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Background: A coronavirus disease 2019 (COVID-19) outbreak led to a worldwide pandemic. COVID-19 not only caused acute symptoms during the severe phase of the disease, but also induced long-term side effects on the functioning of many organs and systems. Symptoms that were associated with the disease and present at least 3 months after recovery were named long COVID. The aim of this study was to assess if mild-to-moderate COVID-19 may lead to the dysfunction of respiratory, cardiovascular, neural, and renal systems in healthy blood donors who recovered from the disease at least 6 months earlier. Methods: Here, we examined 294 adults among volunteer blood donors divided into convalescents (n = 215) and healthy controls (n = 79). Concentrations of soluble CD163, TGF beta, Lp-PLA2, NCAM-1, S100, NGAL, and creatinine were measured either by ELISA or automated methods. The probability value p < 0.05 was considered as statistically significant. Results: We found significant differences in Lp-PLA2, S100, and NCAM-1 between convalescents and never-infected subjects. Lp-PLA2 and NCAM-1 were lower, and S100 higher, in convalescents than in the control group. Conclusion: Mild-to-moderate COVID-19 convalescents are at a low risk of developing lung fibrosis or chronic kidney disease. However, they should regularly carry out their prophylaxis examinations for early detection of possible negative outcomes of COVID-19. [ABSTRACT FROM AUTHOR]

There are few reports on short-term changes in renal function after surgical aortic valve replacement, and data are scarce regarding its impact on long-term outcomes. This is a retrospective study of patients who underwent isolated aortic valve replacement between 2009 and 2020 in four medical centers. Patients with end-stage renal disease were excluded. Renal function was assessed based on short-term changes. Multivariable regression models were used to identify predictors of improvement/deterioration. Cox proportional hazard models were used to assess survival trends. The study included 2402 patients, with a mean age of 69.3 years and a mean eGFR of 82.3 mL/min/1.73 m2. Short-term improvement rates were highest in stage 4 (24.4%) and stage 3 (16.8%) patients. Deterioration rates were highest in stage 1 (38.1%) and stage 2 (34.8%) patients. Deterioration in the chronic kidney disease stage was associated with a higher ten-year mortality (p < 0.001, HR 1.46); an improved stage trended toward improved survival (p = 0.14, HR 0.722). Patients with stage 3 and 4 kidney disease tended to remain stable or improve in the short term after aortic valve replacement while patients at stages 1 and 2 were at increased risk of deteriorating. [ABSTRACT FROM AUTHOR]

Cardiovascular mortality is a leading cause of death in chronic kidney disease (CKD), as is IgA nephropathy (IgAN). The purpose of this study is to find different biomarkers to estimate the outcome of the disease, which is significantly influenced by the changes in vessels (characterized by arterial stiffness) and the heart. In our cross-sectional study, 90 patients with IgAN were examined. The N-terminal prohormone of brain natriuretic peptide (NT-proBNP) was measured as a heart failure biomarker by an automated immonoassay method, while the carboxy-terminal telopeptide of collagen type I (CITP) as a fibrosis marker was determined using ELISA kits. Arterial stiffness was determined by measuring carotid–femoral pulse wave velocity (cfPWV). Renal function and routine echocardiography examinations were performed as well. Based on eGFR, patients were separated into two categories, CKD 1-2 and CKD 3-5. There were significantly higher NT-proBNP (p = 0.035), cfPWV (p = 0.004), and central aortic systolic pressure (p = 0.037), but not CITP, in the CKD 3-5 group. Both biomarker positivities were significantly higher in the CKD 3-5 group (p = 0.035) compared to the CKD 1-2 group. The central aortic systolic pressure was significantly higher in the diastolic dysfunction group (p = 0.034), while the systolic blood pressure was not. eGFR and hemoglobin levels showed a strong negative correlation, while left ventricular mass index (LVMI), aortic pulse pressure, central aortic systolic pressure, and cfPWV showed a positive correlation with NT-proBNP. cfPWV, aortic pulse pressure, and LVMI showed a strong positive correlation with CITP. Only eGFR was an independent predictor of NT-proBNP by linear regression analysis. NT-proBNP and CITP biomarkers may help to identify IgAN patients at high risk for subclinical heart failure and further atherosclerotic disease. [ABSTRACT FROM AUTHOR]

