 patients were examined and 110 (31.4%) were included in this study. The mean age was 55.6 ± 10.9 years, with a higher number of men compared to women. The CKD patients with de novo cardiovascular events and new renal outcome during the study, had significantly increased values of total cholesterol (TC), low density cholesterol lipoprotein (LDL-C) at 6 and 12 months and higher levels of Lp(a), PCSK9, hsCRP and low ankle–brachial index (ABI) and ejection fraction (EF) values compared to patients without cardiovascular and renal events. In CKD patients, PCSK9 > 220 ng/mL was a predictor of cardiovascular events, while the EF < 50% was a predictor for renal outcomes. For CKD patients with PCSK9 > 220 ng/mL and hsCRP > 3 mg/L levels, the time-interval for the new cardiovascular and renal events occurrence were significantly decreased compared to patients displaying low values of these biomarkers.ConclusionThe results of this study show that PCSK9 > 220 ng/mL was predictor for cardiovascular events, while EF < 50% was predictor for CKD progression to ESRD. PCSK9 > 220 ng/mL and hsCRP > 3 mg/L were associated with the occurrence of renal and cardiovascular events earlier.

Background: Magnesium is an essential ion for all living cells because over 300 enzymes require the presence of magnesium for their catalytic action. To date, no group has evaluated magnesium as a cardiovascular risk factor in chronic kidney disease (CKD) subjects, in which closely interrelated factors and potential confounders such as endothelial dysfunction, insulin resistance (the homeostasis model assessment (HOMA) index) and inflammation (expressed as serum C-reactive protein (CRP) levels) were also considered. Methods: Between March 2006 and December 2010, 283 CKD patients were followed up for time-to-event analysis until the occurrence of fatal or nonfatal cardiovascular events. Endothelium-dependent vasodilatation (flow-mediated dilatation; FMD) and endothelium-independent vasodilatation (nitroglycerin-mediated dilatation) of the brachial artery were assessed noninvasively using high-resolution ultrasound. Results: From the univariate analysis of FMD, it appears that a higher magnesium level is associated with less endothelial dysfunction. When a multivariate analysis was performed, magnesium and estimated glomerular filtration rates (eGFR) maintained a strong positive correlation with FMD, supporting the hypothesis that higher levels of magnesium may protect against endothelial damage. In univariate Cox proportional hazards models, FMD, magnesium, high sensitivity CRP, the HOMA index, eGFR, comorbid diabetes, hypertension, smoking status, systolic blood pressure, serum phosphate and intact parathormone emerged as significant predictors for cardiovascular outcomes. Kaplan-Meier curves showed significantly higher cardiovascular mortality rates in CKD patients whose serum magnesium levels were below 2.05 mg/dl. Conclusions: This observational cohort study showed that magnesium may be an independent predictor of future cardiovascular outcomes and is the first study demonstrating such a role in etiologically diagnosed CKD patients, across different stages.