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Introduction: Chronic kidney disease (CKD) can have a profound impact on patients' lives. However, multinational data on patients' lived experience with CKD are scarce., Methods: Individuals from the prospective cohort of DISCOVER CKD (NCT04034992), an observational cohort study, were recruited to participate in one-to-one telephone interviews to explore their lived experience with CKD. A target of 100 participant interviews was planned across four countries (Japan, Spain, the UK, and the USA). These qualitative interviews, lasting ∼60-90 min, were conducted in the local language by trained interviewers with specific experience in CKD, between January and June 2023. Transcribed interviews were translated into English for coding and analysis. Data were coded using qualitative research software., Results: Of the 105 participants interviewed, 103 were included in the final analysis. The average time since CKD diagnosis was 9.5 years, and at least half (50.5%) of participants had CKD stage 3A or 3B. CKD diagnosis was an emotional experience, driven by worry (n = 29/103; 28.2%) and shock (n = 26/103; 25.2%), and participants often reported feeling inadequately informed. Additional information was frequently sought, either online or via other healthcare providers. The proportion of participants reporting no impacts of CKD on their lives was highest in those with CKD stage 1 and 2 (64.3%). Conversely, every participant in the CKD stage 5 on dialysis group reported some impact of CKD on their lives. Across all participants, the most reported impacts were anxiety or depression (37.9%) or ability to sleep (37.9%). The frequency of the reported impacts appeared to increase with disease severity, with the highest rates observed in the dialysis group. In that group, the most frequently reported impact was on the ability to work (80.0%)., Conclusion: Findings from this multinational qualitative study suggest that patients may experience symptoms and signs of disease prior to diagnosis; however, these are often nonspecific and may not be directly associated with CKD. Once diagnosed, the burden of CKD can have a diverse, negative impact on various aspects of patients' lives. This highlights the need for early identification of at-risk individuals, and the importance of early CKD diagnosis and management with guideline-directed therapies to either prevent further deterioration of CKD or slow its progression, thus reducing symptom burden and improving quality of life., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Rationale & Objective: Recent evidence suggests people with nondialysis chronic kidney disease (ND-CKD) experience a substantial burden of symptoms, but informative large-scale studies have been scarce. We assessed the prevalence of symptoms and the association of overall symptom burden with quality of life in patients with moderate to severe CKD., Study Design: Cross-sectional study., Setting & Participants: 4,430 patients with ND-CKD stages 3-5 enrolled in the Chronic Kidney Disease Outcomes and Practice Patterns Study (CKDopps) in Brazil, France, and the United States between 2013 and 2021., Exposure: 13 individual patient-reported symptoms from the Kidney Disease Quality of Life Short Form (KDQOL-SF) questionnaire and an overall symptom burden score (low, intermediate, and high)., Outcome: Physical and mental component summary scores (PCS and MCS) of the KDQOL-SF., Analytical Approach: Adjusted prevalence ratios and generalized estimating equations., Results: Patients (mean age, 68 years; 40% women; mean baseline estimated glomerular filtration rate [eGFR], 30mL/min/1.73m 2 ) were very much to extremely bothered by numerous symptoms ("soreness in muscles," 23%; "washed out or drained," 21%; "cramps, shortness of breath, dry skin, diminished sex life, or numbness in hands or feet," 14%-17%). The adjusted prevalences of "cramps," "washed out or drained," "lack of appetite," "nausea/upset stomach," and "sex life" were greater with more severe CKD and in women (except for "sex life"). A high overall symptom burden was more common in women, in France, and in patients with severe albuminuria and various comorbidities, but not with lower eGFR. The PCS and MCS scores were 13.4 and 7.7 points lower, respectively, for high versus low overall symptom burden., Limitations: Generalizability limited to patients under nephrology care, residual confounding, and inaccurate Brazilian translation of some symptoms., Conclusions: The high symptom burden observed in this large cohort of ND-CKD patients across 3 diverse countries and its strong association with poorer health-related quality of life should inform clinical management of and clinical research in CKD., Plain-Language Summary: Little is known about symptoms in patients with non-dialysis-dependent chronic kidney disease (ND-CKD). In the Chronic Kidney Disease Outcomes and Practice Patterns Study, which enrolled 4,430 patients with CKD stages 3-5 in Brazil, France, and the United States, patients most often reported soreness in muscles, feeling washed out or drained, cramps, shortness of breath, dry skin, altered sex life, and numbness in hands or feet. Cramps, feeling washed out or drained, lack of appetite, and nausea were more often reported at lower levels of kidney function. The overall symptom burden was higher in women than men, in French than in Brazilian or US patients, and in those with severe albuminuria. The higher the symptom burden, the lower were the physical and mental health quality of life scores. The high symptom burden observed in this large cohort of ND-CKD patients across 3 diverse countries and its strong association with poorer health-related quality of life should inform clinical management of and clinical research in CKD., (Copyright © 2024 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Introduction: This analysis examined the baseline characteristics and clinical outcomes of patients with chronic kidney disease (CKD) and rapid or non-rapid estimated glomerular filtration rate (eGFR) decline, using retrospective data from DISCOVER CKD (ClinicalTrials.gov, NCT04034992)., Methods: Data (2008-2020) were extracted from UK Clinical Practice Research Datalink, US TriNetX, US Limited Claims and Electronic Health Record Dataset, and Japan Medical Data Vision. Patients with CKD (two consecutive eGFR measures < 75 mL/min/1.73 m 2 recorded 90-730 days apart) were included. Rapid eGFR decline was defined as an annual decline of > 4 mL/min/1.73 m 2 at 2 years post-index; non-rapid eGFR decline was defined as an annual decline of ≤ 4 mL/min/1.73 m 2 . Clinical outcomes assessed included all-cause mortality, kidney outcomes (composite risk of kidney failure [progression to CKD stage 5] or > 50% eGFR decline, and kidney failure alone), cardiovascular events-including major adverse cardiovascular events (MACE; non-fatal myocardial infarction/stroke and cardiovascular death)-and all-cause hospitalization., Results: Across databases, rapid eGFR decline occurred in 13.7% of 804,237 eligible patients. Mean annual eGFR decline ranged between - 6.21 and - 6.86 mL/min/1.73 m 2 in patients with rapid eGFR decline versus between - 0.11 and - 0.77 mL/min/1.73 m 2 in patients with non-rapid eGFR decline. Rapid eGFR decline was associated with increased comorbidity burden and medication prescriptions. Across databases, the composite risk of kidney failure or > 50% decline in eGFR was significantly greater in patients with rapid versus non-rapid eGFR decline (P < 0.01); all-cause mortality, kidney failure alone, MACE, and all-cause hospitalization each significantly increased in two databases (P < 0.01-0.05)., Conclusion: Understanding patient factors associated with rapid eGFR decline in patients with CKD may help identify individuals who would benefit from proactive management to minimize the risk of adverse outcomes., Trial Registration: ClinicalTrials.gov identifier, NCT04034992., (© 2024. The Author(s).)

Rationale & Objective: Estimates of the incidence of hyperkalemia in patients with chronic kidney disease (CKD) vary widely. Our objective was to estimate hyperkalemia incidence in patients with CKD from routine clinical care, including by level of kidney damage or function and among important patient subgroups., Study Design: Retrospective cohort study., Setting & Participants: 1,771,900 patients with stage 1-4 CKD identified from the US Optum De-Identified electronic health records database., Exposures or Predictors: Impaired kidney damage or function level at baseline based on urinary albumin-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR), respectively, and selected patient subgroups., Outcomes: Hyperkalemia: 2 elevated serum potassium values (≥5.5 mmol/L) from the inpatient setting (2-24 hours apart) or outpatient setting (maximum 7 days apart), or 1 elevated serum potassium value plus pharmacotherapy initiation or hyperkalemia diagnosis (maximum 3 days apart)., Analytical Approach: Incidence rates of hyperkalemia were calculated. Estimates were stratified by UACR and eGFR level at baseline and patient subgroups., Results: Over a mean follow-up of 3.9 years, the incidence of hyperkalemia was 3.37 events/100 person-years (95% confidence intervals, 3.36-3.38). Higher incidence rates were observed with increased UACR and lower eGFR. Highest rates were observed with UACR ≥3,500 (up to 19.1/100 person-years) irrespective of decreased eGFR level. High rates also occurred in patients with type 2 diabetes mellitus (T2DM, 5.43/100 person-years), heart failure (8.7/100 person-years), and those prescribed steroidal mineralocorticoid receptor antagonists (sMRAs, 7.7/100 person-years)., Limitations: Potential misclassification of variables from possible medical coding errors; potential data incompleteness issues if patients received care at institutions not included in Optum., Conclusions: Hyperkalemia is a frequent occurrence in CKD, particularly in patients with T2DM, heart failure, or prescribed sMRAs, indicating the need for regular serum potassium and UACR monitoring in this patient population to help mitigate risk., (© 2024 The Authors.)

