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Background: The World Health Organization recommends a daily sodium intake of less than 2000 mg for adults; however, the Mexican population, like many others globally, consumes more sodium than this recommended amount. Excessive sodium intake is often accompanied by inadequate potassium intake. The association between knowledge, attitudes, and behaviors (KAB) and actual sodium intake has yielded mixed results across various populations. In Mexico, however, salt/sodium-related KAB and its relationship with sodium and potassium intake have not been evaluated., Objective: This study primarily aims to describe salt/sodium-related KAB in a Mexican population and, secondarily, to explore the association between KAB and 24-hour urinary sodium and potassium excretion., Methods: We conducted a cross-sectional study in an adult population from Mexico City and the surrounding metropolitan area. Self-reported KAB related to salt/sodium intake was assessed using a survey developed by the Pan American Health Organization. Anthropometric measurements were taken, and 24-hour urinary sodium and potassium excretion levels were determined. Descriptive statistics were stratified by sex and presented as means (SD) or median (25th-75th percentiles) for continuous variables, and as absolute and relative frequencies for categorical variables. The associations between KAB and sodium and potassium excretion were assessed using analysis of covariance, adjusting for age, sex, BMI, and daily energy intake as covariates, with the Šidák correction applied for multiple comparisons., Results: Overall, 232 participants were recruited (women, n=184, 79.3%). The mean urinary sodium and potassium excretion were estimated to be 2582.5 and 1493.5 mg/day, respectively. A higher proportion of men did not know the amount of sodium they consumed compared with women (12/48, 25%, vs 15/184, 8.2%, P=.01). More women reported knowing that there is a recommended amount for daily sodium intake than men (46/184, 25%, vs 10/48, 20.8%, P=.02). Additionally, more than half of men (30/48, 62.5%) reported never or rarely reading food labels, compared with women (96/184, 52.1%, P=.04). Better salt/sodium-related KAB was associated with higher adjusted mean sodium and potassium excretion. For example, mean sodium excretion was 3011.5 (95% CI 2640.1-3382.9) mg/day among participants who reported knowing the difference between salt and sodium, compared with 2592.8 (95% CI 2417.2-2768.3) mg/day in those who reported not knowing this difference (P=.049). Similarly, potassium excretion was 1864.9 (95% CI 1669.6-2060.3) mg/day for those who knew the difference, compared with 1512.5 (95% CI 1420.1-1604.8) mg/day for those who did not (P=.002). Additionally, higher urinary sodium excretion was observed among participants who reported consuming too much sodium (3216.0 mg/day, 95% CI 2867.1-3565.0 mg/day) compared with those who claimed to eat just the right amount (2584.3 mg/day, 95% CI 2384.9-2783.7 mg/day, P=.01)., Conclusions: Salt/sodium-related KAB was poor in this study sample. Moreover, KAB had a greater impact on potassium excretion than on sodium excretion, highlighting the need for more strategies to improve KAB related to salt/sodium intake. Additionally, it is important to consider other strategies aimed at modifying the sodium content of foods., (©Gabriela Gutiérrez-Salmeán, Paola Vanessa Miranda-Alatriste, Patricio Benítez-Alday, Luis Enrique Orozco-Rivera, Nurit Islas-Vargas, Ángeles Espinosa-Cuevas, Ricardo Correa-Rotter, Eloisa Colin-Ramirez. Originally published in the Interactive Journal of Medical Research (https://www.i-jmr.org/), 18.11.2024.)

Background: Albuminuria is a strong indicator of kidney and cardiovascular risk in patients with chronic kidney disease (CKD). We assessed risk associations between albuminuria at baseline and four months after randomization in a placebo-controlled trial of dapagliflozin and kidney endpoints in patients with CKD and albuminuria, with and without type 2 diabetes., Methods: In this post-hoc analysis of the DAPA-CKD trial, 4304 adult patients with CKD were randomized to dapagliflozin 10mg or placebo as adjunct to maximally tolerated renin-angiotensin-system (RAAS) inhibitors. The primary endpoint was a composite of sustained ≥50% decline in estimated glomerular filtration rate, kidney failure, or death from kidney or cardiovascular cause. The kidney composite endpoint was similar but excluded cardiovascular death. We assessed associations among baseline albuminuria, early change in albuminuria, (baseline to Month 4), and residual albuminuria (Month 4) with the primary composite and kidney composite endpoints using Cox proportional hazards regression analyses., Results: Compared to placebo, dapagliflozin reduced urinary albumin-to-creatinine ratio (UACR; baseline to Month 4) by 36% (95% CI: 30.2%, 42.5%) and 21% (95% CI: 12, 30%) in participants with and without type 2 diabetes, respectively (p-interaction: 0.02). A reduction in UACR from baseline to Month 4 was associated with a lower risk for the primary and kidney composite endpoints with a similar risk gradient for participants with and without type 2 diabetes (p-interaction: 0.10 and 0.19, respectively). Residual albuminuria was associated with a similar risk for the primary and kidney composite endpoints in each treatment arm (p-interaction: 0.19 and 0.18, respectively)., Conclusions: Dapagliflozin reduced albuminuria, and the magnitude of albuminuria reduction showed similar proportional reductions in risks for the primary and kidney composite endpoints in participants with and without type 2 diabetes. Patients with residual albuminuria at Month 4 - whether randomized to dapagliflozin or placebo - experienced relatively high rates of CKD progression kidney endpoints, suggesting that therapies added to RAAS inhibitors and dapagliflozin may be required to sustain kidney and cardiovascular health., Clinical Trial Registry Name and Registration Number: A Study to Evaluate the Effect of Dapagliflozin on Renal Outcomes and Cardiovascular Mortality in Patients with Chronic Kidney Disease (DAPA-CKD), NCT03036150., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Nephrology.)

A global rise in the prevalence of patients with chronic kidney disease (CKD) with end-stage kidney disease (ESKD) has led to a considerable and increasing burden to health systems, patients, and society. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are proven to reduce incidence of cardio-renal outcomes, including onset of ESKD. Recent post hoc analyses of SGLT2 inhibitor trials extrapolate substantial delays in the average time to ESKD over a patient's lifetime. In this article, we explore the possible real-world effects of such a delay by considering the available evidence reporting outcomes following onset of ESKD. From the patient perspective, a delay in reaching ESKD could substantially improve health-related quality of life and result in additional life years without the need for kidney replacement therapies, a target relevant to all CKD subpopulations. Furthermore, should a patient initiate dialysis at an older age as a result of CKD progression, the time spent in receipt of dialysis, and therefore associated healthcare costs, may also be reduced. A delay in progression may also lead to changes in the management of ESKD, such as increased election of conservative care in preference to dialysis, particularly in elderly populations. For younger patients with CKD, those who reach ESKD while employed face considerable work impairment and productivity loss, as may families and care partners of working age. Therefore, a delay to the onset of ESKD will reduce the proportion of their working lives affected by productivity losses or unemployment due to medical reasons. In conclusion, optimised treatment of CKD may lead to a shift in treatment options, but proper and timely implementation is essential for the realisation of improved outcomes., (© 2024. The Author(s).)

Background: Finerenone, a selective non-steroidal mineralocorticoid receptor antagonist, improves kidney and cardiovascular outcomes in patients with chronic kidney disease (CKD) associated with type 2 diabetes (T2D). The FINE-REAL study (NCT05348733) aims to evaluate the characteristics and treatment patterns of participants treated with finerenone in clinical practice., Methods: FINE-REAL is a prospective, single-arm, non-interventional study of patients initiated on finerenone as part of their routine care in accordance with country-approved labels. The study, initiated in June 2022, is expected to be completed by January 2028. The cutoff for this pre-specified interim analysis was June 13, 2023., Results: Participants were recruited across nephrology, endocrinology, cardiology, and primary care settings. Of 556 participants enrolled in the study by the cut-off date, 504 were included in this analysis (median follow-up duration of 7 months [finerenone treatment initiation to last recorded observation]). At baseline, 76.1% of participants were in the high or very high (KDIGO) CKD risk categories. Angiotensin converting enzyme inhibitors/angiotensin receptor blockers and sodium-glucose cotransporter 2 inhibitors were prescribed to 71.8% and 46.6% of participants, respectively. Based on prescribing information, 87.9% and 12.1% of participants initiated finerenone at doses of 10 and 20 mg, respectively. Finerenone treatment was uninterrupted in 92.3% of participants after 7 months' median follow-up. Treatment-emergent adverse events occurred in 110 (21.8%) participants. Hyperkalemia occurred in 25 (5.0%) participants, with no cases leading to death, dialysis, or hospitalization., Conclusion: At this interim analysis, finerenone was initiated in patients with CKD and T2D across various clinical practices participating in the study. Treatment discontinuation and hyperkalemia occurred infrequently., (© 2024. The Author(s).)

Historically, it takes an average of 17 years to move new treatments from clinical evidence to daily practice. Given the highly effective treatments now available to prevent or delay kidney disease onset and progression, this is far too long. The time is now to narrow the gap between what we know and what we do. Clear guidelines exist for the prevention and management of common risk factors for kidney disease, such as hypertension and diabetes, but only a fraction of people with these conditions worldwide are diagnosed, and even fewer are treated to target. Similarly, the vast majority of people living with kidney disease are unaware of their condition, because in the early stages it is often silent. Even among patients who have been diagnosed, many do not receive appropriate treatment for kidney disease. Considering the serious consequences of kidney disease progression, kidney failure, or death, it is imperative that treatments are initiated early and appropriately. Opportunities to diagnose and treat kidney disease early must be maximized beginning at the primary care level. Many systematic barriers exist, ranging from patient to clinician to health systems to societal factors. To preserve and improve kidney health for everyone everywhere, each of these barriers must be acknowledged so that sustainable solutions are developed and implemented without further delay., (Copyright © 2024 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

Historically, it takes an average of 17 years to move new treatments from clinical evidence to daily practice. Given the highly effective treatments now available to prevent or delay kidney disease onset and progression, this is far too long. The time is now to narrow the gap between what we know and what we do. Clear guidelines exist for the prevention and management of common risk factors for kidney disease, such as hypertension and diabetes, but only a fraction of people with these conditions worldwide are diagnosed, and even fewer are treated to target. Similarly, the vast majority of people living with kidney disease are unaware of their condition, because in the early stages, it is often silent. Even among patients who have been diagnosed, many do not receive appropriate treatment for kidney disease. Considering the serious consequences of kidney disease progression, kidney failure, or death, it is imperative that treatments are initiated early and appropriately. Opportunities to diagnose and treat kidney disease early must be maximized beginning at the primary care level. Many systematic barriers exist, ranging from patient to clinician to health systems to societal factors. To preserve and improve kidney health for everyone everywhere, each of these barriers must be acknowledged so that sustainable solutions are developed and implemented without further delay., (© 2024. The Author(s).)

