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People with prior lean mass loss had a ~ 10% higher risk of MOF and ~ 22-26% higher risk of hip fracture, and the results were similar in people on anti-osteoporosis medications. Loss of lean mass is associated with increased fracture risk. Patients should be encouraged to pursue strategies to prevent loss of lean mass., Background: Sarcopenia increases fracture risk. If the risk persists after starting osteoporosis medication, patients may need to be encouraged to pursue strategies to prevent loss of lean mass., Objective: To estimate the effects of loss in appendicular lean mass (ALM) or total body lean mass (TBLM) on subsequent fracture risk and effect modification with anti-osteoporosis medication use., Methods: We conducted a registry-based cohort study linked to population-based data. We identified individuals ≥ 40 years of age with two DXA assessments ≥ 1 year apart and minimum 0.5 years of observation. ALM and TBLM were estimated from weight, sex, and percent fat from DXA (R 2  = 0.91 and 0.84 vs total body DXA, respectively). We report hazard ratios (HR) from Cox regression models estimating time to first incident major osteoporotic fracture (MOF) and hip fracture, adjusted for fracture risk; osteoporosis medication was included as an interaction term and used to stratify analyses., Results: We included 21,249 individuals (mean 67 [SD 10] years, 95% female, 37% on osteoporosis medication). The mean follow-up was 7 years (SD 4). A total of 1868 and 548 people had incident MOF and hip fracture, respectively. People with prior ALM loss (HR per SD 1.09, 95% CI 1.04-1.15) or TBLM loss (HR per SD 1.09, 95% CI 1.42-1.14) had a higher risk of MOF. Hip fracture risk was greater in people with prior ALM loss (HR per SD 1.22, 95% CI 1.12-1.33) and TBLM loss (HR per SD 1.26, 95% CI 1.16-1.38). There were no interactions with anti-osteoporosis medication use (all p > 0.3). When restricted to people on anti-osteoporosis medication, each SD in ALM or TBLM loss was associated with 8-9% increased MOF risk and 18-23% increased hip fracture risk., Conclusions: Loss of lean mass is associated with increased fracture risk among individuals on anti-osteoporosis medication. Patients should be encouraged to pursue strategies to prevent sarcopenia., (© 2024. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

This is a summary of the original article 'Dapagliflozin Utilization in Chronic Kidney Disease and Its Real-World Effectiveness Among Patients with Lower Levels of Albuminuria in the USA and Japan'. The slowing down of kidney function decline is important for managing chronic kidney disease (CKD) and preventing its complications. Clinical trials of dapagliflozin, a sodium-glucose cotransporter-2 inhibitor (SGLT-2i), have shown reductions in disease progression and death in patients with CKD and elevated levels of albuminuria. This summary of research provides an overview of a previously published article that aimed to find out whether dapagliflozin is also effective in patients with lower levels of albuminuria [urinary albumin-to-creatinine ratio (UACR) below 200 mg/g]. Starting dapagliflozin was associated with slower kidney function decline in patients with CKD and UACR below 200 mg/g compared with not starting. This effect was also observed in a subgroup analysis of patients without type 2 diabetes. These results suggest that the established benefits of SGLT-2is may extend to patients with lower levels of albuminuria., (© 2024. The Author(s).)

