Key Points The Predicting Risk of Cardiovascular Disease EVENTs equations optimize risk prediction in the modern era of increasing cardiovascular kidney metabolic disease prevalence. Risk prediction is most helpful to intensify therapy in those with less advanced kidney disease. In those with advanced kidney disease, risk indices provide little utility beyond biomarkers alone such as eGFR and albuminuria. Background Cardiovascular kidney metabolic syndrome is a growing public health problem and leading cause of cardiovascular mortality. We evaluated model performance of the American Heart Association Predicting Risk of Cardiovascular Disease EVENTs (PREVENT) equations in a large single health system population in patients with CKD and across strata of kidney function and compared findings where applicable to those of the pooled cohort equations (PCE). Methods Veterans with eGFR measurements were divided into three groups: eGFR ≥60, eGFR 30–59, and eGFR 15–29. We assessed the base PREVENT equations for total cardiovascular disease (CVD), atherosclerotic CVD (ASCVD), and heart failure as well as add-on equations using albuminuria. Accuracy of equations was assessed with c-index as a measure of discrimination and calibration curve slopes as a measure of calibration. Results Overall c-index was 0.651 for PREVENT-CVD, 0.633 for PREVENT-ASCVD, and 0.673 for PREVENT-heart failure. Discrimination of PREVENT-ASCVD was modestly greater than that of PCE (0.633 versus 0.629, respectively). For all three base PREVENT equations, discrimination declined with advancing kidney disease. Overall calibration slopes for the PREVENT equations ranged from 0.78 to 1.27. PREVENT-ASCVD had superior calibration compared to PCE with a calibration slope of 1.27 and 0.53, respectively. In those with urine albumin to creatinine ratio (UACR) measurements, discrimination of UACR add-on equations improved from base equations in those with less advanced kidney disease (c-index 0.624 for PREVENT-CVD UACR versus 0.607 for PREVENT-CVD base equation in those with eGFR ≥60, and c-index 0.586 for PREVENT-CVD UACR versus 0.563 for PREVENT-CVD base equation in those with eGFR 30–59). This trend was similar for the PREVENT-ASCVD and PREVENT-heart failure UACR add-on equations. Conclusions In a CKD population, the PREVENT equations perform best in those less advanced stages of CKD and cardiovascular kidney metabolic, presenting an opportunity to apply disease-preventing and disease-modifying therapeutics in a timely manner.
Incremental peritoneal dialysis (PD) is defined as prescribing a less-than-standard PD dose. High-certainty evidence to guide safe incremental PD prescription is lacking, resulting in substantial practice variability. We conducted a multinational survey to evaluate current uptake, practice patterns, and clinician perspectives on incremental PD. An online, unit-level survey, comprising 27 questions on incremental PD practice, was purposively disseminated to senior PD unit staff (physicians and/or nurses) from Australia, Canada, and Thailand between June 2023 and September 2025. A total of 254 responses were received from 175 PD units (Australia: 55 (89%) of 62 units; Canada: 49 (60%) of 82 units; Thailand: 71 (34%) of 210 units). Incremental PD was reported as prescribed in fewer than 10% of patients in most units (56%, P = 0.16). Incremental PD definitions varied substantially: continuous ambulatory PD (CAPD) with <4 daily exchanges (75%), automated PD or CAPD performed <7 days/wk (65% and 61%), CAPD <8 L/d (50%), a single long overnight exchange (46%), or automated PD without a day dwell (44%), highlighting the absence of international consensus. Key reported advantages included increased patient satisfaction (81%), willingness to choose PD (75%), and preservation of residual kidney function (64%). Frequently cited disadvantages included patient or caregiver resistance to dose escalation (62%) and needing more frequent monitoring (31%). Quality of life was identified as the most important area for future research. Incremental PD is prescribed infrequently and variably. Concern about patient resistance to dose escalation is a barrier. High-quality data are needed to guide how incremental PD is defined, initiated, and escalated.