Background: Both direct and indirect effects of COVID-19 have been found in all age groups. In particular, adult data demonstrated significant changes in patients with chronic and metabolic disease (e.g., obesity, diabetes, chronic kidney disease (CKD), and metabolic associated fatty liver dysfunction (MAFLD)), while similar pediatric evidence is still limited. We aimed at investigating the impact of the COVID-19 pandemic lockdown on the relationship between MAFLD and renal function in children with CKD due to congenital abnormalities of the kidney and urinary tract (CAKUT). Methods: A total of 21 children with CAKUT and CKD ≥ stage 1 underwent a comprehensive evaluation within 3 months before and 6 months after the first Italian lockdown. Results: At follow-up, CKD patients with MAFLD presented higher BMI-SDS, serum uric acid, triglycerides, and microalbuminuria levels and lower eGFR levels than those without MAFLD (all p < 0.05). Higher ferritin and white blood cell concentrations were also found in patients with CKD diagnosed with MAFLD than peers without MAFLD (both p = 0.01). Compared to children without MAFLD, a higher delta of BMI-SDS, eGFR levels, and microalbuminuria levels was found in patients with MAFLD. Conclusions: Due to the negative influence of the COVID-19 lockdown on cardiometabolic health in childhood, a careful management of children with CKD is warranted. [ABSTRACT FROM AUTHOR]

The cardio-renal syndrome (CRS) type 2 is defined as a progressive loss of renal function following a primary insult to the myocardium that may be either acute or chronic but is accompanied by a decline in myocardial pump performance. The treatment of patients with CRS is difficult, and the disease often progresses to end-stage renal disease that is refractory to conventional therapy. While a good deal of information is known concerning renal injury in the CRS, less is understood about how reflex control of renal sympathetic nerve activity affects this syndrome. In this review, we provide insight into the role of the renal nerves, both from the afferent or sensory side and from the efferent side, in mediating renal dysfunction in CRS. We discuss how interventions such as renal denervation and abrogation of systemic reflexes may be used to alleviate renal dysfunction in the setting of chronic heart failure. We specifically focus on a novel cardiac sensory reflex that is sensitized in heart failure and activates the sympathetic nervous system, especially outflow to the kidney. This so-called Cardiac Sympathetic Afferent Reflex (CSAR) can be ablated using the potent neurotoxin resinferitoxin due to the high expression of Transient Receptor Potential Vanilloid 1 (TRPV1) receptors. Following ablation of the CSAR, several markers of renal dysfunction are reversed in the post-myocardial infarction heart failure state. This review puts forth the novel idea of neuromodulation at the cardiac level in the treatment of CRS Type 2. [ABSTRACT FROM AUTHOR]

Aim: Fibrates have proven efficacy in cardiovascular risk reduction and are commonly used, in addition to statins, to control hypertriglyceridaemia. Their use is often limited due to reduction in glomerular filtration rate at treatment initiation. However, recent studies suggest benign changes in kidney function and improvement of proteinuria, an established early marker of microvascular disease and kidney disease progression. We summarize the evidence from existing trials and provide a summary of effects of fibrates, alone or in combination, on kidney disease progression and proteinuria. Methods and Results: Systematic review and meta-analysis of randomized, controlled trials (PROSPERO CRD42020187764). Out of 12,243 potentially eligible studies, 29 were included in qualitative and quantitative analysis, with a total of 20,176 patients. Mean creatinine increased by 1.05 (95% CI (0.63 to 1.46)) units in patients receiving fibrates vs. comparator, and this was similar in all other subgroups. eGFR showed a bigger decrease in the fibrates arm (SMD −1.99; 95% CI (−3.49 to −0.48)) when all studies were pooled together. Notably, short-term serum creatinine and eGFR changes remained constant in the long-term. Pooled estimates show that fibrates improve albuminuria progression, RR 0.86; 95% CI (0.76 to 0.98); albuminuria regression, RR 1.19; 95% CI (1.08 to 1.310). Conclusions: Fibrates improve albuminuria in patients with and without diabetes when used to treat hyperlipidaemia. The modest creatinine increase should not be a limiting factor for fibrate initiation in people with preserved renal function or mild CKD. The long-term effects on kidney disease progression warrant further study. [ABSTRACT FROM AUTHOR]

