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Background: Dexmedetomidine, a highly selective alpha-2 adrenoceptor agonist with sedative and analgesic effects, has been suggested in recent studies to possess renoprotective properties. Dexmedetomidine may reduce the incidence of delayed graft function and contribute to effective pain control post-renal transplantation. The primary objective of this systematic review was to assess whether dexmedetomidine decreases the occurrence of delayed graft function in renal transplant patients. Methods: Databases including MEDLINE, EMBASE, and CENTRAL were comprehensively searched from their inception until March 2023. The inclusion criteria covered all Randomized Clinical Trials (RCTs) and observational studies comparing dexmedetomidine to control in adult patients undergoing renal transplant surgery. Exclusions comprised case series and case reports. Results: Ten RCTs involving a total of 1358 patients met the eligibility criteria for data synthesis. Compared to the control group, the dexmedetomidine group demonstrated a significantly lower incidence of delayed graft function (OR = 0.71, 95% CI 0.52–0.97, p = 0.03, GRADE: Very low, I2 = 0%). Dexmedetomidine also significantly prolonged time to initiation of rescue analgesia (MD = 6.73, 95% CI 2.32–11.14, p = 0.003, GRADE: Very low, I2 = 93%) and reduced overall morphine consumption after renal transplant (MD = -5.43, 95% CI -7.95 to -2.91, p < 0.0001, GRADE: Very low, I2 = 0%). The dexmedetomidine group exhibited a significant decrease in heart rate (MD = -8.15, 95% CI -11.45 to -4.86, p < 0.00001, GRADE: Very low, I2 = 84%) and mean arterial pressure compared to the control group (MD = -6.66, 95% CI -11.27 to -2.04, p = 0.005, GRADE: Very low, I2 = 87%). Conclusions: This meta-analysis suggests that dexmedetomidine may potentially reduce the incidence of delayed graft function and offers a superior analgesia profile as compared to control in adults undergoing renal transplants. However, the high degree of heterogeneity and inadequate sample size underscore the need for future adequately powered trials to confirm these findings.

Objectives: The evidence on water intake in the prevention of kidney function decline is scarce at population level in well-being individuals at high cardiovascular risk. Therefore, we aimed to longitudinally evaluate the associations between total water intake and subtypes and kidney function, through estimated-Glomerular Filtration Rate (eGFR). Methods: Three-year prospective analysis conducted in 1986 older adults (aged 55–75 year) with overweight/obesity and metabolic syndrome from the PREDIMED-Plus study. Water intake was assessed using validated beverage and food frequency questionnaires. Serum creatinine-based eGFR (SCr-based eGFR; ml/min/1.73 m2) was estimated using the CKD-EPI equation at baseline, one-year and 3-years of follow-up. Mixed-effects linear regression models were fitted to evaluate the associations between baseline total water intake and subtypes, and SCr-based eGFR over 3-years of follow-up. Results: Participants in the highest baseline tertile of total water intake, plain water and water from all fluids showed a lower decrease in SCr-based eGFR after 3-years of follow-up, compared to those in the lowest tertile. Participants with the highest tap water consumption showed a lower SCr-based eGFR decline after 1-year and 3-years of follow-up, in comparerd to participants in the lowest intake category (T3 vs. T1: β: 1.4 ml/min/1.73 m2; 95%CI: 0.5–2.3, β: 1.0; 95%CI: 0.1–2.0, respectively). Conclusions: Plain water rather than other water sources, and especially tap water, was associated with lower kidney function decline assessed through eGFR over 3-years of follow-up, in older individuals at high cardiovascular risk. Trial registration: ISRCTN89898870. Retrospectively registered on 24 July 2014

Background: To explore the value of arterial spin labeled (ASL) and blood oxygen level dependent (BOLD) imaging in evaluating allogeneic kidney function after renal transplantation. Methods: One hundred and thirty-five renal transplant patients were included. Demographic and imaging data were collected. Transplanted renal function, pathology, ASL and BOLD parameters were obtained. The patients were divided into normal, mild and severe injury group. The correlation between BOLD/ASL parameters and clinical data were evaluated. The prediction models were based on ASL and BOLD parameters using multivariate logistic analysis. Cox proportional hazards regression model was used to analyze the effects of gender, age, ASL and BOLD on the survival of renal transplant patients. Results: ASL and BOLD parameters were independently associated with renal function injury and renal allograft positive pathology. The AUC of prediction model for renal allograft function based on ASL and BOLD parameters was 0.85, while the AUC based on BOLD parameters was 0.70. Renal transplantation time showed a positive correlation with age, BOLD parameters and SCr，while a negative correlation with ASL parameters and eGFR. ASL parameter was positively correlated with eGFR and negatively correlated with Scr. BOLD parameter was negatively correlated with eGFR, ASL and positively correlated with Scr. Cox proportional hazards regression model showed that the increase of age could reduce the risk of renal function injury and positive pathology. Conclusions: ASL and BOLD were associated with renal function injury and renal allograft positive pathology. ASL and BOLD had some value in predicting renal allograft function.

Objectives: Not skipping breakfast is associated with a better overall diet quality and lower cardiometabolic risk. However, the impact of calorie intake and dietary quality of breakfast on cardiovascular health remains unexplored. We aimed to study the associations between breakfast energy intake and quality and time trajectories of cardiometabolic traits in high cardiovascular risk participants. Design: Prospective observational exploratory study with repeated measurements. Setting: Spanish older adults. Participants: 383 participants aged 55–75 with metabolic syndrome from PREDIMED-Plus, a clinical trial involving a weight-loss lifestyle intervention based on the Mediterranean diet. Measurements: Participants were followed for 36 months. Longitudinal averages of breakfast energy intake and quality were calculated. Three categories were defined for energy intake: 20−30% (reference), 30% (high). Quality was estimated using the Meal Balance Index; categories were above (reference) or below the median score (low). Natural cubic spline mixed effects regressions described trajectories of cardiometabolic indicators (anthropometry, blood pressure, lipids, glucose, glycated hemoglobin, and kidney function) in breakfast groups. Inter-group differences in predicted values were estimated by linear regressions. Analyses were adjusted for age, sex, PREDIMED-Plus intervention group, education, smoking, physical activity, and total daily kilocalorie intake. Lipid profile analyses were further adjusted for baseline hypercholesterolemia, blood pressure analyses for baseline hypertension, and glucose/glycated hemoglobin analyses for baseline diabetes. Breakfast energy intake analyses were adjusted for breakfast quality, and vice versa. Results: At 36 months, compared to the reference, low- or high-energy breakfasts were associated with differences in body mass index (low: 0.61 kg/m² [95% confidence interval: 0.19; 1.02]; high: 1.18 kg/m² [0.71; 1.65]), waist circumference (low: 2.22 cm [0.96; 3.48]; high: 4.57 cm [3.13; 6.01]), triglycerides (low: 13.8 mg/dL [10.8; 16.8]; high: 28.1 cm [24.7; 31.6]), and HDL cholesterol (low: −2.13 mg/dL [−3.41; −0.85]; high: −4.56 mg/dL [−6.04; −3.09]). At 36 months, low-quality breakfast was associated with higher waist circumference (1.50 cm [0.53; 2.46]), and triglycerides (5.81 mg/dL [3.50; 8.12]) and less HDL cholesterol (−1.66 mg/dL [−2.63; −0.69]) and estimated glomerular filtration rate (−1.22 mL/min/1.73m2 [−2.02; −0.41]). Conclusions: Low- or high-energy and low-quality breakfasts were associated with higher adiposity and triglycerides, and lower HDL cholesterol in high-risk older adults. Low-quality breakfasts were also linked to poorer kidney function.

The current systematic review and meta-analysis was undertaken to assess the efficaciousness of mammalian target of rapamycin (mTOR) inhibitors in transplant subjects with regards to kidney functions and survival, with special reference to co-administration (or absence of) calcineurin inhibitors (CNIs). The analysis was done through searching and retrieving information from online scholarly databases. The collected data represented outcomes after at least twelve months following transplantation of kidney. It was observed that parameters such as glomerular filtration rate (GFR) was improved in subjects administered with mTOR inhibitors, however some studies indicated that acute rejection following biopsy was dominant in subjects administered with mTOR inhibitors. Owing to their complementary mechanisms of action as well as beneficial effects on mitigating nephrotoxicity, concomitantly with favorable outcomes on parameters such as serum creatinine and GFR leading to increased survival, this meta-analysis proposes early utilization of mTOR inhibitors and CNI minimization in subjects with kidney transplantation.

Background: The aim of this study was to investigate whether quantitative changes in lymphocyte subsets and gene expression in peripheral blood (PB) cells are related to the clinical manifestations and pathogenesis of lupus nephritis (LN). Methods: We enrolled 95 pediatric-onset SLE patients with renal involvement who presented with 450 clinical episodes suspicious for LN flare. Percentages of lymphocyte subsets at each episode were determined. We stratified 55 of 95 patients as high or low subset group according to the median percentage of each lymphocyte subset and the association with changes in the eGFR (ΔeGFR) were analyzed. Peripheral blood bulk RNA-seq to identify differentially expressed genes (DEGs) in 9 active LN vs. 9 inactive LN patients and the DEG-derived network was constructed by Ingenuity Pathway Analysis (IPA). Results: The mean ΔeGFR of low NK-low memory CD4+ T-high naive CD4+ T group (31.01 mL/min/1.73 m2) was significantly greater than that of high NK-high memory CD4+ T-low naive CD4+ T group (11.83 mL/min/1.73 m2; P = 0.0175). Kaplan-Meier analysis showed that the median time for ΔeGFR decline to mean ΔeGFR is approximately 10 years for high NK-high memory CD4+ T-low naive CD4+ T group and approximately 5 years for low NK-low memory CD4+ T-high naive CD4+ T group (log-rank test P = 0.0294). Conclusions: Our study highlighted important connections between DEG-derived network, lymphocyte subset composition, and disease status of LN and GN. A novel scoring system based on lymphocyte subset proportions effectively stratified patients into groups with differential risks for declining renal function.