Background: Clinical practice guidelines for patients with chronic kidney disease (CKD) recommend regular monitoring and management of kidney function and CKD risk factors. However, the majority of patients with stage 3 CKD lack a diagnosis code, and data on the implementation of these recommendations in the real world are limited., Aim: To assess the implementation of guideline-directed monitoring and management practices in the real world in patients with stage 3 CKD without a recorded diagnosis code., Methods: REVEAL-CKD (NCT04847531) is a multinational, observational study of patients with stage 3 CKD. Eligible patients had ≥2 consecutive estimated glomerular filtration rate (eGFR) measurements indicative of stage 3 CKD recorded >90 and ≤730 days apart, lacked an International Classification of Diseases 9/10 diagnosis code corresponding to CKD any time before and up to 6 months after the second eGFR measurement. Testing of key measures of care quality were assessed., Results: The study included 435,971 patients from 9 countries. In all countries, the prevalence of urinary albumin-creatinine ratio and albuminuria testing was low. Angiotensin-converting enzyme inhibitor, angiotensin receptor blocker and statin prescriptions were highly variable, and sodium-glucose cotransporter-2 inhibitor prescriptions remained below 21%. Blood pressure measurements were recorded in 20.2%-89.9% of patients., Conclusions: Overall, a large proportion of patients with evidence of stage 3 CKD did not receive recommended, guideline-directed monitoring and management. The variability in standard of care among countries demonstrates a clear opportunity to improve monitoring and management of these patients, most likely improving long-term outcomes., (© 2024 The Author(s). European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

Background: Pomalidomide-based regimens are the cornerstone of treatment for relapsed/refractory MM (RRMM). Despite the high incidence of chronic kidney disease (CKD) in RRMM, individuals with advanced CKD have been excluded from phase II/III RCTs, creating a gap in our understanding of the effects of pomalidomide use in patients with RRMM complicated with advanced CKD. We undertook a cohort to study to understand the efficacy safety of pomalidomide-based regimens among patients with CKD using real-world data., Methods: Population-based, cohort study of patients ≥ 18 years with RRMM treated with pomalidomide in Ontario, Canada. Primary outcome was all-cause mortality. Secondary outcomes were time-to-major adverse kidney events (MAKE), time-to-next treatment, kidney response and safety., Results: Total 748 patients with RRMM utilizing pomalidomide were included; 440 had preserved kidney function, 210 had moderate CKD (eGFR 30-59 mL/min/1.73m 2 ), and 98 had advanced CKD (eGFR < 30 mL/min/1.73m 2 ). Mean age was 70.2 years, 43.3% were women. Patients with advanced CKD had a higher risk of all-cause mortality compared to the preserved kidney function group (aHR 1.37, 95% CI 1.06, 1.78). MAKE was higher in advanced CKD (aHR 1.70, 95% CI 1.03, 2.35). Kidney response was similar between moderate and severe CKD groups (aOR 1.04, 95%, CI 0.56-1.90). Safety outcomes were similar between groups., Conclusions: Patients with advanced CKD and RRMM on pomalidomide-based regimens exhibited reduced survival and a higher risk for MAKE. However, the probability of experiencing some degree of kidney recovery is 50% in both moderate and severe CKD, with comparable safety outcomes., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The efficacy and safety of bisphosphonate therapy for the treatment of osteoporosis and osteopenia in the setting of chronic kidney disease (CKD) is unclear., Objective: To determine the effect of bisphosphonate therapy on fractures, bone mineral density (BMD), and adverse events in adults across the spectrum of CKD and dialysis., Design: Systematic review and individual patient-level meta-analysis., Setting: Searches of Ageline, CINAHL, the Cochrane Library, EMBASE, and Medline from inception to August 25, 2016, supplemented with manual screening and clinicalstudydatarequest.com. Authors were contacted for individual patient-level data., Patients: Randomized, placebo-controlled trials with 100 or more participants that evaluated the treatment of primary osteoporosis/osteopenia in adult men and women with bisphosphonate therapy., Measurements: Study characteristics, quality, and data were assessed independently by 2 reviewers. Outcome measures were fractures, BMD, and adverse events including decline in