Stehlé T, Najhi S, Wei F
… +13 more, Canouï-Poitrine F, Brabant S, Luciani A, Grimbert P, Prié D, Champy CM, Reizine E, Matignon M, Pelegrin T, Fellahi S, Brasseur P, Ingels A, Pigneur F
Am J Kidney Dis
· 2026 Feb · PMID 41238164
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Bai S, Yang X, Sheng Q
… +10 more, Zhang Q, Liu L, Sun S, Wang X, Zhou M, Jia Q, Song K, Niu K, Ding Y, Xia Y
Am J Kidney Dis
· 2026 Mar · PMID 41238163
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RATIONALE & OBJECTIVE: Evidence is limited regarding the associations of nonalcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated fatty liver disease (MAFLD) with the development of nephrolithiasis....RATIONALE & OBJECTIVE: Evidence is limited regarding the associations of nonalcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated fatty liver disease (MAFLD) with the development of nephrolithiasis. This study assessed the associations of NAFLD and MAFLD with the risk of incident nephrolithiasis using data from 2 cohort studies conducted in the People's Republic of China and the United Kingdom. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 26,490 participants without nephrolithiasis at baseline in the Tianjin Chronic Low-grade Systemic Inflammation and Health Cohort Study (TCLSIH) and 294,577 participants in the UK Biobank. EXPOSURE: Fatty liver diagnosed by abdominal ultrasonography in the TCLSIH and by the Hepatic Steatosis Index in the UK Biobank. NAFLD and MAFLD were defined according to standard clinical criteria in both cohorts. OUTCOME: Nephrolithiasis was confirmed by ultrasonography in the TCLSIH and identified through ICD-10 and OPCS-4 in the UK Biobank. ANALYTICAL APPROACH: Cox proportional hazards regression analysis was used to assess the relationship between exposures and incident nephrolithiasis. RESULTS: The TCLSIH and the UK Biobank recorded 806 and 2,743 new cases of nephrolithiasis during a median follow-up period of 4 and 12 years, respectively. Participants in both cohorts showed a significantly increased risk of nephrolithiasis in the setting of NAFLD (TCLSIH: HR, 1.69 [95% CI, 1.46-1.95]; UK Biobank: HR, 1.66 [95% CI, 1.53-1.79]) and MAFLD (TCLSIH: HR, 1.79 [95% CI, 1.55-2.08]; UK Biobank: HR, 1.54 [95% CI, 1.42-1.66]) after multivariable adjustments. LIMITATIONS: Observational nature limits causal inferences; generalizability limited outside of the cohorts studied; limited diagnostic approaches to detect nephrolithiasis; unavailability of stone composition data. CONCLUSIONS: Both NAFLD and MAFLD are associated with a higher risk of nephrolithiasis. The results suggest that NAFLD/MAFLD and their associated metabolic conditions may represent modifiable risk factors for nephrolithiasis. PLAIN-LANGUAGE SUMMARY: Evidence on the association between nonalcoholic fatty liver disease (NAFLD) or metabolic dysfunction-associated fatty liver disease (MAFLD) and the risk of nephrolithiasis remains limited. In this study, we assessed whether NAFLD or MAFLD were associated with an increased risk of developing nephrolithiasis by analyzing data from 2 large prospective cohorts in the People's Republic of China and the United Kingdom. Our findings demonstrated that individuals with NAFLD or MAFLD had a significantly higher risk of incident nephrolithiasis later in life. This increased risk remained consistent across different age and sex groups. Our findings underscore the importance of liver health as a potential risk factor for nephrolithiasis.