Introduction: Additional evidence is necessary to interpret kidney function parameters in young adults, particularly in those with marginal estimated glomerular filtration rate (eGFR) values. Therefore, we aimed to investigate the association between eGFR and adverse outcomes in general young adults. Methods: We performed a nationwide retrospective cohort study using the health-screening database of South Korea. We included young adults aged 20–39 years without a history of major adverse cardiovascular events (MACE) or kidney failure, who underwent nationwide health screening in 2012. The study exposure was eGFR categorized into 15 ml/min per 1.73 m2 intervals. The risks of all-cause mortality and MACE were calculated using Cox regression analysis, adjusted for various clinicodemographic characteristics. Results: In total, 3,132,409 young adults were included in this study. During a median follow-up of 7.3 years, marginal eGFR (60–75 ml/min per 1.73 m2) was not significantly associated with a higher risk of all-cause mortality (adjusted hazard ratio [aHR], 0.80 [0.74–0.87]). The results were similar for MACE outcomes (aHR, 0.94 [0.87-1.01]). Although the presence of dipstick albuminuria had a significant interaction with the association between eGFR categories and all-cause mortality (interaction term P = 0.028), the risks of all-cause mortality were not significantly higher (aHR, 0.98 [0.62, 1.55]) in those with albuminuria and eGFR 60–75 ml/min per 1.73 m2. Conclusion: Marginal eGFR was not associated with higher risks of all-cause mortality and MACE in general young adults. Additional clinical investigations for incidentally found marginal eGFR values may be discouraged in general young adults.

Background: Osteoporosis is characterized by low bone mass and deterioration of bone tissue, which is influenced by both environmental factors and nutritional metabolism. The relationship between biochemical indicators and bone mineral density (BMD) is intricate and involves complex mechanisms. Path analysis, a statistical method that investigates causal relationships and the strength of associations among multiple factors, can be valuable in elucidating the connection between biochemical indicators and BMD. Methods: In this study, we employed advanced statistical techniques, specifically structural equation modeling (SEM) to investigate the intricate interrelationships among a myriad of factors that exert influence on BMD. This analytical approach facilitated not only the identification of the direct relationships between specific variables and BMD but also the exploration of the intricate of indirect pathway through which other variables contribute to the oval impact on BMD. By delving into the direct and indirect effects, we aimed to unravel the complex influences that collectively shape the state of bone health, providing a nuanced understanding of the multifaceted nature of the factors affecting BMD. Results: Our findings revealed that lipid levels had a significant indirect influence on BMD, which was mediated by body mass index (BMI). BMI exhibited both direct and indirect effects on BMD. Uric acid (UA) exerted a significant direct and indirect influence on BMD, with glomerular filtration rate (GFR) acting as the mediator. However, the total effect of UA on BMD was not significant due to the cancellation of positive effect UA on BMD but negative indirect effects of UA through GFR. For females, albumin had a significant direct effect on BMD, whereas this effect was not observed in males. The path analysis models generated results that demonstrated an acceptable fit for both female data (χ2 = 9.63, df = 7, p = 0.21, comparative fit index (CFI) = 0.98, root mean square error of approximation (RMSEA) = 0.05) and male data (χ2 = 6.26, df = 4, p = 0.18, CFI = 0.97, RMSEA = 0.06). Conclusions: Nutritional metabolism plays a crucial role in maintaining BMD in elderly females and males.

Rationale & Objective: This study aimed to assess the effect of exposure to organic pollutants in adults with chronic kidney disease (CKD). Study Design: This was a cross-sectional and longitudinal analysis. Setting and Participants: Forty adults enrolled in the Chronic Renal Insufficiency Cohort (CRIC). Exposures: Exposure at baseline and longitudinally to various organic chemical pollutants. Outcomes: The outcomes were as follows: death; composite of congestive heart failure, myocardial infarction, and stroke; event-free survival from kidney failure or ≥50% decline in estimated glomerular filtration rate (eGFR); and longitudinal trajectory of eGFR. Analytical Approach: We used high-performance liquid chromatography with tandem mass spectrometry to measure urinary concentrations of bisphenols, phthalates, organophosphate pesticides, polycyclic aromatic hydrocarbons, melamine, and cyanuric acid at years 1, 3, and 5 after enrollment in the CRIC. Univariate and multivariable logistic regression were used to examine the association of individual compounds and classes of pollutants with the outcomes. The Cox proportional hazards model and Kaplan-Meier method were used to calculate hazard ratios and 95% CIs for each class of pollutants. Results: Median baseline eGFR and urinary protein-to-creatinine ratio were 33 mL/min/1.73 m2 and 0.58 mg/g, respectively. Of 52 compounds assayed, 30 were detectable in ≥50% of participants. Urinary chemical concentrations were comparable in patients with CKD and healthy individuals from contemporaneous National Health and Nutrition Examination Survey cohorts. Phthalates were the only class with a trend toward higher exposure in patients with CKD. There was an inverse relationship between exposure and the eGFR slopes for bisphenol F, mono-(3-carboxypropyl) phthalate, mono-benzyl phthalate, mono-[2-(carboxymethyl)hexyl] phthalate, and melamine. There were no associations between organic pollutant exposure and cardiovascular outcomes. Limitations: Small sample size, evaluation of single rather than combined exposures. Conclusions: Simultaneous measurement of multiple organic pollutants in adults with CKD is feasible. Exposure levels are comparable with healthy individuals. Select contaminants, especially in the phthalate class, may be associated with more rapid deterioration in kidney function. Plain-Language Summary: The effect of exposure to organic pollutants has not been studied in adults with chronic kidney disease. (CKD). To fill this gap, we measured the exposure to a wide range of chemicals that are found in plastics, personal care products, and food preparation. Overall, the exposure was similar to that noted in the healthy population living in the United States. Only select compounds, mainly phthalates, demonstrated a trend with a more rapid decline in kidney function. These findings provide a useful reference for future studies that aim to evaluate organic pollutant exposure in patients with CKD. This is significant because these exposures represent a modifiable risk factor for disease progression through alterations in diet or lifestyle.

Resumen: Antecedentes: La búsqueda de biomarcadores tempranos de enfermedad renal diabética (ERD) en pacientes con diabetes mellitus tipo 2 (DMT2), como los marcadores genéticos para identificar pacientes vulnerables de la enfermedad, incluso antes de la presencia de una disminución de la estimación de tasa de filtrado glomerular (TFGe) o presencia de microalbuminuria ha cobrado importancia en los últimos años.El polimorfismo rs5186 (A1166C) presente en el gen receptor tipo 1 de la angiotensina II (AGTR1) ha sido asociado a distintos efectos del riesgo de daño renal que suelen estar presentes en pacientes con diabetes mellitus (DM). Se ha descrito que el rs5186 podría influir en la estabilidad de las proteínas que conforman al receptor de la angiotensina II tipo 1 (AT1) alterando su actividad, por lo que podría ser considerado como un factor de riesgo a enfermedad renal crónica (ERC) caracterizada por una disminución progresiva de la TFG. Sin embargo, la asociación del polimorfismo rs5186 del gen AGTR1 con ERD en pacientes con DMT2 ha sido controversial, no concluyente, incluso nula. Las controversias podrían ser por los estudios de asociación y estimación del riesgo del rs5186 previamente reportados incluyen distintos fenotipos clínicos considerados como inductores y potenciadores de ERC, además, los tamaños de las muestras analizadas en pacientes con DMT2 eran pequeñas y no tenían un control estricto en su inclusión, careciendo incluso de marcadores bioquímicos o estadificación KDOQI que han dificultado su análisis. Objetivo: Determinar la asociación del rs5186 del gen AGTR1 con la disminución de TFGe considerada como riesgo al desarrollo de ERD en pacientes con DMT2. Material y métodos: Se analizaron 297 pacientes con DMT2 no emparentados, divididos en 221 controles (KDOQI 1) y 76 casos (KDOQI 2). Se determinaron parámetros de presión arterial, antropometría y bioquímicos. El genotipado del rs5186 del gen AGTR1 se realizó por PCR en tiempo real con uso de sondas TaqMan. Se determinaron frecuencias alélicas, genotípicas y equilibrio de Hardy-Weinberg. El análisis del comportamiento de los datos se determinó con Shapiro-Wilk, la comparación de las variables por t de Student para variables continuas, y X2 para variables categóricas, se usó prueba ANOVA para comparación de medias de más de dos grupos. El efecto del rs5186 a disminución de TFGe se realizó por distintos modelos de herencia ajustados por variables de riesgo a ERD. Se consideró un valor de p < 0,05 como estadísticamente significativo. Se utilizó el software Statistical Package STATA v11. Resultados: Los modelos dominante y sobredominante mostraron un riesgo a la disminución de la TFGe de 1,89 (1,05-3,39, p = 0,031) y 2,01 (1,08-3,73, p = 0,023) en pacientes con DMT2. El riesgo aumentó a 2,54 (1,10-5,89) en el modelo sobredominante en mujeres. Conclusión: En la práctica clínica, la mayoría de las nefropatías progresan lentamente hacia la pérdida definitiva de la función renal, cursando incluso asintomáticas. El presente estudio es el primero en reportar una contribución del rs5186 del gen AGTR1 con una disminución de la TFGe y podría ser considerado como un riesgo a ERD en pacientes con DMT2. Abstract: Background: Early biomarkers search for Diabetic Kidney Disease (DKD) in patients with Type 2 Diabetes Mellitus (T2DM), as genetic markers to identify vulnerable carriers of the disease even before Glomerular Filtration Rate (GFR) decline or microalbuminuria development, has been relevant during the last few years.The rs5186 (A116C) polymorphism of the Angiotensin II Receptor Type I gene (AGTR1), has been associated to multiple effects of renal injury risk, commonly detected in patients with Diabetes Mellitus (DM). It has been described that rs5186 could have an effect in stability proteins that assemble Angiotensin II Receptor Type I (AT1), modifying its action, which is why it should be considered as a risk factor for Chronic Kidney Disease (CKD), characterized by a GFR progressive reduction. Even though, the association between rs5186 AGTR1 gene polymorphism and DKD in patients with T2DM has been controversial, inconclusive, and even absent. This disputable issue might be as a result of association studies in which many and varied clinical phenotypes included are contemplated as CKD inductors and enhancers. Although, the sample sizes studied in patients with T2DM are undersized and did not have a strict inclusion criteria, lacking of biochemical markers or KDOQI classification, which have hindered its examination. Objective: The aim of our study was to establish an association between rs5186 AGTR1 gene polymorphism and GFR depletion, assessed as a risk factor to DKD development in patients with T2DM. Methods: We analyzed 297 not related patients with T2DM, divided into 221 controls (KDOQI 1) and 76 cases (KDOQI 2). Arterial pressure, anthropometric and biochemical parameters were measured. rs5186 of AGTR1 genotyping was performed by TaqMan assay real-time PCR method. Allele and genotype frequencies, and Hardy-Weinberg equilibrium were measured. Normality test for data distribution was analyzed by Shapiro-Wilk test, variable comparison by Student's t-test for continuous variables, and Chi-squared test for categorical variables; ANOVA test was used for mean comparison of more than two groups. Effect of rs5186 to DKD was estimated by multiple heritability adjustment models for risk variables of DKD. Statistical significance was indicated by p < 0.05. Data was analyzed using Statistical Package STATA v11 software. Results: Dominant and Over-dominant models showed a likelihood ratio to GFR depletion of 1.89 (1.05-3.39, p = 0.031) and 2.01 (1.08-3.73, p = 0.023) in patients with T2DM. Risk factor increased to 2.54 (1.10-5.89) in women in Over-dominant model. Conclusión: In clinical practice, most of nephropathies progress at a slow pace into a total breakdown of renal function, even asymptomatic. This is the first study, reporting that rs5186 polymorphism of AGTR1 gene contribution to GFR depletion, and this could be evaluated as a predisposing factor for DKD in patients with T2DM.

