Search

Background Accurate estimation of glomerular filtration rate (GFR) is crucial in living kidney donation. While most estimated GFR (eGFR) equations are based on plasma creatinine, its levels are strongly influenced by muscle mass. Application of cystatin C (cysC)-based estimates before donation may improve both estimation of current GFR and prediction of post-donation GFR. Methods We assessed the performance of Chronic Kidney Disease Epidemiology Collaboration equations based on creatinine (eGFRcreat-2009, eGFRcreat-2021), cysC (eGFRCysC-2012) or both (eGFRcombined-2012, eGFRcombined-2021) for estimating pre- and post-donation (mGFR) GFR in 486 living kidney donors. We subsequently focused on a subgroup of individuals with high/low muscle mass (25% highest/lowest 24-hour urinary creatinine excretion, sex stratified and height indexed). Results Pre-donation eGFRcombined-2012 and eGFRcombined-2021 showed the strongest associations with pre- and post-donation mGFR. Pre-donation eGFRcombined-2021 was most accurate for estimating both pre-donation (bias 0.01 ± 11.9 ml/min/1.73 m2) and post-donation mGFR (bias 1.3 ± 8.5 ml/min/1.73 m2). In donors with high/low muscle mass, cysC-based equations (with or without creatinine) performed better compared with equations based on only creatinine. Conclusions Combined eGFR equations yielded a better estimate of pre- and post-donation mGFR compared with estimates based on creatinine or cysC only. The added value of cysC seems particularly pronounced in donors with high or low muscle mass. [ABSTRACT FROM AUTHOR]

Purpose The objective of this study was to evaluate the impact of a pharmacist consult service on rates of hypoglycemia in adult inpatients with renal dysfunction receiving antidiabetic medications. Methods This was a single-center, institutional review board–approved, quasi-experimental, 2-phase prospective study. Adult inpatients admitted within 48 to 96 hours of hospitalization with a creatine clearance of less than 30 mL/min or estimated glomerular filtration rate of less than 30 mL/min/1.73 m2 and an active antidiabetic medication order were included. Patients located in a critical care unit or with a previous or planned transplantation were excluded. Each phase was conducted over 4 months. The primary endpoint was the change in the incidence of hypoglycemic episodes (blood glucose [BG] of <70 mg/dL) per 100 patient days when comparing the cohorts. Secondary endpoints included the incidence of recurrent and severe (BG of <40 mg/dL) episodes of hypoglycemia per 100 patient days, occurrence of a BG concentration of higher than 300 mg/dL, and length of stay. Results Overall, 150 patients were included in the retrospective preimplementation phase and 172 were included in the prospective postimplementation phase. In the postimplementation group, there was a significant decrease in the rate of hypoglycemia per 100 patient days when compared to the retrospective group (5.8 vs 9.0; incidence rate ratio, 1.55; 95% confidence interval, 1.2-2.0; P < 0.05). There was no difference in secondary endpoints between the groups. Conclusion The implementation of a pharmacy consult service resulted in lower rates of hypoglycemic events, which supports pharmacist involvement to prevent hypoglycemia in this at-risk population. Additional studies involving pharmacists working under collaborative practice agreements may reinforce the results. [ABSTRACT FROM AUTHOR]

Background To examine the agreement of different calculated estimated glomerular filtration rate (eGFR) formulas and measured creatinine clearance (CrCI) at the primary diagnosis of muscle-invasive bladder cancer (MIBC). Materials and Methods We performed a multicenter analysis of patients with MIBC, treated with cisplatin-based neoadjuvant chemotherapy (NAC) and radical cystectomy (RC), or with RC alone, between 2011 and 2021. Baseline eGFR was computed using 4 calculated serum equations including Cockcroft-Gault (CG), MDRD, CKD-EPI 2009, and race-free CKD-EPI 2021. To examine the association between calculated eGFR and measured CrCI, subgroup analyses were performed among patients in whom measured 24-hour urine CrCl was determined. Cisplatin-ineligibility was defined as CrCI and/or eGFR < 60 mL/minute per 1.73 m2. Results Of 956 patients, 30.0%, 33.3%, 31.9%, and 27.7% were found to be cisplatin-ineligible by the CG, MDRD, CKD-EPI, and race-free CKD-EPI equations (P  = .052). The concordance between calculated eGFR formulas was rated substantial (Cohen's kappa (k): 0.66-0.95). Among the subgroup (n  = 245) with measured CrCl, 37 (15.1%) patients had a CrCI less than 60 mL/minute. Concordance between measured CrCl and calculated eGFR was poor (ĸ : 0.29-0.40). All calculated eGFR formulas markedly underestimated the measured CrCI. Specifically, 78%-87.5% of patients with a calculated eGFR between 40 and 59 mL/minute exhibited a measured CrCI ≥ 60 mL/minute. Conclusions Comparing calculated eGFR formulas, similar percentages of patients with MIBC were deemed cisplatin-ineligible. However, a significant number of patients could be upgraded by being cisplatin-fit based on measured CrCI, particularly when the calculated eGFR was falling within the gray range of 40-59 mL/minute. [ABSTRACT FROM AUTHOR]

Purpose To assess the safety of zoledronic acid (ZOL) and denosumab (Dmab) administered following hip fracture in a hospital setting. Methods Patients older than 65 years were treated by a fracture liaison service following hip fracture. Generally, patients who had a glomerular filtration rate (eGFR) > 35 mL/min were treated with ZOL, whereas patients who had previously received bisphosphonates or had a eGFR between 20 and 35 mL/min were treated with Dmab. Adverse events included hypocalcemia (calcium corrected for albumin less than 8.5 mg/day), renal functional impairment (0.5 mg/dL or more increase in serum creatinine) within 30 days of treatment, or a fever (>38 °C) within 48 hours of drug administration. Results Two hundred twenty-eight and 134 patients were treated with ZOL and Dmab, respectively. Mean body temperature was elevated following ZOL administration (0.18 °C P <.001) but remained below 38 °C. Hypocalcemia occurred in 18% and 29% of the ZOL and Dmab groups, respectively (P =.009). Renal functional impairment was observed in 9 and 6 patients (4% and 5%) in the ZOL and Dmab groups, respectively (P =.8). Pretreatment calcium above 9.3 mg/dL was associated with a lower risk of posttreatment hypocalcemia (odds ratio 0.30, 95% confidence interval 0.13-0.68, P =.004). While the absolute risk of hypocalcemia was higher in the Dmab group, multivariate analysis did not find that the choice of drug was predictive of hypocalcemia. Conclusion In-hospital parenteral osteoporosis treatment was rarely associated with fever or renal function impairment but was associated with hypocalcemia. Posttreatment hypocalcemia risk did not vary significantly between patients receiving ZOL or Dmab. [ABSTRACT FROM AUTHOR]

Background Telitacicept, a B lymphocyte stimulator/A proliferation-inducing ligand dual-target fusion protein, has recently been used in autoimmune diseases. We assessed the efficacy and safety of telitacicept in immunoglobulin A nephropathy (IgAN) patients. Methods This study included 42 IgAN patients who received telitacicept treatment, forming the 'whole telitacicept group'. Among them, 20 patients who had not previously received corticosteroid (CS) therapy or immunosuppressive (IS) agents were categorized as the 'newly treated telitacicept subgroup'. Additionally, 28 patients who were selected to match historical controls received conventional IS therapy (CS therapy with/without IS agents) and were classified as the 'conventional IS group'. Telitacicept was partially used in combination with conventional IS therapy, including initial CS in different doses. Various indicators were compared at 4-week intervals up to 24 weeks among the three groups. Results After 24 weeks of treatment, the 24-hour proteinuria decreased from 1.70 g [interquartile range (IQR) 1.05–2.58] to 0.21 g (IQR 0.39–0.13) (P  = .043) in the newly treated telitacicept subgroup, from 1.78 g (IQR 0.97–2.82) to 0.44 g (IQR 1.48–0.16) (P  = .001) in the conventional IS group and from 1.07 g (IQR 0.66–1.99) to 0.26 g (IQR 0.59–0.17) (P  = .028) in the whole telitacicept group. The estimated glomerular filtration rate (eGFR) increased from 76.58 ± 30.26 ml/min/1.73 m2 to 80.30 ± 26.76 ml/min/1.73 m2 (P  = .016) in the newly treated telitacicept subgroup, from 72.73 ± 33.41 ml/min/1.73 m2 to 84.08 ± 26.81 ml/min/1.73 m2 (P  = .011) in the conventional IS group and from 70.10 ± 32.88 ml/min/1.73 m2 to 71.21 ± 31.49 ml/min/1.73 m2 (P  = .065) in the whole telitacicept group. During follow-up periods, the efficacy rates of the three groups did not show statistically significant differences and no serious adverse events were observed. Conclusions Telitacicept may be a safe and effective treatment for IgAN, offering reductions in proteinuria and increases in eGFR similar to conventional IS therapy. After a 24-week follow-up, the incidence of adverse events was lower for telitacicept than for conventional IS therapy. [ABSTRACT FROM AUTHOR]

Background Post-transplant anemia is a prevalent yet often overlooked condition that poses significant risks. Current guidelines consider the same treatment recommendations and goals for these patients as for chronic kidney disease patients not on dialysis. Previous reports demonstrated a lack of awareness and suboptimal management, indicating a pressing need for improvement. We therefore wanted to update the information on post-transplant anemia. We aimed to describe the present state of anemia management, goals and adherence to guidelines within a representative sample of the kidney transplant (KTx) population. Methods We designed a retrospective nationwide multicenter study including outpatients from eight KTx hospitals. Nephrologists gathered data from electronic medical records encompassing demographics, comorbidities, KTx characteristics and immunosuppressive therapy, and information pertaining to anemia management (laboratory values, previously prescribed treatments and subsequent adjustments). The European statement on the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines was the reference for definitions, drug prescriptions and targets. Anemia occurring within the initial 6 months post-transplantation was classified as early onset. Results We included 297 patients with post-transplant anemia aged 62.8 years (standard deviation 13.6), 60% of whom were male. They had received a graft from cardiac death or brain death donors (61.6% and 31.1%, respectively) a median of 2.5 years (0.5–8.7) before. Among them 77% (n  = 228) were classified as having late post-transplant anemia, characterized by a higher prevalence of microcytic and iron deficiency anemia. A total of 158 patients were on erythropoietic-stimulating agents (ESAs) treatment, yet surprisingly 110 of them lacked iron supplementation. Notably, 44 patients had an indication for iron supplementation and among them, 30 exhibited absolute iron deficiency. Out of the 158 patients receiving ESAs, only 39 surpassed the limit for the ESA resistance index, indicating poor response. This resistance was more frequent among patients with early post-transplant anemia (26.1% vs 9.2%). We have identified iron profile, early post-transplant anemia and estimated glomerular filtration rate as factors associated with the highest risk of resistance Conclusion We found that hemoglobin targets are individualized upwards in post-transplant anemia. In this setting, iron therapy continues to be underutilized, especially intravenous, and iron deficiency and prior events (blood transfusion or hospital admission) explain most of the hyporesponsiveness to ESA. This highlights missed opportunities for precise prescription targeting and adherence to established guidelines, suggesting a need for improved management strategies in post-transplant anemia patients. [ABSTRACT FROM AUTHOR]