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.)

Rationale & Objective: Sex differences in cardiovascular disease (CVD) are well established, but whether chronic kidney disease (CKD) modifies these risk differences and whether they differ between atheromatous CVD (ACVD) and nonatheromatous CVD (NACVD) is unknown. Assessing this interaction was the principal goal of this study., Study Design: Prospective cohort study., Setting & Participants: Adults enrolled in the CKD-REIN (CKD-Renal Epidemiology and Information Network) cohort, a nationally representative sample of 40 nephrology clinics in France, from 2013 to 2020., Exposure: Sex., Outcomes: Fatal and nonfatal composite ACVD events (ischemic coronary, cerebral, and peripheral artery disease) and composite NACVD events (heart failure, hemorrhagic stroke, and arrhythmias)., Analytical Approach: Multivariable cause-specific Cox proportional hazards models., Results: 1,044 women and 1,976 men with moderate to severe CKD (median age, 67 vs 69y; mean estimated glomerular filtration rate [eGFR], 32±12 vs 33±12mL/min/1.73m 2 ) were studied. During a median follow-up of 5.0 (IQR, 4.8-5.2) years, the ACVD rate (per 100 patient-years) was significantly lower in women than in men, at 2.1 (95% CI, 1.6-2.5) versus 3.6 (3.2-4.0; P<0.01), whereas the NACVD rate was not, at 5.7 (5.0-6.5) versus 6.4 (5.8-7.0; P=0.55). NACVD had a steeper relationship with eGFR than did ACVD. There was an interaction (P<0.01) between sex and baseline eGFR and the ACVD hazard: the adjusted HR for women versus men was 0.42 (0.25-0.71) at 45mL/min/1.73m 2 and gradually attenuated at lower levels of eGFR, reaching 1.00 (0.62-1.63) at 16mL/min/1.73m 2 . In contrast, the NACVD hazard did not differ between sexes across the eGFR range studied., Limitations: Cardiovascular biomarkers and sex hormones were not assessed., Conclusions: This study shows how the lower risk of ACVD among women versus men attenuates fully with kidney disease progression. The equal risk of NACVD between sexes across CKD stages and its steeper association with eGFR suggest an important contribution of CKD to the development of this CVD type., Plain-Language Summary: Sex differences in the risks of atheromatous and nonatheromatous cardiovascular disease (CVD) are well established in the general population. If or how chronic kidney disease (CKD) might modify these risks is unknown. In this large cohort of 3,010 patients with CKD, women had a lower risk than men of atheromatous CVDs such as coronary artery disease or stroke when they were at an early stage of CKD. This advantage, partly due to women's better cardiovascular risk profile, tended to attenuate as CKD progressed to kidney failure. In contrast, the risk of nonatheromatous CVDs such as heart failure for women with CKD appeared similar to that of men with CKD at all kidney function levels., (Copyright © 2024 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: The use of diuretics in patients on haemodialysis (HD) is thought to maintain diuresis. However, this assumption and the optimal dose are based on little scientific evidence, and associations with clinical outcomes are unclear., Methods: We reported international variations in diuretic use and loop diuretic dose across 27 759 HD patients with dialysis vintage <1 year in the Dialysis Outcomes and Practice Patterns Study phases 2-5 (2002-2015), a prospective cohort study. Doses of torsemide (4:1) and bumetanide (80:1) were converted to oral furosemide-equivalent doses. Adjusted Cox, logistic and linear regressions were used to investigate the association of diuretic use and dose with outcomes., Results: Diuretic utilization varied widely by country at vintage <3 months, ranging from >80% in Germany and Sweden to <35% in the USA, at a median dose ranging from 400-500 mg/day in Germany and Sweden to <100 mg/day in Japan and the USA. Neither diuretic use nor higher doses were associated with a lower risk of all-cause mortality, a higher risk of hospitalization for fracture or elevated parathyroid hormone levels, but the prescription of higher doses (>200 mg/day) was associated with a higher risk of all-cause hospitalization., Conclusions: Substantial international differences exist in diuretic prescriptions, with use and doses much higher in some European countries than the USA. The prescription and higher doses of loop diuretics was not associated with improved outcomes., Competing Interests: D.W., A.K. and B.B. are employees of Arbor Research Collaborative for Health, which administers the DOPPS. R.P.-F. has received consulting fees from Bayer, Boehringer Ingelheim, AstraZeneca, GSK, Akebia, Fibrogen and Fresenius Medical Care and honoraria from Bayer, Boehringer Ingelheim, AstraZeneca, GSK, Akebia, Fibrogen and Fresenius Medical Care and has participated on a data and safety monitoring board for Bayer, Boehringer Ingelheim, AstraZeneca, GSK, Akebia and Fresenius Medical Care. N.T. has received an Société Francophone de Néphrologie Dialyse et Transplantation research grant and Agence Nationale de la Recherche Young Researcher grant, both to their institution; is on the Data Safety Monitoring Committee of the Programme Hospitalier de Recherche Clinique; and is a board member of the French Society of Nephrology, French Society of Physiology and European Society of Clinical Investigation. E.S. reports a grant or contract from Bayer; consulting fees from AstraZeneca; payment or honoraria from the National Kidney Foundation for American Journal of Kidney Diseases editorial board participation; and is on the German Society of Nephrology executive board. S.H.J. has no conflicts of interest to declare. A.V. received payment or honoraria from Baxter and Braun. K.N. received support for the present manuscript from Kyowa Kirin, Kissei, Torii, Bayer, Astellas and Asahi Kasei. P.A.U.T. is member of the CKJ editorial board and has received consulting fees from AstraZeneca, Amgen, Astellas and Leo Pharma; payment or honoraria from Baxter, Astellas and Vifor Pharma and support for attending meetings and/or travel from Hemotech, GSK, and AstraZeneca., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Background: Chronic kidney disease (CKD) is a global health problem with rising prevalence, morbidity, mortality, and associated costs. Early identification and risk stratification are key to preventing progression to kidney failure. However, there is a paucity of data on practice patterns of kidney function assessment to guide the development of improvement strategies, particularly in lower-income countries., Methods: A retrospective observational analysis was conducted in a nationwide laboratory database in Brazil. We included all adult patients with at least one serum creatinine assessment between June 2018 and May 2021. Our primary objective was to determine the proportion of patients with estimated glomerular filtration rate (eGFR) evaluations accompanied by predicted levels of urinary albumin-to-creatinine ratio (pACR) assessments within 12 months., Results: Out of 4,5323,332 serum creatinine measurements, 42% lacked pACR measurements within 12 months. Approximately 10.8% of tests suggested CKD, mostly at stage 3a. The proportion of serum creatinine exams paired with pACR assessment varied according to the CKD stage. Internal Medicine, Cardiology, and Obstetrics/Gynecology were the specialties requesting most of the creatinine tests. Nephrology contributed with only 1.1% of serum creatinine requests for testing., Conclusion: Our findings reveal that a significant proportion of individuals with a creatinine test lack an accompanying urinary albuminuria measurement in Brazil, contrary to the recommendations of the international guidelines. Non-Nephrologists perform most kidney function evaluations, even among patients with presumable advanced CKD. This highlights the urge to incorporate in clinical practice the early detection of CKD and to encourage more collaborative multidisciplinary care to improve CKD management., (© 2024. The Author(s).)