Zhang A, van Zwieten A, Hughes A
… +5 more, Kim S, Lambert K, Torrisi LG, Jaure A, Guha C
Am J Kidney Dis
· 2026 Mar · PMID 41238162
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RATIONALE & OBJECTIVE: Children with chronic kidney disease (CKD) and their families encounter many difficulties adjusting to diet and fluid restrictions, which can reduce adherence to dietary recommendations. This study...RATIONALE & OBJECTIVE: Children with chronic kidney disease (CKD) and their families encounter many difficulties adjusting to diet and fluid restrictions, which can reduce adherence to dietary recommendations. This study describes the perspectives and experiences of children with CKD and their caregivers regarding dietary intake. STUDY DESIGN: Systematic review and thematic synthesis of qualitative studies. SETTING & PARTICIPANTS: Children and adolescents with any stage of CKD and their caregivers. SELECTION CRITERIA FOR STUDIES: MEDLINE, Embase, PsycINFO, and CINAHL were searched from inception to July 2024. These databases were chosen because they cover biomedical, clinical, and qualitative research relevant to pediatric CKD and nutrition. DATA EXTRACTION: All text from the results/conclusion of the primary studies. ANALYTICAL APPROACH: Thematic synthesis. RESULTS: We included 70 studies involving 1,941 participants from 21 countries. We identified 5 themes: (1) frustrated by unpalatable food (unfulfilled by unappetizing meals, uninterested in food due to altered perception of taste, loss of control over food choices), (2) deprived by restrictions (breaking rules out of desperation, constant craving for forbidden food, limiting life participation, parental distress and relational strain from enforcing dietary restrictions), (3) compounding the burden of caregiving and clinical management (overwhelmed by food preparation and dietary demands, financial cost of adhering to special dietary needs), (4) agency in dietary decision making (strengthening nutritional literacy, autonomy in decision making about diet, regaining dietary freedom after transplant), and (5) controlling diet for health (motivated to stay well, instilling coping strategies for dietary adherence). LIMITATIONS: Several included studies did not specify patients' CKD stages. CONCLUSIONS: Children with CKD face dietary challenges leading to frustration, cravings, and occasional dietary nonadherence. These restrictions impact social interactions and daily routines. Strategies that improve nutrition literacy may enhance self-efficacy and social connectedness and facilitate better adherence to dietary recommendations. PLAIN-LANGUAGE SUMMARY: Children with chronic kidney disease (CKD) face significant challenges in following dietary and fluid restrictions, which often affect their daily lives and social interactions. This study examines how children with CKD and their caregivers feel about these restrictions. We reviewed 70 studies to gather the perspectives of patients and caregivers on their dietary experiences. We found that many children felt frustrated by bland foods, and their caregivers often struggled with enforcing recommended diets. Despite these difficulties, both patients and caregivers developed coping strategies such as seeking advice from dietitians and supporting each other. This research highlights the importance of improving nutritional support and emotional well-being to help families manage their children's CKD.
van de Laar SC, de Heus HA, Massey EK
… +4 more, Pengel LHM, Porte RJ, Dor FJMF, Minnee RC
Am J Kidney Dis
· 2026 Feb · PMID 41238161
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RATIONALE & OBJECTIVE: Living donor kidney transplantation is considered the most effective treatment for end-stage kidney disease, but healthy individuals who donate may experience potential threats to their long-term w...RATIONALE & OBJECTIVE: Living donor kidney transplantation is considered the most effective treatment for end-stage kidney disease, but healthy individuals who donate may experience potential threats to their long-term well-being. This meta-analysis assessed the impact of living kidney donation on health-related quality of life (HRQoL) among donors overall and among those at higher risk for negative health impacts. STUDY DESIGN: Systematic review and meta-analysis. SETTING & PARTICIPANTS: Living donors of kidney allografts included in studies of postdonation HRQoL with predefined inclusion and exclusion criteria. Studies were identified through a comprehensive search of Embase, MEDLINE OvidSP, CENTRAL, Web of Science, PsycINFO, and the top 100 rankings in Google Scholar. DATA EXTRACTION: Data were extracted in accordance with PRISMA guidelines, with independent extraction by multiple observers to ensure accuracy. ANALYTICAL APPROACH: Primary outcomes included the 36-item Short-Form Health Survey (SF-36) and its composite mental component summary (MCS) and physical component summary (PCS). These measures were used to compare postdonation HRQoL with predonation levels and to the HRQoL of the general population. Study-level effects were calculated as standardized mean differences for continuous variables. Pooled effects were estimated with a random-effects model using restricted maximum likelihood. RESULTS: The meta-analysis included 73 studies with 14,474 donors. The MCS did not show significant changes at 3, 6, or 12 or more months after donation compared with baseline. However, the PCS was significantly