Background Metabolic surgery is recognized for its effectiveness in weight loss and improving outcomes for individuals with type 2 diabetes mellitus (T2DM). However, its impact on renal function, especially in multi-ethnic Asian populations, remains underexplored. This study investigates mid- and long-term renal outcomes following metabolic surgery in Asian patients with T2DM. Methods This retrospective cohort study utilized data from the Asian Diabetes Surgery Study (ADSS), involving T2DM patients aged 20–79 who underwent metabolic surgery from 2008 to 2015. The primary outcome was the change in estimated glomerular filtration rate (eGFR) at 1, 3, and 5 years post-surgery, with adjustments for confounders. Secondary outcomes included changes in chronic kidney disease (CKD) stages and the relationship between weight loss and eGFR changes. Data were analyzed using univariate and multivariable regression analyses, along with the McNemar test. Results The study included 1513 patients with a mean age of 42.7 years. The results revealed that a significant improvement in eGFR was observed at 1-year post-surgery (112.4 ± 32.0 ml/min/1.73 m², P < .001), with a shift toward less severe CKD stages. However, this improvement was not sustained at 3 and 5 years. No significant correlation was found between weight loss and eGFR changes at 1-year follow-up. Conclusion Metabolic surgery significantly improves renal function at 1 year postoperatively in Asian individuals with T2DM, highlighting its potential benefits beyond glycemic control and weight loss. The long-term effects on renal function require further investigation. [ABSTRACT FROM AUTHOR]

Background Elexacaftor/tezacaftor/ivacaftor (ETI) is a new cystic fibrosis transmembrane conductance regulator (CFTR) modulator that has transformed the respiratory prognosis of people with cystic fibrosis (pwCF). However, its impact on other organs such as the kidneys, where CFTR is expressed, remains unclear. Since pwCF are risk of both kidney disease and urolithiasis, we aimed to study the potential effects of ETI on renal function, volume status, and risk factors for urolithiasis. Methods This prospective, observational, single-center, before–after cohort study, involved adult pwCF eligible for ETI. The changes in plasma and urinary profiles were assessed by comparing renal function (using 2021 CKD-EPIcreatinine and 2021 CKD-EPIcreatinine-cystatin C formulas), volume status (using aldosterone/renin ratio and blood pressure), and risk factors for urolithiasis, at the time of ETI introduction (M0) and 7 months after (M7). Results Nineteen pwCF were included. No significant change in renal function was observed between M0 and M7 (2021 CKD-EPIcreatinine: 105.5 ml/min/1.73 m² at M0 vs. 103.3 ml/min/1.73 m² at M7; P  = .17). There was a significant reduction in aldosterone level (370.3 pmol/l at M0 vs. 232.4 pmol/l at M7; P  = .02) and aldosterone/renin ratio (33.6 at M0 vs. 21.8 at M7; P  = .03). Among the risk factors for urolithiasis, a significant reduction in magnesuria level was found (4.6 mmol/d at M0 vs. 3.8 mmol/d at M7; P  = .01). Conclusion These findings suggest that ETI seem to have no short-term impact on the renal function of adult pwCF and appears to correct secondary hyperaldosteronism due to excessive sweat losses. Further investigations are needed to determine the potential impact of decreased magnesuria observed under ETI therapy on the risk of urolithiasis. [ABSTRACT FROM AUTHOR]

Background Evidence concerning tolerability of sodium-glucose co-transporter-2 (SGLT2) inhibitors in older adults is limited due to under-representation in clinical trials. Our study aimed to determine the extent to which SGLT2 inhibitor intolerance increases with age and explore additional factors associated with intolerance. Methods This retrospective observational study included patients in the Veterans Health Administration who initiated an SGLT2 inhibitor between 1 January 2013 and 31 December 2021. One-year discontinuation served as a proxy for intolerance. Relative risk (RR) for 1-year discontinuation was contrasted across age groups using log-binomial regression to adjust for confounding. Results Of 232 495 patients who initiated an SGLT2 inhibitor, 60 582 (26.1%) discontinued within one year. A difference was observed across age groups, <65, 65–74, 75–84 and ≥85 years, where 25.8%, 25.3%, 28.5% and 34.9% of patients discontinued, respectively (P  < .001). After adjustment for confounding factors, patients 75–84 and ≥85 years were at 8% (RR = 1.08; 95% CI: 1.05, 1.10) and 21% increased risk (RR = 1.21; 95% CI: 1.15, 1.26) for discontinuation, respectively, relative to patients <65 years. Additional risk factors were identified: female (RR = 1.41; 95% CI: 1.37, 1.45), estimated glomerular filtration rate stage 4 (RR = 1.49; 95% CI: 1.39, 1.60), underweight (RR = 1.15; 95% CI: 1.03, 1.29), urinary tract infection history (RR = 1.25; 95% CI: 1.21, 1.30) and yeast infection history (RR = 1.39; 95% CI: 1.27, 1.51). Conclusion No clinically meaningful differences in SGLT2 inhibitor intolerance were observed in patients up to 84 years. Our findings support having closer follow-up when initiating in patients 85 years and older. [ABSTRACT FROM AUTHOR]

Pharmaceutical drugs and other chemicals can impact organogenesis, either during pregnancy or by postnatal exposure of very preterm infants. Corticosteroids are administered to pregnant women at risk of preterm delivery in order to reduce neonatal morbidity and mortality. In addition, high-dose corticosteroid exposure of very preterm infants regularly serves to maintain blood pressure and to prevent and treat bronchopulmonary dysplasia, a form of chronic lung disease in prematurely born infants. Despite clinical benefits, there is increasing evidence of corticosteroid-mediated short- and long-term detrimental developmental effects, especially in the kidney. Here, we performed a detailed morphological and functional analysis of corticosteroid-mediated effects on pronephros development in larval zebrafish. About 24-h postfertilization (hpf) transgenic Tg(wt1b: EGFP) zebrafish larvae were exposed to a set of natural and synthetic corticosteroids (hydrocortisone, dexamethasone, 6α-methylprednisolone, betamethasone, prednisolone, fludrocortisone, 11-deoxycorticosterone) with varying glucocorticoid and mineralocorticoid potency for 24 h at different concentrations. A semiautomated, multiparametric in vivo workflow enabled simultaneous assessment of kidney morphology, renal FITC-inulin clearance, and heart rate within the same larva. All corticosteroids exerted significant morphological and functional effects on pronephros development, including a significant hypertrophy of the pronephric glomeruli as well as dose-dependent increases in FITC-inulin clearance as a marker of glomerular filtration rate. In conclusion, the present study demonstrates a significant impact of corticosteroid exposure on kidney development and function in larval zebrafish. Hence, these studies underline that corticosteroid exposure of the fetus and the preterm neonate should be carefully considered due to potential short- and long-term harm to the kidney. [ABSTRACT FROM AUTHOR]

What mechanisms can link the inhibition of sodium-glucose cotransporter 2 (SGLT2) in the early proximal tubule to kidney and heart protection in patients with and without type 2 diabetes? Due to physical and functional coupling of SGLT2 to other sodium and metabolite transporters in the early proximal tubule (including NHE3, URAT1), inhibitors of SGLT2 (SGLT2i) reduce reabsorption not only of glucose, inducing osmotic diuresis, but of other metabolites plus of a larger amount of sodium than expected based on SGLT2 inhibition alone, thereby reducing volume retention, hypertension and hyperuricemia. Metabolic adaptations to SGLT2i include a fasting-like response, with enhanced lipolysis and formation of ketone bodies that serve as additional fuel for kidneys and heart. Making use of the physiology of tubulo-glomerular communication, SGLT2i functionally lower glomerular capillary pressure and filtration rate, thereby reducing physical stress on the glomerular filtration barrier, tubular exposure to albumin and nephrotoxic compounds, and the oxygen demand for reabsorbing the filtered load. Together with reduced gluco-toxicity in the early proximal tubule and better distribution of transport work along the nephron, SGLT2i can preserve tubular integrity and transport function and, thereby, glomerular filtration rate in the long-term. By shifting transport downstream, SGLT2i may simulate systemic hypoxia at the oxygen sensors in the deep cortex/outer medulla, which stimulates erythropoiesis and, together with osmotic diuresis, enhances hematocrit and thereby improves oxygen delivery to all organs. The described SGLT2-dependent effects may be complemented by off-target effects of SGLT2i on the heart itself and on the microbiome formation of cardiovascular-effective uremic toxins. [ABSTRACT FROM AUTHOR]

BACKGROUND In primary aldosteronism (PA), aldosterone could affect glomerular hemodynamics by elevating renal vascular resistance and glomerular capillary pressure. However, the relationship between plasma aldosterone concentrations (PAC) and glomerular hemodynamics including efferent arteriolar resistance (R e), and afferent arteriolar resistance (R a) in humans is still unclear. The aim of this study was to investigate the relationships of PAC with intraglomerular hemodynamic parameters in patients with PA. METHODS An observational study of glomerular hemodynamics was performed using simultaneous measurements of plasma clearance of para-aminohippurate and inulin (C in; glomerular filtration rate (GFR)) in 17 patients with PA. Kidney function was evaluated by C in, estimated GFR based on serum creatine (eGFRcre) and serum cystatin C (eGFRcys) and creatine clearance (Ccr). Intraglomerular hemodynamic parameters, including R e, R a, and intraglomerular hydrostatic pressure (P glo) were calculated using Gomez's formulae. RESULTS In the 17 PA cases, PAC was significantly correlated with C in (rho = 0.752, P  = 0.001) and eGFRcys (rho = 0.567, P  = 0.018), but was not correlated with eGFRcre and Ccr. PAC was also significantly correlated with P glo, R e, and urinary protein/day (rho = 0.775, P  = 0.0004, rho = 0.625, P  = 0.009, and rho = 0.625, P  = 0.007, respectively). Multivariable regression analysis showed that PAC was significantly associated with C in and R e. In comparing aldosterone-producing adenoma (APA) and non-APA cases, C in was significantly elevated in APA (P  = 0.037), whereas eGFRcre, eGFRcys, and Ccr were not. R e tended to be higher in APA (P  = 0.064). CONCLUSIONS These results suggest high aldosterone causes glomerular hyperfiltration by constricting R e. C in, but not eGFRcre and Ccr, may be useful for evaluating kidney function in PA. [ABSTRACT FROM AUTHOR]