Background: Varying peritoneal dialysis (PD)-related clinical outcomes have been reported in different countries. As a participant of the Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS), this study investigated the characteristics of Korean PD patients, PD facilities and the incidence rates of clinical outcomes including mortality and PD-related outcomes., Methods: From July 2019 to December 2021, a total of 766 Korean PD patients were included for analysis. Poisson regression analysis was used to explore the incidence rates of various clinical events including mortality, modality transfer, exit site or catheter tunnel infection and peritonitis., Results: Among the 766 patients (median age 55.5 years, males 59.5%), 276 were incident and 490 were prevalent PD patients. The incidence rates of events were as follows: all-cause mortality (0.048), modality transfer (0.051), exit site or catheter tunnel infection (0.054) and peritonitis (0.136) events per person year. The most common causative organism for exit site or tunnel infection was staphylococcus species (47%) and that for peritonitis was streptococcus (28%) followed by staphylococcus (27%) species., Conclusions: Up to now, PDOPPS Korea has recruited 766 Korean PD patients and started documentation of major PD-related outcomes which occurred during the follow-up period. The overall incidence rates of clinical outcomes in Korean PD patients were relatively favourable. There was no statistically significant difference in the incidence rates of clinical outcomes according to both facility and patient factors., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Competing Interests: D.J. has previously received consultancy fees, research grants, speaker's honoraria, and travel sponsorships from Baxter Healthcare and Fresenius Medical Care, consultancy fees from AstraZeneca and AWAK, and travel sponsorships from Amgen. He is supported by an Australian National Health and Medical Research Council Leadership Investigator Grant. J.P. has received speaking honoraria from Astra Zeneca, Baxter Healthcare, DaVita Healthcare Partners, Fresenius Medical Care, Dialysis Clinics Incorporated, Satellite Healthcare, and has served as a consultant for Baxter Healthcare, DaVita Healthcare Partners, Fresenius Medical Care, and LiberDi. T.K. has received consultancy fees from VISTERRA as a country investigator and current recipient of the National Research Council of Thailand and received speaking honoraria from Astra Zeneca and Baxter Healthcare. The remaining authors have declared no commercial or financial relationships that could be perceived as potential conflicts of interest associated with this article.

Background: Hypertension is a leading cause of kidney failure, affects most dialysis patients and associates with adverse outcomes. Hypertension can be difficult to control with dialysis modalities having differential effects on sodium and water removal. There are two main types of peritoneal dialysis (PD), automated peritoneal dialysis (APD) and continuous ambulatory peritoneal dialysis (CAPD). It is unknown whether one is superior to the other in controlling blood pressure (BP). Therefore, the aim of our study was to analyse the impact of switching between these two PD modalities on BP levels in a nationally representative cohort., Methods: This was a cohort study of patients on PD from 122 dialysis centres in Brazil (BRAZPD II study). Clinical and laboratory data were collected monthly throughout the study duration. We selected all patients who remained on PD at least 6 months and 3 months on each modality at minimum. We compared the changes in mean systolic/diastolic blood pressures (SBP/DBP) before and after modality transition using a multilevel mixed-model where patients were at first level and their clinics at the second level., Results: We analysed data of 848 patients (814 starting on CAPD and 34 starting on APD). The SBP decreased by 4 (SD 22) mmHg when transitioning from CAPD to APD ( p < 0.001) and increased by 4 (SD 21) mmHg when transitioning from APD to CAPD ( p = 0.38); consistent findings were seen for DBP. There was no significant change in the number of antihypertensive drugs prescribed before and after transition., Conclusions: Transition between PD modalities seems to directly impact on BP levels. Further studies are needed to confirm if switching to APD could be an effective treatment for uncontrolled hypertension among CAPD patients., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: MD, PB and MG have no conflict to declare. BF is a student at Pontifícia Universidade Católica do Paraná. JWL and VR are employed by Fresenius Medical Care. TPM and RPF are employed by Pontifícia Universidade Católica do Paraná and are recipients of scholarships from the Brazilian Council for Research (CNPq), received consulting fees from Astra Zeneca and Baxter Healthcare and speaker honoraria from Astra Zeneca, Lilly-Boehringer, Baxter and Takeda. RPF is employed by Arbor Research Collaborative for Health and received research grants, consulting fees and honoraria from Astra Zeneca, Novo Nordisc, Akebia and Fresenius Medical Care.

Online hemodiafiltration (HDF) is a rapidly growing dialysis modality worldwide. In Brazil, the number of patients with private health insurance undergoing HDF has exceeded the number of patients on peritoneal dialysis. The achievement of a high convection volume was associated with better clinical imprand patient - reported outcomes confirming the benefits of HDF. The HDFit trial provided relevant practical information on the implementation of online HDF in dialysis centers in Brazil. This article aims to disseminate technical information to improve the quality and safety of this new dialysis modality.

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.)

Background: The trajectories of haemoglobin in patients with chronic kidney disease (CKD) have been poorly described. In such patients, we aimed to identify typical haemoglobin trajectory profiles and estimate their risks of major adverse cardiovascular events (MACE)., Methods: We used 5-year longitudinal data from the CKD-REIN cohort patients with moderate to severe CKD enrolled from 40 nationally representative nephrology clinics in France. A joint latent class model was used to estimate, in different classes of haemoglobin trajectory, the competing risks of (i) MACE + defined as the first event among cardiovascular death, non-fatal myocardial infarction, stroke or hospitalization for acute heart failure, (ii) initiation of kidney replacement therapy (KRT) and (iii) non-cardiovascular death., Results: During the follow-up, we gathered 33 874 haemoglobin measurements from 3011 subjects (median, 10 per patient). We identified five distinct haemoglobin trajectory profiles. The predominant profile (n = 1885, 62.6%) showed an overall stable trajectory and low risks of events. The four other profiles had nonlinear declining trajectories: early strong decline (n = 257, 8.5%), late strong decline (n = 75, 2.5%), early moderate decline (n = 356, 11.8%) and late moderate decline (n = 438, 14.6%). The four profiles had different risks of MACE, while the risks of KRT and non-cardiovascular death consistently increased from the haemoglobin decline., Conclusion: In this study, we observed that two-thirds of patients had a stable haemoglobin trajectory and low risks of adverse events. The other third had a nonlinear trajectory declining at different rates, with increased risks of events. Better attention should be paid to dynamic changes of haemoglobin in CKD., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

Introduction: Inflammation is a significant contributor to cardiorenal morbidity and mortality in diabetic kidney disease (DKD). The pathophysiological mechanisms linking systemic, subacute inflammation and local, kidney injury-initiated immune maladaptation is partially understood., Methods: Here, we explored the expression of proinflammatory cytokines in patients with DKD; investigated mouse models of type 1 and type 2 diabetes (T2D); evaluated glomerular signaling in vitro ; performed post hoc analyses of systemic and urinary markers of inflammation; and initiated a phase 2b clinical study (FRONTIER-1; NCT04170543)., Results: Transcriptomic profiling of kidney biopsies from patients with DKD revealed significant glomerular upregulation of interleukin-33 (IL-33). Inhibition of IL-33 signaling reduced glomerular damage and albuminuria in the uninephrectomized db/db mouse model (T2D/DKD). On a cellular level, inhibiting IL-33 improved glomerular endothelial health by decreasing cellular inflammation and reducing release of proinflammatory cytokines. Therefore, FRONTIER-1 was designed to test the safety and efficacy of the IL-33-targeted monoclonal antibody tozorakimab in patients with DKD. So far, 578 patients are enrolled in FRONTIER-1. The baseline inflammation status of participants ( N > 146) was assessed in blood and urine. Comparison to independent reference cohorts ( N > 200) validated the distribution of urinary tumor necrosis factor receptor 1 (TNFR1) and C-C motif chemokine ligand 2 (CCL2). Treatment with dapagliflozin for 6 weeks did not alter these biomarkers significantly., Conclusion: We show that blocking the IL-33 pathway may mitigate glomerular endothelial inflammation in DKD. The findings from the FRONTIER-1 study will provide valuable insights into the therapeutic potential of IL-33 inhibition in DKD., (© 2024 International Society of Nephrology. Published by Elsevier Inc.)

