A large-scale retrospective study enabled deep-learning based pathological assessment of frozen procurement kidney biopsies to predict graft loss and guide organ utilization.

Lesion scores on procurement donor biopsies are commonly used to guide organ utilization for deceased-donor kidneys. However, frozen sections present challenges for histological scoring, leading to inter- and intra-observer variability and inappropriate discard. Therefore, we constructed deep-learning based models to recognize kidney tissue compartments in hematoxylin & eosin-stained sections from procurement needle biopsies performed nationwide in years 2011-2020. To do this, we extracted whole-slide abnormality features from 2431 kidneys and correlated with pathologists' scores and transplant outcomes. A Kidney Donor Quality Score (KDQS) was derived and used in combination with recipient demographic and peri-transplant characteristics to predict graft loss or assist organ utilization. The performance on wedge biopsies was additionally evaluated. Our model identified 96% and 91% of normal/sclerotic glomeruli respectively; 94% of arteries/arterial intimal fibrosis; 90% of tubules. Whole-slide features of Sclerotic Glomeruli (GS)%, Arterial Intimal Fibrosis (AIF)%, and Interstitial Space Abnormality (ISA)% demonstrated strong correlations with corresponding pathologists' scores of all 2431 kidneys, but had superior associations with post-transplant estimated glomerular filtration rates in 2033 and graft loss in 1560 kidneys. The combination of KDQS and other factors predicted one- and four-year graft loss in a discovery set of 520 kidneys and a validation set of 1040 kidneys. By using the composite KDQS of 398 discarded kidneys due to "biopsy findings", we suggest that if transplanted, 110 discarded kidneys could have had similar survival to that of other transplanted kidneys. Thus, our composite KDQS and survival prediction models may facilitate risk stratification and organ utilization while potentially reducing unnecessary organ discard.

Impact of race-neutral eGFR calculations on African American kidney transplant candidate wait time: A single center retrospective analysis.

Race-inclusive estimated glomerular filtration rate (eGFR) could contribute to racial disparity in access to kidney transplantation. The Organ Procurement and Transplantation Network (OPTN) issued a policy allowing waiting time modification for candidates affected by race-inclusive eGFR calculations. Implementation of the new OPTN policy at the kidney transplant program of the Mount Sinai Hospital involved review of 921 African American candidates, of whom 240 (26%) candidates gained a median of 1 year and 10 months. The duration of time candidates gained varied from a minimum of 5 days to a maximum of 12 years and 3 months; 45.4% gained at least 2 years, and 12% gained at least 4 years of wait time. Among those who gained wait time, 20 (8.3%) candidates received deceased donor kidney transplants. Candidates who gained wait time had similar sociodemographic characteristics as those who did not, except that the median age for the former was higher by 3 years (59 vs. 56). Our early data suggest that the current policy on waiting time modification for candidates affected by race-inclusive estimation of GFR has the potential to improve racial disparity in access to kidney transplantation. However, the generalizability of our findings to other centers requires further study.

Outcomes after kidney transplant alone in patients with cirrhosis-A case-control study.

BACKGROUND: Guidelines recommend kidney transplant alone (KTA) in compensated cirrhosis based on a few small studies, but this is not widely performed despite its potential benefit to patients and the organ supply. Our aim was to determine the outcomes of KTA in patients with compensated cirrhosis. STUDY DESIGN: From 1/2012 to 12/2021, outcomes in KTA recipients with compensated cirrhosis were retrospectively compared to patients with chronic liver disease (CLD) but no cirrhosis. Patients with compensated cirrhosis were also compared to a matched cohort (based on age, time on hemodialysis, sex, and ethnicity) of KTA recipients without CLD. The outcomes included patient survival, allograft failure, allograft rejection, serious infection, liver decompensation, and length of stay (LOS). RESULTS: Over 9 years, 1562 KTAs were performed, with 150 (9.6%) patients having CLD mostly due to chronic hepatitis C, and a median follow-up of 3.5 years. 32/150 (21%) had compensated cirrhosis at the time of KTA with a mean MELD-Na of 22 (1.5). Matched controls (n = 189) were identified. We found no differences in patient survival (p = .07), allograft failure (p = .6), allograft rejection (p = .43), rates of serious infection (p = .31), as well as LOS (p = .61) among patients with compensated cirrhosis compared to patients with CLD but no cirrhosis, but with higher rates of liver decompensation (p = .004). Similarly, compared to patients without CLD, patients with cirrhosis had similar rates of patient survival (p = .20), allograft failure (p = .27), allograft rejection (p = .62) and LOS (p = .19) but with higher rates of serious infections (p = .001). CONCLUSIONS: Our study supports the safety and efficacy of KTA in patients with compensated cirrhosis.