lower at 3 months after donation compared with before donation (standardized mean difference, -0.38 [95% CI, -0.72 to -0.05], P = 0.02), which did not persist at 6 or 12 months. Both PCS and MCS scores were significantly higher in donors than in the general population. Donors' HRQoL scores were comparable to or better than those of healthy controls, recipients, patients who underwent a nephrectomy, and patients receiving maintenance dialysis. LIMITATIONS: Heterogeneity in study populations and outcomes, a limited number of studies for certain comparisons, methodological weaknesses of especially older studies, variability across geographies studied, and unaccounted for temporal changes. CONCLUSIONS: Kidney donors reported physical HRQoL to be decreased after living donor nephrectomy, which returned to predonation levels by 6 months. The HRQoL reported by living donors was significantly better than that of the general population and healthy controls. These findings suggest that concerns about postdonation HRQoL need not be a deterrent to potential living kidney donors. TRIAL REGISTRATION: Registered at PROSPERO with study number CRD42024540202. PLAIN-LANGUAGE SUMMARY: This study examined the well-being of living kidney donors after donation by summarizing the findings of 73 studies, which included more than 14,000 donors. Overall, the donors' quality of life remained high. Their physical health was slightly lower 3 months after donation but returned to predonation levels shortly afterward. Their quality of life related to mental health remained unchanged after donation. Donors generally experienced health comparable to or better than that of the general population and other patient groups. Certain factors, such as complications or stress related to the recipient's condition, may temporarily have affected donors' well-being, but most recovered fully within a year. These findings may reassure potential donors that kidney donation does not typically have long-term negative effects on their health.
Am J Kidney Dis
· 2026 Mar · PMID 41238160
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Systemic lupus erythematosus (SLE) is a chronic, multiorgan autoimmune disease, with lupus nephritis (LN) affecting up to 60% of patients. Early diagnosis and treatment are critical for preserving kidney function. Advanc...Systemic lupus erythematosus (SLE) is a chronic, multiorgan autoimmune disease, with lupus nephritis (LN) affecting up to 60% of patients. Early diagnosis and treatment are critical for preserving kidney function. Advances in understanding the immunopathogenesis of LN are driving the development of personalized treatment strategies that hold promise for transforming disease management through interventions targeting distinct immunologic and histopathologic features. In this review, we discuss current and emerging therapies for proliferative and membranous LN with a focus on strategies targeting underlying mechanisms of disease in LN. Glucocorticoids with cytotoxic agents or mycophenolate mofetil (MMF) remain the standard of care, but newer therapies targeting B cells (eg, belimumab and obinutuzumab) and T cells (eg, voclosporin) have proven efficacy as add-on treatments. Novel therapies such as complement and cytokine inhibitors are being evaluated in preclinical and clinical trials. Although maintenance therapy with MMF remains the standard, the distinction between sequential induction and maintenance therapy has become increasingly blurred, and new strategies to reduce long-term disease and pharmacologic toxicity to improve remission and relapse rates are emerging.
Wiebe N, Thompson S, Spellman A
… +2 more, Lam NN, Tonelli M
Am J Kidney Dis
· 2026 Feb · PMID 41238158
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RATIONALE & OBJECTIVE: International guidelines do not consider moderate or severe obesity to be a contraindication to kidney transplantation, but clinical practice suggests otherwise. This study evaluated the likelihood...RATIONALE & OBJECTIVE: International guidelines do not consider moderate or severe obesity to be a contraindication to kidney transplantation, but clinical practice suggests otherwise. This study evaluated the likelihood of kidney transplantation in patients with moderate or severe obesity and how that likelihood compared with patients with other risk factors. STUDY DESIGN: Retrospective population-based cohort study. SETTING & PARTICIPANTS: 96,181 adults with kidney failure, living in Canada between 2000 and 2021. EXPOSURE: Moderate or severe obesity and other risk factors (eg, age groups, diabetes, heart disease). OUTCOME: Time to transplantation and time to allograft failure or death. ANALYTICAL APPROACH: Parametric survival modeling, adjusting for all risk factors. RESULTS: Over a median follow-up period of 2.5 years, 58.2% of patients died, and 16.3% were transplanted. Participants with severe (body mass index [BMI] ≥ 40 kg/m) or moderate (BMI 35.0-39.9 kg/m) obesity were less likely to be transplanted than the control participants (BMI 18.5-24.9 kg/m) (HR, 0.43 [95% CI, 0.39-0.47] and HR, 0.76 [95% CI, 0.71-0.82], respectively). Of 39 characteristics/categories considered, only participants aged ≥80 years were less likely to receive a transplant than those with severe obesity. Transplant recipients were followed for a median of 5.4 years. After those aged ≥65 years, participants with severe obesity were the most likely to experience allograft failure or