Background: Acute kidney injury (AKI), often experienced at the intensive care units, is associated with high morbidity/mortality where ischemia-reperfusion injury is a main causative factor. Succinate accumulation during ischemia contributes to the excessive generation of reactive oxygen species at reperfusion. Inhibition of succinate dehydrogenase has been associated with protective outcome in cardiac ischemia-reperfusion after 24h, but the effects on kidney and mitochondrial functions are less well studied. Aim: To investigate the therapeutic potential of succinate dehydrogenase inhibition, by using dimethyl malonate (DMM), on kidney and mitochondria functions in a mouse model of AKI. Methods: Male C57BL/6J mice were pre-treated with DMM or placebo, i.p. 30min prior to bilateral renal ischemia (20min). After 3-days of reperfusion, glomerular filtration rate (GFR) was calculated from plasma clearance of FITC-inulin. Kidney mitochondria was isolated and mass specific and intrinsic mitochondrial function were evaluated by high resolution respirometry. Kidney sections were stained (i.e., hematoxylin-eosin and TUNEL) and analyzed for histopathological evaluation of injuries and apotosis, respectively. NADPH oxidase activity in kidney and human proximal tubular cell-line (HK2) were measured luminometrically. Results: DMM treatment improved GFR (p

Rationale & Objective: Creatinine-based GFR estimating (eGFRcr) equations may be inaccurate in populations with acute or chronic illness. The accuracy of GFR equations that use cystatin C (eGFRcys) or creatinine-cystatin C (eGFRcr-cys) is not well studied in these populations. Study Design: A systematic review of original articles identified from PubMed and expert sources. Two reviewers screened articles independently and identified those meeting inclusion criteria. Setting & Study Populations: Adults and children with acute or chronic illness. Selection Criteria for Studies: Studies published since 2011 that compared performance of eGFRcr, eGFRcys, and eGFRcr-cys relative to measured GFR (mGFR), used standardized assays for creatinine or cystatin C, and used eGFR equations developed using such assays. Studies of ambulatory clinical populations or research studies in populations with only CKD, kidney transplant recipients, only diabetes, kidney donor candidates, and community-based cohorts were excluded. Data Extraction: Data extracted from full text. Analytical Approach: Bias and percentages of estimates within 30% of mGFR (P30) of eGFR compared with mGFR were evaluated. Results: Of the 179 citations, 26 studies met the inclusion criteria: 24 in adults and 2 in children in clinical populations with cancer (n=5), HIV (n=5), cirrhosis (n=3), liver transplant (n=3), heart failure (n=2), neuromuscular diseases (n=1) critical illness (n=5), and obesity (n=2). In general, eGFRcr-cys had greater accuracy than eGFRcr or eGFRcys equations among study populations with cancer, HIV, and obesity, but did not perform consistently better in cirrhosis, liver transplant, heart failure, neuromuscular disease, and critical illness. Limitations: Participants were selected because of concern for inaccurate eGFRcr, which may bias results. Most studies had small sample sizes, limiting generalizability. Conclusions: eGFRcr-cys improves GFR estimation in populations with a variety of acute and chronic illnesses, providing indications for cystatin C measurement. Performance was poor in many studies, suggesting the need for more frequent mGFR. Plain-Language Summary: Kidney function, specifically glomerular filtration rate (GFR), estimated using creatinine (eGFRcr) is often inaccurate in people with acute and chronic illness. The accuracy of estimates using cystatin C alone (eGFRcys) or together with creatinine (eGFRcr-cys) is not well studied in these populations. We conducted a systematic review to address the knowledge gap. Of the 179 papers reviewed, we identified 26 studies in clinical populations with cancer (n=5); HIV (n=5); cirrhosis (n=3); liver transplant (n=3); heart failure (n=2); neuromuscular disease (n=1); critical illness (n=5); and obesity (n=2). In general, eGFRcr-cys improved the GFR estimation in HIV, cancer, and obesity, providing indications for cystatin C measurement. Performance was poor in many studies, suggesting the need for more frequent measured GFR.

Rationale & Objective: Use of cystatin C in addition to creatinine to estimate glomerular filtration rate (estimated glomerular filtration rate based on cystatin C [eGFRcys] and estimated glomerular filtration rate based on creatinine [eGFRcr], respectively) is increasing. When eGFRcr and eGFRcys are discordant, it is not known which is more accurate, leading to uncertainty in clinical decision making. Study Design: Cross-sectional analysis. Setting & Participants: Four thousand fifty participants with measured glomerular filtration rate (mGFR) from 12 studies in North America and Europe. Exposures: Serum creatinine and serum cystatin C. Outcome(s): Performance of creatinine-based and cystatin C–based glomerular filtration rate estimating equations compared to mGFR. Analytical Approach: We evaluated the accuracy of eGFRcr, eGFRcys, and the combination (eGFRcr-cys) compared to mGFR according to the magnitude of the difference between eGFRcr and eGFRcys (eGFRdiff). We used CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equations to estimate glomerular filtration rate. eGFRdiff was defined as eGFRcys minus eGFRcr and categorized as less than −15, −15 to

Chronic kidney disease (CKD) refers to a range of various pathophysiological processes correlated with abnormal renal function and a progressive loss in GFR. Just as dysbiosis and altered pathology of the gut are accompanied with hypertension, which is a significant CKD risk factor. Gut dysbiosis in CKD patients is associated with an elevated levels of uremic toxins, which in turn increases the CKD progression.According to research results, the gut-kidney axis has a role in the formation of kidney stones, also in IgAN. A number of researchers have categorized the gut microbiota as enterotypes, and others, skeptical of theory of enterotypes, have suggested biomarkers to describe taxa that related to lifestyle, nutrition, and disease status. Metabolome-microbiome studies have been used to investigate the interactions of host-gut microbiota in terms of the involvement of metabolites in these interactions and are yielded promising results. The correlation between gut microbiota and CKD requires further multi-omic researches. Also, with regard to systems biology, studies on the communication network of proteins and transporters such as SLC and ABC, can help us achieve a deeper understanding of the gut-liver-kidney axis communication and can thus provide promising new horizons in the treatment of CKD patients. Probiotic-based treatment is an approach to reduce uremic poisoning, which is accomplished by swallowing microbes those can catalyze URS in the gut. If further comprehensive studies are carried out, we will know about the probiotics impact in slowing the renal failure progression and reducing inflammatory markers.

Objectives: To investigate renal function during denosumab therapy using the estimated glomerular filtration rate based on cystatin C (eGFRcys) which is more accurate than creatinine (eGFRcr) for renal function. Methods: Bone mineral densities (BMDs) of lumbar spine and hip regions, eGFRcys, eGFRcr, creatinine clearance (Ccr), and serum total homocysteine (S-Hcy) were measured during 2-year denosumab therapy in 53 women with osteoporosis naïve to anti-osteoporosis drugs (new group) and 64 women who were switched from long-term bisphosphonate treatment to denosumab therapy (switch group). Results: There were no significant differences in age, eGFRcr, Ccr, eGFRcys, and S-Hcy levels at baseline between the groups. BMDs in the lumbar spine, femoral neck, and total hip increased significantly after 2-year denosumab therapy in both groups. eGFRcr decreased in the switch group, and Ccr decreased in both groups; however, eGFRcys and S-Hcy levels did not change significantly in either group. To investigate the causal factors associated with the decrease in eGFRcr and Ccr, multiple regression analysis was performed in all patients. Denosumab initiation within 3 months after fracture and eGFRcr or Ccr at baseline were independent factors for the decrease in eGFRcr or Ccr during the 2-year denosumab therapy. Decline in creatinine-based renal function could be reflected by increased muscle mass during the ongoing recovery from fracture. Conclusions: Renal function was preserved in all patients, including those in the switch group during denosumab therapy. Creatinine-based renal function should be cautiously interpreted during denosumab therapy in patients with recent fractures.

Objective: To explore the association of diabetic retinopathy (DR) and diabetic macular edema (DME) with renal function in patients with type 2 diabetes mellitus (T2DM). Design: A prospective cohort study. Methods: This single-centre study included patients with no DR, mild non-proliferative DR (NPDR), and no DME at baseline. DR and DME were assessed using 7-field fundus photography and swept-source OCT (SS-OCT). The baseline renal function assessed included the estimated glomerular filtration rate (eGFR) and microalbuminuria (MAU). Cox regression analyses were used to assess the hazard ratio (HR) of renal function with the progression of DR and the development of DME. Results: A total of 1409 patients with T2DM (1409 eyes) were included. During 3 years of follow-up,143 patients had DR progression, and 54 patients developed DME. Low eGFR levels at baseline were associated with the development of DR (HR, 1.044 per 1-SD decrease; 95% CI, 1.035–1.053; P 90 mL/min/1.73 m2, the participants with eGFRs of 60–90 mL/min/1.73 m2 (HR, 1.649; 95% CI, 1.094–2.485; P = 0.017) or 0.05). Conclusions: Abnormal renal profiles (i.e., low levels of eGFR and high levels of MAU) were associated with the progression of DR, but not with the development of DME.