Role of time from transplantation to biopsy in histologic ABMR: A single center report.

BACKGROUND: Allograft biopsies with lesions of Antibody-Mediated Rejection (ABMR) with Microvascular Inflammation (MVI) have shown heterogeneous etiologies and outcomes. METHODS: To examine factors associated with outcomes in biopsies that meet histologic ABMR criteria, we retrospectively evaluated for-cause biopsies at our center between 2011 and 2017. We included biopsies that met the diagnosis of ABMR by histology, along with simultaneous evaluation for anti-Human Leukocyte Antigen (HLA) donor-specific antibodies (DSA). We evaluated death-censored graft loss (DCGL) and used a principal component analysis (PCA) approach to identify key predictors of outcomes. RESULTS: Out of the histologic ABMR cohort (n = 118), 70 were DSA-positive ABMR, while 48 had no DSA. DSA(+)ABMR were younger and more often female recipients. DSA(+)ABMR occurred significantly later post-transplant than DSA(-)ABMR suggesting time-dependence. DSA(+)ABMR had higher inflammatory scores (i,t), chronicity scores (ci, ct) and tended to have higher MVI scores. Immunodominance of DQ-DSA in DSA(+)ABMR was associated with higher i+t scores. Clinical/histologic factors significantly associated with DCGL after biopsy were inputted into the PCA. Principal component-1 (PC-1), which contributed 34.8% of the variance, significantly correlated with time from transplantation to biopsy, ci/ct scores and DCGL. In the PCA analyses, i, t scores, DQ-DSA, and creatinine at biopsy retained significant correlations with GL-associated PCs. CONCLUSIONS: Time from transplantation to biopsy plays a major role in the prognosis of biopsies with histologic ABMR and MVI, likely due to ongoing chronic allograft injury over time.

Influence of patient characteristics and immunosuppressant management on mortality in kidney transplant recipients hospitalized with coronavirus disease 2019 (COVID-19).

The influence of patient characteristics and immunosuppression management on COVID-19 outcomes in kidney transplant recipients (KTRs) remains uncertain. We performed a single-center, retrospective review of all adult KTRs admitted to the hospital with confirmed COVID-19 between 03/15/2020 and 05/15/2020. Patients were followed from the date of admission up to 1 month following hospital discharge or study conclusion (06/15/2020). Baseline characteristics, laboratory parameters, and immunosuppression were compared between survivors and patients who died to identify predictors of mortality. 38 KTRs with a mean baseline eGFR of 52.5 ml/min/1.73 m2 were hospitalized during the review period. Maintenance immunosuppression included tacrolimus (84.2%), mycophenolate (89.5%), and corticosteroids (81.6%) in the majority of patients. Eleven patients (28.9%) died during the hospitalization. Older age (OR = 2.05; 1.04-4.04), peak D-dimer (OR = 1.20; 1.04-1.39), and peak white blood cell count (OR = 1.11; 1.02-1.21) were all associated with mortality among KTRs hospitalized for COVID-19. Increased mortality was also observed among KTRs with concomitant HIV infection (87.5% vs. 36.1%; p < .01). Conversely, immunosuppression intensity and degree of reduction following COVID-19 diagnosis were not associated with either survival or acute allograft rejection. Our findings potentially support a strategy of individualization of immunosuppression targets based on patient-specific risk factors, rather than universal immunosuppression reduction for KTRs at risk from COVID-19.

Apolipoprotein L1 and kidney transplantation.

