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Restless legs syndrome is a common sleep disorder, but there is a paucity of large cohort studies examining the association of restless legs syndrome with clinical outcomes, including all-cause mortality, incident coronary heart disease, stroke and chronic kidney disease. From a nationally representative prospective cohort of over 3 million US veterans [93% male, median follow-up time of 8.1 years (interquartile range: 7.0-8.5 years)] with baseline estimated glomerular filtration rate ≥60 mL min-1 1.73 m-2, a propensity-matched cohort of 7392 patients was created, and the association between incident restless legs syndrome and the following was examined: (1) all-cause mortality; (2) incident coronary heart disease; (3) incident strokes; and (4) incident chronic kidney disease defined as estimated glomerular filtration rate

Traditional risk factors of cardiovascular death in the general population, including body mass index (BMI), serum cholesterol, and blood pressure (BP), are also found to relate to outcomes in the geriatric population, but in an opposite direction. Some degrees of elevated BMI, serum cholesterols, and BP are reportedly associated with lower, instead of higher, risk of death among the elderly. This phenomenon is termed "reverse epidemiology" or "risk factor paradox" (such as obesity paradox) and is also observed in a variety of chronic disease states such as end-stage renal disease requiring dialysis, chronic heart failure, rheumatoid arthritis, and AIDS. Several possible causes are hypothesized to explain this risk factor reversal: competing short-term and long-term killers, improved hemodynamic stability in the obese, adipokine protection against tumor necrosis factor-α, lipoprotein protection against endotoxins, and lipophilic toxin sequestration by the adipose tissue. It is possible that the current thresholds for intervention and goal levels for such traditional risk factors as BMI, serum cholesterol, and BP derived based on younger populations do not apply to the elderly, and that new levels for such risk factors should be developed for the elderly population. Reverse epidemiology of conventional cardiovascular risk factors may have a bearing on the management of the geriatric population, thus it deserves further attention.

Background - In the general population, blacks experience higher mortality than their white peers, attributed in part to their lower socioeconomic status, reduced access to care, and possibly intrinsic biological factors. Patients with kidney disease are a notable exception, among whom blacks experience lower mortality. It is unclear if similar differences affecting outcomes exist in patients with no kidney disease but with equal or similar access to health care. Methods and Results - We compared all-cause mortality, incident coronary heart disease, and incident ischemic stroke using multivariable-adjusted Cox models in a nationwide cohort of 547 441 black and 2 525 525 white patients with baseline estimated glomerular filtration rate ≥60 mL·min-1·1.73 m-2 receiving care from the US Veterans Health Administration. In parallel analyses, we compared outcomes in black versus white individuals in the National Health and Nutrition Examination Survey (NHANES) 1999 to 2004. After multivariable adjustments in veterans, black race was associated with 24% lower all-cause mortality (adjusted hazard ratio, 0.76; 95% confidence interval, 0.75-0.77; P

Rationale There is a paucity of large cohort studies examining the association of obstructive sleep apnoea (OSA) with clinical outcomes including all-cause mortality, coronary heart disease (CHD), strokes and chronic kidney disease (CKD). Objectives We hypothesised that a diagnosis of incident OSA is associated with higher risks of these adverse clinical outcomes. Methods, measurements In a nationally representative cohort of over 3 million (n=3 079 514) US veterans (93% male) with baseline estimated glomerular filtration rate (eGFR)≥60 mL/min/1.73 m2, we examined the association between the diagnosis of incident OSA, treated and untreated with CPAP, and: (1) all-cause mortality, (2) incident CHD, (3) incident strokes, (4) incident CKD defined as eGFR

Background: Protein–energy wasting (PEW) is a common condition in patients with chronic kidney disease (CKD) including dialysis and kidney transplant recipients (TX) and frequently assessed with malnutrition–inflammation score (MIS). We hypothesized that (1) the MIS and PEW parameters are correlated with kidney function and (2) the MIS and PEW parameters are more severe in TX than in non-dialysis (ND) CKD patients with similar eGFR. Methods: In this study, we matched 203 ND-CKD and 203 TX patients from two independently assembled cohorts of patients based on estimated glomerular filtration rate (eGFR) and compared various PEW parameters between the two groups using unadjusted and case-mix adjusted linear regression and conditional logistic regression analysis models. Results: In the combined cohort (n = 406) of patients, the mean ± SD age was 57 ± 12 years; included 55 % men and 35 % diabetics; and demonstrated a mean ± SD baseline eGFR of 29 ± 11 ml/min/1.73 m2. The eGFR correlated positively with serum albumin (ρ = 0.26, p