Rationale & Objective: Estimation of glomerular filtration rate (eGFR) and staging of chronic kidney disease (CKD) are essential to guide management. Although creatinine is routinely used, a recent national task force recommended the use of cystatin C for confirmation. The objective of this study was to examine the following parameters: (1) how cystatin C correlates with creatinine eGFR; (2) how it indicates differences in CKD staging; and (3) how it may affect kidney care delivery. Study Design: Retrospective observational cohort study. Setting & Participants: 1,783 inpatients and outpatients who had cystatin C and creatinine levels drawn within 24 hours at Brigham Health-affiliated clinical laboratories. Predictors: Serum creatinine levels, basic clinical/sociodemographic variables, and reasons for ordering cystatin C from a structured partial chart review. Analytical Approach: Univariate and multivariable linear and logistic regression. Results: Cystatin C-based eGFR was very strongly correlated with creatinine-based eGFR (Spearman correlation ρ = 0.83). Cystatin C eGFR resulted in a change to a later CKD stage in 27%, an earlier stage in 7%, and no change in 66% of patients. Black race was associated with a lower likelihood of change to a later stage (OR, 0.53; 95% CI [0.36, 0.75]; P

Resumen: La enfermedad renal crónica (ERC) es un importante problema de salud pública a nivel mundial afectando a más del 10% de la población española. Se asocia a elevada comorbilidad, mal pronóstico, así como a un gran consumo de recursos en el sistema sanitario. Desde la publicación del último documento de consenso sobre ERC publicado hace siete años, han sido escasas las evidencias y los ensayos clínicos que hayan mostrado nuevas estrategias en el diagnóstico y tratamiento de la ERC, con excepción de los nuevos ensayos en la enfermedad renal diabética. Esta situación ha condicionado que no se hayan actualizado las guías internacionales específicas de ERC. Esta rigidez y actitud conservadora de las guías no debe impedir la publicación de actualizaciones en el conocimiento en algunos aspectos, que pueden ser clave en la detección y manejo del paciente con ERC. En este documento, elaborado en conjunto por diez sociedades científicas, se muestra una actualización sobre conceptos, aclaraciones, criterios diagnósticos, estrategias de remisión y nuevas opciones terapéuticas.Se han revisado las evidencias y los principales estudios publicados en estos aspectos de la ERC, considerándose más bien un documento de información sobre esta patología. El documento incluye una actualización sobre la detección de la ERC, factores de riesgo, cribado, definición de progresión renal, actualización en los criterios de remisión con nuevas sugerencias en la población anciana, monitorización y estrategias de prevención de la ERC, manejo de comorbilidades asociadas, especialmente en diabetes mellitus, funciones del médico de Atención Primaria en el manejo de la ERC y qué no hacer en Nefrología.El objetivo del documento es que sirva de ayuda en el manejo multidisciplinar del paciente con ERC basado en las recomendaciones y conocimientos actuales. Abstract: Chronic kidney disease (CKD) is a major public health problem worldwide that affects more than 10% of the Spanish population. CKD is associated with high comorbidity rates, poor prognosis and major consumption of health system resources. Since the publication of the last consensus document on CKD seven years ago, little evidence has emerged and few clinical trials on new diagnostic and treatment strategies in CKD have been conducted, apart from new trials in diabetic kidney disease. Therefore, CKD international guidelines have not been recently updated. The rigidity and conservative attitude of the guidelines should not prevent the publication of updates in knowledge about certain matters that may be key in detecting CKD and managing patients with this disease. This document, also prepared by 10 scientific societies, provides an update on concepts, clarifications, diagnostic criteria, remission strategies and new treatment options.The evidence and the main studies published on these aspects of CKD have been reviewed. This should be considered more as an information document on CKD. It includes an update on CKD detection, risk factors and screening; a definition of renal progression; an update of remission criteria with new suggestions in the older population; CKD monitoring and prevention strategies; management of associated comorbidities, particularly in diabetes mellitus; roles of the Primary Care physician in CKD management; and what not to do in Nephrology.The aim of the document is to serve as an aid in the multidisciplinary management of the patient with CKD based on current recommendations and knowledge.

Rationale & Objective: Recent studies evaluated and proposed new race-neutral, creatinine-based glomerular filtration rate (GFR) estimation equations. The performance of these equations in diverse potential living kidney donors requires study. Study Design: Cross-sectional study. Setting & Participants: 637 potential living kidney donors from one tertiary hospital with serum creatinine concentration measurement and GFR measurement by iohexol plasma clearance between October 2016 and December 2020. Exposure: Creatinine-based estimation of GFR by Chronic Kidney Disease Epidemiology Collaboration (2009, CKDEPI09; 2021, CKDEPI21) and Modification of Diet in Renal Disease equations with and without inclusion of race coefficient, where applicable. Outcomes: Equation bias, precision, accuracy, and accurate classification of GFR as equal to and above or below 80 mL/min/1.73 m2. Analytical Approach: GFR estimation equation performance compared to measured GFR (mGFR) by iohexol clearance. Results: The median bias of the CKDEPI21 equation underestimated mGFR by 2.8 mL/min/1.73 m2. The bias in the Black subgroup underestimated mGFR by 9.0 mL/min/1.73 m2. Compared to CKDEPI09 with and without race adjustment, the accuracy of CKDEPI21 increased across all subgroups. On average, 3.9% of individuals were misclassified by CKDEPI21 as having a GFR greater than, and 8.9% misclassified less than, 80 mL/min/1.73 m2, compared to 3.1% and 13.2% for CKDEPI09 with race adjustment, respectively. Total misclassification (either above or below 80 mL/min/1.73 m2) was 16.3% for CKDEPI21 and 16.0% for CKDEPI09 (with race adjustment). Limitations: Limited sample of individuals identifying as Black. Lack of cystatin C data. Conclusions: In our potential living donor sample, GFR estimation by creatinine-based CKDEPI21 is less biased and more accurate than previous creatinine-based estimated GFR equations. When evaluated by race, this summative improvement remains in individuals identifying as Asian, Hispanic, or White. More external validation is needed to assess whether the new equation is an improvement over the previous CKDEPI equation with a race coefficient.

Background: Recent clinical trials have shown that sodium-glucose cotransporter 2 (SGLT2) inhibitors have beneficial effects on renal function in heart failure patients. This study confirmed the renoprotective effect of treatment with SGLT2 inhibitors in Japanese patients with chronic heart failure and diabetes and further investigated what cardiac/hemodynamic and noncardiac factors are involved in its effect. Methods: Eligible 50 outpatients with chronic heart failure and type-2 diabetes mellitus chronically taking SGLT2 inhibitors were enrolled. Annual changing rates of estimated glomerular filtration rate (eGFR) were compered before and after treatment with SGLT2 inhibitors and the associations of the change in eGFR slope after SGLT2 inhibitor administration with changes in various clinical and echocardiographic parameters were evaluated. Results: The mean follow-up periods before and after SGLT2 inhibitor administration were 2.6 and 1.9 years, respectively. Changing rates of eGFR per year were significantly improved after treatment with SGLT2 inhibitors (−5.78 ± 7.67 to −0.43 ± 10.81 mL/min/1.73 m2/year, p = 0.006). The daily doses of loop diuretics were not altered after SGLT2 inhibitor administration. Neither decreased body weight nor increased hematocrit was associated with the change in eGFR slope before and after SGLT2 inhibitor administration. While, the decrease in inferior vena cava diameter and the increase in its respiratory collapsibility were significantly correlated with the improvement of eGFR decline slope after SGLT2 inhibitor administration. Conclusions: Our findings indicated that chronic treatment with SGLT2 inhibitors ameliorated annual decline in eGFR in Japanese patients with chronic heart failure, suggesting the possibility that the improvement of venous congestion was involved in its renoprotective effect.

Objective: To determine whether argon-beam-coagulation (ABC) suture-free technique results in more favorable renal function than conventional suture technique after laparoscopic partial nephrectomy., Methods: This study was a single-center, open-label randomized controlled study. A total of 32 patients with T1a renal tumor and R.E.N.A.L score ≤7 were recruited. The primary endpoint of the study was the absolute variation of the ipsilateral split renal function (SRF) at 12 months. The following secondary endpoints were addressed: the 1, 3, 6, and 12-months variation of eGFR; the 1, 3, 6-months variation of SRF; perioperative outcomes (including operative time, warm ischemia time, time to hemostasis, blood loss)., Results: The suture-free group had a significantly shorter operative time (90.4 ± 22.0 minutes vs. 117.8 ± 23.5 minutes, p = 0.003) and warm ischemia time (9.6 ± 4.7 minutes vs. 21.3 ± 8.3 minutes, p < 0.001) than the suture group. At the last follow-up, the change of ipsilateral SRF was 7.5 ± 5.1 ml/min for the suture-free group and 13.1 ± 6.7 ml/min for the suture group (p = 0.014). The change of eGFR demonstrated a similar trend (5.5 ± 4.4 ml/min vs. 12.6 ± 6.0 ml/min, p=0.001). Multivariate linear analysis confirmed that suture-free technique was associated with a less decrease of renal function., Conclusions: Suture-free partial nephrectomy is a feasible technique for T1a renal masses and benefits long-term SRF and eGFR compared to conventional procedure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The sensitivity of currently available screening tools for urothelial carcinoma (UC) remains unsatisfactory particularly at early stages. Hence, we aimed to establish a novel blood-based screening tool for urothelial carcinoma. We measured serum d-amino acid levels in 108 and 192 patients with and without UC individuals in the derivation cohort, and 15 and 25 patients with and without UC in the validation cohort. Serum d-asparagine levels were significantly higher in patients with UC than in those without UC (p < 0.0001). We developed a novel screening equation for the diagnosis of urothelial carcinoma using d-asparagine in serum and estimated the glomerular filtration rate (eGFR). Serum d-asparagine levels adjusted for eGFR exhibited high performance in the diagnosis of UC (AUC-ROC, 0.869; sensitivity, 80.6 %; specificity, 82.7 %), even in early-stage UC (AUC-ROC: 0.859, sensitivity: 83.3 %, specificity: 82.3 %), which were previously misdiagnosed via urinary occult blood or urine cytology. This established strategy combined with urinary occult blood, improves diagnostic ability (sensitivity: 93.7 %, specificity: 70.1 %)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Exposure to brominated flame retardants (BFRs) may contribute the advancement of chronic kidney disease (CKD). The objective is to evaluate the renal effects of BFRs in patients with CKD., Methods: Totally 7235 US participants of whom 1187 (16.41 %) were diagnosed with CKD were screened for this investigation from the National Health and Nutrition Examination Survey (NHANES) database spanning from 2005 to 2016. The isotope dilution gas chromatography high-resolution mass spectrometry (GC/IDHRMS) was employed for identification of 11 polybrominated diphenyl ethers (PBDEs) and PBB153 serving as the exposure factor. A set of covariates concerning basic characteristics, renal function indicators and suffering from diseases of these participants was considered as potential confounding factors. Subgroup analyses to examine the impact of age and gender on the relationship between serum BFRs and CKD, estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (UACR), serum creatinine (Scr), and blood urea nitrogen (BUN). Weighted Quantile Sum (WQS) regression and Quantile G-computation (QGC) analyses were applied to identify relationship of individual BFRs and other anthropometric indicators in CKD., Results: After adjusting for available confounding factors, PBDE100, PBDE28, PBDE85, PBDE47, PBDE99, and PBDE154 were positively correlated with CKD. PBDE28, PBDE66, PBDE47, PBDE183, PBDE100, PBDE99, PBDE85, PBDE154, and PBB153 were significantly negatively correlated with eGFR. PBDE66 and PBDE183 were positively correlated with UACR. PBDE28, PBDE17, PBDE66, PBDE100, PBDE47, PBDE85, PBDE154, PBDE99, PBDE183 and PBB153 were positively correlated with Scr. PBDE17, PBDE28, PBDE154, PBDE66, PBDE47, PBDE99, and PBDE209 were negatively associated with BUN. PBB153 was positively correlated with BUN. The subgroup results gender and age are key factors affecting the relationship of PBDEs and renal function indicators. Both WQS and QGS analyses revealed that exposure to mixed BFR was negatively correlated with eGFR and BUN, of which PBB153 and PBDE66 contributed the most, respectively, as well as positively correlated with Scr, in which PBDE66 contributed the most., Conclusion: Specific BFRs exposure was significantly correlated with renal function indicators, enhancing the potential risk of CKD. This pioneer investigation shed light on an overlooked impact of BFR exposure on CKD in US., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Understanding molecular processes of the early phase of atherosclerotic cardiovascular disease conditions is of utmost importance for early prediction and intervention measures., Methods: We measured 92 cardiovascular-disease-related proteins (Olink, Cardiovascular III) in 2024 elderly participants of the population-based LIFE-Adult study. We analysed the impact of 27 covariables on these proteins including blood counts, cardiovascular risk factors and life-style-related parameters. We also analysed protein associations with 13 subclinical cardiovascular traits comprising carotid intima media thickness, plaque burden, three modes of Vicorder-based pulse-wave velocities, ankle-brachial index and ECLIA-based N-terminal prohormone of brain natriuretic peptide (NT-proBNP)., Results: Estimated glomerular filtration rate, triglycerides and sex where the most relevant covariables explaining more than 1 % variance of 49, 22 and 20 proteins, respectively. A total of 43 proteins were significantly associated with at least one of the analysed subclinical cardiovascular traits. NT-pro-BNP, brachial-ankle pulse-wave velocity (baPWV) and parameters of carotid plaque burden accounted for the largest number of associations. Association overlaps were relatively sparse. Only growth/differentiation factor 15, low density lipoprotein receptor and interleukin-1 receptor type 2 are associated with these three different cardiovascular traits. We confirmed several literature findings and found yet unreported associations for carotid plaque presence (von-Willebrand factor, galectin 4), carotid intima-media thickness (carboxypeptidase A1 andB1), baPWV (cathepsin D) and NT-proBNP (cathepsin Z, low density lipoprotein receptor, neurogenic locus homolog protein 3, trem-like transcript 2). Sex-interaction effects were observed, e.g. for spondin-1 and growth/differentiation factor 15 likely regulated by androgen response elements., Conclusions: We extend the catalogue of proteome biomarkers possibly involved in early stages of cardiovascular disease pathologies providing targets for early risk prediction or intervention strategies., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Aims: Sodium-glucose cotransporter inhibitors (SGLT2-i) improve outcomes in patients with heart failure (HF) and reduced ejection fraction (HFrEF). However, evidence in patients with advanced HF is lacking. We aimed to determine the effect of SGLT2-i in advanced HFrEF compared to their effect on a non-advanced population., Methods: Consecutive HFrEF outpatients who started SGLT2-i were observed for 6-months. Patients were categorized as having advanced or non-advanced HFrEF. The primary outcome was the trend of NTproBNP in the two groups. Secondary outcomes included changes in New York Heart Association (NYHA) class, glomerular filtration rate (GFR), and ejection fraction (LVEF). The association between advanced HF diagnosis and including N-terminal pro-brain natriuretic peptide (NTproBNP) reduction was tested using multivariate analysis., Results: Overall, 105 patients (45 advanced, 60 non-advanced) were included. Mean age was 56 ± 10 years, 22 % were female, and 35 % had ischemic heart disease. Median NTproBNP at baseline for advanced and non-advanced patients was 1672pg/ml (IQR 520-3320) vs. 481 pg/ml (IQR 173-917), respectively (p < 0.001). At follow-up, only non-advanced patients reduced their NTproBNP (-32 % (95 % CI -51 to -3), p < 0.001), while advanced patients had an increase in NTproBNP. LVEF and NYHA class improved only in non-advanced patients. GFR was stable in both subgroups. At multivariate analysis a diagnosis of advanced HF was independently associated with a reduced probability of NTproBNP reduction (OR 0.041 (95 % CI 0.002-0.752), p = 0.031). Only one patient discontinued the drug due to side effects., Conclusion: In advanced HFrEF, SGLT2-i do not impact on NTproBNP, LVEF or NYHA class but are well tolerated., Competing Interests: Declaration of competing interest The authors have not any conflict of interest to declare, (Copyright © 2024 Elsevier Inc. All rights reserved.)