Background and Aims: In the FLOW trial, semaglutide reduced the risks of kidney and cardiovascular (CV) outcomes and death in participants with type 2 diabetes mellitus (T2D) and chronic kidney disease (CKD). These prespecified analyses assessed the effects of semaglutide on CV outcomes and death by CKD severity., Methods: Participants were randomised to subcutaneous semaglutide 1 mg or placebo weekly. The main outcome was a composite of CV death, non-fatal myocardial infarction (MI) ornon-fatal stroke (CV death/MI/stroke) as well as death due to any cause by baseline CKD severity. CKD was categorised by eGFR < or ≥60 mL/min/1.73 m2, UACR < or ≥300 mg/g or KDIGO risk classification., Results: 3533 participants were randomised with a median follow-up of 3.4 years. Low/moderate KDIGO risk was present in 242 (6.9%), while 878 (24.9%) had high and 2412 (68.3%) had very high KDIGO risk. Semaglutide reduced CV death/MI/stroke by 18% (HR 0.82 [95% CI 0.68-0.98]; P = .03), with consistency across eGFR categories, UACR levels and KDIGO risk classification (all P-interaction >.13). Death due to any cause was reduced by 20% (HR 0.80 [0.67-0.95]; P = .01), with consistency across eGFR categories and KDIGO risk class (P-interaction .21 and .23, respectively). The P-interaction treatment effect for death due to any cause by UACR was .01 (<300 mg/g HR 1.17 [0.83-1.65]; ≥300 mg/g HR 0.70 [0.57-0.85])., Conclusions: Semaglutide significantly reduced the risk of CV death/MI/stroke regardless of baseline CKD severity in participants with T2D., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Rationale & Objective: Almost 80% of individuals with chronic kidney disease (CKD) reside in low- and middle-income countries (LMICs) and are potentially underrepresented in randomized controlled clinical trials (RCTs). We assessed the global distribution of RCTs comparing pharmacological treatments for CKD over the past 2 decades, as well as the magnitude and evolution of participation by LMICs., Study Design: Systematic review., Setting & Study Populations: RCTs evaluating pharmacological interventions in adults with CKD., Selection Criteria for Studies: RCTs published between 2003-2023 and indexed in MEDLINE., Data Extraction: Each trial was reviewed and extracted independently by 2 investigators with disagreements settled by consensus or a third reviewer., Analytical Approach: RCT participation of World Bank-defined income groups and geographic regions were described, and the representation indices (RI) according to RCT participants and estimated CKD prevalences were calculated. RCTs were also categorized as global, regional, or national in scope., Results: Among 7,760 identified studies, we included 1,366 RCTs conducted in 84 countries with 301,158 participants. National, regional, and global RCTs represented 85.4%, 3.5%, and 11.1% of studies, respectively. LMICs were included in 34.7% of RCTs. No RCTs included participants from low-income countries, and lower-middle-income countries participated in 13.2%. Of participants from RCTs with available information, 25.4% (n=64,843 of 255,237) were from LMICs. According to the RI, 6 LMICs were overrepresented (>1.25), 7 were adequately represented (0.75-1.25), and 26 were underrepresented (<0.75). Most global CKD RCTs (80.2%) included LMICs; however, LMIC participants constituted only 32.9% of the global trial population. We observed a positive trend in LMIC inclusion over time, rising from 22.9% (n=71of 310) in 2003-2007 to 45.5% (n=140of 308) in 2018-2023., Limitations: The use of an income-group dichotomy, exclusion of nonrandomized studies of intervention, and studies identified in 1 database., Conclusions: Despite an increase in participation over the past 2 decades, individuals with CKD from LMICs remain significantly underrepresented in RCTs. These findings suggest that increased efforts are warranted to increase LMIC representation in pharmacological CKD RCTs., Plain-Language Summary: Chronic kidney disease (CKD) substantially affects people from low- and middle-income countries (LMICs). However, the participation of these countries in randomized controlled trials (RCTs) remains uncertain. To assess the global distribution and representation of these countries in kidney disease research, we reviewed 1,366 CKD drug RCTs published from 2003-2023, conducted in 84 countries involving more than 300,000 participants. LMICs were included in approximately a third of these studies, with their participants making up approximately one-quarter of the total; lower-middle-income countries were poorly represented, and low-income countries were absent. LMICs constituted a third of participants in multinational RCTs. Most LMICs were underrepresented relative to the prevalence of CKD. We observed an increasing inclusion of LMICs, particularly in the last decade. Nonetheless, individuals with CKD from LMICs remain underrepresented in drug RCTs, suggesting that increased efforts are warranted to include representation of these populations in these studies., (Copyright © 2024 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Historically, it takes an average of 17 years for new treatments to move from clinical evidence to daily practice. Given the highly effective treatments now available to prevent or delay kidney disease onset and progression, this is far too long. Now is the time to narrow the gap between what we know and what we do. Clear guidelines exist for the prevention and management of common risk factors for kidney disease, such as hypertension and diabetes, but only a fraction of people with these conditions are diagnosed worldwide, and even fewer are treated to target. Similarly, the vast majority of people living with kidney disease are unaware of their condition, because it is often silent in the early stages. Even among patients who have been diagnosed, many do not receive appropriate treatment for kidney disease. Considering the serious consequences of kidney disease progression, kidney failure, or death, it is imperative that treatments are initiated early and appropriately. Opportunities to diagnose and treat kidney disease early must be maximized beginning at the primary care level. Many systematic barriers exist, ranging from the patient to the clinician to the health systems to societal factors. To preserve and improve kidney health for everyone everywhere, each of these barriers must be acknowledged so that sustainable solutions are developed and implemented without further delay.

We hypothesized that higher scores on the dietary inflammatory index (DII) would be associated with a lower glomerular filtration rate (GFR). This cross-sectional study included 2098 participants from Mexican Teachers Cohort Study, the Health Workers Cohort Study, and the Comitán Study belonging to the RenMex consortium. Energy-adjusted DII scores were estimated using a semi-quantitative food frequency questionnaire (FFQ). eGFR was estimated by the CKD Epidemiology Collaboration equation. Quantile regression models and ordered regression models were estimated to assess the associations of interest. Median age of study participants was 47 years, median eGFR was 102.9 mL/min/1.73m 2 , and the median energy-adjusted DII was 0.89 (range, -2.25, +4.86). The median eGFR was lower in participants in the highest percentile of DII compared to those in the lowest percentile (103.8 vs 101.4). We found that continuous and categorical energy-adjusted DII scores were associated with lower eGFR, especially at the lower percentiles. In adjusted ordered logistic regression, we found that the highest DII category was associated with 1.80 times the odds of belonging to the mildly decreased eGFR category or moderately decreased eGFR category compared lowest DII category (OR: 1.80, 95%CI 1.35, 2.40). A high DII score was associated with a lower eGFR among the Mexican population. Additional studies are crucial to validate these findings and explore potential strategies to reduce the consumption of pro-inflammatory foods as a preventive approach for chronic kidney disease (CKD)., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Hypercalcemia is highly prevalent in kidney transplant recipients with hyperparathyroidism. However, its long-term impact on graft function is uncertain., Methods: We conducted a prospective cohort study investigating adverse graft outcomes associated with persistent hypercalcemia (free calcium > 5.2 mg/dL in ≥ 80% of measures) and inappropriately elevated intact parathyroid hormone (> 30 pg/mL) in kidney transplant recipients. Asymptomatic mild hypercalcemia was monitored unless complications developed., Results: We included 385 kidney transplant recipients. During a 4-year (range 1-9) median follow-up time, 62% of kidney transplant recipients presented persistent hypercalcemia. Compared to kidney transplant recipients without hypercalcemia, there were no significant differences in graft dysfunction (10% vs. 12%, p = 0.61), symptomatic urolithiasis (5% vs. 3%, p = 0.43), biopsy-proven calcium deposits (6% vs. 5%, p = 1.0), fractures (6% vs. 4%, p = 0.64), and a composite outcome of urolithiasis, calcium deposits, fractures, and parathyroidectomy indication (16% vs. 13%, p = 0.55). In a subset of 76 kidney transplant recipients, subjects with persistent hypercalcemia had higher urinary calcium (median 84 [43-170] vs. 38 [24-64] mg/day, p = 0.03) and intact fibroblast growth factor 23 (median 36 [24-54] vs. 27 [19-40] pg/mL, p = 0.04), and lower 25-hydroxyvitamin D levels (11.3 ± 1.2 vs. 16.3 ± 1.4 ng/mL, p < 0.001). In multivariate analysis, pretransplant intact parathyroid hormone < 300 pg/mL was associated with a reduced risk of post-transplant hypercalcemia (OR 0.51, 95% CI 0.32-0.80)., Conclusions: Long-term persistent mild hypercalcemia (tertiary hyperparathyroidism) was frequent in kidney transplant recipients in our series. This condition presented with lower phosphate and 25-hydroxyvitamin D, and higher urinary calcium and intact fibroblast growth factor 23 levels compared to kidney transplant recipients without hypercalcemia, resembling a mild form of primary hyperparathyroidism. Despite these metabolic derangements, the risk of adverse graft outcomes was low., (© 2023. The Author(s) under exclusive licence to Italian Society of Nephrology.)