estimated glomerular filtration rate (eGFR) and hypocalcemia (calcium <2.00 mmol/L)., Methods: Single-stage individual patient-level meta-analysis., Results: Of 39 eligible studies, individual patient-level data was available for 7 studies, all of which were studies of ibandronate. Of 7428 participants (5010 ibandronate, 2418 placebo), 100% were female, 98.6% were white, the mean body mass index was 25.7 kg/m 2 (SD 3.9), 18.9% were smokers and there were 740 fracture events. The mean eGFR was 69.1 mL/min/1.73 m 2 (SD 15.9) including 14.5%, 54.9%, 27.5%, 3.0%, and 0.2% stages G1, G2, G3A, G3B, and G4 CKD. Ibandronate increased hip and lumbar spine BMD and decreased the risk of fracture in the overall population (hazard ratio (HR) 0.871, 95% confidence interval (CI) 0.746, 1.018) but in patients with stage G3B CKD, it increased the risk of fracture (HR 3.862, 95% CI 1.156, 12.903). Ibandronate did not impact eGFR over 12 months but increased the risk of hypocalcemia (HR 1.324, 95% CI 1.056, 1.660) with no evidence of any effect modification by CKD stage (all tests of interaction p > 0.05)., Limitations: Clinically significant heterogeneity among studies, lack of long-term follow-up and bone biopsy results, limited representation of stage G4 and G5 CKD patients., Conclusions: Chronic kidney disease potentially modifies the efficacy but not the safety of bisphosphonate therapy in osteopenia and osteoporosis., Registration: PROSPERO CRD42020145613., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background: Guideline-recommended hyperkalaemia management includes dietary potassium (K + ) restriction, bicarbonate correction, diuretics and K + binders with dose reduction of renin-angiotensin-aldosterone system inhibitors as a last resort. The extent to which these recommendations are implemented is uncertain, as real-world data on hyperkalaemia management are limited. The Tracking Treatment Pathways in Adult Patients with Hyperkalemia (TRACK) study is a multinational, prospective, longitudinal study that is being conducted to address this knowledge gap. We report the design and baseline cohort characteristics of this real-world study of hyperkalaemia management decision-making., Methods: This study enrolled participants within 21 days of an episode of hyperkalaemia in four European countries (UK, Spain, Germany, Italy) and the USA. During the 12-month follow up, data collected will include participant and healthcare provider characteristics (specialty and practice setting), hyperkalaemia treatment objectives and strategies, rationale for management decisions and indicators of response and patient-reported perceptions of their hyperkalaemia treatment., Results: The enrolled cohort includes 1330 participants, mean age 68 years, of whom 31% were women. At baseline, 6% reported heart failure, 55% chronic kidney disease, 29% both and 9% neither. Most participants (57%) were taking an angiotensin-converting enzyme inhibitor, angiotensin receptor blocker or angiotensin receptor/neprilysin inhibitor at baseline. Mineralocorticoid receptor antagonist use was lower (14%)., Conclusions: The prospective TRACK study will shed light on practitioners' hyperkalaemia management decision-making and assess the impact of their decisions on hyperkalaemia recurrence. Understanding practitioners' underlying thought processes will facilitate efforts to improve hyperkalaemia management.ClinicalTrials.gov: NCT05408039., Competing Interests: J.H. and M.P.B. receive salary support from CPC, a non-profit academic research organization affiliated with the University of Colorado, which receives research grant/consulting funding from Agios Pharmaceuticals, Alexion Pharma Good Kaisha, Amgen, Anthos Therapeutics, ARCA Biopharma, AstraZeneca Pharma India, AstraZeneca Pharmaceuticals, AstraZeneca UK, AstraZeneca, Produtos Farmaceuticos, Atentiv, Bayer, Bayer (Proprietary) Limited, Bayer Aktiengesellschaft, Bayer Pharma, Beth Israel Deaconess Medical Center, Better Therapeutics, Bionest Partners, Boston Clinical Research Institute, BMS, CellResearch, Cleerly, Colorado Department of Public Health and Environment, Cook Regentec, CSL Behring, Eidos Therapeutics, EPG Communication Holdings, Esperion Therapeutics, Faraday Pharmaceuticals, HeartFlow, Hummingbird Bioscience, Insmed, Ionis Pharmaceuticals, IQVIA, Janssen Pharmaceuticals, Janssen Research & Development, Janssen Scientific Affairs, Lexicon Pharmaceuticals, LSG, MedImmune, Medpace, Medscape, Merck Sharp & Dohme, Northwell Health, Novartis Pharmaceuticals, Novo Nordisk, Osiris Therapeutics, Pfizer, PPD Development, Prothena Biosciences, Regeneron, Regents of the University of Colorado, Sanifit Therapeutics, Sanofi, Silence Therapeutics, Stanford University, Stealth BioTherapeutics, Brigham & Women's Hospital, Thrombosis Research Institute, UCD iC42 Lab, University of Colorado Denver, University of Pittsburgh, VarmX and WraSer. J.H. also reports owning AstraZeneca stock. N.S., M.B., H.C. and A.