BACKGROUND:Urine tubular biomarkers have previously been associated with chronic kidney disease (CKD) progression independently of estimated glomerular filtration rate (eGFR) and albuminuria. We evaluated whether nine urine tubular biomarkers could improve prediction of kidney failure beyond serum creatinine and urine albumin-to-creatinine ratio among adults with CKD. METHODS:Among 5100 participants in EMPA-KIDNEY, a randomized trial which assessed the effects of empagliflozin 10 mg versus matching placebo among patients with CKD at risk of progression, nine urine creatinine-indexed tubular biomarkers were measured including alpha-1 microglobulin, dickkopf-3, epidermal growth factor [EGF], interleukin-18, kidney injury molecule-1 [KIM-1], monocyte chemoattractant protein-1 [MCP-1], neutrophil gelatinase-associated lipocalin, uromodulin, and human cartilage glycoprotein-40. Outcomes were kidney disease progression ('treated kidney failure', renal death, or sustained ≥40% eGFR decline) and treated kidney failure (maintenance dialysis or kidney transplant). Relative to models based on the linear predictor of the kidney failure risk equation (KFRE), improvements in discrimination were estimated with further addition of the nine tubular biomarkers using absolute difference in Uno's C-index. RESULTS:Over median 3.5 years of follow-up, 1191 participants experienced kidney disease progression and 461 experienced treated kidney failure. KFRE demonstrated excellent discrimination for treated kidney failure [C-index 0.858 (0.840,0.874)] and moderate discrimination for kidney disease progression [0.724 (0.705,0.743)]. Addition of three biomarkers (MCP-1, KIM-1, and EGF) most strongly associated with CKD outcomes yielded some further improvement in predicting kidney failure [absolute difference 0.014 (0.009,0.024)] and kidney disease progression [0.038 (0.026,0.053)]. Prediction of kidney outcomes were only slightly improved when further expanding from three to all ning tubular biomarkers. CONCLUSION:In a wide range of causes of CKD, adding three urine tubular biomarkers (MCP-1, KIM-1, EGF) to KFRE improves estimates of risk of CKD progression.
BACKGROUND:It is difficult for patients to make informed decisions about kidney failure unless they know all their treatment options. Conservative management is an important option infrequently presented alongside other kidney failure treatments by nephrologists. METHODS:We conducted a randomized pilot trial testing the feasibility and acceptability of a communication tool, called Conservative Kidney Management Jumpstart Tool, in assisting nephrologists with discussing conservative management with their patients. We recruited patients aged ≥75 years with stage 4 or 5 chronic kidney disease in the greater Seattle area between April 2023-May 2025. Patients were randomized in 1:1 fashion to either their nephrologists receiving the Tool to use with them at their next clinic visit (intervention) or usual care (control). Our primary outcome and feasibility measure was patient-reported discussion of conservative management during the clinic visit. Our secondary outcome and acceptability measure was change in patients' satisfaction with their nephrologist's serious illness communication skills (using the Quality of Communication Scale, with higher scores indicating higher quality) before and after the visit. We performed an intent-to-treat analysis of the primary endpoint using a chi-square test. We used paired-samples t-tests to assess within-patient changes in the secondary endpoint. RESULTS:We randomized 74 patients (age 80±1, 19% women, 69% White) to either the control (n=37) or intervention (n=37) group. Patients whose nephrologists received the Tool were more likely to discuss conservative management during their clinic visit (60% vs. 19%, p=0.001) than patients in the control group. Patients whose nephrologists received the Tool rated their nephrologist's communication skills at 7.5±2.1 before the visit and 9.0±1.7 after the visit (p<0.001) as compared with 7.8±1.9 and 7.9±1.8 (p=0.54), respectively, among patients in the control group. CONCLUSIONS:The Tool was feasible and acceptable to patients, promoting patient-nephrologist discussion of conservative management and improving patients' satisfaction with their nephrologist's communication skills.