Prospective cohort studies of kidney equity are limited by a focus on advanced rather than early disease and selective recruitment. Whole population studies frequently rely on area-level measures of deprivation as opposed to individual measures of social disadvantage. Here, we linked kidney health and individual census records in the North of Scotland (Grampian area), 2011-2021 (GLOMMS-CORE) and identified incident kidney presentations at thresholds of estimated glomerular filtration rate (eGFR) under 60 (mild/early), under 45 (moderate), under 30 ml/min/1.73m 2 (advanced), and acute kidney disease (AKD). Household and neighborhood socioeconomic measures, living circumstances, and long-term mortality were compared. Case-mix adjusted multivariable logistic regression (living circumstances), and Cox models (mortality) incorporating an interaction between the household and the neighborhood were used. Among census respondents, there were 48546, 29081, 16116, 28097 incident presentations of each respective eGFR cohort and AKD. Classifications of socioeconomic position by household and neighborhood were related but complex, and frequently did not match. Compared to households of professionals, people with early kidney disease in unskilled or unemployed households had increased mortality (adjusted hazard ratios: 95% confidence intervals) of (1.26: 1.19-1.32) and (1.77: 1.60-1.96), respectively with adjustment for neighborhood indices making little difference. Those within either a deprived household or deprived neighborhood experienced greater mortality, but those within both had the poorest outcomes. Unskilled and unemployed households frequently reported being limited by illness, adverse mental health, living alone, basic accommodation, lack of car ownership, language difficulties, and visual and hearing impairments. Thus, impacts of deprivation on kidney health are spread throughout society-complex, serious, and not confined to those living in deprived neighborhoods., (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

The pharmacokinetics in patients dosed with the nanoparticle-based MRI contrast agent SN132D is explained by a size dependent clearance mechanism and this behavior was modeled numerically. Blood samples from 14 patients were analyzed for silicon (a component of the nanoparticle) by ICP-OES. The pharmacokinetic model has only one free parameter and relies on a measured size distribution of the contrast agent and well-established properties of the renal and cardiovascular systems. The model fits well (R 2  = 0.9910) with experimental data from samples taken from ten minutes to two weeks after start of infusion. These results support that the cut-off diameter for human renal filtration is 5.5 nm. The agreement between experiment and model implies that there is little or no plasma protein binding to the nanoparticles., Competing Interests: Declaration of competing interest The authors declare the following competing financial interest(s): All are employed by Spago Nanomedical AB., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The pediatric International IgA Nephropathy (IgAN) Prediction Tool comprises two models with and without ethnicity and is the first method to predict the risk of a 30% decline in estimated glomerular filtration rate (eGFR) or kidney failure in children at the time of biopsy using clinical risk factors and Oxford MEST histology scores. However, it is unknown if the Prediction Tool can be applied after a period of observation post-biopsy. Using an international multi-ethnic cohort of 947 children with IgAN, 38% of whom were followed into adulthood, the Prediction Tool was updated for use one year after biopsy. Compared to the original pediatric Prediction Tool, the updated post-biopsy Prediction Tool had a better model fit with higher R 2 D (51%/50% vs 20%), significant increase in 4-year C-statistics (0.83 vs 0.73/0.69, ΔC 0.09 [95% confidence interval 0.07-0.10] and ΔC 0.14 [0.12-0.15]) and better 4-year calibration with lower integrated calibration indices (0.74/0.54 vs 2.45/1.01). Results were similar after internal validation and when the models were applied two years after biopsy. Trajectories of eGFR after a baseline one year post-biopsy were non-linear and those at higher predicted risk started with a lower eGFR and experienced a more rapid decline over time. In children, eGFR had a variable rate of increase until 15-18 years old and then decreased linearly with a more rapid decline in higher risk groups that was similar to young adults of comparable risk. Thus, the original pediatric Prediction Tool should be used in children at the time of biopsy, and the updated pediatric Prediction Tool should be used to re-evaluate risk one or two years after biopsy., (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

A transplant of a portion of the bladder with an en bloc kidney from a 2-year-old donor was previously reported in a 12-month-old girl due to her extremely small bladder. Bilateral kidneys were transplanted en bloc with their ureters connected to a patch of the donor bladder (bladder patch technique). The long-term outcomes and complications of this technique have not been documented. Here, we report a long-term, 17-year follow-up of this patient with an evaluation of whole bladder functions at 18 years of age. The patient has had no episodes of urinary tract infections. Cystoscopy showed a viable transplanted bladder with a well-perfused mucosa. We observed that the native bladder has stretched over time, forming more than half of the bladder wall. Urodynamic studies showed preserved bladder compliance at 43 mL/cmH 2 O, and native bladder contractility was preserved. Prolonged voiding time and postvoid residual urine were also observed. These findings were suggestive of detrusor underactivity. No reflux across the donor ureterovesical junctions was observed. The recipient was instructed to continue timed voiding and double voiding to empty the bladder. In conclusion, en bloc kidney transplantation with a bladder patch is a feasible and safe option for kidney transplant recipients with a small bladder capacity., Competing Interests: Declaration of competing interest The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation., (Copyright © 2024 American Society of Transplantation & American Society of Transplant Surgeons. All rights reserved.)