PURPOSE OF REVIEW: Consistent associations between variants of the apolipoprotein L1 (APOL1) gene and nondiabetic nephropathy have been reported in individuals of African descent. Donor APOL1 genotype has also been linked to shorter renal allograft survival. This review summarizes recent advances in understanding the biology of APOL1 and their implications to kidney donors and recipients. RECENT FINDINGS: Approximately 12-13% of African Americans have two renal risk APOL1 variants but most do not develop kidney disease. Although the exact mechanisms linking APOL1 genotype to renal injury are not known, evidence from new experimental models suggests APOL1 mutations may accelerate age-related podocyte loss. Recent epidemiological studies indicate potential kidney donors with high-risk APOL1 variants have increased risk of chronic kidney disease (CKD) and donors with high-risk APOL1 variants have lower estimated glomerular filtration rate (eGFR) than those with low-risk variants. The absolute risk of CKD in otherwise healthy individuals carrying high-risk APOL1 mutations is likely low. SUMMARY: Recent studies suggest high-risk APOL1 mutations in kidney donors are linked to shorter graft survival and lower postdonation eGFR. APOL1 genotyping may be used as one of many factors that contribute to assessment of the risk of postdonation CKD and informed decision making.

Differences in Attitudes Toward Immunosuppressant Therapy in a Multi-ethnic Sample of Kidney Transplant Recipients.

Barriers for renal transplant patients to immunosuppressant medication adherence are poorly understood, despite the high rate and toll of non-adherence. We sought to assess factors that contribute to barriers to immunosuppressive medication adherence in an ethnically diverse sample of 312 renal transplant patients recruited from three transplant centers across New York City. Transplant patients who were at least 6 months post-transplant completed questionnaires while waiting for their medical appointment. Ethnic differences were observed on barriers to immunosuppressant adherence. Black and Hispanic participants reported significantly more barriers to adherence compared to Caucasian participants. Differences in perception about the potential harm and necessity of immunosuppressant medications also were present. Using hierarchical multiple regression, age and income were significant predictors of reported barriers to adherence, even while controlling for ethnicity. The most robust predictor of reported barriers was the perception of the medication cost-benefit differential, i.e., the balance between concerns about immunosuppressant medications and their perceived helpfulness (B = - 0.5, p < .001), indicating that varying beliefs about the medication's necessity and utility rather than ethnicity explain the differences in barriers to medication adherence. Future interventions targeting non-adherence should aim to reduce the barriers to adherence by addressing perceived risks and benefits of taking immunosuppressant medication.

Mortality after Renal Allograft Failure and Return to Dialysis.

INTRODUCTION: The outcomes of patients who fail their kidney transplant and return to dialysis (RTD) has not been investigated in a nationally representative sample. We hypothesized that variations in management of transplant chronic kidney disease stage 5 leading to kidney allograft failure (KAF) and RTD, such as access, nutrition, timing of dialysis, and anemia management predict long-term survival. METHODS: We used an incident cohort of patients from the United States Renal Data System who initiated hemodialysis between January 1, 2003 and December 31, 2008, after KAF. We used Cox regression analysis for statistical associations, with mortality as the primary outcome. RESULTS: We identified 5,077 RTD patients and followed them for a mean of 30.9 ± 22.6 months. Adjusting for all possible confounders at the time of RTD, the adjusted hazards ratio (AHR) for death was increased with lack of arteriovenous fistula at initiation of dialysis (AHR 1.22, 95% CI 1.02-1.46, p = 0.03), albumin <3.5 g/dL (AHR 1.33, 95% CI 1.18-1.49, p = 0.0001), and being underweight (AHR 1.30, 95% CI 1.07-1.58, p = 0.006). Hemoglobin <10 g/dL (AHR 0.96, 95% CI 0.86-1.06, p = 0.46), type of insurance, and zip code-based median household income were not associated with higher mortality. Glomerular filtration rate <10 mL/min/1.73 m2 at time of dialysis initiation (AHR 0.83, 95% CI 0.75-0.93, p = 0.001) was associated with reduction in mortality. CONCLUSIONS: Excess mortality risk observed in patients starting dialysis after KAF is multifactorial, including nutritional issues and vascular access. Adequate preparation of patients with failing kidney transplants prior to resuming dialysis may improve outcomes.

Plasma Nitration of High-Density and Low-Density Lipoproteins in Chronic Kidney Disease Patients Receiving Kidney Transplants.