Key Points In nationwide nephrology-referred CKD, sodium-glucose cotransporter 2 inhibitor use was associated with lower cardiovascular event and KRT risk. Associations with cardiovascular events and KRT were consistent in advanced CKD, a group underrepresented in trials. Findings supported the applicability of trial results to a broad nephrology-referred CKD population. Background Sodium-glucose cotransporter 2 inhibitors (SGLT2 inhibitors) reduce cardiovascular (CV) and kidney events in randomized trials, yet evidence on their effectiveness in routine nephrology practice remains limited. We examined CV and kidney outcomes associated with SGLT2 inhibitor initiation in adults with CKD receiving specialist nephrology care. Methods In this nationwide cohort study, we included adults with CKD receiving specialist nephrology care, identified through the Swedish Renal Registry between January 1, 2016, and December 31, 2023. Participants had baseline data on eGFR, urine albumin-to-creatinine ratio, and hemoglobin; those with prior KRT were excluded. Follow-up continued until December 31, 2024. SGLT2 inhibitor use was identified through national pharmacy records and analyzed according to an intention-to-treat approach. Outcomes were major adverse cardiovascular events (MACE), initiation of KRT, all-cause mortality, and a composite of heart failure hospitalization or CV death. Associations were estimated using inverse probability–weighted marginal structural models to address time-dependent confounding. Results Among 32,856 participants (median age 73 years [interquartile range, 63–79]; 36% women; mean eGFR 29.3±16.8 ml/min per 1.73 m 2 ), 1493 (4.5%) were prevalent SGLT2 inhibitor users at baseline and 3491 (10.6%) initiated treatment during follow-up (4984 ever-exposed, 15.2%). SGLT2 inhibitor use was associated with a lower risk of MACE (odds ratio 0.80, 95% confidence interval, 0.71 to 0.91) and KRT (0.67, 0.52 to 0.85). No associations were observed for all-cause mortality (0.95, 0.79 to 1.15) or the composite heart failure outcome (0.87, 0.65 to 1.16), although a lower risk was observed in the incident-user analysis (0.61, 0.38 to 0.98). Associations were generally consistent across prespecified subgroups. Conclusions In adults with CKD managed in specialist nephrology care, SGLT2 inhibitor use was associated with a lower risk of MACE and KRT, extending randomized trial evidence to a broad, real-world CKD population.
KEY POINTS:Children with CKD exhibit markedly lower cardiopulmonary fitness with an absolute maximal oxygen uptake deficit of 10 ml/kg per minute compared with reference values. More than half of the patients show impaired fitness as early as CKD stage 3, highlighting early functional vulnerability. Maximal oxygen uptake is independently associated with modifiable parameters commonly targeted by rehabilitation, supporting tailored intervention strategies. BACKGROUND:Children with CKD are at high cardiovascular risk, yet cardiopulmonary fitness is rarely assessed in routine care. Maximal oxygen uptake (VO 2 max) is a powerful prognostic marker, and Z -score-based evaluations may improve early risk stratification. METHODS:In this prospective multicenter study, children aged 6-17 years with CKD stages 2-5 (Kidney Disease Improving Global Outcome) underwent standardized cardiopulmonary exercise testing (CPET). VO 2 max was expressed as Z -scores using contemporary pediatric reference values. Impaired fitness was defined as VO 2 max Z -score <-1.64. Multivariable linear regression was used to identify independent determinants of VO 2 max. RESULTS:Among 88 enrolled patients (mean age 12±4 years, 67% male), 77 completed a valid CPET. Mean VO 2 max Z -score was -1.8±2.1, corresponding to 33.5±9.2 ml/kg per minute, that is, an absolute lowering of approximately 10 ml/kg per minute compared with age-matched and sex-matched reference values. Overall, 57% had impaired fitness. VO 2 max was progressively lower across higher CKD stages ( P < 0.001 ). In multivariable analysis, higher VO 2 max was independently associated with higher hemoglobin concentration, better pulmonary function (forced expiratory volume in 1 s), better ventilatory efficiency (VE/VCO 2 slope), and higher ventilatory anaerobic threshold, explaining 77% of VO 2 max variability. CONCLUSIONS:Cardiopulmonary fitness is markedly lower in children with CKD, with a clear stage-dependent decline that is already evident at early disease stages. The magnitude of VO 2 max impairment is substantial and related to potentially modifiable clinical and functional factors, supporting early CPET-based screening and the development of targeted, multidisciplinary rehabilitation in pediatric CKD. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER:Clinicaltrials.gov identifier NCT04897672 and Montpellier University Hospital Institutional Review Board (IRB 202100852).