Background In this secondary analysis of the STOP-ACEi trial, we explored the impact of discontinuing or continuing renin–angiotensin system inhibitor therapy in people with advanced chronic kidney disease on cystatin C estimated glomerular filtration rate (eGFR). Methods Cystatin C eGFRs were calculated at baseline, 12, 24 and 36 months using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) cystatin 2012, European Kidney Function Consortium and CKD-EPI Combined 2021 equations. We excluded samples obtained after the initiation of kidney replacement therapy. Primary analysis used complete case analysis and mixed-effects linear regression model, adjusting for minimization variables, baseline value, time-point and treatment by time interaction. Sensitivity analysis was conducted using a pattern mixture model to account for missing data that was not at random. To model the longitudinal cystatin C data with time-to-event data, a joint model was utilized which incorporated the cystatin C measurements at various time points and accounted for the occurrence of kidney replacement therapy. Results The mean cystatin C eGFRs (CKD-EPI 2012) at baseline were 17.8 mg/L [standard deviation (SD 6.3)] and 17.9 mL/min/1.73 m2 (SD 6.3) in the STOP and CONTINUE arms, respectively. The estimated least squares mean difference at 12 months between STOP and CONTINUE arm was –1.46 [95% confidence interval (CI) –2.39 to –0.52, P = .002]. The estimated least squares mean difference at 24 months was –2.27 (95% CI –3.48 to –1.06, P < .001). The estimated least squares mean difference at 36 months was –1.72 (95% CI –3.48 to 0.03, P = .05). Conclusion Our results are consistent with the primary study's analysis and sensitivity analyses support these findings and provide additional insights. Our findings demonstrate the similarity of creatinine and cystatin eGFR results and therefore support the use of cystatin C as an alternative marker of eGFR in advanced CKD, particularly in those in whom creatinine is likely to be less accurate. [ABSTRACT FROM AUTHOR]

Background Creatinine-based equations are the most used to estimate glomerular filtration rate (eGFR). The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), the re-expressed Lund-Malmö Revised (r-LMR) and the European Kidney Function Consortium (EKFC) equations are the most validated. The EKFC and r-LMR equations have been suggested to have better performances in young adults, but this is debated. Methods We collected data (GFR) measured by clearance of an exogenous marker (reference method), serum creatinine, age and sex from 2366 young adults (aged between 18 and 25 years) both from Europe and the USA. Results In the European cohorts (n  = 1892), the bias (in mL/min/1.73 m²) was systematically better for the EKFC and r-LMR equations compared with the CKD-EPI equation [2.28, 95% confidence interval (1.59; 2.91), –2.50 (–3.85; –1.76), 17.41 (16.49; 18.47), respectively]. The percentage of estimated GFR within 30% of measured GFR (P30) was also better for EKFC and r-LMR equations compared with the CKD-EPI equation [84.4% (82.8; 86.0), 87.2% (85.7; 88.7) and 65.4% (63.3; 67.6), respectively]. In the US cohorts (n  = 474), the bias for the EKFC and r-LMR equations was better than for the CKD-EPI equation in the non-Black population [0.97 (–1.69; 3.06), –2.62 (–5.14; –1.43) and 7.74 (5.97; 9.63), respectively], whereas the bias was similar in Black US individuals. P30 results were not different between the three equations in US cohorts. Analyses in sub-populations confirmed these results, except in individuals with high GFR levels (GFR ≥120 mL/min/1.73 m²) for whom the CKD-EPI equation might have a lower bias. Conclusions We demonstrated that both the EKFC and r-LMR creatinine-based equations have a better performance than the CKD-EPI equation in a young population. The only exception might be in patients with hyperfiltration. [ABSTRACT FROM AUTHOR]

Background The diagnosis of acute myocardial infarction (AMI) using high-sensitivity cardiac troponin T (hs-cTnT) remains challenging in patients with kidney dysfunction. Methods In this large, multicenter cohort study, a total of 20 912 adults who underwent coronary angiography were included. Kidney function–specific cut-off values of hs-cTnT were determined to improve the specificity without sacrificing sensitivity, as compared with that using traditional cut-off value (14 ng/L) in the normal kidney function group. The diagnostic accuracy of the novel cut-off values was validated in an independent validation cohort. Results In the derivation cohort (n  = 12 900), 3247 patients had an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. Even in the absence of AMI, 50.2% of participants with eGFR <60 mL/min/1.73 m2 had a hs-cTnT concentration ≥14 ng/L. Using 14 ng/L as the threshold of hs-cTnT for diagnosing AMI led to a significantly reduced specificity and positive predictive value in patients with kidney dysfunction, as compared with that in patients with normal kidney function. The kidney function–specific cut-off values were determined as 14, 18 and 48 ng/L for patients with eGFR >60, 60–30 and <30 mL/min/1.73 m2, respectively. Using the novel cut-off values, the specificities for diagnosing AMI in participants with different levels of kidney dysfunction were remarkably improved (from 9.1%–52.7% to 52.8–63.0%), without compromising sensitivity (96.6%–97.9%). Similar improvement of diagnostic accuracy was observed in the validation cohort (n  = 8012). Conclusions The kidney function–specific cut-off values of hs-cTnT may help clinicians to accurately diagnose AMI in patients with kidney dysfunction and avoid the potential overtreatment in practice. [ABSTRACT FROM AUTHOR]

Background Proenkephalin A 119–159 (penKid) is a novel blood biomarker for real-time assessment of kidney function and was found to be independently associated with worsening kidney function and mortality. A novel penKid-based estimated glomerular filtration rate equation (eGFRPENK-Crea), outperforms current creatinine-based eGFR equations in predicting iohexol or iothalamate plasma clearance-based measured GFR. In this study, we aimed to evaluate the predictive value of penKid and eGFRPENK-Crea for all-cause mortality in stable patients at high cardiovascular risk. Methods Circulating penKid levels were assessed in 615 stable patients hospitalized at the Department of Cardiology at University Hospital Aachen, Germany. The endpoint was all-cause mortality; follow up was 3 years. Results penKid levels were higher in 46 non-survivors [58.8 (IQR 47.5–85.0) pmol/l] compared to 569 survivors [43.8 (IQR 34.0–58.0) pmol/l; P  < .0001]. Univariable Cox regression analyses found penKid and eGFRPENK-Crea to be associated with all-cause mortality (C index 0.703, χ 2 33.27, P  < .00001; C index 0.716, χ 2 36.51, P  < .00001). This association remained significant after adjustment for significant baseline parameters including age, smoking, chronic heart failure, use of diuretics, leucocytes, body mass index, sex, and creatinine (C index 0.799, χ 2 72.06, P  < .00001). Importantly, penKid provided significant added value on top of eGFRCKD-EPI 2021 (eGFRCKD-EPI 2021: C index 0.716, χ 2 34.21; eGFRCKD-EPI 2021 + penKid: C index 0.727, χ 2: 40.02; Delta χ 2 5.81; all P  < .00001) for all-cause mortality prediction in our cohort. Conclusions penKid levels and eGFRPENK-Crea is associated with all-cause mortality within a 3-year follow-up period and the addition of penKid on top of eGFRCKD-EPI 2021 provided significant added value in mortality prediction. [ABSTRACT FROM AUTHOR]

Background Campylobacteriosis in kidney transplant recipients (KTRs) is the most common identified bacterial cause of diarrhea. Risk factors in KTRs are unknown. Methods A 10-year multicentric, retrospective 1:1 case-control study was performed in France between 2010 and 2020. The main aim was to identify factors associated with Campylobacter -related infection in KTRs. The KTRs with a functional graft and campylobacteriosis (positive stool culture and/or blood culture and/or positive nucleic amplification test) and their controls matched on transplantation date within the same center were included. Results We identified 326 patients with campylobacteriosis. The estimated incidence rate of campylobacteriosis was 2.3/1000 patient-years. The infection occurred at a median of 2.4 years posttransplantation. The independent risk factors for campylobacteriosis were use of corticosteroids as maintenance regimen (75.8% vs 66%; P <.001), acute rejection (8.9% vs 4%; P =.048), low lymphocyte count (0.96 vs 1.4 giga/liter (G/L); P <.001), and low basal estimated glomerular filtration rate (eGFR) (44.2 vs 57.5 mL/minute/1.73 m2; P <.001). A fluoroquinolone was initiated in 64 (21.4%) patients, with 51.1% of antimicrobial resistance, whereas almost all strains were erythromycin sensitive. Conclusions Campylobacteriosis has a higher incidence in the 2 first years of transplantation. The factors independently associated with campylobacteriosis are corticosteroids as maintenance immunosuppressive regimen, low lymphocyte counts, low eGFR, and a history of acute rejection. Due to high antimicrobial resistance with fluoroquinolone, the first line of treatment should be azithromycin. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the effectiveness and safety of two different intravenous methylprednisolone (IVMP) pulse doses in patients with severe microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). Methods We emulated a target trial using observational data from the nationwide registry in Japan. Patients with severe glomerulonephritis or diffuse alveolar haemorrhage were selected and pseudo-randomized into three groups using propensity score-based overlap weighting as follows: non-IVMP, IVMP 0.5 g/day and IVMP 1.0 g/day. The primary outcome was all-cause mortality, and the secondary outcomes were composite all-cause mortality and kidney failure, severe relapse and serious infection from 2 to 48 weeks after treatment initiation. To estimate the treatment effects, the Cox proportional hazard model and Fine–Gray subdistribution hazard model were used. Results In this emulated target trial, of 201 eligible patients (MPA, 175; GPA, 26), 6 (3%) died, 4 (2.0%) had kidney failure, 11 (5.5%) had severe relapse, and 40 (19.9%) had severe infections. Hazard ratios (HR) for IVMP 0.5 g/day and IVMP 1.0 g/day pulse groups compared with non-IVMP pulse were as follows: all-cause mortality 0.46 (95% CI: 0.07, 2.81) and 0.07 (95% CI: 0.01, 0.41), respectively; all-cause mortality/kidney failure 1.18 (95% CI: 0.26, 5.31) and 0.59 (95% CI: 0.08, 4.52), respectively; subdistribution HRs for severe relapse were 1.26 (95% CI: 0.12, 13.70) and 3.36 (95% CI: 0.49, 23.29), respectively; and for serious infection 1.88 (95% CI: 0.76, 4.65) and 0.94 (95% CI: 0.28, 3.13), respectively. Conclusion IVMP 1.0 g/day pulse may improve 48-week mortality in patients with severe MPA/GPA. [ABSTRACT FROM AUTHOR]