The innate immune system plays an essential role in regulating the immune responses to kidney transplantation, but the mechanisms through which innate immune cells influence long-term graft survival are unclear. The current study highlights the vital role of trained immunity in kidney allograft survival. Trained immunity describes the epigenetic and metabolic changes that innate immune cells undergo following an initial stimulus, allowing them have a stronger inflammatory response to subsequent stimuli. We stimulated healthy peripheral blood mononuclear cells with pretransplant and posttransplant serum of kidney transplant patients and immunosuppressive drugs in an in vitro trained immunity assay and measured tumor necrosis factor and interleukin 6 cytokine levels in the supernatant as a readout for trained immunity. We show that the serum of kidney transplant recipients collected 1 week after transplantation can suppress trained immunity. Importantly, we found that kidney transplant recipients whose serum most strongly suppressed trained immunity rarely experienced graft loss. This suppressive effect of posttransplant serum is likely mediated by previously unreported effects of immunosuppressive drugs. Our findings provide mechanistic insights into the role of innate immunity in kidney allograft survival, uncovering trained immunity as a potential therapeutic target for improving graft survival., Competing Interests: Declaration of competing interest The authors of this manuscript have conflicts of interest to disclose as described by the American Journal of Transplantation. L. A. B. Joosten is scientific founder of TTxD, LembaTX, and SalvinaTX. M. G. Netea is scientific founder of TTxD and Biotrip. W. J. M. Mulder is scientific founder of TTxD and Biotrip. Other authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Renal failure is a predictor of adverse outcomes in carotid revascularization. There has been debate regarding the benefit of revascularization in patients with severe chronic kidney disease or on dialysis., Methods: Patients in the Vascular Quality Initiative undergoing transcarotid artery revascularization (TCAR), transfemoral carotid artery stenting (tfCAS), or CEA between 2016 and 2023 with an estimated glomerular filtration rate (eGFR) of <30 mL/min/1.73 m 2 or on dialysis were included. Patients were divided into cohorts based on procedure. Additional analyses were performed for patients on dialysis only and by symptomatology. Primary outcomes were perioperative stroke/death/myocardial infarction (MI) (SDM). Secondary outcomes included perioperative death, stroke, MI, cranial nerve injury, and stroke/death. Inverse probability of treatment weighting was performed based on treatment assignment to TCAR, tfCAS, and CEA patients and adjusted for demographics, comorbidities, and preoperative symptoms. The χ 2 test and multivariable logistic regression analysis were used to evaluate the association of procedure with perioperative outcomes in the weighted cohort. Five-year survival was evaluated using Kaplan-Meier and weighted Cox regression., Results: In the weighted cohort, 13,851 patients with an eGFR of <30 (2506 on dialysis) underwent TCAR (3639; 704 on dialysis), tfCAS (1975; 393 on dialysis), or CEA (8237; 1409 on dialysis) during the study period. Compared with TCAR, CEA had higher odds of SDM (2.8% vs 3.6%; adjusted odds ratio [aOR], 1.27; 95% confidence interval [CI], 1.00-1.61; P = .049), and MI (0.7% vs 1.5%; aOR, 2.00; 95% CI, 1.31-3.05; P = .001). Compared with TCAR, rates of SDM (2.8% vs 5.8%), stroke (1.2% vs 2.6%), and death (0.9% vs 2.4%) were all higher for tfCAS. In asymptomatic patients CEA patients had higher odds of MI (0.7% vs 1.3%; aOR, 1.85; 95% CI, 1.15-2.97; P = .011) and cranial nerve injury (0.3% vs 1.9%; aOR, 7.23; 95% CI, 3.28-15.9; P < .001). Like in the primary analysis, asymptomatic tfCAS patients demonstrated higher odds of death and stroke/death. Symptomatic CEA patients demonstrated no difference in stroke, death, or stroke/death. Although tfCAS patients demonstrated higher odds of death, stroke, MI, stroke/death, and SDM. In both groups, the 5-year survival was similar for TCAR and CEA (eGFR <30, 75.1% vs 74.2%; aHR, 1.06; P = .3) and lower for tfCAS (eGFR <30, 75.1% vs 70.4%; aHR, 1.44; P < .001)., Conclusions: CEA and TCAR had similar odds of stroke and death and are both a reasonable choice in this population; however, TCAR may be better in patients with an increased risk of MI. Additionally, tfCAS patients were more likely to have worse outcomes after weighting for symptom status. Finally, although patients with a reduced eGFR have worse outcomes than their healthy peers, this analysis shows that the majority of patients survive long enough to benefit from the potential stroke risk reduction provided by all revascularization procedures., (Copyright © 2024 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Delayed graft function (DGF) increases morbidity and mortality in kidney transplant recipients. Operative parameters, including hemodynamic manipulation through vasopressors and fluids, can impact perfusion to the newly transplanted kidney and influence DGF incidence. We analyzed intraoperative time-series data in 5-minute intervals from kidney transplant recipient operations (N = 545) in conjunction with pretransplant characteristics and postsurgical outcomes, including DGF incidence, 60-day creatinine, and graft survival. Of the operations, 127 DGF events were captured in our cohort from a single academic transplant center (57/278 donations after brainstem death [DBDs], 65/150 donations after circulatory/cardiac death [DCDs], 5/117 live donations). In multiple regression, postanastomosis hypotension defined as mean arterial pressure (MAP) <75 mmHg was a risk factor for DGF independent of conventional predictors of DGF in DCD and DBD kidneys. DCD recipients with DGF had lower average postanastomosis MAP (DGF: 80.1 ± 8.1 mmHg vs no DGF: 76.4 ± 6.7 mmHg, P = .004). Interaction analysis demonstrated above-average doses of vasopressors and crystalloids were associated with improved outcomes when used at MAPs ≤75 mmHg, but they were associated with increased DGF at MAPs >75 mmHg, suggesting that the incidence of DGF can be highly influenced by intraoperative hemodynamic controls. This analysis of surgical time courses has identified potential new strategies for goal-directed anesthesia in renal transplantation., Competing Interests: Declaration of competing interest The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background & Aims: Renal dysfunction is prevalent in advanced chronic liver disease (aCLD) and is associated to liver-related death (LRD). This makes a reliable evaluation of renal function (RF) a crucial aspect. RF can be estimated by formulas or measured by gold standard method. Estimated RF is not reliable in aCLD. However, there is a lack of information on the reliability of formulas in the prediction of LRD., Methods: We analysed a cohort of patients with aCLD in whom RF was measured by the plasma clearance of iohexol (mGFR) and estimated (eGFR) by formulas: MDRD, CKD-EPI, Royal Free Hospital (RFHC), GRAIL and Mindikoglu-eGFR. LRD was defined as death from hepatic causes. Multivariable analysis was used to evaluate association of mGFR or eGFR with LRD., Results: 161 patients were evaluated, with median follow-up of 28 months, 58 died from LRD. In overall group mGFR (OR 0.99; p = 0.022) and formulas: CKD-EPI (OR 0.98; p = 0.044), GRAIL (OR 0.98; p = 0.038) was associated with LRD. In patients with normal creatinine levels (≤ 1.1 mg/dL), mGFR (OR 0.99; p = 0.031) was whereas any formula was not associated with LRD., Conclusions: eGFR appears as an unreliable method for predicting LRDs in aCLD, especially in those with lower creatinine levels. By contrast, mGFR seems to be a superior predictor., Competing Interests: Declaration of competing interest None of the authors have conflicts of interest for the reported study., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Rapid kidney function decline (RKFD) is a main clinical feature of early chronic kidney disease (CKD) in type 2 diabetes (T2D). Environmental and genetic factors influencing RKFD remain inadequately elucidated., Objectives: This study aimed to examine the associations of metals with RKFD among T2D and to further investigate the effect of metal mixtures on RKFD with the modifying effect of genetic susceptibility., Methods: This study included 2209 people with T2D (1942 had genotyping data) free of CKD at baseline from the Dongfeng-Tongji cohort. We used inductively coupled plasma-mass spectrometry (ICP-MS) to measure 23 metals in baseline plasma. Using elastic net (ENET), multivariate logistic regression, and Bayesian kernel machine regression (BKMR) model, we examined independent associations of multiple metals with RKFD. We calculated the environmental risk score (ERS) to assess the effects of metal mixtures on RKFD and the genetic risk score (GRS) to assess genetic susceptibility. RKFD was defined as estimated glomerular filtration rate (eGFR) loss > 3 mL/min/1.73 m 2 /year., Results: During a median of 9.8 years follow-up, 262 participants developed RKFD. Aluminum, vanadium, zinc, selenium, rubidium, tin, barium, and tungsten were screened from ENET. In multivariate logistic models, vanadium, selenium, and tungsten were negatively associated with RKFD, while zinc, tin, and rubidium were positively associated. The BKMR showed a nonlinear association of vanadium and rubidium with RKFD and interactions between metals (barium‑vanadium, barium‑rubidium). The ERS was positive associated with RKFD (per SD increase in ERS, OR = 1.94, 95% CI: 1.66, 2.27). No significant interaction between ERS and GRS was observed on RKFD, however, participants in the highest ERS and GRS group had the highest RKFD risk., Conclusion: Vanadium and rubidium were associated with RKFD in T2D. Metal mixtures was associated with an increased risk of RKFD in T2D, particularly in those at high genetic risk., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Plasma or urinary clearance of exogenous filtration markers is required for assessment of measured glomerular filtration rate. Although multiple methods are available, none is widely used because of their complexity, each has measurement error, and standardization is limited. Recently, a study validated the plasma clearance of a new exogenous filtration marker, relmapirazin, which can be detected by its transdermal fluorescence, potentially simplifying the procedure and increasing access to measured glomerular filtration rate., (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background and Aims: The potential impact of peripheral artery disease (PAD) on kidney outcomes is not well understood. The aim of this study was to explore the association between PAD and end-stage kidney disease (ESKD) and chronic kidney disease (CKD)., Methods: Among 14,051 participants (mean age 54 [SD 6 years]) from the Atherosclerosis Risk in Communities study, we categorized PAD status as symptomatic PAD (intermittent claudication or leg revascularization), asymptomatic PAD (ankle-brachial index [ABI] ≤0.90 without clinical history of symptoms), and ABI 0.91-1.00, 1.01-1.10, 1.11-1.20 (reference), 1.21-1.30, and >1.30. We evaluated their associations with two kidney outcomes: ESKD (the need of renal replacement therapy or death due to kidney disease) and CKD (ESKD cases or an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m 2 with a ≥25 % decline from the baseline) using multivariable Cox proportional hazards models., Results: Over ∼30 years of follow-up, there were 598 cases of incident ESKD and 4686 cases of incident CKD. After adjusting for potential confounders, both symptomatic PAD and asymptomatic PAD conferred a significantly elevated risk of ESKD (hazard ratio 2.28 [95 % confidence interval 1.23-4.22] and 1.75 [1.19-2.57], respectively). Corresponding estimates for CKD were 1.54 (1.14-2.09) and 1.63 (1.38-1.93). Borderline low ABI 0.91-1.00 also showed elevated risk of adverse kidney outcomes after adjustment for demographic variables. Largely consistent results were observed across demographic and clinical subgroups., Conclusions: Symptomatic PAD and asymptomatic PAD were independently associated with an elevated risk of ESKD and CKD. These results highlight the importance of monitoring kidney function in persons with PAD, even when symptoms are absent., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: K.M. reports personal fees from Fukuda Denshi and Kowa Company, Ltd. Outside of the submitted work. The other authors do not have relevant conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background and Aims: Hypertension is a risk factor for developing chronic kidney disease (CKD). Studies of adult participants in the USA reported that hypertension increased the risk of developing CKD even in the non-diabetic population. However, studies in non-diabetic populations are limited and additional studies in other races are required. This study aimed to examine the relationship between hypertension and the development of CKD in non-diabetic Asian adults., Methods and Results: In this longitudinal study, non-diabetic Japanese adults who took annual checkups from 1998 to 2023 were included. CKD was defined as <60 mL/min/1.73 m 2 , and hypertension was classified into four levels according to the guidelines of the American College of Cardiology/American Heart Association. The Weibull accelerated failure time model was selected because the proportional hazards assumption was violated. Of the 7363 (men: 40.3%) people in the final cohort, 2498 (men: 40.1%) developed CKD after a mean follow-up of 7.99 years. Elevated blood pressure (BP) and hypertension stage 2 had a 9% (95% confidence interval [CI]: 1%-16%) and 11% (95% CI: 5%-17%) shorter survival time to CKD onset, respectively, than normal BP. Hypertension stage 1 also had a shorter survival to CKD onset by point estimate, but all 95% CIs crossed 1 in all models., Conclusions: In a relatively healthy Asian population without diabetes, controlling BP to an appropriate range reduces the risk of developing CKD., Competing Interests: Declaration of competing interest This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Yukari Okawa declares a relationship with Zentsuji City that includes employment. Toshiharu Mitsuhashi declares no potential conflict of interest associated with this manuscript., (Copyright © 2024 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Aims: The main objective in this study was to determine the prevalence of Chronic Kidney Disease (CKD) in people with Type 2 Diabetes Mellitus (T2DM) in the Autonomous Community (AC) of Aragon (Spain) and to detect whether or not there is under-registration in the patient's history. As a secundary objetive, it was proposed to study the most relevant demographic and clinical characteristics of people with CKD., Methods: Observational and retrospective real world data study of the population over 18 years of age with a diagnosis of T2DM, between January 2017 and December 2021. A descriptive analysis of qualitative and quantitative variables, and a comparison using the parametric Student's t-test or the non-parametric Mann-Whitney U-test between both groups was performed., Results: The prevalence of T2DM was 8.07 % and that of CKD 31.4 %, with an under-reporting of 47 %. The main risk factor associated with CKD was arterial hypertension (p<0.001), followed by dyslipidemia (p<0.001). The main treatment used for diabetes control was metformin, both in patients with and without CKD (p<0.001). A total of 56.81 % of people with T2DM and CKD did not undergo annual monitoring of their renal function (glomerular filtration rate) or determination of albuminuria., Conclusions: The prevalence of CKD increases in patients with T2DM (31.4 %), and in almost half of patients the diagnosis is not registered (47 %). This under-reporting delays the implementation of measures needed to prevent CKD progression., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest in the conduct of this study., (Copyright © 2024 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)