BMAL1 is a core mammalian circadian clock transcription factor responsible for the regulation of the expression of thousands of genes. Previously, male skeletal-muscle-specific BMAL1-inducible-knockout (iMS-BMAL1 KO) mice have been described as a model that exhibits an aging-like phenotype with an altered gait, reduced mobility, muscle weakness, and impaired glucose uptake. Given this aging phenotype and that chronic kidney disease is a disease of aging, the goal of this study was to determine if iMS-BMAL1 KO mice exhibit a renal phenotype. Male iMS-BMAL1 KO and control mice were challenged with a low potassium diet for five days. Both genotypes responded appropriately by conserving urinary potassium. The iMS-BMAL1 KO mice excreted less potassium during the rest phase during the normal diet but there was no genotype difference during the active phase. Next, iMS-BMAL1 KO and control mice were used to compare markers of kidney injury and assess renal function before and after a phase advance protocol. Following phase advance, no differences were detected in renal mitochondrial function in iMS-BMAL1 KO mice compared to control mice. Additionally, the glomerular filtration rate and renal morphology were similar between groups in response to phase advance. Disruption of the clock in skeletal muscle tissue activates inflammatory pathways within the kidney of male mice, and there is evidence of this affecting other organs, such as the lungs. However, there were no signs of renal injury or altered function following clock disruption of skeletal muscle under the conditions tested. [ABSTRACT FROM AUTHOR]

Background: The results of long-term renal evolution in HCV-infected patients using sofosbuvir and velpatasvir (SOF/VEL), with or without ribavirin (RBV), are lacking. Aims: We evaluated the renal safety for HCV-infected patients receiving SOF/VEL. Methods: Between 1 June 2019 and 6 July 2020, we included 594 HCV-infected patients receiving SOF/VEL +/− RBV for 12 weeks in Taiwan. Viral eradication rate (defined by sustained virological response at week 12 post-treatment; SVR12) and changes to renal function were considered. Results: SVR12 was achieved in 99.3% (590/594) upon per-protocol analysis. Patients saw improved hepatobiliary function and fibrosis after the start of SOF/VEL therapy. For renal function, those with baseline estimated glomerular filtration rate (eGFR) ≥ 60 (mL/min/1.73 m2) experienced transient on-treatment reduction in renal function that improved upon ending treatment, but recurrent eGFR degradation during one-year follow-up. The use of RBV (OR = 5.200, 95% CI: 1.983–13.634, p = 0.001) was a significant risk factor at SVR24, while diabetes mellitus (OR = 2.765, 95% CI: 1.104–6.922, p = 0.030) and the use of RBV (OR = 3.143, 95% CI: 1.047–9.435, p = 0.041) were identified as significant risk factors of worsening renal function at SVR48. SOF/VEL did not worsen renal function among those with stage 4–5 chronic kidney disease (CKD) who were not receiving dialysis. Conclusions: A trend of decline in eGFR at 1 year after SOF/VEL treatment was observed among diabetic patients with baseline eGFR ≥ 60 (mL/min/1.73 m2) and concomitant use of RBV. The close monitoring of renal function is warranted. Further study should be conducted in order to weigh the risks and benefit of RBV. [ABSTRACT FROM AUTHOR]

Denosumab is approved for osteoporosis treatment in subjects with and without chronic kidney disease (CKD). Confirmation is required for its safety, treatment adherence, renal function effect, and mortality in patients with CKD. A retrospective cohort study was conducted to compare new users of denosumab in terms of their two-year drug adherence in all participants (overall cohort) and CKD participants (CKD subcohort), which was defined as baseline estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m2. The eGFR was calculated using the 2021 CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation. We defined high adherence (HA) users as receiving three or four doses and low adherence (LA) users as receiving one or two doses. All-cause mortality was analyzed using Kaplan–Meier curves and Cox regression models. In total, there were 1142 subjects in the overall cohort and 500 subjects in the CKD subcohort. HA users had better renal function status at baseline than LD users in the overall cohort. A decline in renal function was only observed among LD users in the overall cohort. In the CKD subcohort, no baseline renal function difference or renal function decline was demonstrated. The all-cause mortality rate of HA users was lower than LA users in both the overall cohort and CKD. A randomized control trial is warranted to target this unique population to confirm our observations. [ABSTRACT FROM AUTHOR]

Background: The prevalence of chronic kidney disease (CKD) is increasing annually in Taiwan. In addition to traditional risk factors, heavy metals contribute to the development of CKD. The aim of this study was to investigate associations among heavy metals and proteinuria and CKD in the general population in Southern Taiwan. We also explored the interaction and synergetic effects among heavy metals on proteinuria. Methods: We conducted a health survey in the general population living in Southern Taiwan between June 2016 and September 2018. Seven heavy metals were measured: blood lead (Pb) and urine nickel (Ni), chromium (Cr), manganese (Mn), arsenic (As), copper (Cu), and cadmium (Cd). Proteinuria was measured using reagent strips. CKD was defined as an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m2. Results: The mean age of the 2447 participants was 55.1 ± 13.2 years and included 977 males and 1470 females. Participants with high blood Pb and high urine Ni, Mn, Cu, and Cd were significantly associated with proteinuria. Interactions between blood Pb and urine Cr, and between urine Cd and Cu, had significant effects on proteinuria. The participants with high blood Pb and high urine Cu were significantly associated with an eGFR of <60 mL/min/1.73 m2. Conclusion: High blood Pb and high urine Cu may be associated with proteinuria and an eGFR of <60 mL/min/1.73 m2. High urine Ni, Mn, and Cd were significantly associated with proteinuria. Co-exposure to Cd and Cu, and Pb and Cr, may have synergistic effects on proteinuria. [ABSTRACT FROM AUTHOR]