death (HR, 1.70 [95% CI, 1.38-2.02] compared with controls). When we considered combinations of key risk factors, young participants with severe or moderate obesity and few comorbidities were at lower risk for allograft failure or death than participants with other common clinical characteristics. LIMITATIONS: Residual confounding. CONCLUSIONS: Canadian dialysis patients with moderate or severe obesity had a markedly reduced likelihood of receiving a kidney transplant. Although patients with moderate or severe obesity also had a heightened risk of allograft failure or death, the magnitude of the latter was similar to the excess risk associated with other common clinical characteristics. These findings support current practice guidelines and suggest that further work should identify and remove barriers to accessing kidney transplantation among patients with obesity. PLAIN-LANGUAGE SUMMARY: International guidelines do not consider moderate or severe obesity (body mass index ≥35 and ≥40 kg/m, respectively) to be a contraindication to kidney transplantation, but clinical practice suggests otherwise. Canadian dialysis patients with moderate or severe obesity had a reduced likelihood of receiving a kidney transplant (24% and 57%, respectively). Although patients with moderate or severe obesity also had a heightened risk of allograft failure or death (36% and 70%, respectively), the magnitude of the latter was similar to the excess risk associated with other common clinical characteristics that do not exclude a patient from kidney transplantation. These findings support current practice guidelines and suggest that further work should identify and remove barriers to accessing kidney transplantation among patients with moderate and severe obesity.
Am J Kidney Dis
· 2026 Mar · PMID 41205644
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RATIONALE & OBJECTIVE: Kidney transplant (KT) ameliorates the underlying abnormalities contributing to skeletal fragility in chronic kidney disease, but fracture rates increase after transplant. This study sought to asse...RATIONALE & OBJECTIVE: Kidney transplant (KT) ameliorates the underlying abnormalities contributing to skeletal fragility in chronic kidney disease, but fracture rates increase after transplant. This study sought to assess the impact of changes in body composition and mineral metabolism on bone mineral density (BMD) and structure following kidney KT. STUDY DESIGN: 24-month prospective cohort study. SETTING & PARTICIPANTS: 60 incident KT recipients and 361 healthy controls aged 20-60 years. OUTCOMES: Tibia volumetric BMD (vBMD) and cortical dimensions measured using peripheral quantitative computed tomography and areal BMD (aBMD), appendicular lean mass index (ALMI), and fat mass index measured using dual-energy X-ray absorptiometry. ANALYTICAL APPROACH: Analytical Approach: Outcomes were converted to sex-specific z scores for age and compared with those in 361 controls. Quasi-least-squares regression models identified correlates of change. RESULTS: At baseline, ALMI, trabecular and cortical vBMD, cortical thickness, and total hip, femoral neck, and ultradistal radius aBMD were lower in KT recipients versus controls (P ≤ 0.003). During the first 6 months after KT, ALMI, fat mass index, and body mass index (BMI) increased (P < 0.001), whereas tibia trabecular vBMD and lumbar spine aBMD decreased (P ≤ 0.005). Cortical vBMD increased from 6 months onward (P < 0.001) in association with decreasing parathyroid hormone levels (P = 0.004). Cortical thickness decreased between 6 and 24 months (P = 0.002) because of a loss of endocortical bone. Total hip and femoral neck aBMD remained stable for 6 months, then improved through 24 months (P ≤ 0.02). Ultradistal radius aBMD decreased throughout the study (P ≤ 0.003). Higher BMI and ALMI were associated with gains in hip and spine aBMD and trabecular vBMD (all P ≤ 0.02). Corticosteroid dose was negatively associated with changes in spine and hip aBMD and cortical and trabecular vBMD (all P ≤ 0.02). Higher bone turnover marker levels and loss of cortical vBMD and thickness were associated with increases in serum calcium concentrations (P ≤ 0.03). LIMITATIONS: Not generalizable to older KT recipients. CONCLUSIONS: Skeletal deficits in KT recipients largely stabilize or improve beyond 6 months, with the exception of progressive cortical thinning. Strategies are needed to preserve cortical bone before and after KT. Gains in BMI and ALMI may improve bone health in the weight-bearing skeleton following KT. PLAIN-LANGUAGE SUMMARY: We enrolled 60 adults at the time of kidney transplant (KT) and compared measures of bone and muscle mass versus those in 361 healthy individuals. At the time of transplant, KT recipients had low muscle mass, low bone density, and thin bones compared with healthy individuals. After transplant, KT recipients rapidly gained muscle and fat. Despite the adverse effect of corticosteroid medications on bone, hip bone density improved significantly between 6 and 24 months. More muscle was associated with greater gains in hip and spine bone density over 2 years. In contrast, long bones got progressively thinner in association with biomarkers of bone breakdown. This study improves our understanding of the contributions of corticosteroids, muscle, and mineral metabolism on changes in bone density and thickness after KT, as well as the potential for recovery of bone density at selected skeletal sites.