Introduction: Despite the provision of renin-angiotensin-aldosterone-system inhibitors and immunosuppressive therapies, membranous nephropathy often progresses to end-stage kidney disease (ESKD). The objective of this prespecified analysis was to assess the safety and efficacy of dapagliflozin in patients with membranous nephropathy enrolled in the DAPA-CKD trial., Methods: Patients with an estimated glomerular filtration rate (eGFR) of 25-75 mL/min/1.73 m 2 and urinary albumin-to-creatinine ratio (UACR) 200-5,000 mg/g were randomized to dapagliflozin 10 mg once daily or placebo, along with standard-of-care and followed for median 2.4 years. The primary endpoint was a composite of ≥50% sustained decline in eGFR, ESKD, or kidney or cardiovascular death. Exploratory efficacy endpoints included eGFR slope and UACR., Results: Among DAPA-CKD participants with membranous nephropathy, 19 were randomized to dapagliflozin and 24 to placebo. The mean (SD) age was 59.9 ± 12.1 years, the mean eGFR was 45.7 ± 12.1 mL/min/1.73 m 2 , and the median UACR was 1,694.5 (25%, 75% range 891-2,582.5) mg/g. Two of 19 (11%) patients randomized to dapagliflozin and five of 24 (21%) randomized to placebo experienced the primary composite endpoint. Total and chronic mean eGFR slopes for dapagliflozin and placebo were -3.87 and -4.29 and -2.66 and -4.22 mL/min/1.73 m 2 /year, respectively; corresponding between-group mean differences were 0.42 and 1.57 mL/min/1.73 m 2 /year. Dapagliflozin reduced geometric mean (SEM) UACR relative to placebo (-29.3% ± 1.2% vs. -3.6% ± 1.1%; between-group mean difference [95% CI] -26.7 [-50.4, 8.3]). Four (21%) patients randomized to dapagliflozin and seven (29%) randomized to placebo experienced a serious adverse event., Conclusion: In membranous nephropathy, the effects of dapagliflozin on kidney disease progression and albuminuria were generally favorable; there was insufficient power to justify formal inference testing., Competing Interests: G.M.C. served on the Executive Committee of the DAPA-CKD trial. He has served on the Board of Directors of Satellite Healthcare, a non-profit dialysis provider. He has served as Chair or Co-Chair of Trial Steering Committees with Akebia, CSL Behring, Sanifit, and Vertex. He has served as an Advisor to Applaud, Ardelyx, Calico, CloudCath, Durect, Eliaz Therapeutics, Miromatrix, Outset, Renibus, and Unicycive. He has served on Data Safety Monitoring Boards with Bayer, Mineralys, and ReCor. H.J.L.H. reported receiving research support from and serving as a consultant for AstraZeneca during the conduct of the study; serving as a consultant for Bayer, Chinook Tx, CSL Behring, Dimerix, Eli Lilly, Fresenius, Gilead, Novartis, and Travere Therapeutics outside the submitted work; receiving grants and research support from Boehringer Ingelheim and Janssen outside the submitted work; and receiving grants and clinical trial study medication from, and serving as a consultant for Novo Nordisk outside the submitted work. P.B.M. reported receiving lecture fees and travel to meetings support from Vifor, AstraZeneca, Pharmacosmos, Napp, Astellas, lecture fees from Novartis, Astellas, GSK and grants from Boehringer Ingelheim outside the submitted work. J.P.D. reported receiving fees from AstraZeneca for the conduct of this study; fees from Sanofi-Aventis and CSL Behring as part of a steering committee; fees from Novo Nordisk for outcome adjudication for a trial; fees from Goldfinch Bio, Birdrock Bio, and Boehringer Ingelheim for study design; personal fees from Bayer. M.N. reported receiving honoraria from Boehringer Ingelheim, Swixx Biopharma, Roche, Sanofi Genzyme and Omeros. D.C.W. reported receiving personal fees from AstraZeneca during the conduct of the study; personal fees from Astellas, Boehringer Ingelheim, Bayer, GlaxoSmithKline, Janssen, Gilead, Merck Sharp and Dohme, George Clinical, Intas, ProKidney, Tricida, Vifor, and Zydus outside the submitted work; and performing guideline development for KDIGO. R.C.-R. reported receiving personal fees from AstraZeneca, during the conduct of the study; personal fees from Boehringer Ingelheim, personal fees from Amgen, personal fees from Janssen, grants from GlaxoSmithKline, grants and personal fees from Novo Nordisk, personal fees from Medtronic, outside the submitted work. P.R. reported receiving grants and other from AstraZeneca, during the conduct of the study; from Novo Nordisk, Gilead, Bayer, Sanofi-Aventis, and Eli Lilly, outside the submitted work. R.D.T.’s contribution to this manuscript was supported in part by endowments from the Mary M. Conroy Professorship in Kidney Diseases and the Houston J and Florence A Dosswell Center for Development of New Approaches for the Treatment of Hypertension. He also reported receiving personal fees from AstraZeneca, during the conduct of the study; personal fees from AstraZeneca, Bayer Pharma, Calliditas, Boehringer Ingelheim, Relypsa, Amgen, and Novartis, outside the submitted work. A.M.L. reported being a full-time employee and shareholder of AstraZeneca during the conduct of the study. N.J. reports travel grants from AstraZeneca., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Historically, it takes an average of 17 years to move new treatments from clinical evidence to daily practice. Given the highly effective treatments now available to prevent or delay kidney disease onset and progression, this is far too long. The time is now to narrow the gap between what we know and what we do. Clear guidelines exist for the prevention and management of common risk factors for kidney disease, such as hypertension and diabetes, but only a fraction of people with these conditions worldwide are diagnosed, and even fewer are treated to target. Similarly, the vast majority of people living with kidney disease are unaware of their condition, because in the early stages it is often silent. Even among patients who have been diagnosed, many do not receive appropriate treatment for kidney disease. Considering the serious consequences of kidney disease progression, kidney failure, or death, it is imperative that treatments are initiated early and appropriately. Opportunities to diagnose and treat kidney disease early must be maximized beginning at the primary care level. Many systematic barriers exist, ranging from patient to clinician to health systems to societal factors. To preserve and improve kidney health for everyone everywhere, each of these barriers must be acknowledged so that sustainable solutions are developed and implemented without further delay., (© 2024 The Authors. Journal of Renal Care published by John Wiley & Sons Ltd on behalf of European Dialysis & Transplant Nurses Association/European Renal Care Association.)

Background and Hypothesis: Chronic kidney disease (CKD) presents a significant clinical and economic burden to healthcare systems worldwide, which increases considerably with progression towards kidney failure. The DAPA-CKD trial demonstrated that patients with or without type 2 diabetes (T2D) who were treated with dapagliflozin experienced slower progression of CKD versus placebo. Understanding the effect of long-term treatment with dapagliflozin on the timing of kidney failure beyond trial follow-up can assist informed decision-making by healthcare providers and patients. The study objective was therefore to extrapolate the outcome-based clinical benefits of treatment with dapagliflozin in patients with CKD via a time-to-event analysis using trial data., Methods: Patient-level data from the DAPA-CKD trial were used to parameterise a closed cohort-level partitioned survival model that predicted time-to-event for key trial endpoints (kidney failure, all-cause mortality, sustained decline in kidney function, and hospitalisation for heart failure). Data were pooled with a subpopulation of the DECLARE-TIMI 58 trial to create a combined CKD population spanning a range of CKD stages; a parallel survival analysis was conducted in this population., Results: In the DAPA-CKD and pooled CKD populations, treatment with dapagliflozin delayed time to first event for kidney failure, all-cause mortality, sustained decline in kidney function, and hospitalisation for heart failure. Attenuation of CKD progression was predicted to slow the time to kidney failure by 6.6 years (dapagliflozin: 25.2, 95%CI: 19.0-31.5; standard therapy: 18.5, 95%CI: 14.7-23.4) in the DAPA-CKD population. A similar result was observed in the pooled CKD population with an estimated delay of 6.3 years (dapagliflozin: 36.0, 95%CI: 31.9-38.3; standard therapy: 29.6, 95%CI: 25.5-34.7)., Conclusion: Treatment with dapagliflozin over a lifetime time horizon may considerably delay the mean time to adverse clinical outcomes for patients who would go on to experience them, including those at modest risk of progression., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Background: Chronic kidney disease (CKD) is a global concern that presents significant challenges for disease management. Several factors drive CKD prevalence, including primary risk factors, such as type 2 diabetes and hypertension, and an ageing population. Inside CKD is an international initiative that aims to raise awareness of the substantial burden incurred by CKD., Methods: Using a peer-reviewed microsimulation method, the clinical burden of CKD was estimated from 2022 to 2027. Demographic data from the Americas, Europe, and Asia-Pacific/Middle East were used to generate virtual populations and to project the prevalence of CKD, kidney replacement therapy, associated cardiovascular complications, comorbid conditions, and all-cause mortality in the CKD population over the modelled time frame., Findings: Across the 31 participating countries/regions, the total prevalence of CKD was projected to rise to 436.6 million cases by 2027 (an increase of 5.8% from 2022), with most cases (∼80%) undiagnosed. Inside CKD projected a mean of 8859 cases of heart failure, 10,244 of myocardial infarction, and 7797 of stroke per 100,000 patients with CKD by 2027., Interpretation: The clinical impact of CKD is substantial and likely to increase; the high prevalence of undiagnosed cases and associated complications may benefit from the implementation of health policy interventions that promote screening, earlier diagnosis, and interventions to improve outcomes., Funding: AstraZeneca., Competing Interests: AK has received honoraria for lectures from AstraZeneca. ECH, GL, EK, CFC and RCR have received support from AstraZeneca for their contributions to this work. Stanford University School of Medicine has received grants/contracts from NIDDK, NIAID and CSL Behring on behalf of work conducted by GMC. GMC has received consulting fees from AstraZeneca, Akebia, Ardelyx, Renibus, Miromatrix, Sanifit, Unicycive and Vertex. GMC has received royalties/licences from Elsevier. GMC has participated in advisory boards/data safety monitoring boards by Bayer, Mineralys and ReCor. GMC has a leadership/fiduciary role with Satellite Healthcare Board of Directors (which is non-profit). GMC has stock/stock options at Applaud, CloudCath, Durect, Eliaz Therapeutics, Miromatrix, Outset, Renibus and Unicycive. K-UE has received grants from AstraZeneca, Amgen, Bayer, Evotec and Vifor. K-UE has received consulting fees from Akebia, AstraZeneca, Bayer, Otsuka and Retrophin. K-UE has received honoraria/payment for lectures by AstraZeneca and Bayer. K-UE has participated in advisory boards/data safety monitoring boards by AstraZeneca. LR, LW and TC are employees of HealthLumen Ltd, and AstraZeneca provided funding to HealthLumen Ltd for their contributions to this work. HealThink received funding from AstraZeneca based on the contributions of PS to this work. RCR has received grants/contracts from AstraZeneca. Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán has received grants/contracts from Boehringer Ingelheim, Novo Nordisk, Roche and Baxter on behalf of work conducted by RCR. RCR has received consulting feeds from Chinook, Boehringer, Bayer and Medxl. RCR has received honoraria/payment for lectures by AstraZeneca, Amgen, Boehringer, Novo Nordisk and Bayer. SEHA Kidney Care received honoraria payments from AstraZeneca for the contributions of SGH to this work. JJGS, SB, CC and SN are employees and shareholders of AstraZeneca., (© 2024 The Author(s).)