Despite the proven superiority of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) over the Cockcroft–Gault (CG) formula, current guidelines recommend the latter to assess renal function in patients treated with non-vitamin K antagonist oral anticoagulants (NOACs). To assess the relationship between the CG and the recommended CKD-EPI formulas, in a cohort of atrial fibrillation (AF) patients treated with NOACs, and the misclassifications introduced by the CG formula for renal function levels, we estimated renal function with three equations: CG, CKD-EPI with body surface adjustment (1.73 mL/m2, CKD-EPI) and without such adjustment (CKD-EPI_noBSA), in all consecutive AF patients discharged from NOACs from the Cardiology Division of a main city hospital between February 1st and May 31st 2018. We compared the different estimates of glomerular filtration rate and potential renal function class misclassifications. We reclassified 37/115 patients (32.1%) when switching from the CG to the CKD-EPI; and 24/115 (20.8%) switching from the CG to the CKD-EPI_noBSA formulas. Class reallocation was distributed across all levels of renal function, but mostly affected the "hyper-normal" function. In estimating consequences of such reallocation, a change in NOAC dosages would have occurred in 10/115 patients (8.7%) when switching from the CG to the CKD-EPI formula and in 10/115 patients when switching from the CG to the CKD-EPI_noBSA formula. Although the CG method has been traditionally used to calculate renal function in all NOAC studies, a renal dysfunction class reallocation occurs in a substantial fraction of hospital-admitted AF patients with the use of better estimates of renal function. [ABSTRACT FROM AUTHOR]

Diabetes prevalence is constantly increasing and, nowadays, it affects more than 350 million people worldwide. Therefore, the prevalence of diabetic nephropathy (DN) has also increased, becoming the main cause of end-stage renal disease (ESRD) in the developed world. DN is characterized by albuminuria, a decline in glomerular filtration rate (GFR), hypertension, mesangial matrix expansion, glomerular basement membrane thickening, and tubulointerstitial fibrosis. The therapeutic advances in the last years have been able to modify and delay the natural course of diabetic kidney disease (DKD). Nevertheless, there is still an urgent need to characterize the pathways that are involved in DN, identify risk biomarkers and prevent kidney failure in diabetic patients. Rodent models provide valuable information regarding how DN is set and its progression through time. Despite the utility of these models, kidney disease progression depends on the diabetes induction method and susceptibility to diabetes of each experimental strain. The classical DN murine models (Streptozotocin-induced, Akita, or obese type 2 models) do not develop all of the typical DN features. For this reason, many models have been crossed to a susceptible genetic background. Knockout and transgenic strains have also been created to generate more robust models. In this review, we will focus on the description of the new DN rodent models and, additionally, we will provide an overview of the available methods for renal phenotyping. [ABSTRACT FROM AUTHOR]

Background: Atrial fibrillation (AF) is a frequent complication of acute myocardial infarction (AMI) and is associated with a worse prognosis. Patients with chronic kidney disease are more likely to develop AF. Whether the association between AF and glomerular filtration rate (GFR) is also true in AMI has never been investigated. Methods: We prospectively enrolled 2445 AMI patients. New-onset AF was recorded during hospitalization. Estimated GFR was estimated at admission, and patients were grouped according to their GFR (group 1 (n = 1887): GFR >60; group 2 (n = 492): GFR 60–30; group 3 (n = 66): GFR <30 mL/min/1.73 m2). The primary endpoint was AF incidence. In-hospital and long-term (median 5 years) mortality were secondary endpoints. Results: The AF incidence in the population was 10%, and it was 8%, 16%, 24% in groups 1, 2, 3, respectively (p < 0.0001). In the overall population, AF was associated with a higher in-hospital (5% vs. 1%; p < 0.0001) and long-term (34% vs. 13%; p < 0.0001) mortality. In each study group, in-hospital mortality was higher in AF patients (3.5% vs. 0.5%, 6.5% vs. 3.0%, 19% vs. 8%, respectively; p < 0.0001). A similar trend was observed for long-term mortality in three groups (20% vs. 9%, 51% vs. 24%, 81% vs. 50%; p < 0.0001). The higher risk of in-hospital and long-term mortality associated with AF in each group was confirmed after adjustment for major confounders. Conclusions: This study demonstrates that new-onset AF incidence during AMI, as well as the associated in-hospital and long-term mortality, increases in parallel with GFR reduction assessed at admission. [ABSTRACT FROM AUTHOR]