Objectives Temocillin, a carbapenem-sparing β-lactam antibiotic, is commonly used at the standard 4 g/day dosage for treating complicated urinary tract infections (cUTIs). However, pharmacokinetic/pharmacodynamic (PK/PD) data supporting this regimen is limited. This study evaluated the plasma pharmacokinetics (PK) and PTA of temocillin in non-critically ill cUTI patients with varying degrees of renal insufficiency (RI). Methods In this single-centre clinical study, 22 cUTI patients received a fixed 4 g/day (2 g q12h, intravenously) temocillin dose, irrespective of renal function (no RI: n  = 5, mild RI: n  = 8, moderate RI: n  = 9). Plasma samples were collected post-dosing for LC-MS analysis of total and unbound temocillin levels. Monte Carlo simulations were performed based on the established PK/PD target of ≥35% f T > MIC (minimal inhibitory concentration). Results Among patients, the highest plasma drug exposure and PK/PD target attainment were observed in those with moderate RI (median AUC0–12h = 1143 h.mg/L and % f T > MIC = 68%), followed by mild RI patients (median AUC0–12h = 918 h.mg/L and % f T > MIC = 34%), and the lowest in those with healthy kidney function (median AUC0–12h = 692 h.mg/L and % f T > MIC = 26%). Simulations indicated that the 4 g/day temocillin dose achieves 90% PTA only for glomerular filtration rate < 60 mL/min and MIC ≤ 8 mg/L. Conclusion The standard temocillin dose may need to be increased from 4 to 6 g/day to treat non-critically ill cUTI patients, in line with recent EUCAST recommendations. For patients with moderate RI, who experience higher exposure due to reduced renal drug clearance, 4 g/day temocillin remains appropriate. [ABSTRACT FROM AUTHOR]

We are currently facing a pandemic of physical inactivity that might contribute to the growing prevalence of chronic kidney disease (CKD). Here, we summarize currently available evidence on the association between physical activity and CKD, and also review the effects of exercise intervention in affected patients. Physical activity/exercise might act as a polypill against CKD, preventing its development or even exerting beneficial effects once it is established (i.e. improvements in patients' physical fitness and cardiovascular risk, as well as in kidney function). Exercise benefits are also found at advanced CKD stages or in patients under hemodialysis. The biological mechanisms behind the clinical evidence are also discussed. An active lifestyle appears as a cornerstone in CKD prevention and management. [ABSTRACT FROM AUTHOR]

Background Clinical variability among individuals with heterozygous pathogenic/likely pathogenic (P/LP) variants in the COL4A3 / COL4A4 genes (also called autosomal dominant Alport syndrome or COL4A3/COL4A4 -related disorder) is huge; many individuals are asymptomatic or show microhematuria, while others may develop proteinuria and chronic kidney disease (CKD). The prevalence of simple kidney cysts (KC) in the general population varies according to age, and patients with advanced CKD are prone to have them. A possible association between heterozygous COL4A3, COL4A4 and COL4A5 P/LP variants and KC has been described in small cohorts. The presence of KC in a multicenter cohort of individuals with heterozygous P/LP variants in the COL4A3 / COL4A4 genes is assessed in this study. Methods We evaluated the presence of KC by ultrasound in 157 individuals with P/LP variants in COL4A3 (40.7%) or COL4A4 (53.5%) without kidney replacement therapy. The association between presence of KC and age, proteinuria, estimated glomerular filtration rate (eGFR) and causative gene was analyzed. Prevalence of KC was compared with historical case series in the general population. Results Half of the individuals with P/LP variants in COL4A3 / COL4A4 showed KC, which is a significantly higher percentage than in the general population. Only 3.8% (6/157) had cystic nephromegaly. Age and eGFR showed an association with the presence of KC (P  < .001). No association was found between KC and proteinuria, sex or causative gene. Conclusions Individuals with COL4A3 / COL4A4 P/LP variants are prone to develop KC more frequently than the general population, and their presence is related to age and to eGFR. Neither proteinuria, sex nor the causative gene influences the presence of KC in these individuals. [ABSTRACT FROM AUTHOR]

Background Pulmonary haemorrhage with hypoxia caused by anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) has a high early mortality. Avacopan, an oral C5a receptor antagonist, is an approved treatment for AAV, but patients with pulmonary haemorrhage requiring invasive pulmonary ventilation support were excluded from the Avacopan for the Treatment of ANCA-Associated Vasculitis (ADVOCATE) Trial. Methods A retrospective, observational, multicentre case series of AAV patients with hypoxic pulmonary haemorrhage, requiring oxygen support or mechanical ventilation, who received avacopan. Results Eight patients (62.5% female), median age 64 years (range 17–80), seven with kidney involvement, median estimated glomerular filtration rate (eGFR) 11 (range 5–99) mL/min/1.73 m2, were followed for a median of 6 months from presentation. Seven were newly diagnosed (87.5%), five were myeloperoxidase-ANCA and three proteinase 3-ANCA positive. All had hypoxia, four requiring mechanical ventilation (three invasive and one non-invasive). Intensive care unit (ICU) stay for the four patients lasted a median of 9 days (range 6–60). Four received rituximab and cyclophosphamide combination, three rituximab and one cyclophosphamide. Four underwent plasma exchange and one received 2 months of daily extracorporeal membrane oxygenation therapy. Following the initiation of avacopan after a median of 10 days (range 2–40), pulmonary haemorrhage resolved in all patients, even the two who had 1 month of refractory pulmonary haemorrhage prior to avacopan. Additionally, after 1 month, the median prednisolone dose was 5 mg/day (range 0–50), with three patients successfully discontinuing steroid use. Two patients suffered serious infections, two discontinued avacopan, one permanently due to a rash and one temporarily after 3 months due to neutropenia. All patients survived and no re-hospitalization occurred. Conclusion We report the use of avacopan as a component of the treatment for pulmonary haemorrhage with hypoxia in AAV. Despite the life-threatening presentations all patients recovered, but attribution of the positive outcomes to avacopan is limited by the concomitant therapies and retrospective observational design. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to compare The Binding Site's Freelite on Optilite and Diazyme's Kappa/Lambda free light chains (K/L FLC) on Abbott Architect c8000 with healthy and renal insufficient populations and to evaluate their respective reference intervals for serum free light chains (sFLCs). Methods: Two hundred sixty serum samples were measured for creatinine and sFLCs by both assays and a subset by immunofixation electrophoresis. Verification of manufacturer-defined reference intervals was assessed. Results: Kappa free light chains (KFLC) showed excellent correlation of 0.998 R2 with a slope of 0.73. For Lambda free light chains (LFLC), an acceptable correlation of 0.953 R2 was found with a slope of 1.50 as well as a skewnessbased difference with a -12.70 intercept. Healthy estimated glomerular filtration rate (eGFR) =60 reference interval verification of central 95% could not be confirmed for either Freelite or Diazyme although LFLC was much closer than KFLC for both assays with Freelite KFLC recovering only 37% of values within reference interval claims. The K/L FLC ratio did not meet 100% claim for both Freelite (91%) and Diazyme (95%) among those with eGFR =60. Samples with eGFR =59 had increasingly higher levels of KFLC and LFLC for both assays. When comparing worsening eGFR status, Freelite recovered increasingly higher ratios while Diazyme recovered increasingly lower ratios. Conclusions: Healthy reference intervals could not be verified for either Freelite or Diazyme. Renal reference intervals for Freelite are currently warranted while they are not recommended for Diazyme. The differences between these 2 assays can be minimized by standardization efforts such as recalibration. [ABSTRACT FROM AUTHOR]

Context Patients with nonfunctioning adrenal adenomas (NFA) and mild autonomous cortisol secretion (MACS) demonstrate an increased risk of chronic kidney disease (CKD); however, factors associated with CKD are unknown. Objective We aimed to identify the factors associated with CKD and assess the effect of adrenalectomy on kidney function in patients with NFA or MACS. Methods A single-center cohort study of patients with NFA and MACS, 1999 to 2020, was conducted. MACS was diagnosed based on post dexamethasone suppression test (DST) cortisol greater than or equal to 1.8 mcg/dL. Age, sex, dysglycemia, hypertension, therapy with statin, angiotensin-converting enzyme inhibitor, or angiotensin II receptor blocker were included in the multivariable analysis. Outcomes included estimated glomerular filtration rate (eGFR) at the time of diagnosis with MACS or NFA and postadrenalectomy delta eGFR. Results Of 972 patients, 429 (44%) had MACS and 543 (56%) had NFA. At the time of diagnosis, patients with MACS had lower eGFR (median 79.6 vs 83.8 mL/min/1.73 m2; P <.001) than patients with NFA. In a multivariable analysis, factors associated with lower eGFR were older age, hypertension, and higher DST. In 204 patients (MACS: 155, 76% and NFA: 49, 24%) treated with adrenalectomy, postadrenalectomy eGFR improved in both groups starting at 18 months up to 3.5 years of follow-up. Factors associated with increased eGFR were younger age, lower preadrenalectomy eGFR, and longer follow-up period. Conclusion DST cortisol is an independent risk factor for lower eGFR in patients with adrenal adenomas. Patients with both MACS and NFA demonstrate an increase in eGFR post adrenalectomy, especially younger patients with lower eGFR pre adrenalectomy. [ABSTRACT FROM AUTHOR]

