Although donor and recipient characteristics are used to estimate graft failure risk, they remain limited in predicting early acute rejection. We developed and validated a next-generation sequencing (NGS) assay targeting the pre-transplant immunologic profile to predict early acute rejection following kidney transplantation. This prospective, international study enrolled 321 kidney transplant participants across 13 sites, forming discovery and validation cohorts. Peripheral blood was collected prior to transplant and at 1, 3, 6, 12, and 24 months post-transplant, with protocol biopsies performed at 3 and 12 months, as well as any indication biopsies. Biopsies were assessed by a blinded central pathologist according to the 2019 Banff criteria. The pre-transplant risk assessment (PTRA™) test to evaluate RNA expression of a 29-gene signature algorithm designed to predict early acute rejection risk was clinically validated utilizing 122 deceased donor kidney transplant recipients. PTRA classified 31 of 122 participants (25%) as high-risk and 91 (75%) as low-risk. There were 9 early acute rejection events in the first 60 days post-transplant: 6/31 (19%) in the high-risk group and 3/91 (3%) in the low-risk group. PTRA discrimination for early acute rejection at 60 days post-transplant yielded an AUC of 0.78 (95% confidence interval [CI]: 64.4 to 91.5), p<0.001. A cut-off of ≤45 was defined as low-risk and >45 as high-risk for early acute rejection within 60 days post-transplant. Sensitivity 0.67 (95% CI: 0.36 to 0.97), specificity 0.78 (95% CI: 0.70 to 0.86), positive predictive value 0.19 (95% CI: 0.05 to 0.33), and negative predictive value 0.97 (95% CI: 0.93 to 1.00). The odds ratio comparing patients identified as high- vs low-risk by PTRA was 7.04 (95% CI: 1.64 to 30.2), p=0.009. This study validates the ability of PTRA to stratify kidney transplant recipients as high- or low-risk for early acute rejection using a pre-transplant transcriptomic profile, with implications for graft health and personalized treatment management.

Hemodialysis Reliable Outflow (HeRO) graft and femoral arteriovenous graft (fAVG) are alternative options for patients who have exhausted upper extremity AV access due to central venous occlusion. This study aims to provide a contemporary comparison between HeRO and fAVG. Retrospective chart review of consecutive fAVG and HeRO placed between 2016 and 2023 at a multihospital health care system was conducted. Cases were identified using the local Vascular Quality Initiative database and supplemented by charts review. Baseline characteristics, operative details, and follow-up data were obtained. Data were analysed using standard statistical tests, Kaplan-Meier survival analysis, and multivariate Cox proportional hazards. Data for 114 access were collected (68 HeRO, 46 fAVG) from 105 unique patients. HeRO patients were older (66.1 vs 57.7 years), had higher body mass index (31.8 vs 27.9 kg/m2), were more likely to have a history of atrial fibrillation (56% vs 20%), and fewer previous AV accesses (mean 1.4 vs 2.4). The ability to use the graft for hemodialysis was higher in the HeRO group (94% vs 83%; p=0.049). At 36 months, the primary patency rate was 5% for the HeRO graft and 17% for the fAVG (p=0.45), while the secondary patency rates were 30% and 54 (p=0.25), respectively. Thrombosis was the predominant cause of HeRO graft abandonment (78%), whereas infection was most common for fAVGs (44%). On Kaplan Meier analysis, mortality was similar for HeRO and fAVG (p=0.22). Six (9%) patients from the HeRO group and 10 (22%) from the fAVG underwent graft removal due to infection (p=0.05). The rate steal did not differ between both groups (HeRO 6% vs fAVG 11%; p=0.33); however, among fAVG patients, two required access ligation and two underwent limb amputation (HeRO: 0% vs fAVG: 9%; p = 0.01). HeRO is a reasonable alternative for patients who have exhausted upper extremity AV access, offering higher likelihood of obtaining functional patency and fewer complications compared to fAVG.