-K.S. own AstraZeneca stock. A.B. has received consultant fees and grant/other support from Abbott, Association of the British Pharmaceutical Industry, Accentus Medical, Amgen, Amore Health, AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Closer Still Media, Daiichi Sankyo, Health Smart, Janssen, Lattice Point, Lilly, Medtronic, McKinsey, MSD, Napp, Novartis, Novo Nordisk, Pfizer, Remedica, Sanofi Aventis and AirEmail. J.Bover received advisory and/or lecture fees and/or congress travel expenses from AbbVie, Amgen, AstraZeneca, Bayer, CSL-Vifor, GSK, Menarini, Rubió, Sanofi and Theramex. J.Butler has received consultant fees from Abbott, American Regent, Amgen, Applied Therapeutic, AskBio, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, BMS, Cardiac Dimension, Cardiocell, Cardior, CSL Behring, CVRx, Cytokinetics, Daxor, Edwards, Element Science, Faraday, Foundry, G3P, Innolife, Impulse Dynamics, Imbria, Inventiva, Ionis, Levator, Lexicon, Lilly, LivaNova, Janssen, Medtronics, Merck, Occlutech, Owkin, Novartis, Novo Nordisk, Pfizer, Pharmacosmos, Pharmain, Prolaio, Pulnovo, Regeneron, Renibus, Roche, Salamandra, Salubris, Sanofi, SC Pharma, Secretome, Sequana, SQ Innovation, Tenex, Tricog, Ultromics, Vifor and Zoll. P.M.F. has received consultant fees and grant/other support from Allena Pharmaceuticals, Alnylam, Amgen, AstraZeneca, Bayer, Gilead, Novo Nordisk, Otsuka Pharmaceuticals, Rocchetta and Vifor Fresenius and royalties as an author for UpToDate. L.F. serves on data safety monitoring boards for Novo Nordisk and Regeneron and owns Amgen stock. M.P.S. has received advisory board fees and honoraria from AstraZeneca, Bayer, Vifor Pharma Group and Boehringer Ingelheim/Lilly. N.T. has received grants/research support from the Canadian Institutes of Health Research, National Institutes of Health, Kidney Foundation of Canada, Bayer, AstraZeneca, Boehringer Ingelheim, Janssen Pharmaceuticals, Research Manitoba, Otsuka Pharmaceutical, Tricida and Lilly; honoraria or consultation fees from AstraZeneca, Bayer, Boehringer Ingelheim, GSK, Janssen Pharmaceuticals, Otsuka Pharmaceutical, Prokidney, Roche, Tricida and Lilly; and owns stock in ClinPredict, Klinrisk, Quanta, Marizyme, Mesentech, Renibus Therapeutics, PulseData and Tricida. W.C.W. has received consultant fees from Akebia, Anthos, Ardelyx, AstraZeneca, Bayer Boehringer Ingelheim, Cadrenal, GSK, Merck, Natera, Novartis, Pharmacosmos, Unicycive, Vera and Zydus., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Background and Hypothesis: Metabolic acidosis is a common complication of kidney disease and can result in further disease progression. Alkali therapy has been used to treat metabolic acidosis for decades. However, some concerns have been raised regarding its safety and long-term tolerability. Existing data suggest that dietary interventions can be beneficial in the management of chronic kidney disease (CKD). This systematic review and meta-analysis aims to summarize findings from studies comparing dietary interventions with placebo/usual care/no treatment in the management of metabolic acidosis in outpatient adults with CKD., Methods: Medline, Embase, Cochrane Central, CINAHL, and Web of Science Core Collection were searched from inception to June 2022. Our primary outcome measure was change in serum bicarbonate. Any dietary intervention looking to manipulate dietary acid load was considered as an intervention. Data screening and extraction were performed by two independent reviewers. Random effects meta-analysis was performed to pool data., Results: Dietary interventions resulted in clinically significant improvement in serum bicarbonate (mean difference (MD):2.98, 95% CI: [0.77, 5.19]; I2: 91%) and higher eGFR levels (MD: 3.16, 95%CI: [0.24, 6.08], I2: 67%) compared to controls. Serum potassium, albumin and body mass index remained unchanged. Dietary interventions were reported to be safe. Subgroup analyses indicated a superiority of plant-based over non-plant-based interventions in the improvement of acid-base balance and eGFR, however, these findings are from low quality and heterogenous studies., Conclusion: Our findings support the beneficial effects of