Background and Aims Incident heart failure (HF) among individuals with chronic kidney disease (CKD) incurs hospitalizations that burden patients and health care systems. There are few preventative therapies, and the Pooled Cohort equations to Prevent Heart Failure (PCP-HF) perform poorly in the setting of CKD. New drug targets and better risk stratification are urgently needed. Methods In this analysis of incident HF, SomaScan V4.0 (4638 proteins) was analysed in 2906 participants of the Chronic Renal Insufficiency Cohort (CRIC) with validation in the Atherosclerosis Risk in Communities (ARIC) study. The primary outcome was 14-year incident HF (390 events); secondary outcomes included 4-year HF (183 events), HF with reduced ejection fraction (137 events), and HF with preserved ejection fraction (165 events). Mendelian randomization and Gene Ontology were applied to examine causality and pathways. The performance of novel multi-protein risk models was compared to the PCP-HF risk score. Results Over 200 proteins were associated with incident HF after adjustment for estimated glomerular filtration rate at P < 1 × 10−5. After adjustment for covariates including N-terminal pro-B-type natriuretic peptide, 17 proteins remained associated at P < 1 × 10−5. Mendelian randomization associations were found for six proteins, of which four are druggable targets: FCG2B, IGFBP3, CAH6, and ASGR1. For the primary outcome, the C -statistic (95% confidence interval [CI]) for the 48-protein model in CRIC was 0.790 (0.735, 0.844) vs. 0.703 (0.644, 0.762) for the PCP-HF model (P =.001). C -statistic (95% CI) for the protein model in ARIC was 0.747 (0.707, 0.787). Conclusions Large-scale proteomics reveal novel circulating protein biomarkers and potential mediators of HF in CKD. Proteomic risk models improve upon the PCP-HF risk score in this population. [ABSTRACT FROM AUTHOR]

Background Primary membranous nephropathy (PMN) is usually caused by anti-phospholipase A2 receptor (PLA2R) autoantibodies. There are different therapeutic options according to baseline risk. Novel biomarkers are needed to optimize risk stratification and predict and monitor the response to therapy, as proteinuria responses may be delayed. We hypothesized that plasma or urinary cytokines may provide insights into the course and response to therapy in PMN. Methods Overall, 192 data points from 34 participants in the STARMEN trial (NCT01955187), randomized to tacrolimus–rituximab (TAC-RTX) or corticosteroids–cyclophosphamide (GC-CYC), were analysed for plasma and urine cytokines using a highly sensitive chemiluminescence immunoassay providing a high-throughput multiplex analysis. Results Baseline (pretreatment) urinary C-X-C motif chemokine ligand 13 (CXCL13) predicted the therapeutic response to TAC-RTX. Cytokine levels evolved over the course of therapy. The levels of nine plasma and six urinary cytokines correlated with analytical parameters of kidney damage and disease activity, such as proteinuria, estimated glomerular filtration rate and circulating anti-PLA2R levels. The correlation with these parameters was most consistent for plasma and urinary growth differentiation factor 15 (GDF15), plasma tumour necrosis factor α and urinary TNF-like weak inducer of apoptosis. Decreasing plasma GDF15 levels were associated with response to GC-CYC. Four clusters of cytokines were associated with different stages of response to therapy in the full cohort, with the less inflammatory cluster associated with remission. Conclusion PMN displayed characteristic plasma and urine cytokine patterns that evolved over time as patients responded to therapy. Baseline urinary CXCL13 concentration could be a prognostic marker of response to TAC-RTX. [ABSTRACT FROM AUTHOR]

Background This study aimed to assess the prognosis of people with chronic kidney disease (CKD) in Japan using the Kidney Disease: Improving Global Outcomes (KDIGO) heatmap. Methods The prognoses of individuals with estimated glomerular filtration rates (eGFR) <90 mL/min/1.73 m2 were evaluated based on the KDIGO heatmap using an electronic medical record database in Japan. The primary outcome was major adverse cardiovascular events (MACE), a composite of myocardial infarction (MI), stroke, heart failure (HF) hospitalization and in-hospital death (referred to as MACE1). Additionally, ad hoc MACE2 (MI hospitalization, stroke hospitalization, HF hospitalization and in-hospital death) was examined. The secondary outcome was the renal outcome. Results Of the 543 606 individuals included, the mean age was 61.6 ± 15.3 years, 50.1% were male and 40.9% lacked urine protein results. The risk of MACEs increased independently with both eGFR decline and increasing proteinuria from the early KDIGO stages: hazard ratios (95% confidence interval) of MACE1 and MACE2, compared with G2A1 were 1.16 (1.12–1.20) and 1.17 (1.11–1.23), respectively, for G3aA1, and 1.17 (1.12–1.21) and 1.35 (1.28–1.43), respectively, for G2A2. This increased up to 2.83 (2.54–3.15) and 3.43 (3.00–3.93), respectively, for G5A3. Risks of renal outcomes also increased with CKD progression. Conclusions This study is the first to demonstrate the applicability of the KDIGO heatmap in assessing cardiovascular and renal risk in Japan. The risk increased from the early stages of CKD, indicating the importance of early diagnosis and intervention through appropriate testing. [ABSTRACT FROM AUTHOR]

Background Identifying the biomarkers associated with new-onset glomerular filtration rate (GFR) decrease in an initially healthy population could offer a better understanding of kidney function decline and help improving patient management. Methods Here we described the proteomic and transcriptomic footprints associated with new-onset kidney function decline in an initially healthy and well-characterized population with a 20-year follow-up. This study was based on 1087 individuals from the familial longitudinal Suivi Temporaire Annuel Non-Invasif de la Santé des Lorrains Assurés Sociaux (STANISLAS) cohort who attended both visit 1 (from 1993 to 1995) and visit 4 (from 2011 to 2016). New-onset kidney function decline was approached both in quantitative (GFR slope for each individual) and qualitative (defined as a decrease in GFR of >15 ml/min/1.7 m2) ways. We analysed associations of 445 proteins measured both at visit 1 and visit 4 using Olink Proseek® panels and 119   765 genes expressions measured at visit 4 with GFR decline. Associations were assessed using multivariable models. The Bonferroni correction was applied. Results We found several proteins (including PLC, placental growth factor (PGF), members of the tumour necrosis factor receptor superfamily), genes (including CCL18, SESN3), and a newly discovered miRNA—mRNA pair (MIR1205–DNAJC6) to be independently associated with new-onset kidney function decline. Complex network analysis highlighted both extracellular matrix and cardiovascular remodelling (since visit 1) as well as inflammation (at visit 4) as key features of early GFR decrease. Conclusions These findings lay the foundation to further assess whether the proteins and genes herein identified may represent potential biomarkers or therapeutic targets to prevent renal function impairment. [ABSTRACT FROM AUTHOR]

Background Atrial arrhythmia, particularly atrial fibrillation (AF), is known to be associated with renal function decline and increased risk of end-stage kidney disease. In recent years, premature atrial complexes (PACs) as subclinical arrhythmia have been proposed to be a marker of atrial cardiomyopathy and associated with poor clinical outcomes. However, the relationship between excessive daily PAC burden and renal outcomes remains unexplored. Methods This retrospective, all-comers cohort study analyzed 30 488 consecutive Holter monitoring records obtained from a validated Holter databank at a referral medical center in Taiwan between 2011 and 2018. After exclusion, 10 981 patients were categorized into three groups: high daily PAC burden (≥100 beats per day), low PAC burden (<100 beats per day) and the AF group. We used parallel propensity score matching to balance confounding factors between groups. The primary study interest was major adverse kidney events, including an estimated glomerular filtration rate (eGFR) decline of 40%, eGFR <15 mL/min/1.73 m2 or the initiation of hemodialysis. Results After a mean follow-up of 4.07 ± 3.03 years, patients with high PAC burden had a 1.24-fold higher incidence of major adverse kidney events compared with the low PAC burden group [95% confidence interval (CI) 1.03–1.50]. The risk of major adverse kidney events was similar between patients with AF and those with high PAC burden [adjusted hazard ratio (HR) 1.05, 95% CI 0.87–1.25], but significantly higher in the AF group than in the low PAC burden group (adjusted HR 1.29, 95% CI 1.07–1.56). Conclusion Excessive daily PAC burden is associated with a higher risk of major adverse kidney events and has a comparable impact as AF. [ABSTRACT FROM AUTHOR]

Background Patients with chronic kidney disease (CKD) and atrial fibrillation (AF) on oral anticoagulants (OACs) are at high risk of bleeding. Determinants of major bleeding risk in OAC users with AF and CKD are not well established and available bleeding score systems do not perform well in CKD. This study aims to present risk factors associated with major bleeding in a Swedish cohort of OAC-treated patients with CKD G3–5D. Methods We conducted a Swedish register-based cohort study including patients with AF and CKD G3–5D on warfarin or direct OACs (DOACs) between 2009 and 2018. Data were collected from high-quality registers including the Swedish Renal Registry and Auricula, a register for AF and OACs. Risk factors for major bleeding were investigated with Cox regression analysis. Results Of 2453 included patients, 59% were on warfarin (time in therapeutic range 67%) and 41% on DOACs. Major bleeding rates were 8.9/100 patient-years. Factors associated with increased bleeding risk were glomerular filtration rate category, G5/5D versus G3 {hazard ratio [HR] 1.92 [95% confidence interval (CI) 1.43–2.56]}, previous gastrointestinal bleeding [HR 1.77 (95% CI 1.39–2.25)], previous other bleeding [HR 1.33 (95% CI 1.09–1.62)], congestive heart failure [HR 1.36 (95% CI 1.11–1.68)], male sex [HR 1.28 (95% CI 1.03–1.60)] and vascular disease [HR 1.35 (95% CI 1.01–1.79)]. Conclusion Patients with AF and G3–5D on OACs are at a high risk of bleeding. Previous major bleeding and kidney failure are strongly associated with major bleeding. The present study also shows an association between OAC-associated bleeding and male sex, congestive heart failure and vascular disease. Knowledge about determinants of bleeding in advanced CKD is essential when deciding on when to anticoagulate or not. [ABSTRACT FROM AUTHOR]

Background Patients with Fabry disease (FD, α-galactosidase A deficiency or absence) accumulate glycosphingolipids, leading to progressive dysfunction of kidneys, heart and nervous system. Generalizable real-world outcomes following agalsidase beta treatment initiation outside trials are limited. We investigated the associations of long-term agalsidase beta treatment with estimated glomerular filtration rate (eGFR) changes over time and the risk of developing a composite clinical event in a matched analysis of treated and untreated patients with FD. Methods Agalsidase beta–treated adult patients (aged ≥16 years) from the Fabry Registry and adult untreated patients from a natural history cohort were matched 1:1 and X:X (with one occurrence and multiple occurrences of each untreated patient, respectively) by sex, phenotype, age and (for eGFR slope analysis) baseline eGFR. Outcomes included eGFR slope over 5 years and composite clinical event risk (cardiovascular, cerebrovascular or renal event, or death) over 10+ years. As a surrogate indicator of therapeutic response in paediatric patients, the percentage experiencing normalization in plasma globotriaosylceramide (GL-3) from treatment initiation was assessed in patients aged 2 to <16 years. Results Overall, eGFR slopes for 1:1-matched untreated and treated adult patients [122 pairs (72.1% male)] were −3.19 and −1.47 mL/min/1.73 m2/year, respectively (reduction in rate of decline = 53.9%, P  = .007), and for X:X-matched [122 untreated/950 treated (59.4% male)] were −3.29 and −1.56 mL/min/1.73 m2/year, respectively (reduction in rate of decline = 52.6%, P  < .001). Agalsidase beta treatment was associated with lower risk of clinical events, with hazard ratios of 0.41 (P  = .003) and 0.67 (P  = .008) for 1:1-matched and X:X-matched analyses, respectively. Plasma GL-3 declined markedly in paediatric patients and normalized in most within 6 months of treatment initiation. Conclusion Agalsidase beta treatment preserves kidney function and delays progression to severe clinical events among adult patients with FD. Plasma GL-3 levels analysed in paediatric patients showed normalization of elevated pre-treatment levels in most patients. [ABSTRACT FROM AUTHOR]