Background: The sodium-glucose cotransporter type 2 inhibitor dapagliflozin reduces the risk of progressive kidney disease and cardiovascular events in patients with chronic kidney disease, with and without type 2 diabetes. Whether its effects are uniform across the spectrum of age and among men and women is unknown., Objective: We performed a pre-specified analysis in DAPA-CKD to evaluate efficacy and safety of dapagliflozin according to baseline age and sex., Design: Prospective randomized placebo-controlled trial., Participants: A total of 4304 adults with chronic kidney disease (estimated glomerular filtration rate (eGFR) 25-75 mL/min/1.73 m 2 ; urinary albumin-to-creatinine ratio 200-5000 mg/g) with and without type 2 diabetes., Intervention: Dapagliflozin 10 mg versus placebo once daily., Main Measures: Primary endpoint was a composite of ≥ 50% sustained eGFR decline, end-stage kidney disease, and kidney or cardiovascular death. Secondary endpoints included kidney composite endpoint (same as primary composite endpoint but without cardiovascular death), cardiovascular composite endpoint (hospitalized heart failure or cardiovascular death), and all-cause mortality., Key Results: Median follow-up was 2.4 years. Absolute risks of cardiovascular composite endpoint and all-cause mortality were higher in older patients. Absolute risk of kidney composite endpoint was highest in patients < 50 years (10.7 and 6.2 per 100 patient-years in the placebo and dapagliflozin groups, respectively) and lowest in patients ≥ 80 years (3.0 and 1.2 per 100 patient-years in the placebo and dapagliflozin groups, respectively). There was no evidence of heterogeneity of the effects of dapagliflozin on the primary or secondary endpoints based on age or sex. Neither age nor sex modified the effects of dapagliflozin on total or chronic eGFR slope., Conclusions: Dapagliflozin reduced the risks of mortality, cardiovascular events, and CKD progression in older patients, including in septuagenarians and octogenarians who comprised 25% of participants. Ageism and/or therapeutic nihilism should not discourage the use of dapagliflozin in older women and men who are likely to experience considerable benefit., Trial Registry: clinicaltrials.gov NIH TRIAL REGISTRY NUMBER: NCT03036150., (© 2023. The Author(s), under exclusive licence to Society of General Internal Medicine.)

Background: Higher temperatures are associated with higher rates of hospital admissions for nephrolithiasis and acute kidney injury. Occupational heat stress is also a risk factor for kidney dysfunction in resource-poor settings. It is unclear whether ambient heat exposure is associated with loss of kidney function in patients with established chronic kidney disease. We assessed the association between heat index and change in estimated glomerular filtration rate (eGFR) in participants from the DAPA-CKD trial in a post-hoc analysis., Methods: DAPA-CKD was a randomised controlled trial of oral dapagliflozin 10 mg once daily or placebo that enrolled participants aged 18 years or older, with or without type 2 diabetes, with a urinary albumin-to-creatinine ratio of 200-5000 mg/g, and an eGFR of 25-75 mL/min per 1·73 m 2 . In this post-hoc analysis, we explored the association between time-varying daily centre-level heat index (ERA5 dataset) and individual-level change in eGFR in trial participants using linear mixed effect models and case-time series. The DAPA-CKD trial is registered with ClinicalTrials.gov, NCT03036150., Findings: Climate and eGFR data were available for 4017 (93·3%) of 4304 participants in 21 countries (mean age: 61·9 years; mean eGFR: 43·3 mL per 1·73 m 2 ; median 28 months follow-up). Across centres, a heat index of more than 30°C occurred on a median of 0·6% of days. In adjusted linear mixed effect models, within each 120-day window, each 30 days' heat index of more than 30°C was associated with a -0·6% (95% CI -0·9% to -0·3%) change in eGFR. Similar estimates were obtained using case-time series. Additional analyses over longer time-windows showed associations consistent with haemodynamic or seasonal variability, or both, but overall estimates corresponded to an additional 3·7 mL per 1·73 m 2 (95% CI 0·1 to 7·0) loss of eGFR per year in a patient with an eGFR of 45 mL per 1·73 m 2 located in a very hot versus a temperate environment., Interpretation: Higher ambient heat exposure is associated with more rapid eGFR decline in those with established chronic kidney disease. Efforts to mitigate heat exposure should be tested as part of strategies to attenuate chronic kidney disease progression., Funding: None., Competing Interests: Declaration of interests HJLH has received honoraria, paid to his institution (University Medical Center Groningen), for participation in steering committees from AstraZeneca, Janssen, Gilead, Bayer, Chinook, and CSL Pharma; honoraria for participation in advisory boards from Merck, Mitsubishi Tanabe, Janssen, and Mundipharma; fees for consultancy from AstraZeneca, AbbVie, Retrophin, Boehringer Ingelheim, and Novo Nordisk; and research grant support from AstraZeneca, AbbVie, Janssen, and Boehringer Ingelheim. GMC has received fees from AstraZeneca for the DAPA-CKD trial steering committee; serves on the Board of Directors for Satellite Healthcare, a non-profit dialysis provider; has received research grants from the US National Institute of Diabetes and Digestive and Kidney Diseases, US National Institute of Allergy and Infectious Diseases, US National Heart, Lung, and Blood Institute, and CSL Behring; has served on trial steering committees with Akebia, AstraZeneca, Gilead, Sanifit, and Vertex; has served as an adviser to Ardelyx, CloudCath, Durect, Miromatrix, Outset, Renibus, Reata, Sanifit, Unicycive, and Vertex; and has served on data and safety monitoring boards for the National Institute of Diabetes and Digestive and Kidney Diseases, Bayer, Mineralys, and ReCor. RC-R has received honoraria as a consultant from AstraZeneca (DAPA-CKD Steering Committee), Boehringer Ingelheim, Bayer, Chinook, and Novo Nordisk; and research support and speaker fees from AstraZeneca, GSK, and Novo Nordisk. AML is an employee and stockholder of AstraZeneca. NJ has received support from AstaZeneca to attend conferences. JJVM has received payments for his work on clinical trials paid to his employer, Glasgow University; has received payments for consulting; is on the advisory board of Alnylam, Amgen, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Cardurion, Cytokinetics, DAICor, GSK, Ionis Pharmaceuticals, KBP Biosciences, Novartis, and Theracos; and has received personal lecture fees from Abbott, Alkem Metabolics, Eris Lifesciences, Hikma, Lupin, Sun Pharmaceuticals, Medscape/Heart.org, ProAdWise Communications, Radcliffe Cardiology, Servier, and the Corpus. PR has received honoraria to Steno Diabetes Center Copenhagen for lecture fees, steering group participation, and advisory board participation from AstraZeneca, Bayer, Boehringer Ingelheim, Gilead, Novo Nordisk, Sanofi, and Eli Lilly, and research support from AstraZeneca. RDT has received consulting fees from Boehringer Ingelheim, Reata Pharma, and Chinook Pharma; received speakers fees from Medscape; participated in advisory boards for Bayer and Viofor; and participated in data monitoring committees for Akebia and Otsuka. DN reports unrelated work funded by GSK involving studies of kidney function in sub-Saharan Africa. DCW provides ongoing consultancy services to AstraZeneca and has received honoraria for participation in advisory boards and other activities, consultancy fees, or both from Amgen, AstraZeneca, Boehringer Ingelheim, Bayer, KSk, Janssen, Napp, Mundipharma, Medscape, Merck Sharp & Dohme, Pharmacosmos, Reata, Takeda, and Vifor Fresenius. BC has received research grant funding, paid to his employers (University College London and Royal Free London NHS Foundation Trust), from the UK Medical Research Council, the Colt Foundation, and AstraZeneca along with consultancy fees (also paid to his employer) from LifeArc. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background & Aims: To evaluate the association between soft drinks (SDs) consumption and estimated glomerular filtration rate (eGFR) in a Mexican adult population., Methods: We used data from the RenMex consortium (n = 2095) that included the Mexican Teachers Cohort Study (34-65 years), the Health Workers Cohort Study (18-90 years), and the Comitán Study (19-91 years). In this cross-sectional study, we assessed SDs consumption (cola and flavored soda) using a food frequency questionnaire (FFQ) and estimated eGFR using the CKD Epidemiology Collaboration equation. Quantile regression was used to assess the association between SDs consumption and eGFR with eGFR as a continuous variable. Multinomial logistic regression models were used for eGFR categories derived from quantile regression (mildly decreased eGFR, ≥72.9-87.9 mL/min/1.73 m 2 and moderately decreased eGFR, <72.9 mL/min/1.73 m 2 )., Results: Mean age of study participants was 47.2 years, 67.5% were women, and 12.2% had diabetes. eGFR was <60 mL/min/1.73 m 2 in 3.7% of study participants. Mildly decreased eGFR was present in 14.8%, and moderately decreased eGFR was present in 10.1% of study participants. Quantile regression results showed that SDs consumption was associated with lower eGFR at the 10th, 25th, 50th and 75th percentile. Based on the final adjusted multinomial model, ≥7 servings/week was positively associated with moderately decreased eGFR relative to <1 serving/week (Relative Risk Ratio = 1.95; 95% CI: 1.07-3.57)., Conclusion: Our results suggest that higher SDs consumption is associated with lower eGFR. Encouraging healthy dietary choices should be part of the management and prevention of CKD., (Copyright © 2024 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background and Aims: Sodium-glucose cotransporter 2 inhibitors decrease blood pressure in patients with type 2 diabetes, but the consistency and magnitude of blood pressure lowering with dapagliflozin in patients with chronic kidney disease (CKD) is unknown. We conducted a prespecified analysis of the DAPA-CKD trial to investigate the effect of dapagliflozin on systolic blood pressure (SBP) in patients with CKD, with and without type 2 diabetes., Methods: A total of 4304 adults with baseline estimated glomerular filtration rate (eGFR) 25-75 mL/min/1.73m 2 and urinary albumin-to-creatinine ratio (UACR) 200-5000 mg/g were randomized to either dapagliflozin 10 mg or placebo once daily; median follow-up was 2.4 years. The primary endpoint was a composite of sustained ≥50% eGFR decline, end-stage kidney disease, or death from a kidney or cardiovascular cause. Change in SBP was a prespecified outcome., Results: Baseline mean (SD) SBP was 137.1 mmHg (17.4). By Week 2, dapagliflozin compared to placebo reduced SBP by 3.6 mmHg (95% CI 2.8-4.4 mmHg), an effect maintained over the duration of the trial (2.9 mmHg, 2.3-3.6 mmHg). Time-averaged reductions in SBP were 3.2 mmHg (2.5-4.0 mmHg) in patients with diabetes and 2.3 mmHg (1.2-3.4 mmHg) in patients without diabetes. The time-averaged effect of dapagliflozin on diastolic blood pressure (DBP) was 1.0 mmHg (0.6-1.4 mmHg); 0.8 mmHg (0.4-1.3 mmHg) in patients with diabetes and 1.4 mmHg (0.7-2.1 mmHg) in patients without diabetes. Benefits of dapagliflozin on the primary composite and secondary endpoints were evident across the spectrum of baseline SBP and DBP., Conclusion: In patients with CKD and albuminuria, randomization to dapagliflozin was associated with modest reductions in systolic and diastolic BP., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Historically, it takes an average of 17 years to move new treatments from clinical evidence to daily practice. Given the highly effective treatments now available to prevent or delay kidney disease onset and progression, this is far too long. The time is now to narrow the gap between what we know and what we do. Clear guidelines exist for the prevention and management of common risk factors for kidney disease, such as hypertension and diabetes, but only a fraction of people with these conditions worldwide are diagnosed, and even fewer are treated to target. Similarly, the vast majority of people living with kidney disease are unaware of their condition, because in the early stages it is often silent. Even among patients who have been diagnosed, many do not receive appropriate treatment for kidney disease. Considering the serious consequences of kidney disease progression, kidney failure, or death, it is imperative that treatments are initiated early and appropriately. Opportunities to diagnose and treat kidney disease early must be maximized beginning at the primary care level. Many systematic barriers exist, ranging from patient to clinician to health systems to societal factors. To preserve and improve kidney health for everyone everywhere, each of these barriers must be acknowledged so that sustainable solutions are developed and implemented without further delay., (Copyright © 2024 World Kidney Day Steering Committee. Published by Elsevier Inc., on behalf of the International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Historically, it takes an average of 17 years to move new treatments from clinical evidence to daily practice. Given the highly effective treatments now available to prevent or delay kidney disease onset and progression, this is far too long. The time is now to narrow the gap between what we know and what we do. Clear guidelines exist for the prevention and management of common risk factors for kidney disease, such as hypertension and diabetes, but only a fraction of people with these conditions worldwide are diagnosed, and even fewer are treated to target. Similarly, the vast majority of people living with kidney disease are unaware of their condition, because in the early stages it is often silent. Even among patients who have been diagnosed, many do not receive appropriate treatment for kidney disease. Considering the serious consequences of kidney disease progression, kidney failure, or death, it is imperative that treatments are initiated early and appropriately. Opportunities to diagnose and treat kidney disease early must be maximized beginning at the primary care level. Many systematic barriers exist, ranging from patient to clinician to health systems to societal factors. To preserve and improve kidney health for everyone everywhere, each of these barriers must be acknowledged so that sustainable solutions are developed and implemented without further delay. DOI: 10.52547/ijkd.8216.