dietary interventions aimed at reducing acid or adding base in the management of metabolic acidosis and kidney function in adults with CKD, with no adverse effects on serum potassium and nutritional status. Well-designed clinical trials looking at the treatment of metabolic acidosis with dietary interventions with a focus on adding base through fruit and vegetables are required., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Background: Physical inactivity is common among older adults and is associated with poor health outcomes. Medical fitness facilities provide a medically focused approach to physical fitness and can improve physical activity in their communities. This study aimed to assess the relationship between membership in the medical fitness model and all-cause mortality, health care utilization, and major adverse cardiac events in older adults., Methods: A propensity weighted retrospective cohort study linked individuals that attended medical fitness facilities to provincial health administrative databases. Older adults who had at least 1 year of health coverage from their index date between January 1st, 2005 to December 31st 2015 were included. Controls were assigned a pseudo-index date at random based on the frequency distribution of index dates in members. Members were stratified into low frequency attenders (< 1 Weekly Visits) and regular frequency attenders (> 1 Weekly Visits). Time to event models estimated the hazard ratios (HRs) for risk of all-cause mortality and major adverse cardiac event. Negative binomial models estimated the risk ratios (RRs) for risk of hospitalizations, outpatient primary care visits and emergency department visits., Results: Among 3,029 older adult members and 91,734 controls, members had a 45% lower risk of all-cause mortality (HR: 0.55, 95% CI: 0.50 - 0.61), 20% lower risk of hospitalizations (RR: 0.80, 95% CI: 0.75 - 0.84), and a 27% (HR: 0.72, 95% CI: 0.66 - 0.77), lower risk of a major adverse cardiovascular event. A dose-response effect with larger risk reductions was associated with more frequent attendance as regular frequency attenders were 4% more likely to visit a general practitioner for a routine healthcare visit (RR: 1.04, 95% CI: 1.01 - 1.07), but 23% less likely to visit the emergency department (RR: 0.87, 95% CI: 0.82 - 0.92)., Conclusions: Membership at a medical fitness facility was associated with a decreased risk of mortality, health care utilization and cardiovascular events. The medical fitness model may be an alternative approach for public health strategies to promote positive health behaviors in older adult populations., (© 2024. The Author(s).)

Introduction: Patients with kidney failure requiring hemodialysis are at high risk for hyperkalemia between treatments, which is associated with increased cardiovascular morbidity and mortality. Early detection of hyperkalemic events may be useful to prevent adverse outcomes and their associated costs. We performed a cost-utility analysis comparing an intervention where a real-time potassium monitoring device is administered in patients on hemodialysis in comparison to usual care., Methods: We developed a cost-utility model with microsimulation from the perspective of the United States health care payer. Primary outcomes included the monthly cost-effectiveness threshold cost and break-even cost per patient attributable to the intervention and the incremental cost-effectiveness ratio comparing the intervention to usual care. A 25% reduction in hyperkalemic events was applied as a baseline device effectiveness estimate. Concurrent first and second order microsimulations were performed using 10%, 25%, and 50% effectiveness estimates as sensitivity analyses. Results are presented over a 10-year time horizon in 2022 United States dollars and a willingness-to-pay threshold of $100,000 per quality-adjusted life year (QALY) was considered., Results: Over 10 years, threshold and break-even analysis yielded maximum monthly costs of $201.10 and $144.15 per patient, respectively. The intervention was associated with reduced mean costs ($6381.21) and increased mean QALYs (0.03) per patient; therefore, was considered dominant. In sensitivity analysis, the intervention was dominant in 99% of simulations performed at all effectiveness rates., Conclusion: Implementing a real-time potassium monitoring device in patients on hemodialysis has the potential for cost savings and improved outcomes from the perspective of the United States health care payer., (© 2024 International Society of Nephrology. Published by Elsevier Inc.)