Introduction The DAPA-CKD study showed a protective effect of dapagliflozin on kidney function in chronic kidney disease (CKD) patients with and without diabetes mellitus. Although dapagliflozin is expected to be effective also in CKD patients with autosomal dominant polycystic kidney disease (ADPKD), its efficacy and safety in this population remain unknown because ADPKD was an exclusion criterion in the DAPA-CKD study. Therefore, we evaluated the effects of dapagliflozin in CKD patients with ADPKD. Methods We performed a retrospective observational study of seven patients with ADPKD treated with dapagliflozin at Toranomon Hospital, Tokyo, Japan. We analyzed changes in estimated glomerular filtration rate (eGFR) slope and annual height-corrected total kidney volume before and after starting dapagliflozin treatment. Results The median observation period after starting dapagliflozin was 20 months. Four patients received concomitant tolvaptan. The eGFR slope before and after initiation of dapagliflozin could be calculated in six patients and improved in all of them except the one who did not receive a renin-angiotensin system (RAS) inhibitor. Annual height-corrected total kidney volume increased in all patients. Concurrent tolvaptan treatment had no effect. Conclusion In CKD patients with ADPKD, dapagliflozin may increase kidney volume but may have a protective effect on kidney function when used concomitantly with RAS inhibitors. [ABSTRACT FROM AUTHOR]

Background Patients with membranous nephropathy (MN) and poor kidney function or active disease despite previous immunosuppression are underrepresented in clinical trials. It is unknown how effective rituximab is in this population. Methods This prospective, multi-centre, single-arm, real-world study of patients with active MN [urine protein-creatinine ratio (uPCR) >350 mg/mmol and serum albumin <30 g/L, or a fall in estimated glomerular filtration rate (eGFR) of at least 20% or more over at least 3 months] evaluated rituximab in those with contraindications to calcineurin inhibitors and cytotoxic therapy. The primary outcome was change in rate of eGFR decline before and after rituximab. Complete or partial remission were defined as uPCR <30 mg/mmol or uPCR <350 mg/mmol with a ≥50% fall from baseline, respectively. Results A total of 180 patients [median age 59 years, interquartile range (IQR) 48–68] received rituximab and were followed up for a median duration of 17 months. Seventy-seven percent had prior immunosuppression. Median eGFR and uPCR at baseline were 49.2 mL/min/1.73 m2 (IQR 34.4–80.6) and 766 mg/mmol (IQR 487–1057), respectively. The annual rate of decline of eGFR fell from 13.9 to 1.7 mL/min/1.73 m2/year following rituximab (Z score = 2.48, P < .0066). At 18 months 12% and 42% of patients were in complete or partial remission, respectively. Rituximab was well tolerated; patient survival was 95.6% at 2 years and in patients in whom eGFR was available, kidney survival was 93% at 2 years. Conclusion Rituximab significantly reduced the rate of eGFR decline in active MN including those who had received prior immunosuppression or with poor baseline kidney function. [ABSTRACT FROM AUTHOR]

Background We compared kidney and cardiorenal protection in patients without type 2 diabetes across urine albumin–creatinine ratio (UACR) levels after initiation on dapagliflozin for the treatment of chronic kidney disease (CKD). Methods OPTIMISE-CKD is an observational study describing dapagliflozin treatment for CKD. Adult patients with CKD without type 2 diabetes were included in the primary analysis. Baseline UACR was grouped as normal/mildly elevated (0–29 mg/g), low (30–200 mg/g) and high (>200 mg/g). Outcomes were estimated glomerular filtration rate (eGFR) trajectories/slopes, cardiorenal complications and all-cause mortality. Results In total, 1480 patients had low (n  = 796) and high (n  = 684) UACR. The two groups were similar at baseline, aged 75 and 74 years, and 42% and 39% female, respectively. After dapagliflozin initiation, an acute eGFR dip of 3 mL/min/1.73 m2 was observed, followed by a flat development in both groups. The eGFR slope [95% confidence interval (CI)] for patients with low UACR was 0.79 mL/min/1.73 m2 per year (–0.59, 2.56), and similar to patients with high UACR [0.40 mL/min/1.73 m2 per year (–0.46, 1.38)]. Risks of cardiorenal complications and all-cause mortality were similar, with adjusted hazard ratios of 0.89 (95% CI 0.66, 1.19) and 1.10 (95% CI 0.63, 1.92), respectively. Analogous results were found in those with normal/mildly elevated UACR. Conclusions Dapagliflozin in patients without type 2 diabetes for the treatment of CKD demonstrated similar kidney protection, cardiorenal and all-cause mortality risk across UACR levels. This suggests that the efficacy of dapagliflozin found in clinical trials expands to real-world patients with CKD, regardless of albuminuria levels. [ABSTRACT FROM AUTHOR]

A study published in the journal Nephrology Dialysis Transplantation examined the effectiveness of obinutuzumab in treating frequently-relapsing/steroid-dependent minimal change disease (MCD) in adults. The study found that obinutuzumab, a type II anti-CD20 monoclonal antibody, was effective in achieving remission in patients with FR/SD MCD. The study included six patients, and the treatment involved a combination of glucocorticosteroids and obinutuzumab. Further research is needed to determine the long-term efficacy and safety of obinutuzumab for MCD. The article also discusses the use of obinutuzumab in the treatment of focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) in adult patients. The study included six patients with FSGS or MCD who were treated with obinutuzumab. After treatment, all six patients achieved complete remission, and there were no relapses during the follow-up period. The study suggests that obinutuzumab may be an effective and safe treatment option for adult patients with FSGS or MCD. However, the study has limitations, including a small sample size and short follow-up time, and further research is needed to fully understand the long-term outcomes and mechanisms of obinutuzumab treatment. [Extracted from the article]

Background Autosomal dominant Alport Syndrome (ADAS), also known as thin basement membrane disease (TBMD), is caused by pathogenic variants in the COL4A3 and COL4A4 genes. A cystic phenotype has been described in some patients with TBMD, but no genetic studies have been performed. We conducted a genetic and radiologic investigation in a cohort of ADAS patients to analyze the prevalence of multicystic kidney disease (MKD) and its association with chronic kidney disease (CKD). Methods This was a retrospective single-center cohort study. Thirty-one patients showing pathogenic or likely pathogenic variants in COL4A3 or COL4A4 from a cohort of 79 patients with persistent microscopic hematuria were included. Mean follow-up was 9.4 ± 9.6 years. The primary objective of the study was to determine the prevalence of MKD in the cohort of ADAS patients. Secondary objectives were to determine risk factors associated with an estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m2 at the time of genetic and radiologic evaluation and to investigate the coexistence of other genetic abnormalities associated with familial hematuria and cystic kidney disease. Results MKD was found in 16 patients (52%). Mean number of cysts per kidney was 12.7 ± 5.5. No genetic abnormalities were found in a panel of 101 other genes related to familial hematuria, focal segmental glomerulosclerosis and cystic kidney disease. A greater number of patients with MKD had an eGFR <45 mL/min/1.73 m2 (63% vs 7%, P  = .006) and more advanced CKD than patients without MKD. The annual rate of eGFR decline was greater in patients with MKD: –1.8 vs 0.06 mL/min/1.73 m2/year (P  = .009). By multivariable linear regression analysis, the main determinants of eGFR change per year were time-averaged proteinuria (P  = .002) and MKD (P  = .02). Conclusion MKD is commonly found in ADAS and is associated with a worse kidney outcome. No pathogenic variants were found in genes other than COL4A3 / COL4A4. [ABSTRACT FROM AUTHOR]

Background To explore the association between the differences between cystatin C- and creatinine-based estimated glomerular filtration rate (eGFRdiff), and the risk of mortality and cardiovascular (CV) events in individuals with diabetes. Methods Three prospective cohorts analyzed data from adults with diabetes from the Incident, Development, and Prognosis of Diabetic Kidney Disease (INDEED) study (2016–17 to 2020) in China, the National Health Nutrition Examination Survey (NHANES, 1999–2004 to 2019) in the USA and UK Biobank (UKB, 2006–10 to 2022) in the UK. Baseline eGFRdiff was calculated using both absolute difference between cystatin C- and creatinine-based calculations (eGFRabdiff), and the ratio between them (eGFRrediff). Cox proportional hazards regression models were used to investigate the association between eGFRdiff and outcomes including all-cause mortality and incident CV events. Results A total of 8129 individuals from INDEED (aged 60.7 ± 10.0 years), 1634 from NHANES (aged 62.5 ± 14.4 years) and 29 358 from UKB (aged 59.4 ± 7.3 years) were included. At baseline, 43.6%, 32.4% and 42.1% of participants in INDEED, NHANES and UKB, respectively, had an eGFRabdiff value ≥15 mL/min/1.73 m2. During a median follow-up of 3.8 years for INDEED, 15.2 years for NHANES and 13.5 years for UKB, a total of 430, 936 and 6143 deaths and a total of 481, 183 and 5583 CV events occurred, respectively. Each 1-standard deviation higher baseline eGFRabdiff was independently associated with a lower risk of all-cause mortality and CV events, with hazard ratios of 0.77 and 0.82 in INDEED, 0.70 and 0.68 in NHANES, and 0.66 and 0.78 in UKB. Similar results were observed for eGFRrediff. Conclusions eGFRdiff represents a marker of adverse events for diabetes among general population. Monitoring both eGFRcys and eGFRcr yields additional prognostic information and has clinical utility in identifying high-risk individuals for mortality and CV events. [ABSTRACT FROM AUTHOR]