Background: The Dapagliflozin and Prevention of Adverse Outcomes in CKD (DAPA-CKD) trial enrolled patients with estimated glomerular filtration rate 25-75 mL/min/1.73 m 2 and urine albumin-to-creatinine ratio >200 mg/g. The Dapagliflozin Effect on CardiovascuLAR Events-Thrombolysis in Myocardial Infarction 58 (DECLARE-TIMI 58) trial enrolled patients with type 2 diabetes, a higher range of kidney function and no albuminuria criterion. The study objective was to estimate the cost-effectiveness of dapagliflozin in a broad chronic kidney disease population based on these two trials in the UK, Spain, Italy and Japan., Methods: We adapted a published Markov model based on the DAPA-CKD trial but to a broader population, irrespective of urine albumin-to-creatinine ratio, using patient-level data from the DAPA-CKD and DECLARE-TIMI 58 trials. We sourced cost and utility inputs from literature and the DAPA-CKD trial. The analysis considered healthcare system perspectives over a lifetime horizon., Results: Treatment with dapagliflozin was predicted to attenuate disease progression and extend projected life expectancy by 0.64 years (12.5 versus 11.9 years, undiscounted) in the UK, with similar estimates in other settings. Clinical benefits translated to mean quality-adjusted life year (QALY; discounted) gains between 0.45 and 0.68 years across countries. Incremental cost-effectiveness ratios in the UK, Spain, Italy and Japan ($10 676/QALY, $14 479/QALY, $7771/QALY and $13 723/QALY, respectively) were cost-effective at country-specific willingness-to-pay thresholds. Subgroup analyses suggest dapagliflozin is cost-effective irrespective of urinary albumin-to-creatine ratio and type 2 diabetes status., Conclusion: Treatment with dapagliflozin may be cost-effective for patients across a wider spectrum of estimated glomerular filtration rates and albuminuria than previously demonstrated, with or without type 2 diabetes, in the UK, Spanish, Italian and Japanese healthcare systems., Competing Interests: P.M., J.A.D. and P.D.G. are employees of Health Economics and Outcomes Research Ltd, Cardiff, UK. Health Economics and Outcomes Research Ltd received fees from AstraZeneca in relation to this study. D.C.W. provided ongoing consultancy services to AstraZeneca in the last 2 years and has received honoraria and/or consultancy fees from Amgen, AstraZeneca, Boehringer Ingelheim, Bayer, Eledon, Galderma, Gilead, GlaxoSmithKline, George Clinical, Janssen, Merck Sharp and Dohme, ProKidney, Takeda, Vifor and Zydus. He also reports speaking fees from Astellas, AstraZeneca and Vifor, and support for travel/meeting attendance from Astellas, AstraZeneca and Pro. He has served on DSMBs for Eledon, Galderma, Merck, ProKidney and Pathalys. He is a member of the International Society of Nephrology and National Institute of Health Research, UK. P.R. has received honoraria to Steno Diabetes Center Copenhagen for consultancy from AstraZeneca, Astellas, Bayer, Boehringer Ingelheim, Gilead, Novo Nordisk, Merck, Mundipharma, Sanofi and Vifor, and research support from AstraZeneca, Bayer and Novo Nordisk. G.M.C. received fees from AstraZeneca for service on the DAPA-CKD trial steering committee. He serves on the Board of Directors for Satellite Healthcare, a non-profit dialysis provider. He has received research grants to his institution from NIDDK, NIAID and CSL Behring. He has served on trial-steering committees with Akebia, AstraZeneca, Gilead, Sanifit and Vertex. He has served as an advisor to Applaud, Ardelyx, CloudCath, Durect, Eliaz Therapeutics, Miromatrix, Outset, Renibus, Unicycive and Vertex. He has served on DSMBs for NIDDK, Bayer, Mineralys and ReCor. He also declares stock or stock options for Applaud, Ardelyx, CloudCath, Durect, Eliaz Therapeutics, Miromatrix, Outset and Renibus. R.C.-R. has received honoraria as consultant from AstraZeneca, Boehringer Ingelheim, Bayer, Chinook, AbbVie and Novo Nordisk, and research support from AstraZeneca, Boehringer Ingelheim, Roche and Novo Nordisk. He has received speaking fees from AstraZeneca, Boehringer Ingelheim, Novo Nordisk and Amgen. K.T. has honoraria as lecture fee from Novartis, AstraZeneca, Ono, Daiichi-Sankyo, Takeda, Otsuka, Bayer and Kyowa-Kirin. He has received research support from AstraZeneca, Ono, Bayer, Kyowa-Kirin, Otsuka, Takeda and Daiichi-Sankyo. S.B. and J.J.G.S. are employees of AstraZeneca., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Background: A sizeable proportion of patients with chronic kidney disease (CKD) are reported to be frail. Here we examined the safety and efficacy of dapagliflozin in patients with CKD by frailty level., Methods: Adults with CKD, with/without type 2 diabetes, with an estimated glomerular filtration rate (eGFR) of 25-75 mL/min/1.73 m2, and urinary albumin-to-creatinine ratio 200-5 000 mg/g were randomized to dapagliflozin (10 mg/day) or placebo. The primary endpoint was a composite of sustained ≥50% eGFR decline, end-stage kidney disease (ESKD), or death from kidney or cardiovascular (CV) causes., Results: Frailty index (FI), assessed by Rockwood cumulative deficit approach, was calculable in 4 303/4 304 (99.9%) patients: 1 162 (27.0%) in not-to-mildly frail (FI ≤0.210), 1 642 (38.2%) in moderately frail (FI 0.211-0.310), and 1 499 (34.8%) in severely frail categories (FI >0.311). Dapagliflozin reduced the risk of the primary composite endpoint across all FI categories (hazard ratios [95% confidence interval {CI}]: 0.50 [0.33-0.76], 0.62 [0.45-0.85], and 0.64 [0.49--0.83], respectively; p-interaction = 0.67). Results were similar for secondary outcomes including kidney composite outcome (sustained ≥50% eGFR decline, ESKD or death from kidney cause; p-interaction = 0.44), CV endpoint (heart failure hospitalization or CV death; p-interaction = 0.63), and all-cause mortality (p-interaction p = .42). Results were consistent when using FI as a continuous variable. Occurrence of serious adverse events was numerically lower in patients receiving dapagliflozin versus placebo in all FI categories (16.9% vs 20.1%, 26.3% vs 30.7%, and 42.9% vs 47.8%, in not-to-mildly, moderately, and severely frail categories, respectively)., Conclusions: The relative benefit of dapagliflozin for all outcomes was consistent across all frailty categories, with no difference in associated safety., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Significance Statement: Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are foundational therapy for CKD but are underused, in part because they are frequently withheld and not restarted due to hyperkalemia, AKI, or hospitalization. Consequently, ensuring persistent use of ACE inhibitors and ARBs in CKD has long been a major clinical priority. In this joint analysis of the CREDENCE and DAPA-CKD trials, the relative risk of discontinuation of ACE inhibitors and ARBs was reduced by 15% in patients randomized to sodium-glucose cotransporter 2 (SGLT2) inhibitors. This effect was more pronounced in patients with urine albumin:creatinine ratio ≥1000 mg/g, for whom the absolute benefits of these medications are the greatest. These findings indicate that SGLT2 inhibitors may enable better use of ACE inhibitors and ARBs in patients with CKD., Background: Strategies to enable persistent use of renin-angiotensin system (RAS) blockade to improve outcomes in CKD have long been sought. The effect of SGLT2 inhibitors on discontinuation of RAS blockade has yet to be evaluated., Methods: We conducted a joint analysis of canagliflozin and renal events in diabetes with established nephropathy clinical evaluation (CREDENCE) and dapagliflozin and prevention of adverse outcomes in CKD (DAPA-CKD), two randomized, double-blind, placebo-controlled, event-driven trials of SGLT2 inhibitors in patients with albuminuric CKD. The main outcome was time to incident temporary or permanent discontinuation of RAS blockade, defined as interruption of an ACE inhibitor or ARB for at least 4 weeks or complete cessation during the double-blind on-treatment period. Cox regression analyses were used to estimate the treatment effects from each trial. Hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were pooled with fixed effects meta-analysis to obtain summary treatment effects, overall and across key subgroups., Results: During median follow-up of 2.2 years across both trials, 740 of 8483 (8.7%) patients discontinued RAS blockade. The relative risk for discontinuation of RAS blockade was 15% lower in patients randomized to receiving SGLT2 inhibitors (HR, 0.85; 95% CI, 0.74 to 0.99), with consistent effects across trials ( P -heterogeneity = 0.92). The relative effect on RAS blockade discontinuation was more pronounced among patients with baseline urinary albumin:creatinine ratio ≥1000 mg/g (pooled HR, 0.77; 95% CI, 0.63 to 0.94; P -heterogeneity = 0.009)., Conclusions: In patients with albuminuric CKD with and without type 2 diabetes, SGLT2 inhibitors facilitate the use of RAS blockade., Clinical Trial Registry Name and Registration Number: ClinicalTrials.gov, NCT02065791 and NCT03036150 ., Podcast: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/JASN/2023&#95;11&#95;21&#95;JASN0000000000000248.mp3., (Copyright © 2023 by the American Society of Nephrology.)