Aggressive NIH is a common histopathological lesion found at the sites of venous stenosis in arteriovenous fistula (AVF) and arteriovenous grafts (AVG). Inflammatory mediators have been proposed to play a pathogenic role in NIH, but there is paucity of data evaluating this hypothesis in clinical studies or in animal models. Serum levels of inflammatory mediators can potentially identify patients at high risk of AVF and AVG dysfunction. In a cross-sectional cohort study of 754 HD patients who were part of the NIED study cohort, we examined the associations between inflammatory markers including serum interleukin (IL) 1β, IL-6, C-reactive protein (CRP), and tumor necrosis factor-α (TNF-α) and type of vascular access. Unadjusted and multivariate-adjusted linear regression models were used. In addition, time-dependent regression model was used to assess the association between inflammatory markers and mortality. We observed that in the multivariate-adjusted model, inflammatory mediators interleukin-6 (IL-6), interleukin-1L-ß (IL-1ß), and C-reactive protein (CRP), the predicted value in hemodialysis patients, are lowest in patients with AVF and highest in central venous catheter (CVC) and AVG even in case-mix and malnutrition-inflammation complex syndrome (MICS)-adjusted models. IL-6 and CRP levels fall consistently in the same patients when AVG or CVC is changed to AVF and increase if the same patient changes access from AVF to AVG or CVC. Obesity is a risk factor for fistula failure and fistulas are associated with the lowest mortality compared with CVC and AVG. We did not find any statistically significant association between tumor necrosis factor-α (TNF- α) and vascular access outcomes. Higher levels of inflammatory mediators seen in CVC and AVG compared with AVF could potentially explain the higher mortality seen in patients with CVC and AVG compared with AVF. © 2013 Wiley Periodicals, Inc.

The association between pretransplant serum albumin concentration and post-transplant outcomes in kidney transplant recipients is unclear. We hypothesized that in transplant-waitlisted hemodialysis patients, lower serum albumin concentrations are associated with worse post-transplant outcomes. Linking the 5-year patient data of a large dialysis organization (DaVita) to the Scientific Registry of Transplant Recipients, we identified 8961 hemodialysis patients who underwent first kidney transplantation. Mortality or graft failure and delayed graft function (DGF) risks were estimated by Cox regression (hazard ratio [HR]) and logistic regression (Odds ratio [OR]), respectively. Patients were 48 ± 13 years old and included 37% women and 27% diabetics. The higher pretransplant serum albumin was associated with lower mortality, graft failure and DGF risk even after multivariate adjustment for case-mix, malnutrition-inflammation complex and transplant related variable. Every 0.2 g/dL higher pretransplant serum albumin concentration was associated with 13% lower all-cause mortality (HR = 0.87 [95% confidence interval: 0.82-0.93]), 17% lower cardiovascular mortality (HR = 0.83[0.74-0.93]), 7% lower combined risk of death or graft failure (HR = 0.93[0.89-0.97]) and 4% lower DGF risk (OR = 0.96[0.93-0.99]). Hence, lower pretransplant serum albumin level is associated with worse post-transplant outcomes. Clinical trials to examine interventions to improve nutritional status in transplant-waitlisted hemodialysis patients and their impacts on post-transplant outcomes are indicated.

A body mass index (BMI) below morbid obesity range is often a requirement for kidney transplant wait-listing, but data linking BMI changes to mortality during the waitlist period are lacking. By linking the 6-year (7/2001-6/2007) national databases of a large dialysis organization and the Scientific Registry of Transplant Recipients, we identified 14 632 waitlisted hemodialysis patients without kidney transplantation. Time-dependent survival models examined the mortality predictability of 13-week-averaged BMI, pretransplant serum creatinine as a muscle mass surrogate and their changes over time. The patients were on average 52 ± 13 years old, 40% women and had a BMI of 26.9 ± 6.3 kg/m². Each kg/m² increase of BMI was associated with a death hazard ratio (HR) of 0.96 (95%CI: 0.95-0.97). Compared to the lowest creatinine quintile, the 4th and 5th quintiles had death HRs of 0.75 (0.66-0.86) and 0.57 (0.49-0.66), respectively. Compared to minimal (< ± 1 kg) weight change over 6 months, those with 3 kg- < 5 kg and ≥ 5 kg weight loss had death HRs of 1.31 (1.14-1.52) and 1.51 (1.30-1.75), respectively. Similar associations were observed with creatinine changes over time. Transplant-waitlisted hemodialysis patients with lower BMI or muscle mass and/or unintentional weight or muscle loss have higher mortality in this observational study. Impact of intentional weight change remains unclear.

Overweight (body mass index [BMI] = 25-30 kg/m2) and obesity (BMI ≥ 30 kg/m2) have become mass phenomena with a pronounced upward trend in prevalence in most countries throughout the world and are associated with increased cardiovascular risk and poor survival. In patients with end stage renal disease (ESRD) undergoing maintenance hemodialysis an 'obesity paradox' has been consistently reported, i.e., a high BMI is incrementally associated with better survival. Whereas this 'reverse epidemiology' of obesity is relatively consistent in maintenance hemodialysis patients, studies in peritoneal dialysis patients have yielded mixed results. Moreover, the effect of pre-and post-transplant obesity in kidney transplanted patients on long-term graft and patient survival has not been well established. However, BMI is unable to differentiate between adiposity and muscle mass and may not be an acceptable metric to assess the body composition of ESRD patients. Assessing lean body mass, in particular skeletal muscle, and fat mass separately are needed in ESRD patients using gold standard techniques such as imaging techniques. Alternatively, inexpensive and routinely measured surrogate markers such as serum creatinine, waist and hip circumference or mid-arm muscle circumference can be used. We have reviewed and summarized salient recent data pertaining to body composition and clinical outcomes about the association of survival and body composition in maintenance dialysis patients and kidney transplanted recipients. © 2011 Kowsar M.P.Co. All rights reserved.