Background: Atrial fibrillation (AF) and chronic kidney disease (CKD) often coexist, but the real-world data after approval of direct oral anticoagulants (DOACs) are still lacking in Japan. We investigated the association of the baseline renal function and adverse clinical events and risk of adverse clinical events with DOACs compared to warfarin for each renal functional level in Japanese AF patients. Methods: The present substudy was based on the SAKURA AF Registry, a Japanese multicenter observational registry (median follow-up period: 39 months). The creatinine clearance (CrCl) values were estimated by the Cockcroft–Gault formula, and divided into normal renal function, and mild and moderate-severe CKD (CrCl ≥ 80, 50–79, <50 mL/min). Results: In the SAKURA AF Registry, the baseline CrCl data were available for 3242 patients (52% for DOAC and 48% for warfarin user). The relative risk of adverse clinical events was significantly higher in the patients with a CrCl < 50 mL/min as compared to those with a CrCl ≥ 80 mL/min (adjusted HRs: 2.53 for death, 2.53 for cardiovascular [CV] events, 2.13 for strokes, and 1.83 for major bleeding). Risks of all adverse clinical events were statistically even between DOAC and warfarin users for each renal function level. Conclusion: Moderate–severe CKD was associated with a higher mortality, CV events, strokes, and major bleeding than normal renal function. The safety and effectiveness of DOACs over warfarin were similar for each renal function level. By a worsening renal function, the incidence of adverse clinical events increased, especially deaths and CV events as compared to strokes and major bleeding. [ABSTRACT FROM AUTHOR]

Background: Although gout is accompanied by the substantial burden of kidney disease, there are limited data to assess renal function as a therapeutic target. This study evaluated the importance of implementing a "treat-to-target" approach in relation to renal outcomes. Methods: Patients with gout who underwent continuous urate-lowering therapy (ULT) for at least 12 months were included. The effect of ULT on renal function was investigated by means of a sequential comparison of the estimated glomerular filtration rate (eGFR). Results: Improvement in renal function was only demonstrated in subjects in whom the serum urate target of <6 mg/dL was achieved (76.40 ± 18.81 mL/min/1.73 m2 vs. 80.30 ± 20.41 mL/min/1.73 m2, p < 0.001). A significant difference in the mean change in eGFR with respect to serum urate target achievement was shown in individuals with chronic kidney disease stage 3 (−0.35 ± 3.87 mL/min/1.73 m2 vs. 5.33 ± 11.64 mL/min/1.73 m2, p = 0.019). Multivariable analysis predicted that patients ≥65 years old had a decreased likelihood of improvement (OR 0.31, 95% CI 0.13–0.75, p = 0.009). Conclusions: The "treat-to-target" approach in the long-term management of gout is associated with better renal outcomes, with a greater impact on those with impaired renal function. [ABSTRACT FROM AUTHOR]

Background: Although gout is accompanied by the substantial burden of kidney disease, there are limited data to assess renal function as a therapeutic target. This study evaluated the importance of implementing a "treat-to-target" approach in relation to renal outcomes. Methods: Patients with gout who underwent continuous urate-lowering therapy (ULT) for at least 12 months were included. The effect of ULT on renal function was investigated by means of a sequential comparison of the estimated glomerular filtration rate (eGFR). Results: Improvement in renal function was only demonstrated in subjects in whom the serum urate target of <6 mg/dL was achieved (76.40 ± 18.81 mL/min/1.73 m2 vs. 80.30 ± 20.41 mL/min/1.73 m2, p < 0.001). A significant difference in the mean change in eGFR with respect to serum urate target achievement was shown in individuals with chronic kidney disease stage 3 (−0.35 ± 3.87 mL/min/1.73 m2 vs. 5.33 ± 11.64 mL/min/1.73 m2, p = 0.019). Multivariable analysis predicted that patients ≥65 years old had a decreased likelihood of improvement (OR 0.31, 95% CI 0.13–0.75, p = 0.009). Conclusions: The "treat-to-target" approach in the long-term management of gout is associated with better renal outcomes, with a greater impact on those with impaired renal function. [ABSTRACT FROM AUTHOR]