Introduction: Peritoneal dialysis (PD) guidelines recommend a 14-day break-in period after catheter placement, yet this period could be shortened with new insertion techniques., Methods: We conducted a prospective cohort study to compare percutaneous vs. surgical catheter insertion in a newly established PD program. The break-in period was intentionally shortened to <24 h to start PD almost immediately., Results: We included 223 subjects who underwent percutaneous (34%) or surgical (66%) catheter placement. Compared to the surgical group, the percutaneous group had a higher proportion of early dialysis initiation within 24 h (97% vs. 8%, p < 0.001), similar successful initiation rates (87% vs. 92%, p = 0.34), and shorter lengths of stay (12 [9-18] vs. 18 [14-22] days, p < 0.001). Percutaneous insertion increased the likelihood of successful PD initiation within 24 h (OR 74, 95% CI 31-182), without increasing major complications., Conclusion: Percutaneous placement could represent a cost-effective and efficient technique to shorten break-in periods., (© 2023 International Society for Apheresis and Japanese Society for Apheresis.)

Background: Insulin resistance (IR) is a pathophysiologic hallmark of type 2 diabetes and associated with the presence of chronic kidney disease (CKD). Experimental studies suggest that endothelin-1 increases IR. We assessed the association between IR and cardio-renal outcomes and the effect of the selective endothelin receptor antagonist atrasentan on IR in patients with type 2 diabetes and CKD., Methods: We used data from the RADAR and SONAR trials that recruited participants with type 2 diabetes and CKD [eGFR 25-75 mL/min/1.73 m², urine albumin-to-creatinine ratio of 300-5000 mg/g]. IR was calculated using the homeostatic model assessment (HOMA-IR). The association between HOMA-IR and the pre-specified cardio-renal outcomes was assessed using multivariable Cox proportional hazards regression, and effects of atrasentan on HOMA-IR by a linear mixed effect model., Results: In the SONAR trial, each log-unit increase in HOMA-IR was associated with an increased risk of the composite cardio-renal outcome [hazard ratio 1.32 (95%CI 1.09,1.60; p = 0.004)], kidney outcome [hazard ratio 1.30 (95%CI 1.00,1.68; p-value = 0.048)], and the kidney or all-cause mortality outcome [hazard ratio 1.25 (95%CI 1.01,1.55; p-value = 0.037)]. After 12 weeks treatment in the RADAR trial (N = 123), atrasentan 0.75 mg/day and 1.25 mg/day compared to placebo reduced HOMA-IR by 19.1 (95%CI -17.4, 44.3) and 26.7% (95%CI -6.4, 49.5), respectively. In the SONAR trial (N = 1914), atrasentan 0.75 mg/day compared to placebo reduced HOMA-IR by 9.6% (95%CI 0.6, 17.9)., Conclusions: More severe IR is associated with increased risk of cardio-renal outcomes. The endothelin receptor antagonist atrasentan reduced IR., Trial Registration: RADAR trial (Reducing Residual Albuminuria in Subjects With Diabetes and Nephropathy With AtRasentan): NCT01356849. SONAR trial (The Study Of Diabetic Nephropathy With AtRasentan) NCT01858532., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Rationale & Objective: In FIDELITY, finerenone improved cardiorenal outcomes in patients with chronic kidney disease (CKD) and type 2 diabetes. This analysis explores the efficacy and safety of finerenone in Hispanic patients., Study Design: Post hoc analysis of the FIDELITY prespecified pooled analysis of the FIDELIO-DKD and FIGARO-DKD randomized control trials., Setting & Participants: Patients with type 2 diabetes and CKD (urinary albumin-to-creatinine ratio [UACR] of ≥30 to <300 mg/g and estimated glomerular filtration rate [eGFR] of ≥25-≤90 mL/min/1.73 m 2 , or UACR of ≥300 to ≤5,000 and eGFR of ≥25 mL/min/1.73 m 2 ) on optimized renin-angiotensin system blockade., Intervention: Finerenone or placebo., Outcomes: Cardiovascular composite (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure); kidney composite (kidney failure, sustained ≥57% eGFR decline, or renal death); change in UACR., Results: Of 13,026 patients, 2,099 (16.1%) self-identified as Hispanic. Median follow-up was 3.0 years. The cardiovascular composite outcome occurred in 10.0% of Hispanic patients receiving Finerenone and in 12.3% of Hispanic patients receiving placebo (HR, 0.80; 95% CI, 0.62-1.04). This was consistent with non-Hispanic patients (HR, 0.87; 95% CI, 0.79-0.97; P interaction = 0.59). The kidney composite outcome occurred in 6.5% and 6.6% of Hispanic patients with finerenone and placebo, respectively (HR, 0.94; 95% CI, 0.67-1.33). The risk reduction was consistent with that observed in non-Hispanic patients (HR, 0.75; 95% CI, 0.64-0.87; P interaction = 0.22). Finerenone reduced UACR by 32% at month 4 in both Hispanic and non-Hispanic patients versus placebo ( P  < 0.001 for both patient groups). The safety profile of finerenone and incidence of hyperkalemia was similar between Hispanic and non-Hispanic patient groups., Limitations: Small sample size, short follow-up time, and lower treatment adherence in the Hispanic population., Conclusions: Overall, the efficacy and safety of finerenone were similar in Hispanic and non-Hispanic patients with CKD and type 2 diabetes., Funding: Bayer AG., Trial Registration: ClinicalTrials.gov identifier: NCT02540993, NCT02545049., Plain-Language Summary: Chronic kidney disease (CKD) in patients with type 2 diabetes occurs more frequently in Hispanic patients than in non-Hispanic patients, with a more rapid progression to kidney failure. Treatment with finerenone reduces the risk of having a kidney or heart event (such as starting dialysis or having a heart attack) in patients with CKD and type 2 diabetes. Because clinical trials that investigate treatments for CKD and type 2 diabetes have not included enough Hispanic patients, the benefits of treatments particularly for Hispanic patients are frequently unknown. This study explores the benefits of finerenone in Hispanic patients. Overall, the study shows that finerenone can provide kidney and heart benefits in Hispanic patients with CKD and type 2 diabetes, as it does in non-Hispanic patients., (© 2023 The Authors.)

BACKGROUND: In the DAPA-CKD (Dapagliflozin in Patients with Chronic Kidney Disease) trial, dapagliflozin improved kidney and cardiovascular outcomes in patients with chronic kidney disease (CKD) with or without type 2 diabetes (T2D). In this post hoc analysis of DAPA-CKD, we assessed the effects of dapagliflozin on the correction and prevention of anemia. METHODS: The DAPA-CKD trial randomized patients (1:1) with an estimated glomerular filtration rate of 25 to 75 ml/min/1.73 m2 and a urinary albumin-to-creatinine ratio of 200 to 5000 mg/g to receive dapagliflozin 10 mg or placebo daily. Hematocrit was measured at baseline, 2 weeks, 2 and 4 months, and every 4 months thereafter. Anemia was defined as hematocrit less than 39% in men and less than 36% in women. Correction and incidence of anemia were defined as two consecutive measurements above or below these thresholds relative to baseline, respectively, during follow-up. We classified anemia-related adverse events using data from site investigator reports. RESULTS: Mean age of the 4304 participants was 61.8 years, and 67.5% had T2D. Among the 4292 (99.7%) participants with baseline hematocrit data, 1716 (40.0%) had anemia. Over the 2.4-year median follow-up, patients assigned to dapagliflozin had an increase in hematocrit of 2.3 percentage points (95% confidence interval [CI], 2.1 to 2.5) greater than those assigned to placebo. Among patients with anemia at baseline, anemia was corrected in 443 (53.3%) patients randomized to receive dapagliflozin and 247 (29.4%) patients randomized to receive placebo (hazard ratio, 2.29; 95% CI, 1.96 to 2.68). Among patients without anemia at baseline, 10.4% of patients assigned to dapagliflozin developed incident anemia compared with 23.7% in the placebo group (hazard ratio, 0.39; 95% CI, 0.31 to 0.48). Anemia-related adverse events occurred in 2.2% of patients assigned to dapagliflozin compared with 3.8% assigned to placebo. Effects of dapagliflozin on the correction and prevention of anemia were consistent in patients with and without T2D. The adverse event profile was similar to that known for dapagliflozin. CONCLUSIONS: This exploratory analysis suggests that dapagliflozin is associated with the prevention or correction of anemia in patients with CKD with and without T2D. (Funded by AstraZeneca; ClinicalTrials.gov number, NCT03036150.)