Traditional methods of surgical decision making heavily rely on human experience and prompt actions, which are variable. A data-driven system that generates treatment recommendations based on patient states can be a substantial asset in perioperative decision-making for cases of intraoperative hypotension in which suboptimal management is associated with acute kidney injury (AKI), a common and morbid postoperative complication. In this retrospective cohort study, we analyzed 50,021 surgeries from 42,547 adult patients who underwent major surgery at a quaternary care hospital between 2014 and 2020. We developed a deep reinforcement learning model to recommend the optimum doses of intravenous fluids and vasopressors during surgery to avoid intraoperative hypotension and AKI defined by Kidney Disease: Improving Global Outcomes serum creatinine criteria within three days following surgery. The developed model replicated 69% of physician's decisions for the dosage of vasopressors and proposed higher or lower dosage of vasopressors than received in 10% and 21% of the treatments, respectively. In terms of intravenous fluids, the model's recommendations were within 0.05 ml/kg/15 min of the actual dose in 41% of the cases, with higher or lower doses recommended for 27% and 32% of the treatments, respectively. The reinforcement learning policy resulted in a higher estimated policy value compared to the physicians' actual treatments, as well as random policies and zero-drug policies. AKI incidence was lowest in patients who received medication dosages that aligned with our agent model's decisions. Our findings suggest that implementation of the model's policy has the potential to lower postoperative AKI and improve other outcomes driven by intraoperative hypotension.

Long-term outcome after kidney transplantation remains limited due to high risks of cardiovascular, infectious and malignant premature death. Uremic solutes, such as urea and symmetric dimethylarginine (SDMA) are suggested to contribute to higher oxidative stress, chronic low-grade inflammation, and excess mortality. Therefore, we evaluated the associations of urea and SDMA with all-cause and cause-specific mortality in kidney transplant recipients. Baseline plasma SDMA was measured using liquid chromatography-mass spectrometry in kidney transplant recipients enrolled in the prospective TransplantLines Food and Nutrition Biobank and Cohort Study (Groningen, The Netherlands). We assessed prospective associations of SDMA with all-cause and cause-specific mortality using Cox regression. We included 628 adult kidney transplant recipients (56% male, age: 53±13 years, eGFR: 52±20 ml/min/1.73m2) at 5.4 [interquartile range: 1.8-12.0] years after transplantation. Median plasma urea was 9.6 [7.3, 13.4] mmol/L and plasma SDMA was 20 [15-25] µg/dL. In Cox regression analyses, both plasma urea (hazard ratio per doubling: 2.21, 95% CI: 2.22 to 2.85) and plasma SDMA (hazard ratio per doubling: 2.69, 95% CI: 1.95 to 3.70) were strongly associated with a higher risk of all-cause mortality. These associations remained for SDMA but not urea in a fully adjusted model and the observed associations were generally similar for all causes of death. Plasma urea and SDMA are both associated with a higher mortality risk in outpatient kidney transplant recipients. In a model including both urea and SDMA, only the association of SDMA with mortality remained.

Hyponatremia is the most common electrolyte disorder and is encountered by physicians across multiple specialties. Its management requires precise correction of the serum sodium level, which may benefit from the involvement of specialists, particularly nephrologists. This study aimed to evaluate the impact of nephrology consultation on mortality. This retrospective observational study included patients with severe hyponatremia (serum sodium level ≤120 mEq/L) at admission or during hospitalization between January 2014 and June 2024 in two tertiary care centers. Nephrology consultation was defined as any therapeutic involvement by nephrologists within 24 hours of the onset of severe hyponatremia. The association of nephrology consultation with in-hospital and 30-day mortality was assessed using inverse probability of treatment weighting based on propensity scores. A total of 942 patients were included in the analysis, of whom 342 (36%) received nephrology consultation and 600 (64%) did not. The median (interquartile range) age was 73 (62-82) years, 430 (46%) patients were female, and serum sodium levels were 118 (116-119) mEq/L. In weighted logistic regression analyses, nephrology consultation was associated with lower in-hospital and 30-day mortality (odds ratio [OR], 0.55; 95% confidence interval [CI], 0.37-0.83 and OR, 0.62; 95% CI, 0.40-0.96, respectively). Osmotic demyelination syndrome occurred in three patients, with no significant difference in incidence between the two groups (P = 0.27). Early nephrology consultation was associated with lower in-hospital and 30-day mortality in patients with severe hyponatremia, underscoring the importance of collaboration between nephrologists and other specialties in its management.