Background: Ultra-processed foods (UPFs) are associated with adverse health. Plant foods can be highly processed. It is not clear whether plant- and animal-sourced UPFs are associated chronic kidney disease (CKD) risk. Methods: Data came from the Cardiovascular Health Study, a prospective cohort of 2,661 older adults (≥65 years). The exposure was UPF intake, classified as plant- or animal-sourced in servings/day using the Nova framework from food frequency questionnaires (1989-1990, 1995-1996). The outcome was incident CKD (estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m 2 ) and absolute eGFR change (up to 18 years). Time-dependent Cox and linear models were used to examine the associations between total, plant-, and animal-sourced UPF, and minimally-processed food (MPF) intake with incident CKD and eGFR change. Results: After a median 6.8 years follow-up and adjusting for demographics and health behaviors, those in the highest tertiles of total and animal-sourced UPF intake had 26% and 37% higher risk of incident CKD compared to the lowest tertile (Hazard Ratio (HR) 1.26; 95% CI 1.08, 1.47; p-trend=0.003 and HR 1.37; 95% CI 1.17, 1.60; p-trend<0.001, respectively). Per standard deviation higher plant-sourced UPF was associated with higher CKD risk (HR 1.07; 95% CI 1.01, 1.13) but not in categorical analyses (p-trend=0.12). Higher total MPF was associated with 20% lower risk of incident CKD (HR 0.80 for tertile 3 vs. 1; 95% CI 0.69, 0.95; p-trend = 0.008). Replacing three servings of total MPF with total UPF (HR 1.02; 95% CI 1.001, 1.03, p=0.04) and plant-sourced MPF with plant-sourced UPF (HR 1.02; 95% CI 1.002, 1.05, p=0.03) was weakly associated with elevated risks of CKD. No associations were observed for eGFR change. Competing risks analyses for mortality attenuated estimates. Conclusions: Total, and animal-sourced UPF were associated with incident CKD and plant-sourced UPF was modestly associated. Health benefits of plant foods may be dampened by ultra-processing, but additional work is needed in younger populations.
Background Few effective drug treatments exist for dialysis patients with heart failure with preserved ejection fraction (HFpEF). This study aimed to evaluate the effects of henagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, on cardiac structure, and its safety in such population. Methods In this multicenter, randomized, double-blind, placebo-controlled trial, dialysis patients with HFpEF were randomly assigned (1:1) to receive henagliflozin or placebo for 24 weeks. All enrolled participants received conventional therapy. The primary outcome was the change in left ventricular mass index (LVMI) from baseline to week 24. The secondary outcomes were the changes in left atrial volume index (LAVI), E/e’, e’, and N-terminal pro-brain natriuretic peptide (NT-proBNP) and safety. Efficacy was assessed in the intention-to-treat population. Safety was assessed in the as-treated population. Analysis of covariance was used to assess treatment effects. Results A total of 112 participants were randomly assigned to the henagliflozin group (n=56) and the placebo group (n=56). Of these, 60 participants were on hemodialysis and 52 were on peritoneal dialysis. From baseline to week 24, henagliflozin resulted in a greater reduction inleast-squares mean (±SE) change in LVMI than placebo (-3.27±1.71 g/m 2 versus 2.01±1.69 g/m 2 ), with a between-group difference of -5.27 g/m 2 (95% confidence interval [CI], -10.02 to -0.53 g/m 2 ; P =0.03). In the prespecified subgroup by dialysis modality, the between-group difference in LVMI change from baseline to week 24 was -6.86 g/m 2 (95% CI, -14.02 to 0.29 g/m 2 ) among participants on peritoneal dialysis and -3.91 g/m 2 (95% CI, -10.45 to 2.63 g/m 2 ) among participants on hemodialysis. No between-group differences in secondary outcomes were observed. The incidence of adverse events was similar between the henagliflozin and placebo groups (36% vs. 34%). Conclusions Henagliflozin was associated with a greater reduction in LVMI at week 24 compared with placebo and was tolerable in dialysis patients with HFpEF. Larger studies are needed to confirm the LVMI-lowering effect of henagliflozin.