Background: The Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial assessed dapagliflozin versus placebo, in addition to standard therapy, in patients with chronic kidney disease (CKD) and albuminuria, and was terminated prematurely due to overwhelming efficacy. The study objective was to model the long-term clinical outcomes of DAPA-CKD beyond the trial follow-up., Methods: A Markov model extrapolated event incidence per 1000 patients and CKD progression rates for patients receiving dapagliflozin or placebo over a 10-year time horizon. We derived treatment-specific CKD stage transition matrices using DAPA-CKD trial data. We extrapolated relevant efficacy endpoints using parametric survival equations for all-cause mortality and generalized estimating equations for recurrent events., Results: When extrapolated over a 10-year period, patients randomized to dapagliflozin spent more time in CKD stages 1-3 and less in stages 4-5 than placebo [0.65 (95% CrI 0.41, 0.90) and -0.23 (95% CrI -0.45, 0.00) years per patient, respectively]. Dapagliflozin prevented an estimated 83 deaths and 51 patients initiating kidney replacement therapy per 1000 patients over 10 years. Predicted rates of hospitalized heart failure and abrupt declines in kidney function were reduced (19 and 39 estimated events per 1000 patients, respectively)., Conclusions: Adding dapagliflozin to standard therapeutic management of CKD is expected to have long-term cardiorenal benefit beyond what has been demonstrated in the DAPA-CKD trial, with patients predicted to live longer with fewer complications., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

Background The DAPA-CKD (Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease) trial (NCT03036150) demonstrated that dapagliflozin reduced the risk of kidney and cardiovascular events in patients with chronic kidney disease and albuminuria with and without type 2 diabetes. We aimed to determine whether baseline cardiovascular medication use modified the dapagliflozin treatment effect. Methods and Results We randomized 4304 adults with baseline estimated glomerular filtration rate 25 to 75 mL/min per 1.73 m 2 and urinary albumin:creatinine ratio 200 to 5000 mg/g to dapagliflozin 10 mg or placebo once daily. The primary end point was a composite of ≥50% estimated glomerular filtration rate decline, end-stage kidney disease, and kidney or cardiovascular death. Secondary end points included a kidney composite end point (primary composite end point without cardiovascular death), a cardiovascular composite end point (hospitalized heart failure or cardiovascular death), and all-cause mortality. We categorized patients according to baseline cardiovascular medication use/nonuse. Patients were required by protocol to receive a stable (and maximally tolerated) dose of a renin-angiotensin-aldosterone system inhibitor. We observed consistent benefits of dapagliflozin relative to placebo, irrespective of baseline use/nonuse of renin-angiotensin-aldosterone system inhibitors (98.1%), calcium channel blockers (50.7%), β-adrenergic antagonists (39.0%), diuretics (43.7%), and antithrombotic (47.4%), and lipid-lowering (15.0%) agents. Use of these drugs in combination with dapagliflozin did not increase the number of serious adverse events. Conclusions The safety profile and efficacy of dapagliflozin on kidney and cardiovascular end points in patients with chronic kidney disease were consistent among patients treated and not treated at baseline with a range of cardiovascular medications. Registration Information clinicaltrials.gov. Identifier: NCT03036150.

Background: In patients with autosomal dominant polycystic kidney disease (ADPKD), there is limited evidence of the rate of cyst progression after kidney transplantation., Aims: To compare the height-adjusted total kidney volume (Ht-TKV) before and after transplantation in kidney transplant recipients (KTR) with -ADPKD., Materials and Methods: Retrospective cohort study. The estimate of Ht-TKV was calculated by the ellipsoid volume equation using measurements from CT or yearly MRI scans before and after transplantation., Results: We included 30 patients with -ADPKD who underwent kidney transplantation (age 49 ± 10.1 years, 11 (37%) females, dialysis vintage 3 (1 - 6) years, and 4 (13%) underwent unilateral nephrectomy during the peritransplant period). The median follow-up time was 5 years (range 2 - 16 years). Transplantation was associated with a significant decrease in Ht-TKV after transplantation in 27 (90%) KTR. Median Ht-TKV decreased from 1,708 (IQR 1,100 - 2,350) mL/m to 710 (IQR 420 - 1,380) mL/m after 6 years of follow-up (p < 0.001), with a mean Ht-TKV change rate per year after transplantation of -1.4, -11.8, -9.7, -12.7, -7.0, and -9.4% after 1, 2, 3, 4, 5, and 6 years, respectively. Even in 2 (7%) KTR without regression, the annual growth was < 1.5% per year after transplantation., Conclusion: Kidney transplantation reduced Ht-TKV after the first 2 years of transplantation, and this decline was continuous for more than 6 years of follow-up.

Objective: To determine whether the benefits of dapagliflozin in patients with type 2 diabetes and chronic kidney disease (CKD) in the Dapagliflozin And Prevention of Adverse Outcomes in CKD trial (DAPA-CKD) varied by background glucose-lowering therapy (GLT)., Research Design and Methods: We randomized 4,304 adults (including 2,906 with type 2 diabetes) with a baseline estimated glomerular filtration rate (eGFR) 25-75 mL/min/1.73 m2 and urinary albumin-to-creatinine ratio of 200-5,000 mg/g to dapagliflozin 10 mg or placebo once daily (NCT03036150). The primary end point was a composite of ≥50% eGFR decline, end-stage kidney disease, and kidney or cardiovascular cause of death. Secondary end points included a kidney composite end point (primary composite end point without cardiovascular death), a cardiovascular composite end point (hospitalized heart failure or cardiovascular death), and all-cause mortality. In this prespecified analysis, we investigated the effects of dapagliflozin on these and other outcomes according to baseline GLT class or number of GLTs., Results: The effects of dapagliflozin on the primary composite outcome were consistent across GLT classes and according to the number of GLTs (all interaction P > 0.08). Similarly, we found consistent benefit of dapagliflozin compared with placebo on the secondary end points regardless of background GLT class or number of GLTs. The same applied to the rate of decline in the eGFR rate and safety end points. Dapagliflozin reduced the initiation of insulin therapy during follow-up compared with placebo (hazard ratio 0.72; 95% CI 0.54-0.96; P = 0.025)., Conclusions: Dapagliflozin reduced kidney and cardiovascular events in patients with type 2 diabetes and CKD across baseline GLT class or classes in combination., (© 2023 by the American Diabetes Association.)

Chronic kidney disease (CKD) represents a major challenge for Latin American (LatAm) because of its epidemic proportions. Therefore, the current status and knowledge of CKD in Latin America is not clearly understood. Moreover, there is a paucity of epidemiologic studies that makes the comparison across the countries even more difficult. To address these gaps, a virtual kidney expert opinion meeting of 14 key opinion leaders from Argentina, Chile, Colombia, Costa Rica, Dominican Republic, Ecuador, Guatemala, Mexico, and Panama was held in January 2022 to review and discuss the status of CKD in various LatAm regions. The meeting discussed the following: (i) epidemiology, diagnosis, and treatment of CKD, (ii) detection and prevention programs, (iii) clinical guidelines, (iv) state of public policies about diagnosis and management of chronic kidney disease, and (v) role of innovative therapies in the management of CKD. The expert panel emphasized that efforts should be made to implement timely detection programs and early evaluation of kidney function parameters to prevent the development or progression of CKD. Furthermore, the panel discussed the importance of raising awareness among health care professionals; disseminating knowledge to the authorities, the medical community, and the general population about the kidney and cardiovascular benefits of novel therapies; and the need for timely updating of clinical practice guidelines, regulatory policies, and protocols across the region., (© 2023 Published by Elsevier Inc. on behalf of the International Society of Nephrology.)

Unassigned: Kidney replacement therapy (KRT) initiated in Latin America towards the second half of the 20th century, starting with dialytic therapies and, shortly thereafter, with kidney transplant. By the end of 2021, close to half a million Latin Americans were under KRT, with an overall unadjusted prevalence of 872 per million persons (pmp), yet with significant heterogeneity between nations. By treatment modality, 68% of prevalent patients were treated with hemodialysis (HD), 9% with peritoneal dialysis (PD), and 23% were living with a functioning kidney graft (LFG). In the last decade, HD is the KRT that has had the largest growth, and it also has incorporated newer and better technologies. Nevertheless, Latin America shows heterogeneity between countries, and as a region we are far from achieving full accessibility to all in need of KRT. While there has been growth and improvement in existing renal dialysis registries, and several countries that did not previously have these registries have implemented them, there are still some nations with limited or absent registry implementation. The number of nephrologists in the region is heterogeneous, with only four countries having an appropriate group of specialists. The remaining nations have an important need to expand nephrology training programs. SLANH is a major regional player in addressing these topics and supporting the expansion of appropriate nephrology programs to improve inequalities and patient care. (Rev Invest Clin. 2023;75(6):300-8)., (Copyright: © 2023 Permanyer.)

Aims: Dapagliflozin was approved for use in patients with chronic kidney disease (CKD) based on results of the DAPA-CKD trial, demonstrating attenuation of CKD progression and reduced risk of cardio-renal outcomes and all-cause mortality (ACM) versus placebo, in addition to standard therapy. The study objective was to assess the potential medical care cost offsets associated with reduced rates of cardio-renal outcomes across 31 countries and regions., Materials and Methods: A comparative cost-determination framework estimated outcome-related costs of dapagliflozin plus standard therapy versus standard therapy alone over a 3-year horizon based on the DAPA-CKD trial. Incidence rates of end-stage kidney disease (ESKD), hospitalizations for heart failure (HHF), acute kidney injury (AKI), and ACM were estimated for a treated population of 100,000 patients. Associated medical care costs for non-fatal events were calculated using sources from a review of publicly available data specific to each considered setting., Results: Patients treated with dapagliflozin plus standard therapy experienced fewer incidents of ESKD (7,221 vs 10,767; number needed to treat, NNT: 28), HHF (2,370 vs 4,684; NNT: 43), AKI (4,110 vs. 5,819; NNT: 58), and ACM (6,383 vs 8,874; NNT: 40) per 100,000 treated patients versus those treated with standard therapy alone. Across 31 countries/regions, reductions in clinical events were associated with a 33% reduction in total costs, or a cumulative mean medical care cost offset of $264 million per 100,000 patients over 3 years., Limitations and Conclusions: This analysis is limited by the quality of country/region-specific data available for medical care event costs. Based on the DAPA-CKD trial, we show that treatment with dapagliflozin may prevent cardio-renal event incidence at the population level, which could have positive effects upon healthcare service delivery worldwide. The analysis was restricted to outcome-associated costs and did not consider the cost of drug treatments and disease management.