Higher body mass index (BMI) appears paradoxically associated with better outcomes in patients with chronic kidney disease. Whereas higher BMI reflects both increased visceral and subcutaneous fat and/or muscle mass, a combined assessment of BMI and waist circumference may enable differentiation of visceral adiposity from muscle and/or nonvisceral fat mass. We examined the association of BMI and waist circumference with all-cause mortality in a prospective cohort of 993 kidney transplant recipients. Associations were examined in Cox models with adjustment for demographic and comorbid conditions and for inflammatory markers. Unadjusted death hazard ratios (95%CI) associated with one standard deviation higher BMI and waist circumference were 0.94 (0.78, 1.13), p = 0.5 and 1.20 (1.00, 1.45), p = 0.05, respectively. Higher BMI was associated with lower mortality after adjustment for waist circumference (0.48 [0.34, 0.69], p < 0.001), and higher waist circumference was more strongly associated with higher mortality after adjustment for BMI (2.18 [1.55-3.08], p < 0.001). The associations of waist circumference with mortality remained significant after additional multivariable adjustments. Higher BMI and waist circumference display opposite associations with mortality in kidney transplant recipients. Waist circumference appears to be a better prognostic marker for obesity than BMI.

Previous observational studies using differing methodologies have yielded inconsistent results regarding the association between glycemic control and outcomes in diabetic patients receiving maintenance hemodialysis (MHD). We examined mortality predictability of A1C and random serum glucose over time in a contemporary cohort of 54,757 diabetic MHD patients (age 63 ± 13 years, 51% men, 30% African Americans, 19% Hispanics). Adjusted all-cause death hazard ratio (HR) for baseline A1C increments of 8.0-8.9, 9.0-9.9, and ≥10%, compared with 7.0-7.9% (reference), was 1.06 (95% CI 1.01-1.12), 1.05 (0.99-1.12), and 1.19 (1.12-1.28), respectively, and for time-averaged A1C was 1.11 (1.05-1.16), 1.36 (1.27-1.45), and 1.59 (1.46-1.72). A symmetric increase in mortality also occurred with time-averaged A1C levels in the low range (6.0-6.9%, HR 1.05 [95% CI 1.01-1.08]; 5.0-5.9%, 1.08 [1.04-1.11], and ≤5%, 1.35 [1.29-1.42]) compared with 7.0-7.9% in fully adjusted models. Adjusted all-cause death HR for time-averaged blood glucose 175-199, 200-249, 250-299, and ≥300 mg/dL, compared with 150-175 mg/dL (reference), was 1.03 (95% CI 0.99-1.07), 1.14 (1.10-1.19), 1.30 (1.23-1.37), and 1.66 (1.56-1.76), respectively. Hence, poor glycemic control (A1C ≥8% or serum glucose ≥200 mg/dL) appears to be associated with high all-cause and cardiovascular death in MHD patients. Very low glycemic levels are also associated with high mortality risk. [ABSTRACT FROM AUTHOR]

BACKGROUND: Depression is associated with impaired quality of life and increased morbidity and mortality in patients with end-stage renal disease. Little is known about the prevalence and correlates of depression in kidney transplant recipients. In this study, we aimed to compare depressive symptoms between kidney transplant recipients and wait-listed dialysis patients and identify the correlates of depressive symptoms in the transplant recipient population. STUDY DESIGN: Observational cross-sectional study using the Center for Epidemiologic Studies Depression Scale (CES-D) to assess the severity of depressive symptoms. A cutoff score of 18 was used to identify the presence of depression. SETTING & PARTICIPANTS: 1,067 kidney transplant recipients and 214 wait-listed dialysis patients were asked to participate; the final analysis included 854 kidney transplant and 176 wait-listed dialysis patients, respectively. PREDICTORS: Sociodemographic and clinical variables. OUTCOME: Severity of depressive symptoms and presence of depression (CES-D score > or = 18). RESULTS: The prevalence of depression was 33% versus 22% in wait-listed versus transplant patients, respectively (P = 0.002). In multivariate regression, number of comorbid conditions, estimated glomerular filtration rate, perceived financial situation, and marital status were significant and independent predictors of depression in the transplant recipient group. Treatment modality was associated significantly with the presence of depression, even after adjustment for clinical and sociodemographic variables (OR, 2.01; 95% CI, 1.25-3.23; P = 0.004). LIMITATIONS: Self-reported measurement of depressive symptoms. CONCLUSIONS: The prevalence of depression is lower in transplant recipients than in wait-listed patients. However, one-fifth of transplant patients are still at high risk of clinically significant depression. Comorbid conditions, socioeconomic status, and treatment modality predicted depressive symptoms in patients with end-stage renal disease. [ABSTRACT FROM AUTHOR]