BACKGROUND:Lactoferrin, a multifunctional iron-binding glycoprotein with anti-inflammatory properties is reported to be effective in anemia in pregnant women and patients with malignancy but has not been tested elaborately in CKD. METHODS:In this randomized, open-label trial, 185 patients (intention to treat) with iron-deficiency anemia (hemoglobin less than 10 g/dL, transferrin saturation less than 20%) were enrolled: 90 with CKD not on dialysis (CKD-ND) and 95 with dialysis-dependent CKD (CKD-5D). Patients were randomized to receive either oral iron (30 mg/day liposomal iron) or oral iron plus lactoferrin (100 mg twice daily) for 3 months. The primary outcome was change in hemoglobin. Secondary outcomes included iron indices and inflammatory markers (CRP, IL-6, ESR, hepcidin). RESULTS:In the intention-to-treat analysis, lactoferrin plus iron resulted in significantly greater improvements in hemoglobin and iron parameters than iron alone in both CKD-ND and CKD-5D patients. Mean hemoglobin increased by 1.95±1.19 versus 1.33±0.86 g/dL in CKD-ND and by 1.73±0.96 versus 1.11±0.93 g/dL in CKD-5D patients receiving lactoferrin plus iron and iron alone, respectively. Improvements in iron indices were also greater with addon lactoferrin treatment. Mean difference in hepcidin levels were -20.24±15.99 vs -16.03±40.65 ng/dL in CKD-ND and -15.29±8.73 vs -20.99±20.16 ng/dL in CKD-5D patients treated with lactoferrin plus iron and iron alone respectively. CONCLUSION:Among patients with CKD-associated anemia, adjunctive lactoferrin therapy improved hemoglobin and iron parameters compared with oral iron alone in both non-dialysis-dependent and dialysis-dependent patients. Lactoferrin was also associated with modest improvements in inflammatory status, although effects on individual inflammatory markers were inconsistent. These findings suggest that lactoferrin may be a useful adjunct to oral iron therapy for the management of anemia in CKD especially in resource limited settings.
People with hemodialysis-dependent kidney failure have a high incidence of cardiovascular morbidity and mortality, the etiologies of which remain incompletely understood. Recent work has suggested that the hemodialysis procedure itself induces transient episodes of myocardial contractile dysfunction, a phenomenon known as intradialytic myocardial stunning (IDMS). IDMS likely results in repetitive injury to the heart and, as such, may be an underappreciated risk factor which at least partly underlies the high rate of cardiovascular events in this population. However, many important questions about IDMS remain. In this manuscript, we review the evidence base on IDMS. First, we provide a proposed working definition of this entity, placing it within the historical context of other syndromes of transient myocardial contractile abnormalities such as those caused by ischemia or by neurogenic (stress) cardiomyopathy. We then outline the seminal evidence supporting the hypothesis that IDMS is a specific form of Tako-tsubo (stress) cardiomyopathy. We next discuss the epidemiology of IDMS, including incidence, risk factors, sequelae, and potential contributions to the development of cardiovascular disease in people receiving maintenance hemodialysis. Finally, we focus on the frontiers of IDMS research by identifying avenues of future study, including potential mechanisms which can be investigated using novel techniques, and identify gaps in the current understanding of IDMS which provide a roadmap for future studies.
BACKGROUND AND OBJECTIVES:Blood pressure variability (BPV) has been recognized as a cardiovascular risk factor beyond mean blood pressure, but its role in ischemic stroke among patients receiving hemodialysis remains incompletely defined, particularly across stroke subtypes. We evaluated the association between visit-to-visit BPV and incident ischemic stroke in a multicenter hemodialysis cohort. DESIGN, SETTING, PARTICIPANTS, MEASUREMENTS:In this prospective cohort study, 1,136 patients undergoing maintenance hemodialysis were enrolled from 12 centers. Pre-dialysis blood pressure measurements were collected over a standardized 12-week baseline period (approximately 36 readings per patient). BPV was quantified using the coefficient of variation (CV) and analyzed per 10% greater CV and by tertiles. The primary outcome was incident ischemic stroke, including large artery atherosclerosis (LAA) and small vessel occlusion (SVO). Fine-Gray competing risk models were used to estimate subdistribution hazard ratios (sHRs), adjusting for demographics, blood pressure, comorbidities, medication, and dialysis-related factors. RESULTS:During a median follow-up of 54 months, 144 patients developed ischemic stroke. Higher systolic BPV was independently associated with greater stroke risk (sHR per 10% greater CV, 1.74; 95% confidence interval [CI], 1.10-2.76, P=0.02) in the clinically adjusted model, with consistent findings in extended analyses. In subtype-specific analyses, systolic BPV was significantly associated with LAA and showed a directionally consistent but attenuated association with SVO after extended adjustment. In contrast, diastolic BPV showed weaker associations that were not statistically significant after multivariable adjustment. CONCLUSIONS:Higher systolic BPV was independently associated with ischemic stroke in patients receiving hemodialysis, with the most consistent subtype-specific association observed for large artery atherosclerosis. These findings suggest that systolic BPV may serve as a clinically accessible marker of cerebrovascular risk beyond mean blood pressure in this high-risk population.
