AIM:People with diabetes receiving haemodialysis are at increased risk of diabetic retinopathy (DR) and other ocular complications. Despite this heightened vulnerability, evidence on the prevalence of such conditions in this population is limited.  This review aimed to synthesise the existing literature on the prevalence of DR and other ocular conditions, and to evaluate screening rates in people with diabetes undergoing haemodialysis. METHODS:A systematic search of MEDLINE, EMBASE and CINAHL databases was conducted to identify studies reporting on the prevalence of DR, diabetic maculopathy and other ocular conditions in people with diabetes on haemodialysis. Eight articles meeting inclusion criteria were included. Pooled prevalence estimates and 95% confidence intervals (CIs) were calculated using random-effects models. RESULTS:The pooled prevalence of DR was 49.1% (95% CI: 23.1-75.4), while diabetic maculopathy prevalence was 32.5% (95% CI: 10.9-59.1). Other ocular complications reported included cataracts (53.4%), conjunctival calcification (63%) and corneal calcification (45.3%). Notably, 54.3% (95% CI: 35.4-72.6) of individuals on haemodialysis had not undergone eye screening in over two years. CONCLUSION:This review reveals a high prevalence of DR and other ocular complications in people with diabetes undergoing haemodialysis, alongside significant under-screening. Future research should focus on developing and accessing targeted interventions to improve screening uptake in this vulnerable population.

Background and hypothesis In chronic kidney disease (CKD) the nitric oxide (NO)-soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate (cGMP) pathway is impaired. Runcaciguat, an sGC activator, activates heme-free sGC, restoring cGMP production. This phase 2a trial studied the efficacy, safety, and tolerability of runcaciguat in CKD patients with or without sodium-glucose co-transporter-2 inhibitor (SGLT2i). Methods Patients with CKD and established atherosclerotic cardiovascular disease or heart failure, plus type 2 diabetes (T2D) and/or hypertension, were enrolled. All were receiving stable maximum tolerated renin-angiotensin system inhibitors with or without SGLT2i. They were randomized 3:1 to runcaciguat once daily, titrated weekly (30-120 mg if tolerated), or placebo for 8 weeks. The primary efficacy endpoint was urine albumin-to-creatinine ratio (UACR) (average of post-randomization Days 22, 29, and 57 vs baseline). CONCORD was separately powered for CKD and T2D with stable SGLT2i comedication, CKD and T2D without SGLT2i, and non-diabetic CKD. Results Of 243 patients randomized, 229 were included in the full analysis set (FAS) and 170 in the per-protocol set (PPS). In the PPS, UACR decreased by -45.2% versus placebo with runcaciguat in patients with CKD without SGLT2i (P < 0.001) and by -48.1% versus placebo in patients with CKD taking SGLT2i (P = 0.02) In the FAS, the relative reductions were -46.9% (P < 0.001) and -44.8% (P = 0.01), respectively. No significant difference was observed between patients with or without SGLT2i. In non-diabetic CKD, UACR was reduced versus baseline with runcaciguat, but the change was not statistically significant (P = 0.10). Serious treatment-emergent adverse events were reported in 7% of patients receiving runcaciguat and 8% receiving placebo. Conclusion Runcaciguat improved albuminuria in patients with CKD, irrespective of concomitant SGLT2i. Runcaciguat was well tolerated. sGC activation may represent a novel kidney-protective treatment in CKD patients (funded by Bayer AG; ClinicalTrials.gov number, NCT04507061).