Cisplatin remains a key chemotherapy for many solid tumors, but its dose-limiting nephrotoxicity affects up to one-third of patients and has no effective pharmacologic prevention beyond hydration and magnesium supplementation. Preclinical studies highlight sodium-glucose cotransporter 2 (SGLT2) inhibitors as promising nephroprotective agents during cisplatin therapy, independent of glucose lowering. We conducted a PubMed search using predefined terms related to cisplatin nephrotoxicity and SGLT2 inhibitors, identifying seven non-diabetic rodent studies. Across these models, SGLT2 inhibitors consistently attenuated kidney injury through complementary mechanisms: suppression of inflammatory, oxidative, and apoptotic pathways, activation of AMP-activated protein kinase-dependent autophagy, reduction of kidney platinum accumulation, and, uniquely, correction of cisplatin-induced hypomagnesemia, a clinically significant complication. Protective effects occurred without compromising cisplatin's antitumor efficacy in vitro. Overall, these findings support SGLT2 inhibitors as a mechanistically versatile strategy that targets key injury pathways in platinum nephrotoxicity. Although prospective clinical application remains untested, the strong biologic rationale, reproducibility across models, and established safety of SGLT2 inhibitors in other populations underscore the urgency of translation. Future clinical trials should incorporate rigorous assessments of kidney function, tubular injury biomarkers, and urinary extracellular vesicle profiling to define the safety, efficacy, and mechanistic insights of SGLT2 inhibitors in cisplatin nephrotoxicity.

Patient adherence limits the effectiveness of preventive pharmacologic therapy (PPT) for urinary stone disease (USD), highlighting the need for accurate adherence monitoring. We assessed associations between potassium citrate adherence measures, changes in 24-hour urine parameters, and the risk of recurrent stone events. In this retrospective cohort study, we identified adults enrolled in Medicare with USD, a baseline 24-hour urine collection (2010-2019), hypocitraturia or low urine pH, a prescription for potassium citrate monotherapy, and a follow-up urine collection. We defined two adherence measures: (1) percentage of days covered (PDC) using pharmacy claims and (2) change in urinary potassium between baseline and follow-up divided by medication dose (ΔK/dose). We assessed the association of these measures with changes in urinary citrate and pH using analysis of covariance, and the association between adherence and recurrent stone events using Cox models. Among 793 patients meeting study criteria, 504 (63.6%) were adherent based on pharmacy claims (PDC≥80%) and 389 (49.1%) based on ΔK/dose≥0.5. Compared to PDC≥80%, ΔK/dose≥0.5 had a stronger association with change in urinary citrate (p<0.001) and pH (p<0.001). Compared to PDC≥80%, patients with PDC<80% had a higher risk of recurrent stone events (hazard ratio [HR] 1.431; 95% confidence interval [CI], 1.049-1.952), whereas ΔK/dose was not statistically significantly associated with recurrent stone events (HR 1.032; 95% CI, 0.740-1.439). There are clinically meaningful differences in potassium citrate adherence measures. ΔK/dose was more strongly associated with the change in urinary citrate and pH. However, only PDC was significantly associated with recurrent stone events.

Approximately half of people on maintenance hemodialysis exhibited impairment on a standardized, performance-based assessment of functional cognition. The functional cognitive test correlated strongly with a traditional cognitive screening tool but weakly with self-report functional assessments. Older age and ethnic minority were significant predictors of functional cognitive impairment. People on maintenance hemodialysis are often unable to perform everyday activities without assistance. The extent to which their functional limitations are related to cognitive impairment is unclear. Our primary aim was to estimate the proportion of people on maintenance hemodialysis who demonstrate impairment on a standardized, performance-based test of functional cognition. We conducted a quantitative descriptive, cross-sectional study across two dialysis centers in Toronto, Canada. We administered a functional cognitive assessment (University of California San Diego Performance-Based Skills Assessment-Brief [UPSA-B]), a cognitive screening tool (Montreal Cognitive Assessment [MoCA]), and two self-report measures of everyday functioning (Barthel Index and Lawton-Brody Instrumental Activities of Daily Living [IADL] scale) during the first hour of a hemodialysis session. We calculated the proportion of participants with UPSA-B scores indicating functional cognitive impairment (<78). We also calculated correlations between the UPSA-B and the MoCA, Barthel Index, and Lawton-Brody IADL scale and used multivariable logistic regression to explore predictors of impairment on the UPSA-B. One hundred and five people on hemodialysis consented to participate. The mean age was 68 (12) years, 71% were male, and the median dialysis vintage was 36 months. 56 (54%) participants displayed impairment on the UPSA-B (95% confidence interval [CI], 44% to 64%). There was a strong correlation between the UPSA-B and the MoCA (r=0.67, P < 0.001) and weak correlations between the UPSA-B and the Barthel Index (r=0.38, P < 0.001) and Lawton-Brody IADL scale (r=0.39, P < 0.001). Older age (odds ratio, 1.13; 95% CI, 1.07 to 1.20) and ethnicity (odds ratio, 17.8; 95% CI, 4.71 to 67.50) were significant predictors of impairment on the UPSA-B in multivariable modeling. Functional cognitive impairment appears to be common in people on hemodialysis. Future research should investigate approaches such as cognitive rehabilitation to support everyday functioning in this population.