BACKGROUND: Previous studies showed an association between the presence of restless legs syndrome (RLS) and mortality in patients on dialysis therapy. An association between RLS and cardiovascular risk also was reported in the general population. However, no prospective study to date assessed the association between the presence of RLS and mortality in kidney transplant recipients. In a prospective cohort study (Transplantation and Quality of Life-Hungary Study), we tested the hypothesis that the presence of RLS predicts mortality in transplant recipients. STUDY DESIGN: Prospective cohort study was performed. SETTINGS & PARTICIPANTS: 804 kidney transplant recipients followed up at a single outpatient transplant center were enrolled in the study. Sociodemographic parameters, laboratory data, and medical history were collected at baseline. Data for 4-year outcomes were collected prospectively from patient charts. PREDICTOR: Presence of RLS assessed using the RLS Questionnaire. OUTCOME & MEASUREMENTS: We defined 3 primary outcomes: mortality with functioning graft, return to dialysis therapy, and the combined outcome of these 2. RESULTS: Mean age was 49 +/- 13 years, estimated glomerular filtration rate was 49 +/- 19 mL/min/1.73 m(2), and median time after transplantation was 54 months. During the 4 years, 97 patients died and 63 patients returned to dialysis therapy. Mortality at 4 years was significantly greater in patients who had RLS at baseline: univariate hazard ratio for the presence of RLS was 2.53 (95% confidence interval, 1.31 to 4.87). In multivariate Cox proportional hazard analysis, the presence of RLS significantly predicted mortality (hazard ratio, 2.02; 95% confidence interval, 1.03 to 3.95) after adjustment for several covariables. LIMITATIONS: The RLS Questionnaire was not validated in transplant recipients. We lacked information for key variables, including HLA mismatch, panel reactive antibodies, cold ischemic time, acute rejection episodes, viral infections, smoking status, and dyslipidemia. CONCLUSIONS: RLS, a potentially treatable disease, is a significant risk factor for mortality in kidney transplant recipients. Copyright © 2007 by Elsevier Inc. [ABSTRACT FROM AUTHOR]

Background: In the United States, universal screening for human T-lymphotropic virus (HTLV) in deceased organ donors was discontinued in 2009. Since then, the transplant guideline suggests considering targeted screening. However, the outcomes of this change in HTLV screening have not been evaluated., Methods: Using the Organ Procurement and Transplantation Network database between 2010 and 2022, we analyzed the HTLV antibody screening frequency and seroprevalence in potential deceased organ donors and their correlations with HTLV infection risks, including race and high-risk behaviors for blood-borne pathogen infection. Although targeted screening has not been established for HTLV, we hypothesized that screening rates should correlate with the proportions of donors with infection risk if screening is targeted. We also evaluated the organ utilization of HTLV-seropositive donors., Results: Of 130 284 potential organ donors, 22 032 (16.9%) were tested for HTLV antibody. The proportion of donors tested for HTLV varied between Organ Procurement Organizations (median [interquartile range], 3.8% [1.0%-23.2%]; range, 0.2%-99.4%) and was not correlated to HTLV infection risks. There were 48 seropositive donors (0.22%), and at least 1 organ from 42 of these donors (87.5%) was transplanted. The number of organs recovered and transplanted per donor was significantly lower in HTLV-seropositive than in HTLV-negative donors (recovered, 2 [2-3] versus 3 [3-5], P  < 0.001; transplanted, 2 [1-3] versus 3 [2-4], P  < 0.001). However, HTLV-1 infection was not attributed as the cause of nonrecovery except for only 1 HTLV-seropositive donor., Conclusions: HTLV screening practices varied across the United States. Our findings suggest that targeted screening was not performed after the elimination of universal screening., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2024 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Background: It is unclear whether kidney grafts from deceased donors with acute kidney injury (AKI) are more vulnerable to calcineurin inhibitor nephrotoxicity, and whether de novo use of belatacept is more beneficial than tacrolimus for recipients of these types of kidney transplants., Methods: In this retrospective cohort study using the US Organ Procurement and Transplantation Network database, we created 1:4 matches with highly similar characteristics for recipients of AKI-donor kidneys receiving belatacept versus tacrolimus for initial maintenance immunosuppression and compared outcomes for graft function, patient and graft survival, and rejection., Results: The matched cohort consisted of 567 and 2268 recipients administered belatacept and tacrolimus, respectively. Posttransplant estimated glomerular filtration rate was significantly higher in the belatacept group at 6 mo (58.2 ± 24.2 versus 54.6 ± 21.6 mL/min/1.73 m2, P < 0.001); however, the between-group difference did not reach statistical significance at 12 mo (57.2 ± 24.3 versus 55.7 ± 22.2 mL/min/1.73 m2, P = 0.057). Median follow-up periods were 3.2 and 3.1 y for patient and graft survival, respectively. There were no significant differences between belatacept versus tacrolimus for mortality (hazard ratio 1.18 [95% confidence interval, 0.95-1.47], P = 0.14) or death-censored graft failure (hazard ratio 1.17 [0.85-1.61], P = 0.33). Rejection rate within 12 mo was significantly higher in the belatacept group (13% versus 7%, P < 0.001)., Conclusions: In this matched cohort study, initial use of belatacept for AKI-donor kidney recipients was associated with small benefits in early graft function when compared with tacrolimus. Although rejection risk was significantly higher in recipients administered belatacept, patient and graft survival were not significantly different between groups., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