Key PointsIn this analysis of Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation, canagliflozin reduced the risk of first and subsequent all-cause hospitalization by 14%.post hocSodium-glucose cotransporter 2 inhibitor reduced the risk of hospitalization by 15%, with consistent effects irrespective of kidney function, albuminuria, and diabetes status.Absolute reductions in hospitalizations with sodium-glucose cotransporter 2 inhibitor in patients with CKD are substantial, with major implications for individuals and health systems.BackgroundUnplanned hospitalization, irrespective of cause, is a meaningful outcome for patients, caregivers, clinicians, and health systems. The effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors on all-cause hospitalization in patients with CKD have not been systematically evaluated.MethodsWe conducted a post hoc analysis of the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation trial to evaluate the effect of canagliflozin on nonelective all-cause hospitalization using Cox proportional hazards models, with recurrent events analysis to assess effects on first and subsequent hospitalizations. We performed inverse variance weighted meta-analysis of three placebo-controlled SGLT2 inhibitor CKD-focused trials to assess the relative and absolute effects of SGLT2 inhibitors on first and subsequent all-cause hospitalizations overall and across clinically relevant subgroups. For analyses of cause-specific hospitalization, adverse events that were reported by investigators but not adjudicated were used.ResultsOver a median follow-up of 2.6 years, 3015 hospitalizations occurred among 1543 of 4401 (35%) participants in the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation trial. Compared with placebo, canagliflozin reduced the risk of first all-cause hospitalization (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.80 to 0.98; P = 0.02) and first and subsequent hospitalizations (HR, 0.86; 95% CI, 0.76 to 0.96; P = 0.007). In a meta-analysis of three placebo-controlled SGLT2 inhibitor CKD-focused trials, SGLT2 inhibitors reduced the risk of first and subsequent hospitalizations from any cause by 15% (HR, 0.85; 95% CI, 0.78 to 0.95; P < 0.001), with consistent effects irrespective of diabetes, baseline kidney function, and albuminuria (all P interactions > 0.50). Reductions were driven by hospitalizations due to infection, cardiac, renal or urinary, and metabolism or nutritional disorders. We estimated that SGLT2 inhibition in CKD would prevent 36 (95% CI, 13 to 56) unplanned hospitalizations per 1000 patient-years of treatment, across a broad range of patients.ConclusionsSGLT2 inhibitors reduce the risk of hospitalizations from any cause in patients with CKD, irrespective of diabetes status, kidney function, and degree of albuminuria.Clinical Trial registry name and registration number:NCT02065791.

AIMS:To evaluate whether type 2 diabetes status modifies the efficacy and safety of combining zibotentan (zibo), a selective endothelin receptor antagonist, and dapagliflozin (dapa) compared to placebo plus dapagliflozin in individuals with chronic kidney disease (CKD). METHODS AND MATERIALS:We conducted a post hoc analysis of the ZENITH-CKD trial, a multicentre 12-week, double-blind, randomized, active-controlled, phase 2b study involving 447 participants with CKD (261 with and 186 without type 2 diabetes). Participants were assigned to zibotentan (0.25 or 1.5 mg) plus dapagliflozin 10 mg or placebo plus dapagliflozin 10 mg. Changes in urinary albumin-to-creatinine ratio (UACR) and markers of fluid retention (bodyweight and B-type natriuretic peptide [BNP]) were compared in participants with and without type 2 diabetes. RESULTS:Zibo/dapa 0.25/10 mg changed UACR by -37.7% (90% CI: -40.4, -23.4) compared to placebo/dapa in participants without diabetes and by -17.9% (90% CI: -31.3, -2.0) in participants with diabetes (p-interaction 0.096). Effects of zibo/dapa 1.5/10 mg on UACR were consistent regardless of diabetes status (-34.0% (90% CI: -45.0, -20.8) vs. -33.0% (90% CI: -42.2, -22.5), p-interaction 0.921). Changes in body weight and BNP did not differ by diabetes status. Fluid retention occurred in five participants with diabetes assigned to zibo/dapa 1.5/10 mg and one participant with diabetes in the zibo/dapa 0.25/10 mg group. Fluid retention did not occur in those without diabetes in both zibo/dapa groups. With placebo/dapa, fluid retention occurred in one participant without diabetes and in none with diabetes. CONCLUSIONS:Combination therapy with zibotentan and dapagliflozin demonstrated consistent efficacy and safety across CKD patients with and without type 2 diabetes.