Background: Epidemiological evidence emphasizes air pollutants' role in chronic kidney disease (CKD). Volatile organic compounds (VOCs) contribute to air pollution, yet research on VOCs and kidney damage, especially gender disparities, is limited., Methods: This study analyzed NHANES data to explore associations between urinary VOC metabolite mixtures (VOCMs) and key kidney-related parameters: estimated glomerular filtration rate (eGFR), albumin-to-creatinine ratio (ACR), chronic kidney disease (CKD), and albuminuria. Mediation analyses assessed the potential mediating roles of biological aging (BA) and serum albumin in VOCM mixtures' effects on kidney damage. Sensitivity analyses were also conducted., Results: The mixture analysis unveiled a noteworthy positive association between VOCM mixtures and the risk of developing CKD, coupled with a significant negative correlation with eGFR within the overall participant cohort. These findings remained consistent when examining the female subgroup. However, among male participants, no significant link emerged between VOCM mixtures and CKD or eGFR. Furthermore, in both the overall and female participant groups, there was an absence of a significant correlation between VOCM mixtures and either ACR or albuminuria. On the other hand, in male participants, while no significant correlation was detected with albuminuria, a significant positive correlation was observed with ACR. Pollutant analysis identified potential links between kidney damage and 1,3-butadiene, toluene, ethylbenzene, styrene, xylene, acrolein, crotonaldehyde and propylene oxide. Mediation analyses suggested that BA might partially mediate the relationship between VOCM mixtures and kidney damage., Conclusion: The current findings highlight the widespread exposure to VOCs among the general U.S. adult population and indicate a potential correlation between exposure to VOC mixtures and compromised renal function parameters, with notable gender disparities. Females appear to exhibit greater sensitivity to impaired renal function resulting from VOCs exposure. Anti-aging treatments may offer some mitigation against kidney damage due to VOCs exposure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Sacubitril/valsartan is a foundational therapy for patients with heart failure. Although current U.S. Food and Drug Administration labeling does not provide guidance regarding initiation or continuation of sacubitril/valsartan in patients with worsening kidney function, guidelines identify estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m 2 as a contraindication to therapy., Objectives: This study aims to assess the safety and efficacy of continuing sacubitril/valsartan in patients with deterioration of kidney function below an eGFR of 30 mL/min/1.73 m 2 ., Methods: The association between a deterioration in eGFR <30 mL/min/1.73 m 2 , efficacy and safety outcomes, and treatment with sacubitril/valsartan vs renin-angiotensin system inhibitor were evaluated using time updated Cox models in a post hoc parallel trial analyses of PARADIGM-HF and PARAGON-HF., Results: Among 8,346 randomized patients in PARADIGM-HF and 4,746 in PARAGON-HF, 691 (8.3%) and 613 (12.9%), respectively, had an eGFR <30 mL/min/1.73 m 2 at least once in follow-up. Patients experiencing such deterioration were at higher risk of the primary outcome in both PARADIGM-HF and PARAGON-HF. However, the incidence of the primary outcome remained lower with sacubitril/valsartan vs renin-angiotensin system inhibitor, regardless of deterioration in kidney function in both PARADIGM-HF (P interaction  = 0.50) and PARAGON-HF (P interaction  = 0.64). Rates of key safety outcomes were higher among patients experiencing eGFR deterioration; however, rates were similar between treatment groups including among those who remained on treatment., Conclusions: Patients experiencing deterioration of kidney function to a value below eGFR 30 mL/min/1.73 m 2 faced high risk of cardiovascular and kidney disease outcomes. Continuation of sacubitril/valsartan was associated with persistent clinical benefit and no incremental safety risk. These data support continuation of sacubitril/valsartan for heart failure treatment even when eGFR declines below this threshold (PARADIGM-HF [Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure], NCT01035255; and PARAGON-HF [Prospective Comparison of ARNI with ARB Global Outcomes in HF with Preserved Ejection Fraction], NCT01920711)., Competing Interests: Funding Support and Author Disclosures The PARADIGM-HF and PARAGON-HF trials were funded by Novartis. Dr Chatur is supported by the Canadian Arthur J.E. Child’s Cardiology Fellowship. Dr Beldhuis has received a grant from the Dutch Heart Foundation. Dr Claggett has received consulting fees from Amgen, AO Biome, Biogen, Boehringer Ingelheim, Corvia, Gilead, Myokardia, Cardurion, and Novartis. Dr McCausland has received research funding from NIDDK, Satellite Healthcare, Fifth Eye, Novartis, and Lexicon paid directly to his institution; has received consulting fees from GlaxoSmithKline, and Zydus Therapeutics; and has received expert witness fees from Rubin-Anders Scientific. Dr Neuen has received fees for advisory boards, steering committee roles, scientific presentations, and travel support from AstraZeneca, Bayer, Boehringer Ingelheim, Cambridge Healthcare Research, Cornerstone Medical Education, the Limbic, Medscape, and Janssen, with all honoraria paid to The George Institute for Global Health. Dr Desai has received research grant support from Abbott, AstraZeneca, Alnylam, Bayer, and Novartis; and has received consulting fees and/or honoraria from Abbott, AstraZeneca, Alnylam, Axon Therapeutics, Avidity Biopharma, Bayer, Biofourmis, GlaxoSmithKline, Merck, Novartis, Parexel, Regeneron, River2Renal, Roche, Verily, Veristat, and Zydus. Dr Rouleau has received consulting fees from AstraZeneca. Dr Zile has received fees for serving on a steering committee from Abbott and Ironwood Pharma; has received consulting fees from Boston Scientific and MyoKardia; has received grant support and fees for serving on a steering committee from CVRx and Medtronic; has received fees for serving on an eligibility committee from EBR Systems and V-Wave; has received fees for serving on a clinical events committee from Endotronics; and has received fees for serving on a data and safety monitoring board from Merck. Dr Packer has received consulting fees from 89bio, Abbvie, Actavis, Alderlyx, Amarin, Amgen, AstraZeneca, Attralus, Boehringer Ingelheim, Caladrius, Casana, CSL Behring, Cytokinetics, Imara, Lilly, Medtronic, Moderna, Novartis, Pharmacosmos, Reata, Regeneron, Relypsa, and Salamandra. Dr Lefkowitz is an employee of Novartis. Dr McMurray has received grants and his employer paid by AstraZeneca, Theracos, and GlaxoSmithKline during the conduct of the study; has received grants and his employer being paid by Novartis, Amgen, Bristol-Myers Squibb, Bayer, Abb-vie, Dal-Cor, Kidney Research UK, and Cardurion and grants from British Heart Foundation. Dr Solomon has received research grants from Actelion, Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer, BMS, Celladon, Cytokinetics, Eidos, Gilead, GlaxoSmithKline, Ionis, Lilly, Mesoblast, MyoKardia, National Institutes of Health/NHLBI, Neurotronik, Novartis, NovoNordisk, Respicardia, Sanofi Pasteur, Theracos, and US2.AI; and has received consulting fees from Abbott, Action, Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Boehringer-Ingelheim, BMS, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi-Sankyo, GlaxoSmithKline, Lilly, Merck, Myokardia, Novartis, Roche, Theracos, Quantum Genomics, Cardurion, Janssen, Cardiac Dimensions, Tenaya, Sanofi-Pasteur, Dinaqor, Tremeau, CellProThera, Moderna, American Regent, Sarepta, Lexicon, Anacardio, Akros, and Puretech Health. Dr Vaduganathan has received research grant support, has served on advisory boards, or has had speaker engagements with American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, BMS, Boehringer Ingelheim, Chiesi, Cytokinetics, Lexicon Pharmaceuticals, Merck, Novartis, Novo Nordisk, Pharmacosmos, Relypsa, Roche Diagnostics, Sanofi, and Tricog Health; and has participated on clinical trial committees for studies sponsored by AstraZeneca, Galmed, Novartis, Bayer AG, Occlutech, and Impulse Dynamics. Dr Pfeffer has reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024. Published by Elsevier Inc.)