In kidney transplantation, pairing recipients with the highest longevity with low-risk allografts to optimize graft-donor survival is a complex challenge. Current risk prediction models exhibit limited discriminative and calibration capabilities and have not been compared to modern decision-assisting tools. We aimed to develop a highly accurate risk-stratification index using artificial intelligence (AI) techniques. Using data from the UNOS database (156,749 deceased kidney transplants, 2007-2021), we randomly divided transplants into training (80%) and validation (20%) sets. The primary measure was death-censored graft survival. Four machine learning models were assessed for calibration (integrated Brier score [IBS]) and discrimination (time-dependent concordance [CTD] index), compared with existing models. We conducted decision curve analysis and external validation using UK Transplant data. The Deep Cox mixture model showed the best discriminative performance (area under the curve [AUC] = 0.66, 0.67, and 0.68 at 6, 9, and 12 years post-transplant), with CTD at 0.66. Calibration was adequate (IBS = 0.12), while the kidney donor profile index (KDPI) model had lower CTD (0.59) and AUC (0.60). AI-based D-TOP outperformed the KDPI in evaluating transplant pairs based on graft survival, potentially enhancing deceased donor selection. Advanced computing is poised to influence kidney allocation schemes., Competing Interests: Disclosure: T.F. is a current employee of the United States Veterans Health Administration. However, the views and opinions expressed herewith do not reflect the official views or opinions of and are not endorsed by the United States Veteran Health Administration. The other authors have no conflicts of interest to report., (Copyright © ASAIO 2024.)

The UK Deceased Donor Kidney Transplant Outcome Prediction (UK-DTOP) Tool, developed using advanced artificial intelligence (AI), significantly enhances the prediction of outcomes for deceased-donor kidney transplants in the UK. This study analyzed data from the UK Transplant Registry (UKTR), including 29,713 transplant cases between 2008 and 2022, to assess the predictive performance of three machine learning models: XGBoost, Random Survival Forest, and Optimal Decision Tree. Among these, XGBoost demonstrated exceptional performance with the highest concordance index of 0.74 and an area under the curve (AUC) consistently above 0.73, indicating robust discriminative ability and calibration. In comparison to the traditional Kidney Donor Risk Index (KDRI), which achieved a lower concordance index of 0.57, the UK-DTOP model marked a significant improvement, underscoring its superior predictive accuracy. The advanced capabilities of the XGBoost model were further highlighted through calibration assessments using the Integrated Brier Score (IBS), showing a score of 0.14, indicative of precise survival probability predictions. Additionally, unsupervised learning via k-means clustering was employed to identify five distinct clusters based on donor and transplant characteristics, uncovering nuanced insights into graft survival outcomes. These clusters were further analyzed using Bayesian Cox regression, which confirmed significant survival outcome variations across the clusters, thereby validating the model's effectiveness in enhancing risk stratification. The UK-DTOP tool offers a comprehensive decision-support system that significantly refines pre-transplant decision-making. The study's findings advocate for the adoption of AI-enhanced tools in healthcare systems to optimize organ matching and transplant success, potentially guiding future developments in global transplant practices.

Background: We aimed to assess contemporary transplant outcomes among kidney recipients with amyloidosis, as the treatment and prognosis of amyloidosis have shown improvement over time., Methods: Using the US Organ Procurement and Transplantation Network database, we initially evaluated the changes in patient and graft survival among kidney recipients with amyloidosis from 2002 to 2021. We then compared transplant outcomes between recipients with amyloidosis versus those with diabetic and nondiabetic causes of kidney failure, creating 1:4 matches with highly similar characteristics separately for deceased donor kidney transplant (DDKT) and living donor kidney transplant (LDKT) during the last decade (2012-2021)., Results: We identified 643 kidney recipients with amyloidosis during 2002-2021. Patient and death-censored graft survival improved over time. In the matching analysis for 207 DDKT and 166 LDKT recipients with amyloidosis during 2012-2021, patient survival was not significantly different between amyloidosis and diabetes groups in both DDKT (log-rank, P = 0.057) and LDKT (P = 0.99). Compared with the nondiabetes group, patient survival in the amyloidosis group was not significantly different for DDKTs (P = 0.56) but was significantly lower for LDKTs (P = 0.04). Death-censored graft failure risk was not significantly different between amyloidosis and diabetes or nondiabetes groups for both DDKTs (P = 0.78 and 0.75) and LDKTs (P = 0.40 and 0.24)., Conclusions: In this well-matched cohort study, we found no significant differences in patient and graft survival between kidney recipients with amyloidosis and those with diabetes. Similarly, these outcomes were not significantly different between those with amyloidosis versus nondiabetic causes, except for patient survival of LDKT recipients., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Proteinuria poses a substantial risk for the progression of chronic kidney disease (CKD) and its related complications. Kidneys excrete hundreds of individual proteins, some with a potential impact on CKD progression or as a marker of the disease. However, the available data on specific urinary proteins and their relationship with CKD severity remain limited. Therefore, we aimed to investigate the urinary proteome and its association with kidney function in CKD patients and healthy controls. The proteomic analysis of urine samples showed CKD stage-specific differences in the number of detected proteins and the exponentially modified protein abundance index for total protein (p = 0.007). Notably, specific urinary proteins such as B2MG, FETUA, VTDB, and AMBP exhibited robust negative associations with kidney function in CKD patients compared to controls. Also, A1AG2, CD44, CD59, CERU, KNG1, LV39, OSTP, RNAS1, SH3L3, and UROM proteins showed positive associations with kidney function in the entire cohort, while LV39, A1BG, and CERU consistently displayed positive associations in patients compared to controls. This study suggests that specific urinary proteins, which were found to be negatively or positively associated with the kidney function of CKD patients, can serve as markers of dysfunctional or functional kidneys, respectively., (© 2024. The Author(s).)