Objectives: Peritoneal dialysis (PD) allows patients increased autonomy and flexibility; however, both infectious and non-infectious complications may lead to technique failure, which shortens treatment longevity. Maintaining patients on PD remains a major challenge for nephrologists. This study aims to describe nephrologists' perspectives on technique survival in PD., Design: Qualitative semistructured interview study. Transcripts were thematically analysed., Setting and Participants: 30 nephrologists across 11 countries including Australia, the USA, the UK, Hong Kong, Canada, Singapore, Japan, New Zealand, Thailand, Colombia and Uruguay were interviewed from April 2017 to November 2019., Results: We identified four themes: defining patient suitability (confidence in capacity for self-management, ensuring clinical stability and expected resilience), building endurance (facilitating access to practical support, improving mental well-being, optimising quality of care and training to reduce risk of complications), establishing rapport through effective communications (managing expectations to enhance trust, individualising care and harnessing a multidisciplinary approach) and confronting fear and acknowledging barriers to haemodialysis (preventing crash landing to haemodialysis, facing concerns of losing independence and positive framing of haemodialysis)., Conclusion: Nephrologists reported that technique survival in PD is influenced by patients' medical circumstances, psychological motivation and positively influenced by the education and support provided by treating clinicians and families. Strategies to enhance patients' knowledge on PD and communication with patients about technique survival in PD are needed to build trust, set patient expectations of treatment and improve the process of transition off PD., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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.)

Aims: To describe treatment pathways for key glucose-lowering therapies in individuals with chronic kidney disease (CKD) and type 2 diabetes (T2D) using retrospective data from DISCOVER CKD (NCT04034992)., Methods: Data were extracted from the UK Clinical Practice Research Datalink (CPRD) linked to Hospital Episode Statistics data (2008-2020) and the US integrated Limited Claims and Electronic Health Records Database (LCED; 2012-2019). Eligible individuals were aged ≥18 years with CKD, identified by two consecutive estimated glomerular filtration rate (eGFR) measures (15-<75 mL/min/1.73 m 2 ; 90-730 days apart; index date was the second measurement) and T2D. Chronological treatment pathways for glucose-lowering therapies prescribed on or after CKD index to end of follow-up were computed. Median time and proportion of overall follow-up time on treatment were described for each therapy by database and by eGFR and urinary albumin-to-creatinine ratio (UACR) categories., Results: Of 36,951 and 4339 eligible individuals in the CPRD and LCED, respectively, median baseline eGFR was 67.8 and 64.9 mL/min/1.73 m 2 ; 64.2 and 63.9% received metformin prior to index; and median (interquartile range) time on metformin during follow-up was 917 (390-1671) and 454 (192-850) days (accounting for ~75% of follow-up time in both databases). The frequency of combination treatment increased over time. There were trends towards decreased metformin prescriptions with decreasing eGFR and increasing UACR within each eGFR category., Conclusions: Individuals with CKD and T2D had many combinations of therapies and substantial follow-up time on therapy. These results highlight opportunities for improved CKD management., (© 2023 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Rationale & Objective: Itching is a frequent symptom experienced by people with chronic kidney disease (CKD). We investigated the associations of CKD-associated pruritus (CKD-aP) with clinical outcomes., Study Design: This was a longitudinal cohort study., Setting & Participants: Patients from Brazil, France, and the United States enrolled in the Chronic Kidney Disease Outcomes and Practice Patterns Study (CKDopps) from 2013 to 2021, an international prospective cohort study of adults with nondialysis dependent CKD, and an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m 2 were included., Exposure: CKD-aP was self-reported by response to the question: "During the past 4 weeks, to what extent were you bothered by itchy skin?", Outcomes: The outcomes were as follows: CKD progression, kidney replacement therapy (KRT) initiation, mortality, hospitalization, cardiovascular events, infection events., Analytical Approach: Associations with time-to-event outcomes were investigated using Cox proportional hazards models adjusted for potential confounders., Results: There were 4,410 patients from 91 clinics with a median age of 69 years and a median eGFR at patient questionnaire completion of 29 (21-38) mL/min/1.73 m 2 . The proportion of patients not at all, somewhat, moderately, very much, and extremely bothered by itchy skin was 49%, 27%, 13%, 7%, and 3%, respectively. Patients with more advanced stages of CKD, older age, and greater comorbidities reported to be more likely bothered by itchy skin. Among patients at least moderately bothered, 23% were prescribed at least 1 pharmacotherapy (35% in the United States, 19% in France, 4% in Brazil), including antihistamine (10%), gabapentin (6%), topical corticosteroids (4%), pregabalin (3%), or sedating antihistamine (3%). The HR (95% CI) for patients extremely (vs not at all) bothered was 1.74 (1.11-2.73) for all-cause mortality, 1.56 (1.11-2.18) for all-cause hospitalization, and 1.84 (1.22-2.75) for cardiovascular events. As CKD-aP severity increased, patients also had higher rates of infection events ( P  = 0.04); CKD-aP severity was not associated with KRT initiation ( P  = 0.20) or CKD progression ( P  = 0.87)., Limitations: The limitations were 25% nonresponse rate, recall bias, and residual confounding factors., Conclusions: These results demonstrate a strong association between severe itch and clinical outcomes, providing the nephrology community new insights into the possible adverse consequences of CKD-aP in individuals with nondialysis CKD, and warrant further exploration., Plain-Language Summary: Chronic kidney disease-associated pruritus (CKD-aP) is a common disturbing symptom of chronic kidney disease (CKD). This article analyzes longitudinal data from the Chronic Kidney Disease Outcomes and Practice Patterns Study (CKDopps) to describe prevalence of CKD-aP in 4,410 individuals with nondialysis CKD, and its association with clinical outcomes. We found that 51% of the surveyed population were bothered by pruritus. CKD-aP was more prevalent in those with more advanced stages of CKD, older age, and with more comorbid conditions. Compared to those not at all bothered by pruritus, those who were extremely bothered had a higher risk of all-cause mortality, hospitalizations, and cardiovascular events. Severity of CKD-aP was not associated with CKD progression or initiation of kidney replacement therapy., (© 2023 The Authors.)

Chronic kidney disease (CKD) affects over 850 million people globally, and the need to prevent its development and progression is urgent. During the past decade, new perspectives have arisen related to the quality and precision of care for CKD, owing to the development of new tools and interventions for CKD diagnosis and management. New biomarkers, imaging methods, artificial intelligence techniques, and approaches to organizing and delivering healthcare may help clinicians recognize CKD, determine its etiology, assess the dominant mechanisms at given time points, and identify patients at high risk for progression or related events. As opportunities to apply the concepts of precision medicine for CKD identification and management continue to be developed, an ongoing discussion of the potential implications for care delivery is required. The 2022 KDIGO Controversies Conference on Improving CKD Quality of Care: Trends and Perspectives examined and discussed best practices for improving the precision of CKD diagnosis and prognosis, managing the complications of CKD, enhancing the safety of care, and maximizing patient quality of life. Existing tools and interventions currently available for the diagnosis and treatment of CKD were identified, with discussion of current barriers to their implementation and strategies for improving the quality of care delivered for CKD. Key knowledge gaps and areas for research were also identified., (Copyright © 2023 KDIGO: Kidney Disease Improving Global Outcomes. Published by Elsevier Inc. All rights reserved.)