Background Immunoglobulin A vasculitis with nephritis (IgAVN) is the most common vasculitis in children. Due to a lack of evidence, treatment recommendations are based on expert opinion, resulting in variation. The aim of this study was to describe the clinical presentation, treatment and outcome of an extremely large cohort of children with biopsy-proven IgAVN in order to identify prognostic risk factors and signals of treatment efficacy. Methods Retrospective data were collected on 1148 children with biopsy-proven IgAVN between 2005 and 2019 from 41 international paediatric nephrology centres across 25 countries and analysed using multivariate analysis. The primary outcome was estimated glomerular filtration rate (eGFR) and persistent proteinuria at last follow-up. Results The median follow-up was 3.7 years (interquartile range 2–6.2). At last follow-up, 29% of patients had an eGFR <90 mL/min/1.73 m2, 36% had proteinuria and 3% had chronic kidney disease stage 4–5. Older age, lower eGFR at onset, hypertension and histological features of tubular atrophy and segmental sclerosis were predictors of poor outcome. There was no evidence to support any specific second-line immunosuppressive regimen being superior to others, even when further analysing subgroups of children with reduced kidney function, nephrotic syndrome or hypoalbuminemia at onset. Delayed start of immunosuppressive treatment was associated with a lower eGFR at last follow-up. Conclusion In this large retrospective cohort, key features associated with disease outcome are highlighted. Importantly, there was no evidence to support that any specific immunosuppressive treatments were superior to others. Further discovery science and well-conducted clinical trials are needed to define accurate treatment and improve outcomes of IgAVN. [ABSTRACT FROM AUTHOR]

Background Optimal antibiotic dosing for Staphylococcus aureus bloodstream infections (BSI) is still controversial. One reason is inter-individual variation in pharmacokinetics, which may be influenced by various patient-related factors, particularly in critically ill patients. Objectives To describe the population pharmacokinetics (PopPK) of the antibiotic flucloxacillin in patients with S. aureus BSI. Subsequently, we sought to translate the model into a user-friendly app for generating a priori and a posteriori time–concentration curves and dose recommendations to optimize dosing regimens. Methods Total and unbound flucloxacillin concentrations were included from 49 patients from a prospective cohort study conducted during clinical routine, including non-critically ill and critically ill individuals who received intermittent bolus applications. These data were analysed using non-linear mixed-effects modelling. Results Most patients (98%) were treated with 2 g of flucloxacillin every 4 h. We developed a joint model that simultaneously described total and unbound concentrations. The model included an allometric effect of glomerular filtration rate on clearance and albumin on the albumin dissociation constant. The latter was especially important, as in our population the unbound fraction was higher at 11.5% (16.7% for critically ill patients) compared with reported values of approximately 5%. Based on our joint model, we developed a web-based app for optimizing dosing regimens of flucloxacillin. Conclusions By utilizing data from clinical routine, we were able to create a predictive PopPK model of flucloxacillin and identify influential covariates. The web-based app is currently being validated in a clinical trial. [ABSTRACT FROM AUTHOR]

Background The concentrations of linezolid, its optimal regimen and the associated side effects in elderly patients remain unclear. Methods In this multicentre, prospective study, elderly patients receiving linezolid at four tertiary hospitals in Beijing between May 2021 and December 2022 were included. Linezolid concentrations and haematological toxicity were monitored dynamically. Risk factors for linezolid overexposure and moderate-to-severe linezolid-induced thrombocytopenia (M/S LIT) were analysed, and a predictive model of M/S LIT was developed. Results A total of 860 linezolid concentrations were measured in 313 patients. The median trough concentrations of linezolid were 24.4 (15.3, 35.8) mg/L at 36–72 h and 26.1 (17.0, 38.1) mg/L at 5–10 days (P  = 0.132). Severe linezolid exposure was independently associated with age, estimated glomerular filtration rate (eGFR) and the worst SOFA score (SOFA1), and we further recommended dose regimens for elderly patients based on these findings. The incidences of linezolid-induced thrombocytopenia(LIT) and M/S LIT were 73.5% and 47.6%, respectively. M/S LIT was independently correlated with treatment duration, average trough concentration (TDMa), baseline platelet count, eGFR and baseline SOFA score (SOFA0). The developed nomogram predicted M/S LIT with an area under the curve of 0.767 (95% CI 0.715–0.820), a sensitivity of 71.1% and a specificity of 73.2%. Conclusions Linezolid trough concentrations increased dramatically in the elderly, by about 10 mg/L in patients aged 65–80 years, followed by a further increase of 10 mg/L for every 10 years of age. Therapeutic drug monitoring is recommended in elderly patients receiving linezolid. The developed nomogram may predict M/S LIT and guide dosage adjustments of linezolid. Clinical trial registration number : ChiCTR2100045707 [ABSTRACT FROM AUTHOR]

The article discusses the controversy surrounding the inclusion of race in estimating glomerular filtration rate (GFR) for chronic kidney disease (CKD) diagnosis and treatment. Traditionally, racial adjustments have been made to creatinine-based GFR estimates, but medical students and activists have argued that this is a form of racism. As a result, a task force recommended the adoption of a race-free GFR estimate, which has led to major policy changes. However, the author argues that excluding race from GFR estimation may lead to inaccurate CKD diagnoses and harm patients. They propose using separate formulas for Blacks and non-Blacks to provide unbiased estimates for both groups. The article also discusses the unintended consequences of race-neutral GFR estimates on kidney transplant accessibility and survival rates. The author concludes that precision medicine, not racism, should guide CKD diagnosis and treatment decisions. [Extracted from the article]

Background Chronic kidney disease (CKD) is a growing global health concern. Identifying individuals in routine clinical care with new-onset CKD at high risk of rapid progression of the disease is imperative to guide allocation of prophylactic interventions, but community-based data are limited. We aimed to examine the risk of rapid progression, kidney failure, hospitalization and death among adults with incident CKD stage G3 and to clarify the association between predefined risk markers and rapid CKD progression. Methods Using plasma creatinine measurements for the entire Danish population from both hospitals and primary care, we conducted a nationwide, population-based cohort study, including adults in Denmark with incident CKD stage G3 in 2017–2020. We estimated 3-year risks of rapid progression (defined by a confirmed decline in estimated glomerular filtration rate of ≥5 mL/min/1.73 m2/year), kidney failure, all-cause hospitalization and death. To examine risk markers, we constructed a heat map showing the risk of rapid progression based on predefined markers: albuminuria, sex, diabetes and hypertension/cardiovascular disease. Results Among 133 443 individuals with incident CKD stage G3, the 3-year risk of rapid progression was 14.6% [95% confidence interval (CI) 14.4–14.8]. The 3-year risks of kidney failure, hospitalization and death were 0.3% (95% CI 0.3–0.4), 53.3% (95% CI 53.0–53.6) and 18.1% (95% CI 17.9–18.4), respectively. In the heat map, the 3-year risk of rapid progression ranged from 7% in females without albuminuria, hypertension/cardiovascular disease or diabetes, to 46%–47% in males and females with severe albuminuria, diabetes and hypertension/cardiovascular disease. Conclusion This population-based study shows that CKD stage G3 is associated with considerable morbidity in a community-based setting and underscores the need for optimized prophylactic interventions among such patients. Moreover, our data highlight the potential of using easily accessible markers in routine clinical care to identify individuals who are at high risk of rapid progression. [ABSTRACT FROM AUTHOR]

Creatinine-based estimated glomerular filtration rate (eGFR) is imprecise at individual level, due to non-GFR-related serum creatinine determinants, including atypical muscle mass. Cystatin C has the advantage of being independent of muscle mass, a feature that led to the development of race- and sex-free equations. Yet, cystatin C–based equations do not perform better than creatinine-based equations for estimating GFR unless both variables are included together. The new race-free Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation had slight opposite biases between Black and non-Black subjects in the USA, but has poorer performance than that the previous version in European populations. The European Kidney Function Consortium (EKFC) equation developed in 2021 can be used in both children and adults, is more accurate in young and old adults, and is applicable to non-white European populations, by rescaling the Q factor, i.e. population median creatinine, in a potentially universal way. A sex- and race-free cystatin C–based EKFC, with the same mathematical design, has also be defined. New developments in the field of GFR estimation would be standardization of cystatin C assays, development of creatinine-based eGFR equations that incorporate muscle mass data, implementation of new endogenous biomarkers and the use of artificial intelligence. Standardization of different GFR measurement methods would also be a future challenge, as well as new technologies for measuring GFR. Future research is also needed into discrepancies between cystatin C and creatinine, which is associated with high risk of adverse events: we need to standardize the definition of discrepancy and understand its determinants. [ABSTRACT FROM AUTHOR]

Background Mental health problems, particularly anxiety and depression, are common in patients with chronic kidney disease (CKD) and negatively impact quality of life, treatment adherence and mortality. However, the degree to which mental health and addiction services are utilized by those with CKD is unknown. We examined the history of mental health and addiction service use of individuals across levels of kidney function. Methods We performed a population-based cross-sectional study using linked healthcare databases from Ontario, Canada from 2009 to 2017. We abstracted the prevalence of individuals with mental health and addiction service use within the previous 3 years across levels of kidney function [estimated glomerular filtration rate (eGFR) ≥60, 45 to <60, 30 to <45, 15 to <30, <15 ml/min/1.73 m2 and maintenance dialysis]. We calculated prevalence ratios (PRs) to compare prevalence across kidney function strata, while adjusting for age, sex, year of cohort entry, urban versus rural location, area-level marginalization and Charlson comorbidity index. Results Of 5 956 589 adults, 9% (n  = 534 605) had an eGFR <60 ml/min/1.73 m2 or were receiving maintenance dialysis. Fewer individuals with an eGFR <60 ml/min/1.73 m2 had a history of any mental health and addiction service utilization (crude prevalence range 28–31%) compared with individuals with an eGFR ≥60 ml/min/1.73 m2 (35%). Compared with an eGFR ≥60 ml/min/1.73 m2, the lowest prevalence of individuals with any mental health and addiction service utilization was among those with an eGFR of 15 to <30 ml/min/1.73 m2 {adjusted PR 0.86 [95% confidence interval (CI) 0.85 to 0.88]}, an eGFR <15 ml/min/1.73 m2 [adjusted PR 0.81 (95% CI 0.76–0.86)] and those receiving maintenance dialysis [adjusted PR 0.83 (95% CI 0.81–0.84)]. Less use of outpatient services accounted for differences in service utilization. Conclusions Mental health and addiction service utilization is common but less so in individuals with advanced CKD in Ontario, Canada. [ABSTRACT FROM AUTHOR]