Background:Finerenone improves cardiovascular and renal outcomes in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD), but real-world data are limited. The FINE-REAL study (NCT05348733) is examining the use of finerenone (10 or 20 mg) in participants with CKD and T2D in routine clinical practice. Methods:FINE-REAL is an ongoing global, prospective, single-arm, non-interventional study. This preplanned interim analysis was conducted 2 years after the first participant first visit. Assessments included demographics, concomitant medications and safety. Results:Data were available for 1916 participants with a median age of 68 years [interquartile range (IQR) 59-74], 65% male, with a median follow-up of 260 days (IQR 139-357). The baseline mean estimated glomerular filtration rate (Chronic Kidney Disease Epidemiology Collaboration equation) was 54 ml/min/1.73 m2 (standard deviation 24) and the median urine albumin:creatinine ratio was 293 mg/g (IQR 86-783). Prior/concomitant medications included renin-angiotensin system inhibitors (73%), sodium-glucose cotransporter 2 inhibitors (53%) and glucagon-like peptide 1 receptor agonists (29%). Finerenone 10 mg/day was initiated in 1548 (81%) participants and 367 (19%) were initiated on 20 mg/day. During follow-up, 404 of the 1548 participants starting at 10 mg (26%) increased their dose to 20 mg. Finerenone was continuously administered for up to 1 year in 85% of participants, interrupted in 6% and discontinued in 13%. The most common adverse events were hyperkalaemia (8% of participants; leading to discontinuation in 1% and hospitalization in 0.3%; fatal in none), urinary tract infection (4%) and urogenital tract haemorrhage (including haematuria) (3%). Conclusions:In this real-world population, most participants initiated finerenone at 10 mg and remained on that dose. Finerenone was well tolerated and safety was consistent with the known profile of the drug. This interim analysis and future data from FINE-REAL will help to guide decision-making regarding the use of finerenone in participants with CKD and T2D.

AIMS:In the PIVOTAL trial, a proactive high-dose regimen of intravenous iron sucrose, compared to a lower-dose reactive regimen, reduced the risk of first and recurrent events of the primary endpoint in haemodialysis patients. We present the various approaches of recurrent event analyses for the primary endpoint and for the composite of cardiovascular (CV) death or heart failure hospitalization and their non-fatal components. METHODS AND RESULTS:Patients were randomized to a proactive maintenance dose of iron sucrose (average 264 mg/month) or a reactive treatment regimen (average 145 mg/month). We compared the results of time-to-first event analyses with recurrent event analysis using the negative binomial model and methods proposed by Wei-Lin-Weissfeld, Andersen and Gill, Lin, Wei, Yang and Ying [LWYY], Mao and Lin, and Rondeau and colleagues. The 2141 haemodialysis patients were followed for a median of 2.1 years and experienced 936 primary recurrent events, which is 42% higher than the number of 658 first events. Proactive regimen patients had 429 primary events (19.4/100 patient-years) compared with 507 events in the reactive regimen patients (24.6/100 patient-years) (rate ratio 0.77, 95% confidence interval [CI] 0.66-0.92, p = 0.0027, LWYY). Recurrent events were also reduced in the proactive regimen for the composite of CV mortality and heart failure hospitalizations (rate ratio 0.73, 95% CI 0.56-0.93, p = 0.013). Recurrent event analyses based on other approaches were very similar to those given above based on the method of LWYY. CONCLUSION:A higher dose of chronic intravenous iron therapy compared to a lower dose substantially reduced the total burden of important recurrent events of death and CV disease in patients with end-stage kidney disease receiving maintenance haemodialysis therapy.

BACKGROUND:Patients with chronic kidney disease are at increased risk of stroke and frequently have cerebral microbleeds. Whether such patients also encounter an increased risk of recurrent stroke has not been firmly established. We aimed to determine whether impaired kidney function is associated with the risk of recurrent stroke, and microbleed presence, distribution and severity. METHODS:We used pooled data from the Microbleeds International Collaborate Network to investigate associations of impaired kidney function, defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. Our primary outcome was a composite of recurrent ischaemic stroke (IS) and intracranial haemorrhage (ICrH). Secondary outcomes included: (1) individual components of the primary outcome; (2) modification of the primary outcome by microbleed presence or anticoagulant use and (3) microbleed presence, distribution and severity. RESULTS:11 175 patients (mean age 70.7±12.6, 42% female) were included, of which 2815 (25.2%) had impaired kidney function. Compared with eGFR ≥60, eGFR <60 was associated with a higher risk of the primary outcome (adjusted HR, aHR 1.33 (95% CI 1.14 to 1.56), p<0.001) and higher rates of the recurrent IS (aHR 1.33 (95% CI 1.12 to 1.58)). Reduced eGFR was not associated with ICrH risk (aHR 1.07 (95% CI 0.70 to 1.60)). eGFR was also associated with microbleed presence (adjusted OR, aOR 1.14 (95% CI 1.03 to 1.26)) and severity (aOR 1.17 (95% CI 1.06 to 1.29)). Compared with having no microbleeds, eGFR was lower in those with strictly lobar microbleeds (adjusted mean difference (aMD) -2.10 mL/min/1.73 cm2 (95% CI -3.39 to -0.81)) and mixed microbleeds (aMD -2.42 (95% CI -3.70 to -1.15)), but not strictly deep microbleeds (aMD -0.67 (95% CI -1.85 to 0.51)). CONCLUSIONS:In patients with IS or transient ischaemic attack, impaired kidney function was associated with a higher risk of recurrent stroke and higher microbleeds burden, compared with those with normal kidney function. Further research is needed to investigate potential additional measures for secondary prevention in this high-risk group.