Rationale & Objective: The Kidney Failure Risk Equation (KFRE) predicts the 2-year risk of kidney failure for patients with chronic kidney disease (CKD). Translating KFRE-predicted risk or estimated glomerular filtration rate (eGFR) into time to kidney failure could inform decision making for patients approaching kidney failure., Study Design: Retrospective cohort., Setting & Participants: CKD Outcomes and Practice Patterns Study (CKDOPPS) cohort of patients with an eGFR<60mL/min/1.73m 2 from 34 US nephrology practices (2013-2021)., Exposure: 2-year KFRE risk or eGFR., Outcome: Kidney failure defined as initiation of dialysis or kidney transplantation., Analytical Approach: Accelerated failure time (Weibull) models used to estimate the median, 25th, and 75th percentile times to kidney failure starting from KFRE values of 20%, 40%, and 50%, and from eGFR values of 20, 15, and 10mL/min/1.73m 2 . We examined variability in time to kidney failure by age, sex, race, diabetes status, albuminuria, and blood pressure., Results: Overall, 1,641 participants were included (mean age 69±13 years; median eGFR of 28mL/min/1.73m 2 [IQR 20-37mL/min/1.73 m 2 ]). Over a median follow-up period of 19 months (IQR, 12-30 months), 268 participants developed kidney failure, and 180 died before reaching kidney failure. The median estimated time to kidney failure was widely variable across patient characteristics from an eGFR of 20mL/min/1.73m 2 and was shorter for younger age, male sex, Black (versus non-Black), diabetes (vs no diabetes), higher albuminuria, and higher blood pressure. Estimated times to kidney failure were comparably less variable across these characteristics for KFRE thresholds and eGFR of 15 or 10mL/min/1.73m 2 ., Limitations: Inability to account for competing risks when estimating time to kidney failure., Conclusions: Among those with eGFR<15mL/min/1.73m 2 or KFRE risk>40%), both KFRE risk and eGFR showed similar relationships with time to kidney failure. Our results demonstrate that estimating time to kidney failure in advanced CKD can inform clinical decisions and patient counseling on prognosis, regardless of whether estimates are based on eGFR or the KFRE., Plain-Language Summary: Clinicians often talk to patients with advanced chronic kidney disease about the level of kidney function expressed as the estimated glomerular filtration rate (eGFR) and about the risk of developing kidney failure, which can be estimated using the Kidney Failure Risk Equation (KFRE). In a cohort of patients with advanced chronic kidney disease, we examined how eGFR and KFRE risk predictions corresponded to the time patients had until reaching kidney failure. Among those with eGFR<15mL/min/1.73m 2 or KFRE risk > 40%), both KFRE risk and eGFR showed similar relationships with time to kidney failure. Estimating time to kidney failure in advanced CKD using either eGFR or KFRE can inform clinical decisions and patient counseling on prognosis., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Rationale & Objective: Conservative kidney management (CKM) is a viable treatment option for many patients with chronic kidney disease. However, CKM practices and resources in the United States are not well described. We undertook this study to gain a better understanding of factors influencing uptake of CKM by describing: (1) characteristics of patients who choose CKM, (2) provider practice patterns relevant to CKM, and (3) CKM resources available to providers., Study Design: Cross-sectional study., Setting & Participants: This study is a cross-sectional analysis of data from US nephrology clinics enrolled in the chronic kidney disease Outcomes and Practice Patterns Study (CKDopps) collected between 2014 and 2020. Data for this study includes chart-abstracted characteristics of patients with an estimated glomerular filtration rate ≤30mL/min/1.73m 2 (n=1018) and available information on whether a decision had been made to pursue CKM at the time of kidney failure, patient (n=407) reports of discussions about forgoing dialysis, and provider (n=26) responses about CKM delivery and available resources in their health systems., Analytical Approach: Descriptive statistics were used to report patient demographics, clinical information, provider demographics, and clinic characteristics., Results: Among data from 1018 patients, 68 (7%) were recorded as planning for CKM. These patients were older, had more comorbidities, and were more likely to require assistance with transfers. Of the 407 patient surveys, 18% reported a conversation about forgoing dialysis with their nephrologist. A majority of providers felt comfortable discussing CKM; however, no clinics had a dedicated clinic or protocol for CKM., Limitations: Inconsistent survey terminology and unlinked patient and provider responses., Conclusions: Few patients reported discussion of forgoing dialysis with their providers and even fewer anticipated a choice of CKM on reaching kidney failure. Most providers were comfortable discussing CKM, but practiced in clinics that lacked dedicated resources. Further research is needed to improve the implementation of a CKM pathway., Plain-Language Summary: For older comorbid adults with kidney failure, conservative kidney management (CKM) can be an appropriate treatment choice. CKM is a holistic approach with treatment goals of maximizing quality of life and preventing progression of chronic kidney disease (CKD) without initiation of dialysis. We investigated US CKM practices and found that among 1018 people with CKD, only 7% were planning for CKM. Of 407 surveyed patients, 18% reported a conversation with their provider about forgoing dialysis. In contrast, most providers felt comfortable discussing CKM; however, none reported working in an environment with a dedicated CKM clinic or protocol. Our data show the need for further CKM education in the United States as well as dedicated resources for its delivery., (© 2023 The Authors.)

Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Sustained low-efficiency dialysis is a hybrid form of kidney replacement therapy that has gained increasing popularity as an alternative to continuous forms of kidney replacement therapy in intensive care unit settings. During the COVID-19 pandemic, the shortage of continuous kidney replacement therapy equipment led to increasing usage of sustained low-efficiency dialysis as an alternative treatment for acute kidney injury. Sustained low-efficiency dialysis is an efficient method for treating hemodynamically unstable patients and is quite widely available, making it especially useful in resource-limited settings. In this review, we aim to discuss the various attributes of sustained low-efficiency dialysis and how it is comparable to continuous kidney replacement therapy in efficacy, in terms of solute kinetics and urea clearance, and the various formulae used to compare intermittent and continuous forms of kidney replacement therapy, along with hemodynamic stability. During the COVID-19 pandemic, there was increased clotting of continuous kidney replacement therapy circuits, which led to increased use of sustained low-efficiency dialysis alone or together with extra corporeal membrane oxygenation circuits. Although sustained low-efficiency dialysis can be delivered with continuous kidney replacement therapy machines, most centers use standard hemodialysis machines or batch dialysis systems. Even though antibiotic dosing differs between continuous kidney replacement therapy and sustained low-efficiency dialysis, reports of patient survival and renal recovery are similar for continuous kidney replacement therapy and sustained low-efficiency dialysis. Health care studies indicate that sustained low-efficiency dialysis has emerged as a cost-effective alternative to continuous kidney replacement therapy. Although there is considerable data to support sustained low-efficiency dialysis treatments for critically ill adult patients with acute kidney injury, there are fewer pediatric data, even so, currently available studies support the use of sustained low-efficiency dialysis for pediatric patients, particularly in resource-limited settings., (© 2023. The Author(s) under exclusive licence to Italian Society of Nephrology.)

Dialysis treatment has improved the survival of patients with kidney failure. However, the hospitalization and mortality rates remain alarmingly high, primarily due to incomplete uremic toxin elimination. High-volume hemodiafiltration (HDF) has emerged as a promising approach that significantly improves patient outcomes by effectively eliminating medium and large uremic toxins, which explains its increasing adoption, particularly in Europe and Japan. Interest in this therapy has grown following the findings of the recently published CONVINCE study, as well as the need to understand the mechanisms behind the benefits. This comprehensive review aims to enhance the scientific understanding by explaining the underlying physiological mechanisms that contribute to the positive effects of HDF in terms of short-term benefits, like hemodynamic tolerance and cardiovascular disease. Additionally, it explores the rationale behind the medium-term clinical benefits, including phosphorus removal, the modulation of inflammation and oxidative stress, anemia management, immune response modulation, nutritional effects, the mitigation of bone disorders, neuropathy relief, and amyloidosis reduction. This review also analyzes the impact of HDF on patient-reported outcomes and mortality. Considering the importance of applying personalized uremic toxin removal strategies tailored to the unique needs of each patient, high-volume HDF appears to be the most effective treatment to date for patients with renal failure. This justifies the need to prioritize its application in clinical practice, initially focusing on the groups with the greatest potential benefits and subsequently extending its use to a larger number of patients.

Introduction: Despite recognized geographic and sex-based differences in hemoglobin in the general population, these factors are typically ignored in patients with chronic kidney disease (CKD) in whom a single therapeutic range for hemoglobin is recommended. We sought to compare the distribution of hemoglobin across international nondialysis CKD populations and evaluate predictors of hemoglobin., Methods: In this cross-sectional study, hemoglobin distribution was evaluated in each cohort overall and stratified by sex and estimated glomerular filtration rate (eGFR). Relationships between candidate predictors and hemoglobin were assessed from linear regression models in each cohort. Estimates were subsequently pooled in a random effects model., Results: A total of 58,613 participants from 21 adult cohorts (median eGFR range of 17-49 ml/min) and 3 pediatric cohorts (median eGFR range of 26-45 ml/min) were included with broad geographic representation. Hemoglobin values varied substantially among the cohorts, overall and within eGFR categories, with particularly low mean hemoglobin observed in women from Asian and African cohorts. Across the eGFR range, women had a lower hemoglobin compared to men, even at an eGFR of 15 ml/min (mean difference 5.3 g/l, 95% confidence interval [CI] 3.7-6.9). Lower eGFR, female sex, older age, lower body mass index, and diabetic kidney disease were all independent predictors of a lower hemoglobin value; however, this only explained a minority of variance (R 2 7%-44% across cohorts)., Conclusion: There are substantial regional differences in hemoglobin distribution among individuals with CKD, and the majority of variance is unexplained by demographics, eGFR, or comorbidities. These findings call for a renewed interest in improving our understanding of hemoglobin determinants in specific CKD populations., (© 2023 Published by Elsevier, Inc., on behalf of the International Society of Nephrology.)