The recurrence of primary focal segmental glomerulosclerosis (FSGS) after kidney transplantation is associated with a high graft loss rate with standard treatments based on plasmapheresis with/without rituximab. We present 2 consecutive cases of nongenetic early severe recurrent FSGS refractory to rituximab and anti-interleukin 1 treatment and with a partial response to plasmapheresis. Case 1 was a 22-year-old man who was rescue-treated for recurrence 36 weeks after transplantation with obinutuzumab (1000 mg/1.73 m 2 , 1 dose) and daratumumab (18 mg/kg each dose, 8 doses), resulting in plasmapheresis discontinuation and a drop of proteinuria from 29 to 2.3 g/d. Proteinuria increased with circulating CD38 + plasma cells and responded to an additional daratumumab dose. Currently, the proteinuria is 1.8 g/d, 14.5 months after discontinuing plasmapheresis and starting obinutuzumab and daratumumab therapy. Case 2 was a 15-year-old girl who was plasmapheresis dependent with 2 g/d proteinuria 82 weeks after transplantation, with a Tesio catheter in the right jugular vein as the only possible vascular access. After treatment with obinutuzumab and daratumumab (1 dose each), she achieved stable complete remission (0.3 g/d proteinuria) with persistent plasmapheresis discontinuation. These cases suggest the potential of combining obinutuzumab with daratumumab for the treatment of recurrent FSGS., Competing Interests: Declaration of competing interests The authors of this manuscript have no conflicts of interest to disclose as described in the American Journal of Transplantation., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Understanding normal aging of kidney function is pivotal to help distinguish individuals at particular risk for chronic kidney disease. Glomerular filtration rate (GFR) is typically estimated via serum creatinine (eGFRcrea) or cystatin C (eGFRcys). Since population-based age-group-specific reference values for eGFR and eGFR-decline are scarce, we aimed to provide such reference values from population-based data of a wide age range. In four German population-based cohorts (KORA-3, KORA-4, AugUR, DIACORE), participants underwent medical exams, interview, and blood draw up to five times within up to 25 years. We analyzed eGFRcrea and eGFRcys cross-sectionally and longitudinally (12,000 individuals, age 25-95 years). Cross-sectionally, we found age-group-specific eGFRcrea to decrease approximately linearly across the full age range, for eGFRcys up to the age of 60 years. Within age-groups, there was little difference by sex or diabetes status. Longitudinally, linear mixed models estimated an annual eGFRcrea decline of -0.80 [95% confidence interval -0.82, -0.77], -0.79 [-0.83, -0.76], and -1.20 mL/min/1.73m 2 [-1.33, -1.08] for the general population, "healthy" individuals, or individuals with diabetes, respectively. Reference values for eGFR using cross-sectional data were shown as percentile curves for "healthy" individuals and for individuals with diabetes. Reference values for eGFR-decline using longitudinal data were presented as 95% prediction intervals for "healthy" individuals and for individuals with diabetes, obesity, and/or albuminuria. Thus, our results can help clinicians to judge eGFR values in individuals seen in clinical practice according to their age and to understand the expected range of annual eGFR-decline based on their risk profile., (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Administrative claims data could provide a unique opportunity to identify acute rejection (AR) events using specific antirejection medications and to validate rejected data reported to the Organ Procurement and Transplantation Network. This retrospective cohort study examined differences in registry-reported events and those identified using claims data among adult kidney transplant recipients from 2012 to 2017 using Standard Analysis Files from the US Renal Data System. Rejection rates, survival estimates, and center-level differences were assessed using each approach. Among 45 880 first-time kidney transplant recipients, we identified 3841 AR events within 12 months of transplant reported by centers in the registry; claims data yielded 2945 events. Of all events occurring within 12 months of transplant, 48.5% were reported using registry only, 32.9% were identified using claims only, and 18.6% were identified using both approaches. A 3-year death-censored graft survival probability was 90.0%, 88.4%, and 81.2% (P < .001) for ARs identified using registry only, claims data only, and both approaches, respectively. The large discordance between registry-reported and claims-based events suggests incomplete and potentially inaccurate reporting of events in the Organ Procurement Transplant Network registry. These findings have important implications for analyses that use AR data and underscore the need for improved capture of clinically meaningful events., Competing Interests: Declaration of competing interest The authors of this manuscript have conflicts of interest to disclose, as described by the American Journal of Transplantation. S. Mohan receives grant funding from Kidney Transplant Collaborative and the National Institute of Health (NIH, Bethesda, MD), and personal fees from Sanofi, Kidney International Reports, and the Health Services Advisory Group outside of the submitted work. The other authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation., (Copyright © 2024 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)

Pharmacologic interventions to slow chronic kidney disease progression, such as ACE-inhibitors, angiotensin receptor blockers, or sodium glucose co-transporter 2 inhibitors, often produce acute treatment effects on glomerular filtration rate (GFR) that differ from their long-term chronic treatment effects. Observational studies assessing the implications of acute effects cannot distinguish acute effects from GFR changes unrelated to the treatment. Here, we performed meta-regression analysis of multiple trials to isolate acute effects to determine their long-term implications. In 64 randomized controlled trials (RCTs), enrolling 154,045 participants, we estimated acute effects as the mean between-group difference in GFR slope from baseline to three months, effects on chronic GFR slope (starting at three months after randomization), and effects on three composite kidney endpoints defined by kidney failure (GFR 15 ml/min/1.73m 2 or less, chronic dialysis, or kidney transplantation) or sustained GFR declines of 30%, 40% or 57% decline, respectively. We used Bayesian meta-regression to relate acute effects with treatment effects on chronic slope and the composite kidney endpoints. Overall, acute effects were not associated with treatment effects on chronic slope. Acute effects were associated with the treatment effects on composite kidney outcomes such that larger negative acute effects were associated with lesser beneficial effects on the composite kidney endpoints. Associations were stronger when the kidney composite endpoints were defined by smaller thresholds of GFR decline (30% or 40%). Results were similar in a subgroup of interventions with supposedly hemodynamic effects that acutely reduce GFR. For studies with GFR 60 mL/min/1.73m 2 or under, negative acute effects were associated with larger beneficial effects on chronic GFR slope. Thus, our data from a large and diverse set of RCTs suggests that acute effects of interventions may influence the treatment effect on clinical kidney outcomes., (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

International consensus supports the development of standardized protocols for measured glomerular filtration rate (mGFR) to facilitate the integration of mGFR testing in both clinical and research settings. To this end, the European Kidney Function Consortium convened an international group of experts with relevant experience in mGFR. The working group performed an extensive literature search to inform the development of recommendations for mGFR determination using 1-compartment plasma clearance models and iohexol as the exogenous filtration marker. Iohexol was selected as it is non-radio labeled, inexpensive, and safe, can be assayed at a central laboratory, and the other commonly used non-radio-labeled tracers have been (inulin) or are soon to be (iothalamate) discontinued. A plasma clearance model was selected over urine clearance as it requires no urine collection. A 1 compartment was preferred to 2 compartments as it requires fewer samples. The recommendations are based on published evidence complemented by expert opinion. The consensus paper covers practical advice for patients and health professionals, preparation, administration, and safety aspects of iohexol, laboratory analysis, blood sample collection and sampling times using both multiple and single-sample protocols, description of the mGFR mathematical calculations, as well as implementation strategies. Supplementary materials include patient and provider information sheets, standard operating procedures, a study protocol template, and support for mGFR calculation., (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background: Although serum magnesium deficiency is linked to higher cardiovascular disease risk, its association with chronic kidney disease (CKD) remains unclear., Objectives: This study aimed to evaluate the relationship between dietary magnesium intake and CKD development in adults with clinically normal kidney function., Methods: The prospective observational cohort study evaluated 188,510 participants (median age, 57.0 y; female, 54.1%) from the UK Biobank. Dietary magnesium intake was assessed through a 24-h dietary recall questionnaire compromising a list of 206 foods and 32 beverages and categorized into quintiles. The primary outcome was incident CKD diagnosed through International Classification of Diseases-10 and Office of Population Censuses and Surveys 4 codes. Incident CKD, defined as estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m 2 , was also assessed in a subcohort with creatinine follow-up data., Results: The median magnesium intake amount per person was 323.2 mg/d [interquartile range (IQR): 269.4-382.7 mg/d]. During 1,826,038.1 person-years of follow-up (median: 9.6 y; IQR: 9.3-10.3 y), CKD developed in 5,878 participants. The incidence of CKD was progressively higher in participants with lower magnesium intake (2.8%, 2.8%, 3.0%, 3.2%, and 3.7% in Q5-Q1, respectively). Cox regression analysis revealed that the hazard ratios (HRs) for incident CKD increased in a stepwise manner toward lower magnesium intake quintiles {adjusted HR (95% confidence interval [CI])-Q4: 0.97 (0.89, 1.06); Q3: 1.05 (0.96, 1.14); Q2: 1.12 (1.03, 1.21); Q1: 1.30 (1.20, 1.41)} relative to Q5 (P-linearity < 0.001). Similar results were observed with eGFR-defined CKD outcome [adjusted HR (95% CI)-Q4: 1.09 (0.92, 1.28); Q3: 1.15 (0.98, 1.35); Q2: 1.21 (1.03, 1.42); Q1: 1.41 (1.20, 1.65) relative to Q5; P-linearity < 0.001]., Conclusions: Lower dietary magnesium intake was associated with higher risk of incident CKD in adults with clinically normal kidney function. Further controlled studies are required to establish the potential benefit of adequate magnesium intake., (Copyright © 2024. Published by Elsevier Inc.)

In the general population, decreases in glomerular filtration rate (GFR) are associated with subsequent development of chronic kidney disease (CKD), cardiovascular disease (CVD), and death. It is unknown if low estimated GFR (eGFR) before or early after kidney donation was also associated with these risks. One thousand six hundred ninety-nine living donors who had both predonation and early (4-10 weeks) postdonation eGFR were included. We studied the relationships between eGFR, age at donation, and the time to sustained eGFR<45 (CKD stage 3b) and <30 mL/min/1.73m 2 (CKD stage 4), hypertension, diabetes mellitus (DM), CVD, and death. Median follow-up was 12 (interquartile range, 6-21) years. Twenty-year event rates were 5.8% eGFR<45 mL/min/1.73m 2 ; 1.2% eGFR<30 mL/min/1.73m 2 ; 29.0% hypertension; 7.8% DM; 8.0% CVD; and 5.2% death. The median time to eGFR<45 mL/min/1.73m 2 (N = 79) was 17 years, and eGFR<30 mL/min/1.73m 2 (N = 22) was 25 years. Both low predonation and early postdonation eGFR were associated with eGFR<45 mL/min/1.73m 2 (P < .0001) and eGFR<30 mL/min/1.73m 2 (P < .006); however, the primary driver of risk for all ages was low postdonation (rather than predonation) eGFR. Predonation and postdonation eGFR were not associated with hypertension, DM, CVD, or death. Low predonation and early postdonation eGFR are risk factors for developing eGFR<45 mL/min/1.73m 2 (CKD stage 3b) and <30 mL/min/1.73m 2 (CKD stage 4), but not CVD, hypertension, DM, or death., Competing Interests: Declaration of competing interest The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation., (Copyright © 2024 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)