RATIONALE & OBJECTIVE: Sodium/glucose cotransporter 2 (SGLT2) inhibitors substantially slow progression of chronic kidney disease and reduce the risk of acute kidney injury, but their effects on kidney physiology are inc...RATIONALE & OBJECTIVE: Sodium/glucose cotransporter 2 (SGLT2) inhibitors substantially slow progression of chronic kidney disease and reduce the risk of acute kidney injury, but their effects on kidney physiology are incompletely understood. This study assessed the effects of empagliflozin on a comprehensive set of urinary tubular and glomerular biomarkers. STUDY DESIGN: Randomized controlled trial. SETTING & PARTICIPANTS: 2,752 participants from EMPA-KIDNEY. EXPOSURE: Empagliflozin, 10 mg daily, versus placebo. OUTCOME: Urine biomarkers indexed to urinary creatinine and averaged across on-study time points. Urine biomarkers included markers of glomerular disease (albumin, total protein); proximal tubular reabsorption (α-microglobulin [A1M]); functional tubular reserve (epidermal growth factor [EGF], uromodulin [UMOD]); tubular injury/inflammation (kidney injury molecule-1 [KIM-1], neutrophil gelatinase-associated lipocalin [NGAL]); and tubular ischemia/stress (dickkopf-3 [DKK-3], monocyte chemoattractant protein-1 [MCP-1]). ANALYTICAL APPROACH: Mixed model repeated measures. RESULTS: Allocation to empagliflozin reduced urinary albumin by 19% (95% CI, -24% to -14%), total protein by 7% (-11% to -2%), and UMOD by 63% (-65% to -61%). It increased A1M by 29% (25%-34%), DKK-3 by 22% (16%-29%), and NGAL by 7% (0-13%). Overall, there were no significant effects on EGF (1% [-1% to 4%]), KIM-1 (2% [-1% to 6%]), and MCP-1 (0 [-4% to 3%]). The magnitude of effects on biomarker levels was generally similar at 2 and 18 months of follow-up. The large reductions in UMOD were evident regardless of baseline diabetes status, primary cause of kidney disease, and level of estimated glomerular filtration rate (eGFR) and/or albuminuria. Exploratory mediation analyses suggest that reductions in albuminuria and UMOD accounted for 32% (15% to 52%) of the beneficial effect of empagliflozin on chronic eGFR slope. LIMITATIONS: The mediation analyses cannot be used to formally confirm that UMOD reduction is a causal mediator for the kidney benefits of SGLT2 inhibitors. CONCLUSIONS: SGLT2 inhibition imparts a large and sustained reduction in urinary UMOD and also increases some biomarkers partially reabsorbed by proximal tubules without consistently affecting markers of tubular injury. These effects deserve further detailed experimental exploration, particularly the effect on thick ascending limb-derived UMOD, which could represent a novel mechanism of kidney protection. PLAIN-LANGUAGE SUMMARY: Sodium/glucose cotransporter 2 inhibitors or "flozins" are medications that prevent kidney failure and acute kidney injury in a broad range of patients with kidney disease. However, exactly how these drugs exert their kidney protective effects is incompletely understood. In a large clinical trial involving patients with varying causes of kidney disease, empagliflozin reduced excretion of 2 common proteins in the urine (albumin and uromodulin). The substantial reduction in uromodulin was unexpected and is of particular interest because uromodulin is manufactured in a later part of the kidney beyond the site of action of empagliflozin. New experiments are needed to understand these results and assess whether the effect on uromodulin can explain the benefits of flozins for the kidney.