Aim: To validate the Klinrisk machine learning model for prediction of chronic kidney disease (CKD) progression in patients with type 2 diabetes in the pooled CANVAS/CREDENCE trials., Materials and Methods: We externally validated the Klinrisk model for prediction of CKD progression, defined as 40% or higher decline in estimated glomerular filtration rate (eGFR) or kidney failure. Model performance was assessed for prediction up to 3 years with the area under the receiver operating characteristic curve (AUC), Brier scores and calibration plots of observed and predicted risks. We compared performance of the model with standard of care using eGFR (G1-G4) and urine albumin-creatinine ratio (A1-A3) Kidney Disease Improving Global Outcomes (KDIGO) heatmap categories., Results: The Klinrisk model achieved an AUC of 0.81 (95% confidence interval [CI] 0.78-0.83) at 1 year, and 0.88 (95% CI 0.86-0.89) at 3 years. The Brier scores were 0.020 (0.018-0.022) and 0.056 (0.052-0.059) at 1 and 3 years, respectively. Compared with the KDIGO heatmap, the Klinrisk model had improved performance at every interval (P < .01)., Conclusions: The Klinrisk machine learning model, using routinely collected laboratory data, was highly accurate in its prediction of CKD progression in the CANVAS/CREDENCE trials. Integration of the model in electronic medical records or laboratory information systems can facilitate risk-based care., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

This systematic review investigates the certainty of evidence (CoE) regarding noise annoyance as a determinant of biological changes known to contribute to disease development. We searched PubMed MEDLINE, EMBASE, Cochrane Central, and CINAHL for English-language comparative studies conducted on humans of any age from 1 January 1940, to 28 August 2023. Further, studies that provided quantitative data on the relationship between noise annoyance and biomarkers of interest were included. Where possible, random-effects meta-analyses were used to calculate the odds ratios of noise annoyance on biomarkers and biological conditions considered to be risk factors for developing health effects. The risk of bias of individual studies was assessed using the Risk of Bias of Non-randomized Studies of Exposures (ROBINS-E) instrument. The CoE for each outcome was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. The search identified 23 primary studies reporting on relevant biomarkers. Although some studies and pooled estimates suggest a possible association between noise annoyance and biological measures, the CoE overall is very low due to concerns with the risk of bias, inconsistency, and imprecision in the estimates of effects. In the context of environmental impact assessment, where guidelines aim to mitigate the prevalence of populations experiencing a high level of noise annoyance, our results suggest that such practices should be grounded in the understanding that annoyance is health-relevant because it reflects an undesirable reaction to noise, rather than a precursor to chronic physical health conditions.

Background and Hypothesis: Identifying meaningful estimated glomerular filtration rate (eGFR) reductions in younger adults (<65 years) could guide prevention efforts. To aid in interpretation and identification of young adults at risk, we examined the association of population-level eGFR percentiles relative to the median by age and clinical outcomes., Methods: We conducted a retrospective cohort study of 8.7 million adults from Ontario, Canada from age 18 to 65 from 2008 to 2021 with an eGFR measure (both single outpatient value and repeat measures). We calculated median eGFR values by age and examined the association of reduced eGFR percentiles (≤10th, 5th, 2.5th and 1st) with outcomes using time to event models. Outcomes were a composite of all-cause mortality, major adverse cardiac outcomes (MACE) with/without heart failure (MACE+) and kidney failure as well as each component individually., Results: From age 18 to 65, the median eGFR declined with age (range 128 to 90) and across percentiles [eGFR ranges 102 to 68 for ≤10th, 96 to 63 for ≤5th, 90 to 58 for ≤2.5th and 83 to 54 for 1st]. The adjusted rate for any adverse outcome was elevated at ≤ 10th percentile (HR 1.14 95%CI 1.10-1.18) and was consistent for all-cause mortality, MACE, MACE+ and predominant for kidney failure (HR 5.57 95%CI 3.79-8.19) compared to the median eGFR for age. Young adults with an eGFR in the lower percentiles were less likely to be referred to a specialist, have a repeat eGFR or albumin to creatinine ratio measure., Conclusions: eGFR values at the 10th percentile or lower based on a population-level distribution are associated with adverse clinical outcomes and in younger adults (18 to 39) this corresponds to a higher level of eGFR that may be underrecognized. Application of population-based eGFR percentiles may aid interpretation and improve identification of younger adults at risk., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Background: Patients with kidney failure treated with maintenance haemodialysis (HD) require appropriate small molecule clearance. Historically, a component of measuring 'dialysis adequacy' has been quantified using urea kinetic modelling that is dependent on the HD prescription. However, the impact of dialysate flow rate on urea clearance remains poorly described in vivo and its influence on other patient-important outcomes of adequacy is uncertain., Methods: We searched