Outcome prediction for live-donor kidney transplantation improves clinical and patient decisions and donor selection. However, the concurrently used models are of limited discriminative or calibration power and there is a critical need to improve the selection process. We aimed to assess the value of various artificial intelligence (AI) algorithms to improve the risk stratification index. We evaluated pre-transplant variables among 66 914 live-donor kidney transplants (performed between 01/12/2007-01/06/2021) from the United Network of Organ Sharing database, randomized into training (80%) and test (20%) sets. The primary outcome measure was death-censored graft survival. We tested four machine learning models for discrimination (time-dependent concordance index, CTD, and area under the ROC curve) and calibration (integrated Brier score, IBS). We used decision curve analysis to assess the potential clinical utility. Among the models, the deep Cox mixture model showed the best discriminative performance (AUC = 0.70, 0.68, and 0.68 at 5, 10, and 13 years post-transplant, respectively). CTD reached 0.70, 0.67, and 0.66 at 5, 10, and 13 years post-transplant. The IBS score was 0.09, indicating good calibration. In comparison, applying the Living Kidney Donor Profile Index (LKDPI) on the same cohort produced a CTD of 0.56 and an AUC of 0.55-0.58 only. Decision curve analysis showed an additional net benefit compared to the LKDPI, 'Treat all' and 'Treat None' approaches. Our AI-based deep Cox mixture model, termed Live-Donor Kidney Transplant Outcome Prediction outperforms existing prediction models, including the LKDPI, with the potential to improve decisions for optimum live donor selection by ranking potential transplant pairs based on graft survival. This model could be adopted to improve the outcomes of paired exchange programs., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Competing Interests: None declared.

Background: Therapeutic donors (TDs) are individuals who undergo organ removal for medical treatment with no replacement organ, and the organ is then transplanted into another person. Transplant centers in the United States have started using TDs for kidney transplantation (KT). TD-KT recipient outcomes may be inferior to those of non-TD-living-donor (non-TD-LD)-KT or deceased-donor (DD)-KT because of the conditions that led to nephrectomy; however, these outcomes have not been sufficiently evaluated., Methods: This was a retrospective cohort study using Organ Procurement and Transplantation Network data. Via optimal matching methods, we created 1:4 fivesomes with highly similar characteristics for TD-KT and non-TD-LD-KT recipients and then separately for TD-KT and DD-KT recipients. We compared a 6-mo estimated glomerular filtration rate (eGFR) between groups (primary endpoint) and a composite of death, graft loss, or eGFR <30 mL/min/1.73 m 2 at 6 mo (secondary)., Results: We identified 36 TD-KT recipients with 6-mo eGFR. There was also 1 death and 2 graft losses within 6 mo. Mean ± SD 6-mo eGFR was not significantly different between TD-KT, non-TD-LD-KT, and DD-KT recipients (59.9 ± 20.7, 63.3 ± 17.9, and 59.9 ± 23.0 mL/min/1.73 m 2 , respectively; P > 0.05). However, the 6-mo composite outcome occurred more frequently with TD-KT than with non-TD-LD-KT and DD-KT (18%, 2% [ P < 0.001], and 8% [ P = 0.053], respectively)., Conclusions: Early graft function was no different between well-matched groups, but TD-KT demonstrated a higher risk of otherwise poor 6-mo outcomes compared with non-TD-LD-KT and DD-KT. Our results support selective utilization of TD kidneys; however, additional studies are needed with more detailed TD kidney information to understand how to best utilize these kidneys., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2023 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Background: Acceptable post-transplant outcomes were reported in kidney transplant recipients from donors with coronavirus disease 2019 (COVID-19); however, there are no comparative studies with well-matched controls., Methods: This multicenter, prospective observational study, which included three transplant centers in the United States, enrolled 61 kidney recipients from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected deceased donors. Using optimal matching methods, we matched every recipient to three comparators receiving kidneys from SARS-CoV-2-negative deceased donors with otherwise highly similar characteristics in the same transplant centers to compare 6-month eGFR., Results: Among recipients of SARS-CoV-2-infected donor kidneys, one recipient died with a functional graft within 6 months. Mean 6-month eGFR was not significantly different between SARS-CoV-2-infected and noninfected donor groups (55±21 and 57±25 ml/min per 1.73 m 2 , respectively; P = 0.61). Six-month eGFR in recipients from SARS-CoV-2-infected donors who died of reasons other than COVID-19 was not significantly different from those from SARS-CoV-2-negative donors (58±22 and 56±25 ml/min per 1.73 m 2 , respectively; P = 0.51). However, recipients from donors who died of COVID-19 had significantly lower 6-month eGFR than those from SARS-CoV-2-negative donors (46±17 and 58±27 ml/min per 1.73 m 2 , respectively; P = 0.03). No donor-to-recipient SARS-CoV-2 transmission was observed., Conclusions: Six-month eGFR was not significantly different between recipients of kidneys from SARS-CoV-2-infected and noninfected donors. However, those receiving kidneys from donors who died of COVID-19 had significantly lower 6-month eGFR. Donor-to-recipient SARS-CoV-2 transmission was not observed., (Copyright © 2023 by the American Society of Nephrology.)