Background: Patient-reported outcome measures (PROMs) are widely recognized as valuable predictors of clinical outcomes in peritoneal dialysis (PD). Our study aimed to explore the connections between patient-reported constipation and clinical outcomes., Methods: We assessed constipation in patients across 22 facilities participating in the Thailand Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS) from 2014 to 2017. Constipation diagnosis utilized objective assessment tools such as the Bristol stool form scale (BSFS) and a self-reported questionnaire known as the constipation severity score (CSS). The BSFS is a 7-level scale that visually inspects feces based on texture and morphology, while the CSS measures constipation duration and severity using a 5-point Likert scale for various factors. We employed Cox proportional hazards model regression to determine the associations between constipation and clinical outcomes, including mortality, hemodialysis (HD) transfer and peritonitis., Results: Among 975 randomly selected PD patients from 22 facilities, 845 provided written informed consent, and 729 completed CSS questionnaire. Constipation was prevalent in the PD population (13%), particularly among older patients, those who were caregiver dependent, had diabetes and poorer nutritional status (indicated by lower time-averaged serum albumin, potassium, creatinine and phosphate concentrations). Twenty-seven percent of which experiencing symptoms of constipation for over a year. Notably, self-reported constipation at baseline was significantly associated with a shorter time to first peritonitis and higher rates of peritonitis and death. However, no significant association was found between constipation and HD transfer after adjusting for various factors, including age, gender, PD vintage, comorbidities, shared frailty by study sites and serum albumin., Conclusion: Patient-reported constipation independently correlated with increased risks of peritonitis and all-cause mortality, though no such correlation was observed with HD transfer. These findings underscore the need for further investigation to identify effective interventions for constipation in PD patients., (© 2023 Asian Pacific Society of Nephrology.)

Aim: To assess whether the peritoneal dialysis (PD) centres included in the Peritoneal Dialysis Outcomes and Practise Patterns Study (PDOPPS) in Thailand are representative of other PD centres in the country, based on 8 key performance indicators (KPIs 1-8)., Methods: A retrospective analysis was conducted comparing PD-related clinical outcomes between PD centres included in the PDOPPS (the PDOPPS group) and those not included (the non-PDOPPS group) from January 2018 to December 2019. Logistic regression analysis was used to identify predictors associated with achieving the target KPIs., Results: Of 181 PD centres, 22 (12%) were included in the PDOPPS. PD centres in the PDOPPS group were larger and tended to serve more PD patients than those in the non-PDOPPS group. However, the process and outcome KPIs (KPIs 1-8) were comparable between the 2 groups. Large hospitals (≥120 beds), providing care to ≥100 PD cases and having experience for >10 years were independent predictors of achieving the peritonitis rate target of <0.5 episodes/year. Most PD centres in Thailand showed weaknesses in off-target haemoglobin levels and culture-negative peritonitis rate., Conclusions: The PD centres included in Thai PDOPPS were found to be representative of other PD centres in Thailand in terms of clinical outcomes. Thus, Thai PDOPPS findings may apply to the broader PD population in Thailand., (© 2023 Asian Pacific Society of Nephrology.)

Introduction: Clinical trials often have short follow-ups, and long-term outcomes such as survival must be extrapolated. Current extrapolation methods often produce a wide range of survival values. To minimize uncertainty in projections, we developed a novel method that incorporates formally elicited expert opinion in a Bayesian analysis and used it to extrapolate survival in the placebo arm of DAPA-CKD, a phase 3 trial of dapagliflozin in patients with chronic kidney disease (NCT03036150)., Methods: A summary of mortality data from 13 studies that included DAPA-CKD-like populations and training on elicitation were provided to six experts. An elicitation survey was used to gather the experts' 10- and 20-year survival estimates for patients in the placebo arm of DAPA-CKD. These estimates were combined with DAPA-CKD mortality and general population mortality (GPM) data in a Bayesian analysis to extrapolate long-term survival using seven parametric distributions. Results were compared with those from standard frequentist approaches (with and without GPM data) that do not incorporate expert opinion., Results: The group expert-elicited estimate for 20-year survival was 31% (lower estimate, 10%; upper estimate, 40%). In the Bayesian analysis, the 20-year extrapolated survival across the seven distributions was 14.9-39.1%, a range that was 2.4- and 1.6-fold smaller than those produced by the frequentist methods (0.0-56.9% without and 0.0-39.2% with GPM data)., Conclusions: Using expert opinion in a Bayesian analysis provided a robust method for extrapolating long-term survival in the placebo arm of DAPA-CKD. The method could be applied to other populations with limited survival data., (© 2023. The Author(s).)

Chronic kidney disease (CKD) is a serious public health issue affecting thousands of people worldwide. CKD diagnosis is usually made by Estimated Glomerular Filtration Rate (eGFR) and albuminuria, which limit the knowledge of the mechanisms behind CKD progression. The aim of the present study was to identify changes in the metabolomic profile that occur as CKD advances. In this sense, 77 plasma samples from patients with CDK were evaluated by 1D and 2D Nuclear Magnetic Resonance Spectroscopy (NMR). The NMR data showed significant changes in the metabolomic profile of CKD patients and the control group. Principal component analysis (PCA) clustered CKD and control patients into three distinct groups, control, stage 1 (G1)-stage 4 (G4) and stage 5 (G5). Lactate, glucose, acetate and creatinine were responsible for discriminating the control group from all the others CKD stages. Valine, alanine, glucose, creatinine, glutamate and lactate were responsible for the clustering of G1-G4 stages. G5 was discriminated by calcium ethylenediamine tetraacetic acid, magnesium ethylenediamine tetraacetic acid, creatinine, betaine/choline/trimethylamine N-oxide (TMAO), lactate and acetate. CKD G5 plasma pool which was submitted in MetaboAnalyst 4.0 platform (MetPA) analysis and showed 13 metabolic pathways involved in CKD physiopathology. Metabolic changes associated with glycolysis and gluconeogenesis allowed discriminating between CKD and control patients. The determination of involved molecules in TMAO generation in G5 suggests an important role in this uremic toxin linked to CKD and cardiovascular diseases. The aforementioned results propose the feasibility of metabolic assessment of CKD by NMR during treatment and disease progression., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Background: In contrast to guidelines related to lipid therapy in other areas, 2012 Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommend conducting a lipid profile upon diagnosis of chronic kidney disease (CKD) and treating all patients older than 50 years without defining a target for lipid levels. We evaluated multinational practice patterns for lipid management in patients with advanced CKD under nephrology care., Methods: We analyzed lipid-lowering therapy (LLT), LDL- cholesterol (LDL-C) levels, and nephrologist-specified LDL-C goal upper limits in adult patients with eGFR < 60 ml/min from nephrology clinics in Brazil, France, Germany, and the United States (2014-2019). Models were adjusted for CKD stage, country, cardiovascular risk indicators, sex, and age., Results: LLT treatment differed significantly by country, from 51% in Germany to 61% in the US and France (p = 0.002) for statin monotherapy. For ezetimibe with or without statins, the prevalence was 0.3% in Brazil to 9% in France (< 0.001). Compared with patients not taking lipid-lowering therapy, LDL-C was lower among treated patients (p < 0.0001) and differed significantly by country (p < 0.0001). At the patient level, the LDL-C levels and statin prescription did not vary significantly by CKD stage (p = 0.09 LDL-C and p = 0.24 statin use). Between 7-23% of untreated patients in each country had LDL-C ≥ 160 mg/dL. Only 7-17% of nephrologists believed that LDL-C should be < 70 mg/dL., Conclusion: There is substantial variation in practice patterns regarding LLT across countries but not across CKD stages. Treated patients appear to benefit from LDL-C lowering, yet a significant proportion of hyperlipidemia patients under nephrologist care are not receiving treatment., (© 2023. The Author(s).)