BACKGROUND:Patients with chronic kidney disease (CKD) are at increased risk of ischemic stroke (IS) and intracerebral hemorrhage, so the safety and efficacy of early direct oral anticoagulant (DOAC) initiation in those with CKD are of clinical relevance. METHODS:OPTIMAS (Optimal Timing of Anticoagulation After Acute Ischemic Stroke With Atrial Fibrillation) was a multicenter, randomized, parallel-group, open-label trial with blinded outcome assessment, recruiting patients with IS and atrial fibrillation from 100 UK hospitals between 2019 and 2024. Participants were randomized 1:1, stratified by stroke severity, to early (within 4 days of onset) or delayed (at days 7-14) DOAC initiation. CKD was defined as a past medical history of known CKD, collected according to trial protocol as part of the case report form. For this prespecified subgroup analysis, the trial cohorts were classified according to the presence or absence of CKD. Whether CKD modified the treatment effect of early DOAC initiation was determined by fitting mixed effects logistic regression models with interaction terms between CKD and treatment group. The primary outcome was a composite outcome of recurrent IS, symptomatic intracranial hemorrhage, and systemic arterial embolism. Key secondary outcomes included the individual components of the primary outcome and all-cause mortality. RESULTS:We included 3601 patients (mean age, 78±10 years; 45% female), 543 with CKD. There were 116 primary outcome events: 97 (3.2%) in the normal kidney function group and 19 (3.5%) in the CKD group. There was no difference between early and delayed DOAC initiation for the primary outcome in either the normal kidney function group (odds ratio, 1.01 [95% CI, 0.67-1.51]) or the CKD group (odds ratio, 0.90 [95% CI, 0.36-2.25]; Pinteraction=0.822). Similarly, for the secondary outcomes, we detected no modification of the treatment effect according to CKD (Pinteraction values of 0.637, 0.386, and 0.107 for IS, symptomatic intracranial hemorrhage, and all-cause mortality, respectively). CONCLUSIONS:Our findings suggest that CKD does not modify the effects of early versus delayed DOAC initiation after acute IS. Based on these results, early DOAC initiation should not be withheld in patients with CKD. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT03759938.

AIM:This review aims to map the existing literature on the use of diabetes technology in people receiving dialysis, with a focus on utilization, accuracy, and effectiveness. METHODS:A scoping review was conducted using the Joanna Briggs Institute methodology, with systematic searches of Medline, Embase, and CINAHL for studies on diabetes technologies in dialysis populations. RESULTS:The search identified 1060 continuous glucose monitoring (CGM) and 1467 continuous subcutaneous insulin infusion or automated insulin delivery (CSII/AID) records, with 64 studies included. Eighteen studies assessed CGM accuracy, reporting mean absolute relative difference (MARD) values ranging from 8.1% to 29%, with over 97% of readings falling within Clarke error grid zones A or B. Thirteen studies compared glycemic markers, finding that HbA1c underestimated glucose by 7.3 mmol/mol, while glycated albumin showed a stronger correlation (r = 0.508). Four studies reported on dialysis effects, showing that people on automated peritoneal dialysis (APD) had lower mean glucose levels (181 ± 64 mg/dL) compared to continuous ambulatory peritoneal dialysis (CAPD) (238 ± 67 mg/dL; P < .05). Eleven studies evaluating diabetes treatment efficacy using CGM found that dulaglutide significantly reduced glucose CV from 28.1% to 19.8% (P = .003). Twenty-two studies examining glycemic outcomes reported that TIR was lower on dialysis days (80.2%, P = .02). Finally, four AID studies reported TIR improvements of up to 37.6% and a 1.5 mmol/L reduction in glucose (P = .003). CONCLUSION:This review highlights the potential of CGM and AID to improve diabetes outcomes in people on dialysis. While their clinical utility is evident, broader access and further research are needed to optimize their use in this high-risk population.