Background: The current social and legal landscape is likely to foster the medicinal and recreational use of cannabis. Synthetic cannabinoid use is associated with acute kidney injury (AKI) in case reports; however, the association between natural cannabis use and AKI risk in patients with advanced chronic kidney disease (CKD) is unknown. Materials and Methods: From a nationally representative cohort of 102,477 U.S. veterans transitioning to dialysis between 2007 and 2015, we identified 2215 patients with advanced CKD who had undergone urine toxicology (UTOX) tests within a year before dialysis initiation and had inpatient serial serum creatinine levels measured within 7 days after their UTOX test. The exposure of interest was cannabis use compared with no use as ascertained by the UTOX test. We examined the association of this exposure with AKI using logistic regression and inverse probability of treatment weighting with extensive adjustment for potential confounders. Results: The mean age of the overall cohort was 61 years; 97% were males, 51% were African Americans, 97% had hypertension, 76% had hyperlipidemia, and 75% were diabetic. AKI occurred in 56% of the cohort, and in multivariable-adjusted analysis, cannabis use (when compared with no substance use) was not associated with significantly higher odds of AKI (odds ratio 0.85, 95% confidence interval 0.38-1.87; p =0.7). These results were robust to various sensitivity analyses. Conclusions: In this observational study examining patients with advanced CKD, cannabis use was not associated with AKI risk. Additional studies are needed to characterize the impact of cannabis use on risk of kidney disease and injury.

Kidney transplants (KT) from hepatitis C (HCV) viremic donors to HCV negative recipients has shown promising renal outcomes, however, high incidence of cytomegalovirus (CMV) viremia were reported. We performed a prospective cohort study of 52 HCV negative KT recipients from Methodist University Hospital including 41 receiving transplants from HCV aviremic donors and 11 from HCV viremic donors. CMV specific CD4+ and CD8 + T cell immunity was measured by intracellular flow cytometry assay. Primary outcome was the development of positive CMV specific CD4+ and CD8 + T cell immune response in the entire cohort and each subgroup. The association between donor HCV status and CMV specific CD4+ and CD8 + T cell immune response was analyzed by Cox proportional hazard models. Mean recipient age was 48 ± 13 years, with 73% male and 82% African American. Positive CMV specific CD4+ and CD8 + T cell immune response was found in 53% and 47% of the cohort at 1 month, 65% and 70% at 2 months, 80% and 75% at 4 months, 89% and 87% at 6 months, and 94% and 94% at 9 months post-transplant, respectively. There was no significant difference in the incidence of positive CMV specific T cell immune response between recipients of transplants from HCV aviremic donors compared to HCV viremic donors in unadjusted (for CD8+: HR = 1.169, 95%CI: 0.521-2.623; for CD4+: HR = 1.208, 95%CI: 0.543-2.689) and adjusted (for CD8+: HR = 1.072, 95%CI: 0.458-2.507; for CD4+: HR = 1.210, 95%CI: 0.526-2.784) Cox regression analyses. HCV viremia in donors was not associated with impaired development of CMV specific T cell immunity in this cohort.