Use of proton-pump inhibitors (PPIs) is common in patients with chronic kidney disease (CKD). PPIs and many uremic toxins (UTs) are eliminated by the kidney's tubular organic anion transporter system. In a cross-sectional study, we sought to evaluate the association between PPI prescription and serum concentrations of various UTs. We studied a randomly selected sub-group of participants in the CKD-REIN cohort (adult patients with a confirmed diagnosis of CKD and estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m 2 ) with available frozen samples collected at baseline. PPI prescription was recorded at baseline. Serum concentrations of 10 UTs were measured using a validated liquid chromatography tandem mass spectrometry technique. Multiple linear regression was performed, with the log UT concentration as the dependent variable. Of the 680 included patients (median age: 68 years; median eGFR: 32 mL/min/1.73 m 2 ), 31% had PPI prescriptions at baseline. Patients using PPIs had higher levels of certain UTs in comparison to other patients, including total and free indoxyl sulfate (IS), total and free p-cresylsulfate, total and free p-cresylglucuronide (PCG), phenylacetylglutamine (PAG), free kynurenine, and free hippuric acid. After adjustment for baseline co-morbidities, number of co-prescribed drugs, and laboratory data, including eGFR, associations between PPI prescription and elevated serum concentrations of free and total IS, free and total PCG, and PAG remained significant. Our results indicate that PPI prescription is independently associated with serum UT retention. These findings are interesting to better understand the factors that may modulate serum UT concentration in CKD patients, however, they will need to be confirmed by longitudinal studies.

We investigated the shape of the relationship between longitudinal uric acid (UA) and the hazard of kidney failure and death in chronic kidney disease (CKD) patients, and attempted to identify thresholds associated with increased hazards. We included CKD stage 3-5 patients from the CKD-REIN cohort with one serum UA measurement at cohort entry. We used cause-specific multivariate Cox models including a spline function of current values of UA (cUA), estimated from a separate linear mixed model. We followed 2781 patients (66% men, median age, 69 years) for a median of 3.2 years with a median of five longitudinal UA measures per patient. The hazard of kidney failure increased with increasing cUA, with a plateau between 6 and 10 mg/dl and a sharp increase above 11 mg/dl. The hazard of death had a U-shape relationship with cUA, with a hazard twice higher for 3 or 11 mg/dl, compared to 5 mg/dl. In CKD patients, our results indicate that UA above 10 mg/dl is a strong risk marker for kidney failure and death and that low UA levels below 5 mg/dl are associated with death before kidney failure., (© 2023. The Author(s).)

Background: In FIGARO-DKD, finerenone reduced the risk of cardiovascular events in patients with type 2 diabetes (T2D) and stage 1-4 chronic kidney disease (CKD). In FIDELIO-DKD, finerenone improved kidney and cardiovascular outcomes in patients with advanced CKD. This analysis further explores kidney outcomes in FIGARO-DKD., Methods: FIGARO-DKD (NCT02545049) included patients with urine albumin-to-creatinine ratio (UACR) 30-<300 mg/g and estimated glomerular filtration rate (eGFR) 25-90 mL/min/1.73 m2 or UACR 300-5000 mg/g and eGFR ≥60 mL/min/1.73 m2. Outcomes included two composite kidney endpoints, a composite of ≥40% decrease in eGFR from baseline sustained over ≥4 weeks, kidney failure or renal death, and a composite of ≥57% decrease in eGFR from baseline sustained over ≥4 weeks, kidney failure or renal death. Changes in albuminuria and eGFR slope were also analyzed. Kidney and CV outcomes were evaluated by baseline UACR., Results: A lower incidence rate for the eGFR ≥40% kidney composite endpoint was observed with finerenone compared with placebo, but the between-group difference was not significant [hazard ratio (HR) = 0.87; 95% confidence interval (CI): 0.76-1.01; P = .069]. A greater treatment effect was observed on the eGFR ≥57% kidney composite endpoint (HR = 0.77; 95% CI: 0.60-0.99; P = 0.041) with a 36% relative risk reduction for end-stage kidney disease. A larger magnitude of effect on kidney outcomes was observed with finerenone versus placebo for patients with severely increased albuminuria than with moderately increased albuminuria. Improvements in UACR, eGFR slope and cardiovascular risk were evident in both subgroups with finerenone., Conclusions: The present analyses suggest that finerenone protects against kidney disease progression and cardiovascular events in patients with T2D and early- or late-stage CKD., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

Introduction: It is well established that chronic kidney disease (CKD) results in a significant burden on patients' health and health care providers. However, detailed estimates of the health care resource utilization (HCRU) of CKD are limited, particularly those which consider severity, comorbidities, and payer type. This study aimed to bridge this evidence gap by reporting contemporary HCRU and costs in patients with CKD across the US health care providers., Methods: Cost and HCRU estimates of CKD and reduced kidney function without CKD (estimated glomerular filtration rate [eGFR]: 60-75 and urine albumin-to-creatinine ratio [UACR]: <30) were derived for US patients included in the DISCOVER CKD cohort study, using linked inpatient and outpatient data from the limited claims-EMR data set (LCED) and TriNetX database. Patients with a history of transplant or undergoing dialysis were not included. HCRU and costs were stratified by CKD severity using UACR and eGFR., Results: Overall health care costs ranged from $26,889 (A1) to $42,139 (A3), and from $28,627 (G2) to $42,902 (G5) per patient per year (PPPY), demonstrating a considerable early disease burden which continued to increase with declining kidney function. The PPPY costs of later stage CKD were particularly notable for patients with concomitant heart failure ($50,191 [A3]) and those covered by commercial payers ($55,735 [A3])., Conclusions: Health care costs and resource use associated with CKD and reduced kidney function pose a substantial burden across health care systems and payers, increasing in line with CKD progression. Early CKD screening, particularly of UACR, paired with proactive disease management may provide both an improvement to patient outcomes and a significant HCRU and cost saving to health care providers., (© 2023 International Society of Nephrology. Published by Elsevier Inc.)

Introduction: Gout occurs frequently in patients with kidney disease and can lead to a significant burden on quality of life. Gout prevalence, and its association with outcomes in hemodialysis (HD) and peritoneal dialysis (PD) populations located in North America, is unknown., Methods: We used data from North America cohorts of 70,297 HD patients (DOPPS, 2012-2020) and 5117 PD patients (PDOPPS, 2014-2020). We used three definitions of gout for this analysis: (1) having an active prescription for colchicine or febuxostat; (2) having an active prescription for colchicine, febuxostat, or allopurinol; or (3) having an active prescription for colchicine, febuxostat, or allopurinol, or prior diagnosis of gout. Propensity score matching was used to compare outcomes among patients with versus without gout. Outcomes included erythropoietin resistance index (ERI=erythropoiesis stimulating agent dose per week/(hemoglobin×weight)), all-cause mortality, hospitalization, and patient-reported outcomes (PROs)., Results: The gout prevalence was 13% in HD and 21% in PD; it was highest among incident dialysis patients. Description of previous history of gout was rare, and identification of gout defined by colchicine (2%-3%) or febuxostat (1%) prescription was less frequent than by allopurinol (9%-12%). Both HD and PD patients with gout (versus no gout) were older, were more likely male, had higher body mass index, and had higher prevalence of cardiovascular comorbidities. About half of patients with a gout history were prescribed urate-lowering therapy. After propensity score matching, mean ERI was 3%-6% higher for gout versus non-gout patients while there was minimal evidence of association with clinical outcomes or PROs., Conclusion: In a large cohort of PD and HD patients in North America, we found that gout occurs frequently and is likely under-reported. Gout was not associated with adverse clinical or PROs., (Copyright © 2022 by the American Society of Nephrology.)