BACKGROUND:Treatment with the sodium-glucose cotransporter 2 (SGLT2) inhibitor, dapagliflozin, attenuates progression of kidney disease and reduces the risks of heart failure and death in patients with chronic kidney disease (CKD). Data on the effects of dapagliflozin on health-related quality of life (HRQoL) are limited. METHODS:Adults with CKD, with and without type 2 diabetes, with estimated glomerular filtration rate (eGFR) 25-75 mL/min/1.73m2 and urinary albumin-to-creatinine ratio 200-5000 mg/g were randomized to dapagliflozin (10 mg/day) or placebo. We assessed HRQoL using the Kidney Disease Quality of Life (KDQOL-36) questionnaire at baseline and at 12, 24, and 36 months. In this prespecified analysis, we determined the overall effects of dapagliflozin versus placebo. RESULTS:A total of 4032/4304 (94%) randomized participants (mean age 62(12) years, 32% female) had information on KDQOL-36 at baseline. Mean scores on the physical health composite (PHC); mental health composite (MHC); and kidney disease symptoms, effects, and burden were similar between randomized groups at baseline. During a median follow-up of 2.3 (Interquartile range: 1.9, 2.6) years, mean scores were significantly higher in participants randomized to dapagliflozin for PHC (0.71 [95% CI: 0.30, 1.31]), MHC (0.62 [95%CI: 0.14, 1.11]) kidney disease symptoms (1.33 [95% CI: 0.57, 2.10]), kidney disease effects (1.34 [95% CI: 0.43, 2.26]) and kidney disease burden (1.46 [95%CI: 0.30, 2.62]). Participants randomized to dapagliflozin were significantly less likely to experience a clinically meaningful (≥10 units) decline in PHC relative to placebo (hazard ratio [HR] 0.84 (95% CI: 0.74, 0.96). Corresponding HRs for ≥10-unit decline in MHC, and kidney disease symptoms, effects, and burden were 0.95 (95% CI: 0.85, 1.07), 0.84 (95% CI: 0.75, 0.94), and 0.84 (95% CI: 0.72, 0.97) and 0.93 (95% CI: 0.84, 1.02), respectively. CONCLUSIONS:In participants with CKD with and without type 2 diabetes, treatment with dapagliflozin slowed the decline in physical health, reduced worsening of symptoms, and lessened the effect of kidney disease.

Background Non-anaemic iron deficiency is highly prevalent in people living with chronic kidney disease (CKD) but is underdiagnosed and undertreated, especially in earlier stages of CKD. A multicentre trial assessing the effect of intravenous iron supplementation in iron-deficiency but not anaemic people with CKD included a qualitative sub-study that aimed to explore the patient experience and psychosocial impact of living with CKD and iron deficiency, and the experience of the therapeutic intervention (intravenous iron and exercise).Methods Semi-structured interviews were conducted with 23 trial participants blinded to treatment. Topics explored included experiences of living with CKD and iron deficiency, symptoms, social and leisure activities, quality of life, and participants' views and experiences of receiving the therapeutic intervention. Thematic analysis was used to identify and report themes.Results Six overarching themes were identified: lack of awareness of iron deficiency; overwhelming feelings of tiredness; feeling limited; balancing emotions; perceptions and experiences of therapeutic treatment received; and impact of trial participation on life participation. Trial participation, specifically the exercise training, was perceived to be beneficial, with improvements in life participation and psychological wellbeing experienced. However, there were no clear differences between treatment groups, with mixed perceptions about which therapeutic treatment was received.Conclusions The impact of tiredness on individuals with CKD is profound and can result in reduced vitality, impaired ability to engage in life activities and emotional conflict. Improved communication and support about psychosocial impact and management of symptoms, particularly fatigue, for people with CKD may be required, alongside effective therapeutic interventions, to improve symptom management and quality of life.

Vitamin D deficiency is common in patients with end stage kidney disease (ESKD) and is a strong predictor of death from cardiovascular disease, infections and cancer. Currently only 68 https://doi.org/10.1186/ISRCTN15087616 ). Recruitment commenced in March 2017.