Background: Acute hospitalizations are common in patients with chronic kidney disease (CKD) and often lead to decreases in health-related quality of life and increased care costs., Objective: To determine the effects of dapagliflozin on first hospitalizations and all (first and subsequent) hospitalizations and to explore effects on cause-specific hospitalizations., Design: Post hoc analysis of a randomized, double-blind, placebo-controlled clinical trial. (ClinicalTrials.gov: NCT03036150)., Setting: 386 ambulatory practice sites in 21 countries from 2 February 2017 through 12 June 2020., Participants: Adults with an estimated glomerular filtration rate of 25 to 75 mL/min/1.73 m 2 and a urinary albumin-creatinine ratio of 200 to 5000 mg/g, with and without type 2 diabetes., Intervention: Dapagliflozin, 10 mg once daily, or matching placebo (1:1 ratio)., Measurements: The effects of dapagliflozin on first hospitalizations for any cause, all hospitalizations, and cause-specific (first and recurrent) hospitalizations were determined. The reported system organ class was used to evaluate reasons for admission. Hospitalizations were analyzed using Cox proportional hazards regression models (first hospitalization), the Lin-Wei-Yang-Ying method (all hospitalizations or death), and negative binomial models (cause-specific hospitalizations)., Results: The study included 4304 patients (mean age, 61.8 years; 33.1% women). During a median follow-up of 2.4 years, 2072 hospitalizations were reported among 1224 (28.4%) participants. Compared with placebo, dapagliflozin reduced risk for a first hospitalization (hazard ratio, 0.84 [95% CI, 0.75 to 0.94]) and all hospitalizations or death (rate ratio, 0.79 [CI, 0.70 to 0.89]). There was no evidence that the effects of dapagliflozin on first and all hospitalizations varied by baseline presence of type 2 diabetes ( P for interaction = 0.60 for each). Compared with placebo, dapagliflozin reduced the rate of admissions due to cardiac disorders, renal and urinary disorders, metabolism and nutrition disorders, and neoplasms., Limitations: This was a post hoc analysis and should be viewed as hypothesis-generating. Hospitalizations and causes were reported by site investigators and were not centrally adjudicated., Conclusion: Dapagliflozin reduced the risk for hospitalization for any cause in patients with CKD with and without type 2 diabetes., Primary Funding Source: AstraZeneca.

Introduction: Expanded hemodialysis (HDx) is expected to provide enhanced permeability of medium-sized molecules, selective solute retention, and better internal retrofiltration. The primary objective of this study was to compare the efficiency for removal of β2-microglobulin with 3 different extracorporeal therapies (ETs): high-flux hemodialysis (HF), online hemodiafiltration (OL-HDF), and HDx. The secondary objective was to evaluate the efficiency of removal of other uremic toxins, including urea, phosphate, CRP, IL-6, IL-10, TNF-⍺, indoxyl sulfate, and p-cresol., Methods: This single-center, randomized, and cross-over study was performed. Patients were randomized to determine the initial modality of treatment, each period lasted 4 weeks and between one modality and another, there was a washout period of 1 week. Reduction ratios (RRs) of different-size molecules and albumin were calculated for the different ET., Results: Twenty-two patients were included, β2-microglobulin RR was greater during both OL-HDF and HDx as compared to HF (RR 62% vs. 73% vs. 27%, respectively, p = &lt;0.0001), and there was no significant difference between HDx and OL-HDF (p = 0.09). A decrease in serum phosphate levels was observed in the HDx and OL-HDF periods, contrary to an increase in HF (-0.79 mg/dL vs. -1.02 mg/dL vs. + 0.11 mg/dL, respectively, p = &lt;0.0001). There was no difference in RRs of other molecules (BUN, CRP, IL-6, IL-10, TNF-⍺, indoxyl sulfate, and p-Cresol). There was no decrease in serum albumin in any ET., Conclusion: HDx provides enhanced removal of β2-microglobulin and phosphate as compared to HF, and similar efficacy as with OL-HDF. HDx should be considered an alternative to chronic convective therapies., (© 2023 S. Karger AG, Basel.)

Background: Dapagliflozin reduces kidney failure risk in patients with CKD but can result in a reversible acute reduction in eGFR upon treatment initiation. Determinants of this eGFR reduction and its associations with efficacy and safety outcomes are unknown., Methods: The DAPA-CKD trial randomized 4304 adults with CKD and albuminuria to once-daily dapagliflozin 10 mg or placebo, added to standard care. We prespecified an analysis comparing the effects of dapagliflozin among patients who experienced relative reductions in eGFR (>10% or >0%-10%) or an increase in eGFR from baseline to 2 weeks and assessed long-term efficacy and safety thereafter., Results: A total of 4157 (96.6%) patients had eGFR data available at baseline and at 2 weeks. In the dapagliflozin and placebo groups, 1026 (49.4%) and 494 (23.7%), respectively, experienced an acute reduction in eGFR >10%. Among patients receiving dapagliflozin, those with an acute reduction in eGFR >10% experienced a long-term eGFR decline of -1.58 ml/min per 1.73 m 2 per year compared with -2.44 and -2.48 ml/min per 1.73 m 2 per year among those experiencing a less pronounced reduction or increase in eGFR, respectively ( P -interaction=0.05). In the placebo group, long-term eGFR decline was -3.27, -3.84, and -3.77 ml/min per 1.73 m 2 per year for acute eGFR reduction subgroups of >10%, >0%-10%, or increase in eGFR ( P -interaction=0.48). Rates of serious adverse events and adverse events of special interest in patients randomized to dapagliflozin were unrelated to the acute eGFR change., Conclusions: Among patients with CKD and albuminuria treated with dapagliflozin, an acute reduction in eGFR (from baseline to 2 weeks) is not associated with higher rates of CKD progression. Clinical Trial registration number: A Study to Evaluate the Effect of Dapagliflozin on Renal Outcomes and Cardiovascular Mortality in Patients With Chronic Kidney Disease (Dapa-CKD) NCT03036150., (Copyright © 2022 by the American Society of Nephrology.)

Plasma exposure of the endothelin receptor antagonist atrasentan varies between individuals and is associated with nephroprotective effects and the risk of heart failure. We examined the influence of genetic polymorphisms on atrasentan plasma exposure and pharmacodynamic effects. We performed a substudy of the Study of Diabetic Nephropathy With Atrasentan (SONAR) trial which enrolled adults with type 2 diabetes and chronic kidney disease (estimated glomerular filtration rate: 25-75 mL/min/1.73 m 2 , and a urine albumin-to-creatinine ratio of 300-5,000 mg/g). Single nucleotide polymorphisms (SNPs) were determined for prespecified membrane transporters, metabolizing enzymes, and the endothelin-1 peptide. The associations among genotype, atrasentan plasma exposure, and the effect of atrasentan on the prespecified kidney and heart failure hospitalization (HHF) outcomes was assessed with Cox proportional hazards regression models. Of 3,668 patients randomized, 2,329 (63.5%) consented to genotype analysis. Two SNPs in the SLCO1B1 gene (rs4149056 and rs2306283), encoding the hepatic organic anion transporter 1B1 (OATP1B1), showed the strongest association with atrasentan plasma exposure. Based on their SLCO1B1 genotype, patients were classified into normal (atrasentan area under the plasma-concentration time curve from zero to infinity (AUC 0-inf ) 41.3 ng·h/mL) or slow (atrasentan AUC 0-inf 49.7 ng·h/mL, P < 0.001) OATP1B1 transporter phenotypes. Among patients with a normal OATP1B1 phenotype, the hazard ratio (HR) with atrasentan for the primary kidney and HHF outcomes were 0.61 (95% confidence interval (CI): 0.45-0.81) and 1.35 (95% CI: 0.84-2.13), respectively. In the slow transporter phenotype, HRs for kidney and HHF outcomes were 1.95 (95% CI: 0.95-4.03, P-interaction normal phenotype = 0.004), and 4.18 (95% CI: 1.37-12.7, P-interaction normal phenotype = 0.060), respectively. OATP1B1 gene polymorphisms are associated with significant between-patient variability in atrasentan plasma exposure and long-term efficacy and safety., (© 2022 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Introduction: Background: the differences in bioelectrical impedance vector analysis (BIVA) results from different analyzers that use different bioelectrical impedance analysis (BIA) measurement technologies are not known. This study aimed to identify the degree of agreement between the BIVA results of four different BIA measurement techniques and to evaluate the degree of agreement between their estimates of fat-free mass (FFM) and fat mass (FM) and those determined by the gold-standard method of dual-energy X-ray absorptiometry (DEXA) in a subgroup of patients without overhydration. Methods: a cross-sectional study was conducted with hemodialysis (HD) patients with end-stage renal disease (ESRD) aged 18 to 65 years. BIA was measured with four different techniques: spectroscopic (BIA-BIS), multifrequency (BIA-MF), single-frequency (BIA-SF), and segmental multifrequency (BIA-MS) techniques. The differences and concordance between the components of the BIA (resistance, reactance, and phase angle) of the four devices were analyzed. Patients with a normal hydration status were identified, and concordance between FM and FFM measurements with each impedance device and DEXA was observed only in these patients. Results: thirty patients were included. The concordance between the components of BIA ranged from good to excellent (phase angle: intraclass correlation coefficient (ICC) = 0.82, 95 % confidence interval (CI): 0.77-0.93; resistance: ICC = 0.98, 95 % CI: 0.92-0.99). The overall concordance for BIVA diagnosis between the analyzers was substantial for hydration (k = 0.71, 95 % CI: 0.71-0.72) and for body tissues (k = 0.68, 95 % CI: 0.67-0.68). Bland-Altman plots showed the lowest bias between BIA-BIS and DEXA for both FM and FFM. Conclusions: the agreement among the four devices was good for diagnosis by BIVA. The BIA-BIS analyzer and DEXA had the lowest bias for both FFM and FM, although with higher limits of agreement. The lowest limits of agreement were found with the BIA-MS analyzer.