Oxidative stress (OS) is essential in uremia-associated comorbidities, including renal anemia. Complications experienced by hemodialysis (HD) patients, such as hypoxemia and uremic toxins accumulation, induce OS and premature death of red blood cells (RBC). We aimed to characterize reactive oxygen species (ROS) production and antioxidant pathways in HD-RBC and RBC from healthy controls (CON-RBC) and evaluate the role of uremia and hypoxia in these pathways. ROS production, xanthine oxidase (XO) and superoxide dismutase (SOD) activities, glutathione (GSH), and heme oxygenase-1 (HO-1) levels were measured using flow cytometry or spectrophotometry in CON-RBC and HD-RBC (pre- and post-HD), at baseline and after 24 h incubation with uremic serum (S-HD) and/or under hypoxic conditions (5% O 2 ). Ketoprofen was used to inhibit RBC uremic toxins uptake. HD-RBC showed higher ROS levels and lower XO activity than CON-RBC, particularly post-HD. GSH levels were lower, while SOD activity and HO-1 levels of HD-RBC were higher than control. Hypoxia per se triggered ROS production in CON-RBC and HD-RBC. S-HD, on top of hypoxia, increased ROS levels. Inhibition of uremic toxins uptake attenuated ROS of CON and HD-RBC under hypoxia and uremia. CON-RBC in uremia and hypoxia showed lower GSH levels than cells in normoxia and non-uremic conditions. Redox mechanisms of HD-RBC are altered and prone to oxidation. Uremic toxins and hypoxia play a role in unbalancing these systems. Hypoxia and uremia participate in the pathogenesis of OS in HD-RBC and might induce RBC death and thus compound anemia., (© 2022 John Wiley & Sons Ltd.)

Background: Conservative care is increasingly considered an alternative to kidney replacement therapy for kidney failure management, mostly among the elderly. We investigated its status and the barriers to its implementation from patients' and providers' perspectives., Methods: We analysed data from 1204 patients with advanced chronic kidney disease (CKD) [estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2] enrolled at 40 nationally representative nephrology clinics (2013-16) who completed a self-administered questionnaire about the information they received and their preferred treatment option, including conservative care, if their kidneys failed. Nephrologists (n = 137) also reported data about their clinics' resources and practices regarding conservative care., Results: All participating facilities reported they were routinely able to offer conservative care, but only 37% had written protocols and only 5% had a person or team primarily responsible for it. Overall, 6% of patients were estimated to use conservative care. Among nephrologists, 82% reported they were fairly or extremely comfortable discussing conservative care, but only 28% usually or always offered this option for older (>75 years) patients approaching kidney failure. They used various terminology for this care, with conservative management and non-dialysis care mentioned most often. Among patients, 5% of those >75 years reported receiving information about this option and 2% preferring it., Conclusions: Although reported by nephrologists to be widely available and easily discussed, conservative care is only occasionally offered to older patients, most of whom report they were not informed of this option. The lack of a person or team responsible for conservative care and unclear information appear to be key barriers to its implementation., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

Background: Patients with end-stage kidney disease (ESKD) who start unplanned dialysis therapy are more likely to be treated with hemodialysis (HD) using a central venous catheter, which has been associated with a greater risk of infections and other complications, as well as with a higher long-term risk of death. Urgent-start PD is an alternative that has been suggested as an option for starting dialysis in these cases, with potentially better patient outcomes. However, the definition of urgent-start PD is not homogeneous, and no study, to our knowledge, has compared clinical outcomes among urgent start, early start, and conventional start of PD. In this study, we aimed to compare these types of initiation of dialysis therapy in terms of a composite outcome of patient survival and technique failure., Methods: This is a retrospective, multicenter, cohort study, involving data from 122 PD clinics in Brazil. We used the following: Urgent-start groups refer to patients who initiated PD within 72 h after the PD catheter insertion; early-start groups are those starting PD from 72 h to 2 weeks after the catheter insertion; and conventional-start groups are those who used the PD catheter after 2 weeks from its insertion. We analyzed the composite endpoint of all causes of patient's mortality and technique failure (within the initial 90 days of PD therapy) using the following three different statistical models: multivariate Cox, Fine and Gay competing risk, and a multilevel model., Results: We included 509 patients with valid data across 68 PD clinics. There were 38 primary outcomes, comprising 25 deaths and 13 technique failures, with a total follow-up time of 1,393.3 months. Urgent-start PD had no association with the composite endpoint in all three models., Conclusion: Unplanned PD seems to be a safe and feasible option for treatment for patients with non-dialysis ESKD in urgent need of dialysis., Competing Interests: Author RP-F received research grants, consulting fees, and speaker honorarium from Baxter Healthcare. Authors PB and TM received consulting fees and speaker honorarium from Baxter Healthcare. Author PB receive occasional speaking honoraria from Baxter Global. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hangai, Pecoits-Filho, Blake, da Silva, Barretti and de Moraes.)

Objectives: The aims of the study are to re-evaluate kidney function in workers exposed and not exposed to heat stress after 2 years and to compare kidney function cross-shift using creatinine and cystatin C., Methods: Participants were workers from a metallurgical industry. The clinical and biochemical markers of hydration and kidney function were evaluated before and after a single shift in work., Results: We included 14 workers (6 in the heat group and 8 in the control group). The serum creatinine levels did not change during the follow-up period. Cross-shift, creatinine-based eGFR (estimated glomerular filtration rate) decreased, and cystatin C-based eGFR was maintained in the heat and control groups., Conclusions: Workers exposed to heat stress maintained their kidney function after a 2-year follow-up. Cystatin C is a better kidney function marker than creatinine for cross-shift assessments in this setting., Competing Interests: Conflict of Interest: L.M., R.P.-F., and F.B.N. have received travel grants from Danone Research to attend the Hydration for Health Scientific Conference. M.A.V. works at Pro-Rim Foundation., (Copyright © 2022 American College of Occupational and Environmental Medicine.)

Introduction: Finerenone, a selective nonsteroidal mineralocorticoid receptor antagonist, has favourable effects on cardiorenal outcomes in patients with mild-to-severe chronic kidney disease with increased albuminuria and type 2 diabetes., Methods: Two large, randomized trials have evaluated the effects of finerenone on clinical outcomes. The first trial (FIDELIO-DKD) investigated renal outcomes, and the second (FIGARO-DKD) cardiovascular outcomes., Results: Patients in the two studies had a high intrinsic risk of hyperkalemia due to type 2 diabetes, treatment with optimized doses of an inhibitor of the renin-angiotensin system, and, in some patients, their advanced chronic kidney disease. This was reflected in the incidence of hyperkalemia in the placebo group during the trials. Patients on finerenone had a significantly higher incidence of hyperkalemia compared with patients on placebo, but treatment discontinuation due to hyperkalemia was low, and no patients experienced death attributable to hyperkalemia. Structured routine potassium monitoring with temporary treatment interruption and dose reduction, as used in the two trials, should ensure the safe use of finerenone to protect the kidneys and cardiovascular system of patients with albuminuric chronic kidney disease and type 2 diabetes., Conclusions: The aim of this document is to highlight the routine potassium management required when using finerenone and to provide practical recommendations., (© 2022 The Authors. Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd.)

Mineralocorticoid receptor (MR) activation is involved in propagating kidney injury, inflammation, and fibrosis and in the progression of chronic kidney disease (CKD). Multiple clinical studies have defined the efficacy of MR antagonism in attenuating progressive kidney disease, and the US Food and Drug Administration recently approved the nonsteroidal mineralocorticoid receptor antagonist (MRA) finerenone for this indication. In this review, we consider the basic science and clinical applicability of MR antagonism. Because hyperkalemia constitutes a constraint to implementing evidence-based MR blockade, we review MRA-associated hyperkalemia in the context of finerenone and discuss evolving mitigation strategies to enhance the safety and efficacy of this treatment. Although the FIDELIO-DKD and FIGARO-DKD clinical trials focused solely on patients with type 2 diabetes mellitus, we propose that MR activation and the resulting inflammation and fibrosis act as a substantive pathogenetic mediator not only in people with diabetic CKD but also in those with CKD without diabetes. We close by briefly discussing both recently initiated and future clinical trials that focus on extending the attributes of MR antagonism to a wider array of nondiabetic kidney disorders, such as patients with nonalbuminuric CKD., (Copyright © 2022 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)