Background Identification of patients likely to experience substantial loss of eGFR is required to detect a kidney protective treatment effect in clinical trials; this is usually achieved by restricting inclusion of patients with elevated albuminuria. However, not all patients with elevated albuminuria show progressive eGFR loss. The eGFR slope before the trial may better predict whether patients experience loss in eGFR during the trial. We assessed the effect of dapagliflozin on eGFR slope according to patients' eGFR slope before enrollment (pretrial eGFR slope) in the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease study. Methods We recorded eGFR data for 2 or less to 2 years from electronic medical records for 4304 patients with CKD before enrollment in the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease study. We used linear regression to estimate within-patient pre-enrollment eGFR trajectory. We evaluated the association of pre-enrollment eGFR trajectory with total and chronic eGFR slopes and a kidney composite end point. We also determined the degree to which pre-enrollment eGFR trajectory modified the effects of dapagliflozin. Results Eight hundred and seventy (20% of the total cohort) patients with three or more historical eGFR measurements were evaluated (mean [SD] pre-enrollment eGFR slope: -6.1 [6.1] ml/min per 1.73 m(2)/year). The benefit of dapagliflozin in reducing total (P interaction 0.02) and chronic (P interaction 0.02) eGFR slopes was more pronounced in patients with steeper preinclusion eGFR trajectory (rapid progressors; eGFR slope <-5 ml/min per 1.73 m(2)/year), as was the benefit of dapagliflozin on the kidney composite end point (P interaction 0.02). Conclusions Determination of pretrial eGFR trajectory may help to identify patients with CKD at higher and lower risks of progression and those more likely to benefit from targeted intervention.

AIMS:To develop a position statement that identifies research priorities in diabetic kidney disease and provides recommendations to researchers and research funders on how best to address them. METHODS:A one-day research workshop was conducted, bringing together research experts in diabetes and kidney disease, healthcare professionals, and people living with diabetes, to identify and prioritise research recommendations. RESULTS:The following key areas were identified as needing increased focus: Understanding causal mechanisms in diabetic kidney disease Prevention of diabetic kidney disease Addressing health inequalities Improving diagnosis Improving care Supporting self-management CONCLUSIONS: This position statement outlines recommendations to address the urgent need to tackle diabetic kidney disease and calls on the diabetes and kidney research communities to act upon these recommendations to ensure future research works to eliminate unfair and avoidable disparities in health.

Background CKD carries a variable risk for multiple adverse outcomes, highlighting the need for a personalized approach. This study evaluated several novel biomarkers linked to key disease mechanisms to predict the risk of kidney failure (first event of eGFR <15 ml/min per 1.73 m(2) or KRT), all-cause mortality, and a composite of both. Methods We included 2884 adults with nondialysis CKD from 16 nephrology centers across the United Kingdom. Twenty-one biomarkers associated with kidney damage, fibrosis, inflammation, and cardiovascular disease were analyzed in urine, plasma, or serum. Cox proportional hazards models were used to assess biomarker associations and develop risk prediction models. Results Participants had mean age 63 (15) years; 58% were male and 87% White. Median eGFR was 35 (25-47) ml/min per 1.73 m2, and the median urinary albumin-to-creatinine ratio was 197 (32-895) mg/g. During median 48 (33-55) months of follow-up, 680 kidney failure events and 414 all-cause mortality events occurred. For kidney failure, a model combining three biomarkers (soluble TNF receptor 1, soluble cluster of differentiation 40, and urinary collagen type 1 alpha 1 chain) showed good discrimination (C-index, 0.86; 95% confidence interval [CI], 0.83 to 0.89) but was outperformed by a model using established risk factors (age, sex, ethnicity, eGFR, and urinary albumin-to-creatinine ratio; C-index, 0.90; 95% CI, 0.88 to 0.92). For all-cause mortality, a model using three biomarkers (high-sensitivity cardiac troponin T, N-terminal pro-brain natriuretic peptide, and soluble urokinase plasminogen activator receptor) demonstrated equivalent discrimination (C-index, 0.80; 95% CI, 0.75 to 0.84) to an established risk factor model (C-index, 0.80; 95% CI, 0.76 to 0.84). For the composite outcome, the biomarker model discrimination (C-index, 0.78; 95% CI, 0.76 to 0.81) was numerically higher than for established risk factors (C-index, 0.77; 95% CI, 0.74 to 0.80), and the addition of biomarkers to the established risk factors led to a small but statistically significant improvement in discrimination (C-index, 0.80; 95% CI, 0.77 to 0.82; P value <0.01). Conclusions Risk prediction models incorporating novel biomarkers showed comparable discrimination to established risk factors of kidney failure and all-cause mortality.Clinical Trial registry name and registration number:ClinicalTrials.gov, NCT04084145.