KEY POINTS:This qualitative study explored patient, caregiver, and provider perceived barriers to retransplantation after kidney allograft loss. We identified four medical and nonmedical barriers to retransplantation and four additional barriers to pursuing living donor retransplantation. System-, transplant center-, provider-, and patient-level approaches to address these barriers are highlighted. BACKGROUND:Many kidney transplant recipients experience graft loss, and retransplantation offers a significant survival benefit when compared with waitlisted patients. Yet, trends related to preemptive relisting/retransplantation are suboptimal. Little empirical evidence has explored barriers to kidney retransplantation. We aimed to identify the predominant barriers to retransplantation after graft loss and factors that hinder the pursuit of living kidney donor (LKD) retransplantation. METHODS:This was a qualitative study that used an interpretive descriptive design. Participants included patients with a history of graft loss, caregivers who supported them, and transplant nephrologists, recruited using purposive and snowball sampling techniques. Data collection entailed semistructured interviews that were coded, and an inductive thematic analysis was conducted. RESULTS:We synthesized the perspectives of 23 patients, 23 caregivers, and 11 transplant nephrologists representing 11 Canadian transplant programs. Through our analysis, we identified four key barriers to retransplantation: high antibody sensitization resulting in scarcity of compatible donors; prevalence of comorbidities leading to ineligibility or wait list withdrawal; history of nonadherence among the recipients leading to ineligibility or delays in transplant referral and reevaluation; and delayed referrals and poor coordination of retransplant workup. Additional barriers to LKD retransplantation included patient preference for deceased donor transplantation that was unlikely to change after graft loss; perceived smaller pool of eligible LKDs felt to have been exhausted with the first transplant; the psychological burden of unresolved issues related to previous LKD transplant loss; and overall structural barriers to living kidney donation. CONCLUSIONS:This analysis highlights both medical and nonmedical barriers to retransplantation and that the pursuit of retransplantation entails persistent as well as additional and compounding challenges. A list of implications that arise from these findings is presented. Given the well-established benefits of kidney transplantation and that graft loss remains a leading cause of dialysis initiation, these findings have important implications for the nephrology community.
Background: Kidney tubular secretion is a critical mechanism for the clearance of numerous metabolites, toxins, and drugs. In populations with advanced chronic kidney disease (CKD), low (worse) tubular secretion has been associated with an increased risk of cardiovascular disease (CVD). However, it remains unknown whether this relationship is also present in the general population. Methods: In this case-cohort study, we selected a 10% random subcohort (n=1246) from Trøndelag Health Study (HUNT-3, a Norwegian community-dwelling population cohort) and we also sampled 141 CVD death cases that occurred outside of the subcohort. We developed a summary secretion score by averaging urine-to-plasma ratios of twelve endogenous secreted solutes, with lower ratios indicating worse tubular secretion. Weighted Cox proportional hazards models were used to assess the relationship between the summary secretion score and the risk of CVD mortality. Results: The mean (SD) age was 51 (14) years, 54.4% were females, 6% had prevalent CVD, and median (IQR) eGFR was 99 (90-110) mL/min/1.73m 2 at baseline. In multivariable models adjusted for demographics, CVD risk factors, eGFR, and albuminuria, each SD lower summary secretion score was associated with 27% higher risk of CVD mortality (95% CI 1.03, 1.56). Results were similar across major demographic categories and among those with or without eGFR <60 ml/min/1.73 m 2 or albuminuria >30 mg/g at baseline. Conclusions: Among community-dwelling participants, lower tubular secretion was associated with increased CVD mortality independent of eGFR, albuminuria, and other CKD risk factors.