Aims Many studies show the association between malnutrition and poor prognosis in heart failure (HF) patients. Our research aimed to analyse sex differences in patients with HF with reduced ejection fraction (HFrEF), emphasizing nutritional status and the influence of selected parameters on the prognosis. Methods and results We enrolled 276 consecutive patients diagnosed with HFrEF. Nutritional status was assessed using Mini Nutritional Assessment (MNA), geriatric nutritional risk index (GNRI), and body mass index (BMI). The mean follow-up period was 564.4 ± 346.3 days. The analysed group included 81.2% of men. The median age was 58, interquartile range (IQR) 49–64 years. Among all patients, almost 60% were classified as NYHA III or IV. Half of the participants were at risk of malnutrition, and 2.9% were malnourished. During follow-up, 72 (26.1%) patients died. The female sex was not associated with a higher occurrence of malnutrition (P = 0.99) or nutritional risk (P = 0.85), according to MNA. Coherently, GNRI scores did not differ significantly between the sexes (P = 0.29). In contrast, BMI was significantly higher in males (29.4 ± 5.3 vs. 25.9 ± 4.7; P < 0.001). Impaired nutritional status assessed with any method (MNA, GNRI, BMI) was not significantly associated with a worse prognosis. In multivariable analysis, NYHA class, lower estimated glomerular filtration rate, higher B-type natriuretic peptide (BNP), higher N-terminal fragment of proBNP, and higher uric acid were independent of sex and age predictors of all-cause mortality. Conclusion There were no sex differences in the nutritional status in the HFrEF patients, apart from lower BMI in females. Impaired nutritional status was not associated with mortality in both men and women. [ABSTRACT FROM AUTHOR]

Background Diabetic kidney disease (DKD) poses a significant challenge globally as a complication of diabetes. Hyaluronan (HA), a critical non-sulfated glycosaminoglycan in the extracellular matrix, plays a pivotal role in the progression of DKD. This study assesses the predictive significance of HA's corresponding receptor, RHAMM (receptor for HA-mediated motility), in DKD pathogenesis in type 2 diabetes (T2DM) patients. Methods Enzyme-linked immunosorbent assays were utilized to measure plasma and urine levels of HA, CD44 and RHAMM in 99 diabetic patients. Immunohistochemistry staining was employed to examine HA deposition, CD44 and RHAMM expressions from 18 biopsy-proven DKD patients. Spearman correlation analysis, linear regression and receiver operating characteristic (ROC) analysis were conducted to establish associations between plasma HA, CD44 and RHAMM levels, and clinical parameters in DKD patients with T2DM. Results Elevated plasma and urine HA, CD44 and RHAMM levels were notably observed in the severe renal dysfunction group. Plasma RHAMM exhibited positive correlations with HA (r = 0.616, P  < .001) and CD44 (r = 0.220, P  < .001), and a negative correlation with estimated glomerular filtration rate (eGFR) (r = –0.618, P  < .001). After adjusting for other potential predictors, plasma RHAMM emerged as an independent predictor of declining eGFR (β = –0.160, P  < .05). Increased HA, CD44 and RHAMM levels in kidney biopsies of DKD patients were closely associated with heightened kidney injury. The ROC curve analysis highlighted an area under the curve (AUC) of 0.876 for plasma RHAMM, indicating superior diagnostic efficacy compared to CD44 in predicting DKD pathogenesis. The combined AUC of 0.968 for plasma RHAMM, HA and CD44 also suggested even greater diagnostic potential for DKD pathogenesis. Conclusion These findings provide initial evidence that elevated RHAMM levels predict DKD pathogenesis in T2DM patients. The formation of a triple complex involving HA, CD44 and RHAMM on the cell surface shows promise as a targetable biomarker for early intervention to mitigate severe renal dysfunctions. [ABSTRACT FROM AUTHOR]

The worldwide prevalence and incidence rates of end-stage renal disease have been increasing, and the trend is pronounced in Taiwan. This is especially evident in southern Taiwan, where the wet-bulb globe temperature (WBGT) is consistently higher than in other regions. The association between kidney function and WBGT has not been fully investigated. Therefore, the aim of this study was to evaluate the association between estimated glomerular filtration rate (eGFR) and WBGT and variations in this association across different geographic regions in Taiwan. We used the Taiwan Biobank (TWB) to obtain data on community-dwelling individuals, linked these data with WBGT data obtained from the Central Weather Bureau and then processed the data using a machine learning model. WBGT data were recorded during the working period of the day from 8:00 a.m. to 5:00 p.m. These data were then compiled as 1-year, 3-year and 5-year averages, recorded prior to the survey year of the TWB of each participant. We identified 114 483 participants who had WBGT data during 2012–2020. Multivariable analysis showed that, in northern Taiwan, increases in 1- and 3-year averages of WBGT during the working period (β = −0.092, P  = .043 and β = −0.193, P  < .001, respectively) were significantly associated with low eGFR. In southern Taiwan, increases in 1-, 3- and 5-year averages of WBGT during the working period (β = −0.518, P  < .001; β = −0.690, P  < .001; and β = −0.386, P  = .001, respectively) were gnificantly associated with low eGFR. These findings highlight the importance of heat protection for people working outdoors or in high-temperature environments as a measure to prevent negative impacts on kidney function. Moreover, we observed that in southern Taiwan, every 1°C increase in WBGT had a greater impact on the decrease in eGFR compared with other regions in Taiwan. [ABSTRACT FROM AUTHOR]

Background Fibroblast growth factor 23 (FGF-23) and other markers of chronic kidney disease–mineral and bone disorder (CKD-MBD) provide valuable insights into disease processes, treatment options and patient prognosis. However, limited research has explored potential associations with ethnicity or season, particularly in multi-ethnic populations residing in high-latitude regions. Methods We evaluated CKD-BMD markers in a diverse cohort of CKD patients, who were participants of The CANADIAN AIM to PREVENT (the CAN AIM to PREVENT) study. FGF-23, calcium, phosphate, 25-hydroxyvitamin D (25-OHD) and intact parathyroid hormone (iPTH) in 1234 participants with pre-dialysis CKD (mean estimated glomerular filtration rate: 41.8 ± 14.3 mL/min) were analyzed. Mixed-effects general linear regression models adjusted for demographic and biological factors were used to compare repeated measurements across patient groups categorized by ethnicity (East Asian, White, South Asian, Black, Southeast Asian) and seasons. Results Compared with other groups, White participants exhibited 8.0%–18.5% higher FGF-23 levels, Black participants had 0.17–0.32 mg/dL higher calcium levels, White participants had 10.0%–20.1% higher 25-OHD levels, South Asian participants had 7.3%–20.1% lower 25-OHD levels and Black participants had 22.1–73.8% higher iPTH levels, while East Asian participants had 10.7%–73.8% lower iPTH levels. Seasonal variations were also observed. FGF-23 levels were 11.9%–15.5% higher in summer compared with other seasons, while calcium levels were 0.03–0.06 mg/dL lower in summer. 25-OHD levels were 5.6%–10.6% higher in summer and autumn compared with other seasons. Conclusions This study shows that FGF-23 and CKD-MBD markers in a Canadian pre-dialysis CKD cohort vary independently by ethnicity and season. Further research is needed to understand the reasons and clinical significance of these findings. [ABSTRACT FROM AUTHOR]

Background The increasing incidence of chronic kidney disease (CKD) is straining the capacity of outpatient clinics. Remote healthcare delivery might improve CKD follow-up compared with conventional face-to-face follow-up. Patient-reported outcomes (PROs) are used to empower remote follow-up and patient engagement. The consequences of shifting from face-to-face follow-up to remote outpatient follow-up on kidney function, health resource utilisation and quality of life remain unknown. Methods We conducted a multicentre pragmatic non-inferiority trial at three outpatient clinics in the Central Denmark Region. A total of 152 incident outpatients with CKD were randomised (1:1:1) to either PRO-based, PRO-telephone follow-up or standard of care (SoC). The primary outcome was the annual change in kidney function measured by the slope of the estimated glomerular filtration rate (eGFR). The non-inferiority margin was an eGFR of 2.85 ml/min/1.73 m2/year. Mean differences were estimated using intention-to-treat (ITT), per protocol and random coefficient models. Results Mean eGFR slope differences between PRO-based and SoC were −0.97 ml/min/1.73 m2/year [95% confidence interval (CI) −3.00–1.07] and −1.06 ml/min/1.73 m2/year (95% CI −3.02–0.89) between PRO-telephone and SoC. Non-inferiority was only established in the per-protocol analysis due to CIs exceeding the margin in the ITT group. Both intervention groups had fewer outpatient visits: −4.95 (95% CI −5.82 to −4.08) for the PRO-based group and −5.21 (95% CI −5.95 to −4.46) for the PRO-telephone group. We found no significant differences in quality of life, illness perception or satisfaction. Conclusion Differences in the eGFR slope between groups were non-significant and results on non-inferiority were inconclusive. Thus, transitioning to remote PRO-based follow-up requires close monitoring of kidney function. Reducing patients' attendance in the outpatient clinic was possible without decreasing either quality of life or illness perception. ClinicalTrials.gov identifier: NCT03847766 [ABSTRACT FROM AUTHOR]

Background General and abdominal obesity are prevalent, with established associations to frailty in the elderly. However, few studies have investigated these associations in patients with chronic kidney disease (CKD), yielding inconsistent results. Methods This cross-sectional study analysed data from the National Health and Nutrition Examination Survey (NHANES 2003–2018). Frailty was evaluated by the 36-item frailty index. General obesity was defined as a body mass index (BMI) >30 kg/m2; abdominal obesity was identified if waist circumference (WC) reached 102 cm in men and 88 cm in women. The associations of general and abdominal obesity with frailty were analysed using weighted multivariate logistic regression and restricted cubic splines. The interaction of general and abdominal obesity with frailty was examined. Results A total of 5604 adult patients (median age 71 years, 42% men) with CKD were included in this analysis, with a median estimated glomerular filtration rate of 57.3 ml/min/1.73 m2. A total of 21% were frail with general obesity and 32% were frail with abdominal obesity. Neither general nor abdominal obesity alone was associated with frailty. There was an interaction between general and abdominal obesity with frailty. Compared with individuals with normal BMI and WC, those with both general and abdominal obesity, rather than either alone, exhibited significantly increased odds of frailty {odds ratio [OR] 1.53 [95% confidence interval (CI) 1.20–1.95]}. General obesity was associated with being frail only when CKD patients had abdominal obesity [OR 1.59 (95% CI 1.08–2.36)]. Conclusions There may be an interaction between general and abdominal obesity with frailty in patients with CKD. Interventions aimed at preventing frailty should consider both aspects. [ABSTRACT FROM AUTHOR]