Am J Kidney Dis
· 2025 Dec · PMID 41143760
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Hematologic abnormalities including both cytopenias and cytoses are the rule rather than the exception in the first year after kidney transplantation, yet many are benign reflections of immunosuppression, infection proph...Hematologic abnormalities including both cytopenias and cytoses are the rule rather than the exception in the first year after kidney transplantation, yet many are benign reflections of immunosuppression, infection prophylaxis, or residual chronic kidney disease. In this Core Curriculum, we distill the evidence on the disorders clinicians encounter most often, cytopenias including neutropenia, lymphopenia, anemia, thrombocytopenia, and thrombotic microangiopathy, as well as cytoses including eosinophilia, lymphocytosis, erythrocytosis, and thrombocytosis. Each is framed by typical timing, dominant mechanisms, key drugs or pathogens, and decision making checkpoints. Five real-world cases illustrate how to differentiate harmless findings from conditions that mandate prompt action, such as drug-induced marrow suppression, cytomegalovirus reactivation, antibiotic-triggered eosinophilia, posttransplant erythrocytosis, and thrombotic microangiopathy. Adopting this problem-oriented approach can reduce unnecessary drug interruptions, target hematology referrals, and preserve both patient safety and allograft longevity.
Am J Kidney Dis
· 2026 Jan · PMID 41135690
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RATIONALE & OBJECTIVE: The Kidney Donor Risk Index (KDRI) is widely used to rank the quality of deceased-donor kidneys and is integrated into the U.S. kidney allograft allocation system. However, the KDRI has modest pred...RATIONALE & OBJECTIVE: The Kidney Donor Risk Index (KDRI) is widely used to rank the quality of deceased-donor kidneys and is integrated into the U.S. kidney allograft allocation system. However, the KDRI has modest predictive accuracy for allograft survival, and recent revisions to the KDRI, which removed donor race and hepatitis C virus status, also revealed model calibration problems. This study aimed to evaluate novel approaches for predicting posttransplant allograft survival. STUDY DESIGN: Retrospective cohort study using Organ Procurement and Transplantation Network data from May 1, 2007, through December 31, 2021. PREDICTORS: (1) Donor demographic and clinical variables (established predictors); (2) longitudinal laboratory data from the donor's terminal hospitalization, such as serum creatinine (new predictors); and (3) recipient clinical variables (new predictors). SETTING & PARTICIPANTS: 75,867 adult kidney recipients at U.S. OUTCOMES: The primary outcome was time to all-cause allograft failure over 3 years. A secondary outcome was delayed graft function, defined as dialysis in the first week after the transplant. ANALYTICAL APPROACH: We implemented and compared machine-learning statistical models versus traditional modeling approaches (ie, proportional hazards for the primary outcome and logistic regression of the secondary outcome) that incorporated various combinations of predictors. The performance metrics used to assess discrimination were the integrated (time-dependent) area under the curve (AUC) for allograft survival and the AUC for delayed graft function. To assess calibration, we calculated Brier scores and visually compared the predicted outcomes with the observed ones. Predictive performance was assessed in a 20% testing data split. RESULTS: Neither machine-learning models nor the addition of longitudinal laboratory data from the donor hospitalization to traditional models improved discrimination. For the primary outcome, the final model (named the Kidney Allograft Survival Index) used a proportional hazards modeling approach. Adding recipient variables improved model discrimination (integrated AUC, 0.68) and achieved excellent calibration for the overall cohort and subgroups. The final model for delayed allograft function used logistic regression, included recipient variables, and had an AUC of 0.75 with acceptable calibration. LIMITATIONS: No external validation. CONCLUSIONS: Improving the discrimination and calibration of kidney allograft survival prediction models is achievable by including recipient characteristics. These enhanced models have potential to improve the system of kidney allocation.