Embase, MEDLINE and the Cochrane Library from inception until April 2022 for randomized controlled trials and observational trials comparing a higher dialysate flow rate (800 ml/min) and lower dialysate flow rate (300 ml/min) with a standard dialysis flow rate (500 ml/min) in adults (age ≥18 years) treated with maintenance HD (>90 consecutive days). We conducted a random effects meta-analysis to estimate the pooled mean difference in dialysis adequacy as measured by Kt/V or urea reduction ratio (URR)., Results: A total of 3118 studies were identified. Of those, nine met eligibility criteria and four were included in the meta-analysis. A higher dialysate flow rate (800 ml/min) increased single-pool Kt/V by 0.08 [95% confidence interval (CI) 0.05-0.10, P  < .00001] and URR by 3.38 (95% CI 1.97-4.78, P  < .00001) compared with a dialysate flow rate of 500 ml/min. Clinically relevant outcomes including symptoms, cognition, physical function and mortality were lacking and studies were generally at a moderate risk of bias due to issues with randomization sequence generation, allocation concealment and blinding., Conclusion: A higher dialysate flow increased urea-based markers of dialysis adequacy. Additional high-quality research is needed to determine the clinical, economic and environmental impacts of higher dialysate flow rates., Competing Interests: P.K. is a consultant to Quanta Dialysis Technologies. C.B. has an ownership interest in Precision Advanced Digital Manufacturing. N.T. has equity in Quanta Dialysis Technologies and reports grants from Tricida, AstraZeneca, Janssen, Boehringer Ingelheim/Eli Lilly, Bayer, the Canadian Institutes for Health Research and the Kidney Foundation of Canada; personal fees from Tricida, AstraZeneca, Janssen, Boehringer Ingelheim/Eli Lilly, Bayer, Otsuka, Renibus, Roche, ClinPredict and Klinrisk; and other payments from ClinPredict, Klinrisk, Tricida and PulseData. ClinPredict and Klinrisk are engaged in efforts to develop and implement models for CKD progression in health systems. D.C. is funded by a KRESCENT New Investigator Award. Y.I., R.B., R.E., K.G. and R.W. report no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Background: Modern organ allocation systems are tasked with equitably maximizing the utility of transplanted organs. Increasing the use of deceased donor organs at risk of discard may be a cost-effective strategy to improve overall transplant benefit. We determined the survival implications and cost utility of increasing the use of marginal kidneys in an older adult Canadian population of patients with end-stage kidney disease., Methods: We constructed a cost-utility model with microsimulation from the perspective of the Canadian single-payer health system for incident transplant waitlisted patients aged 60 y and older. A kidney donor profile index score of ≥86 was considered a marginal kidney. Donor- and recipient-level characteristics encompassed in the kidney donor profile index and estimated posttransplant survival scores were used to derive survival posttransplant. Patients were followed up for 10 y from the date of waitlist initiation. Our analysis compared the routine use of marginal kidneys (marginal kidney scenario) with the current practice of limited use (status quo scenario)., Results: The 10-y mean cost and quality-adjusted life-years per patient in the marginal kidney scenario were estimated at $379 485.33 (SD: $156 872.49) and 4.77 (SD: 1.87). In the status quo scenario, the mean cost and quality-adjusted life-years per patient were $402 937.68 (SD: $168 508.85) and 4.37 (SD: 1.87); thus, the intervention was considered dominant. At 10 y, 62.8% and 57.0% of the respective cohorts in the marginal kidney and status quo scenarios remained alive., Conclusions: Increasing the use of marginal kidneys in patients with end-stage kidney disease aged 60 y and older may offer cost savings, improved quality of life, and greater patient survival in comparison with usual care., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Purpose of Review: Identifying patients with risk of developing progressive chronic kidney disease (CKD) early is an important step in improving kidney care. This review discusses four recently developed models, two which predict risk of new onset disease, and two which predict progression earlier in the course of disease., Recent Findings: Several models predicting CKD incidence and progression have been recently developed and externally validated. A connecting theme across these models is the use of data beyond estimated glomerular filtration rate, allowing for greater accuracy and personalization. Two models were developed with stratification by diabetes status, displaying excellent model fit with and without variables like use of diabetes medication and hemoglobin A1C. Another model was designed to be patient facing, not requiring the knowledge of any laboratory values for use. The final model was developed using lab data and machine learning. These models demonstrated high levels of discrimination and calibration in external validation, suggesting suitability for clinical use., Summary: Models that predict risk of CKD onset and progression have the potential to significantly reduce disease burden, financial cost, and environmental output from CKD through upstream disease prevention and slowed progression. These models should be implemented and evaluated prospectively in primary care settings., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)