Long-term liver outcome in hepatitis C virus (HCV)-negative kidney recipients who acquired HCV infection from viremic donors is of intense interest in the transplant community. We evaluated the incidence of fibrosis in liver biopsy specimens of recipients who were transplanted with HCV-infected grafts., Methods: Patients were evaluated in the hepatology clinic, and 29 patients agreed to undergo liver biopsy. The liver histology was scored by the meta-analysis of histological data in viral hepatitis scoring system and was assessed by hepatopathologists. The fibrosis score was compared between patients who initiated direct-acting antiviral (DAA) within 6 wk (n = 6) and after 6 wk (n = 29)., Results: Eighty-nine aviremic patients were transplanted with HCV-infected grafts between March 2018 and October 2019. All patients developed HCV infection and were treated with DAA treatment after kidney transplantation (median, 70 d; interquartile range, 55-85 d). All patients (n = 89) achieved sustained virologic response with DAA. The median follow-up time from kidney transplant to liver biopsy was 28 mo (interquartile range, 26-30 mo). Twenty-five patients (86%) had F0, and 4 patients (14%) had F1 fibrosis. No patient had advanced fibrosis (F3-F4). Grade 1 inflammation was present in 6 (21%) patients, whereas 26 (90%) patients had iron accumulation in the hepatocytes and reticuloendothelial cells. There was no difference in the fibrosis score between patients who received treatment within 6 wk versus after 6 wk ( P = 0.55)., Conclusions: Kidney transplantation of HCV-infected graft to HCV-negative recipients is safe and has no long-term liver-related complications with successful eradication of HCV. In our cohort, delayed treatment did not affect sustained virologic response or liver histology., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2022 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Kidney transplantation (KT) from deceased donors with hepatitis C virus (HCV) into HCV-negative recipients has become more common. However, the risk of complications such as BK polyomavirus (BKPyV) remains unknown. We assembled a retrospective cohort at four centers. We matched recipients of HCV-viremic kidneys to highly similar recipients of HCV-aviremic kidneys on established risk factors for BKPyV. To limit bias, matches were within the same center. The primary outcome was BKPyV viremia ≥1000 copies/ml or biopsy-proven BKPyV nephropathy; a secondary outcome was BKPyV viremia ≥10 000 copies/ml or nephropathy. Outcomes were analyzed using weighted and stratified Cox regression. The median days to peak BKPyV viremia level was 119 (IQR 87-182). HCV-viremic KT was not associated with increased risk of the primary BKPyV outcome (HR 1.26, p = .22), but was significantly associated with the secondary outcome of BKPyV ≥10 000 copies/ml (HR 1.69, p = .03). One-year eGFR was similar between the matched groups. Only one HCV-viremic kidney recipient had primary graft loss. In summary, HCV-viremic KT was not significantly associated with the primary outcome of BKPyV viremia, but the data suggested that donor HCV might elevate the risk of more severe BKPyV viremia ≥10 000 copies/ml. Nonetheless, one-year graft function for HCV-viremic recipients was reassuring., (© 2021 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Introduction: Chronic kidney disease (CKD) is a major public health issue in the USA. Identification of monogenic causes of CKD, which are present in ∼10% of adult cases, can impact prognosis and patient management. Broad gene panels can provide unbiased testing approaches, which are advantageous in phenotypically heterogeneous diseases. However, the use and yield of broad genetic panels by nephrologists in clinical practice is not yet well characterized., Methods: Renal genetic testing, ordered exclusively for clinical purposes, predominantly by general and transplant nephrologists within the USA, was performed on 1,007 consecutive unique patient samples. Testing was performed using a commercially available next-generation sequencing-based 382 gene kidney disease panel. Pathogenic (P) and likely pathogenic (LP) variants were reported. Positive findings included a monoallelic P/LP variant in an autosomal dominant or X-linked gene and biallelic P/LP variants in autosomal recessive genes., Results: Positive genetic findings were identified in 21.1% (212/1,007) of cases. A total of 220 positive results were identified across 48 genes. Positive results occurred most frequently in the PKD1 (34.1%), COL4A5 (10.9%), PKD2 (10.0%), COL4A4 (6.4%), COL4A3 (5.9%), and TTR (4.1%) genes. Variants identified in the remaining 42 genes comprised 28.6% of the total positive findings, including single positive results in 26 genes. Positive results in >1 gene were identified in 7.5% (16/212) of cases., Conclusions: Use of broad panel genetic testing by clinical nephrologists had a high success rate, similar to results obtained by academic centers specializing in genetics., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Purpose of Review: Diet plays an important role in slowing progression of chronic kidney disease in native and transplanted kidneys. There is limited evidence on the association on dietary intake with renal allograft function. Mechanisms of major nutrients and dietary patterns with focusing on a plant-based diet related to kidney transplant health and longevity are reviewed., Recent Findings: High dietary protein intake may adversely affect renal allograft. Low protein plant-focused diets such as Dietary Approaches to Stop Hypertension, plant-dominant low-protein diet and Mediterranean diets appear associated with favorable outcomes in slowing renal allograft function decline. The mechanism may be related to a change in renal hemodynamic by decreasing glomerular hyperfiltration from low dietary protein intake and plant-based ingredients. Recent observational studies of association between dietary protein intake and kidney allograft outcomes are conflicting. Although strong evidence is still lacking, a low protein diet of 0.6-0.8 g/kg/day with at least 50% of the protein source from plant-based components in kidney transplant recipients with stable kidney allograft function should be considered as the dietary target., Summary: Dietary intervention with low-protein plant-focused meals may improve outcomes in kidney transplant recipients, but the evidence remains limited and further studies are warranted., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Kidney transplantation (KT) from hepatitis C virus infected (HCV+) donors to HCV negative recipients achieve excellent graft function but have relatively higher rates of post-KT co-infections presumably due to prolonged HCV viremia in transmission-and-treat approach. Ezetimibe acts as an antagonist of Niemann-Pick C1-Like 1 receptor required for HCV entry and theoretically can reduce HCV viremia. However, no data is available to examine the role of ezetimibe as a bridge therapy between KT surgery and direct acting antiviral (DAA) initiation. A retrospective cohort study including 70 HCV+ to HCV negative KT recipients from Methodist University Hospital and Vanderbilt University Medical Center was performed to determine the association between ezetimibe usage and HCV viremia. Twenty patients received ezetimibe daily while 50 patients did not. Primary outcome of study was mean HCV RNA level at 1-2 weeks post-KT and before initiation of DAA. Median (IQR) viral load (VL) in log copies/ml was one log lower in ezetimibe group versus non-ezetimibe group (4.1 [3.7-5.3] vs. 5.1 [4.4-5.5], P = .01), and highest VL was also lower in ezetimibe group (4.2 [3.7-5.4] vs. 5.4 [4.7-5.9], P = .006). We concluded that ezetimibe bridge therapy might be associated with reduction in HCV VL while waiting for DAA initiation in HCV+ to HCV negative KT recipients., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)