BACKGROUND: Functional abnormalities of high-density lipoprotein (HDL) could contribute to cardiovascular disease in chronic kidney disease patients. We measured a validated marker of HDL dysfunction, nitrated apolipoprotein A-I, in kidney transplant recipients to test the hypothesis that a functioning kidney transplant reduces serum nitrated apoA-I concentrations. METHODS: Concentrations of nitrated apoA-I and apoB were measured using indirect sandwich ELISA assays on sera collected from each transplant subject before transplantation and at 1, 3, and 12 months after transplantation. Patients were excluded if they have history of diabetes, treatment with lipid-lowering medications or HIV protease inhibitors, prednisone dose > 15 mg/day, nephrotic range proteinuria, serum creatinine > 1.5 mg/dL, or active inflammatory disease. Sera from 18 transplanted patients were analyzed. Four subjects were excluded due to insufficient data. Twelve and eight patients had creatinine < 1.5 mg/dL at 3 and 12 months after transplantation, respectively. RESULTS. Nitrated apoA-I was significantly reduced at 12 months after transplantation (p = 0.039). The decrease in apoA-I nitration was associated with significant reduction in myeloperoxidase (MPO) activity (p = 0.047). In contrast to apoA-I, nitrated apoB was not affected after kidney transplantation. CONCLUSIONS: Patients with well-functioning grafts had significant reduction in nitrated apoA-I 12 months after kidney transplantation. Further studies are needed in a large cohort to determine if nitrated apoA-I can be used as a valuable marker for cardiovascular risk stratification in chronic kidney disease.

Intravenous immunoglobulin in kidney transplantation.

PURPOSE OF REVIEW: Antibody-mediated injury of renal allografts has assumed increasing importance with the availability of potent immunosuppressants directed against T-lymphocytes. Intravenous immunoglobulin (IVIG) has been used for prevention and treatment of antibody-mediated rejection. The review summarizes recent advances that shed light on mechanisms of action of IVIG and outlines current roles of IVIG in kidney transplantation. RECENT FINDINGS: Observational studies support the use of IVIG for desensitization and treatment of acute rejection. Most studies are small and uncontrolled, but a matched case-control study reported a better survival with incompatible live-donor kidney transplant after desensitization using IVIG-containing regimens compared with dialysis or waiting for compatible transplant. Recent data indicate that variations in glycosylation and amino acid sequence cause the crystallizable fragment of immunoglobulin G to assume specific conformations that have high affinity for canonical crystallizable fragment receptors (FcR) or a newly discovered class of FcRs, labelled type II FcRs. Signaling through type II FcRs appears to trigger anti-inflammatory pathways. SUMMARY: Recent discoveries expand our understanding of the mechanism of action of IVIG. Future research is expected to clarify the relevance of these findings to humans and could lead to the development of novel immunomodulatory agents.

Relationship between the Soluble F11 Receptor and Annexin A5 in African Americans Patients with Type-2 Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) is characterized by endothelial dysfunction, increased thrombogenicity, and inflammation. The soluble human F11 receptor (sF11R) and annexin A5 (ANXA5) play crucial roles in inflammatory thrombosis and atherosclerosis. We examined the relationship between circulating sF11R and ANXA5 and their impact on endothelial function. The study included 125 patients with T2DM. Plasma levels of sF11R and ANXA5 were quantified by ELISA. Microvascular function was assessed using the vascular reactivity index (VRI). Large artery stiffness was assessed by carotid-femoral pulse wave velocity (PWV). Carotid intima-media thickness (CIMT) was assessed by B-mode ultrasound imaging. The mean age of patients in the study was 59.7 ± 7.8 years, 78% had hypertension, 76% had dyslipidemia, and 12% had CKD. sF11R correlated positively with ANXA5 levels (ß = 0.250, p = 0.005), and correlated inversely with VRI and total nitic oxide (NO), (ß = −0.201, p = 0.024; ß = −0.357, p = 0.0001, respectively). Multivariate regression analysis revealed that sF11R was independently associated with ANXA5 in the total population and in patients with HbA1c > 6.5% (ß = 0.366, p = 0.007; ß = 0.425, p = 0.0001, respectively). sF11R and ANXA5 were not associated with vascular outcome, suggesting that they may not be reliable markers of vascular dysfunction in diabetes. The clinical significance of sF11R/ANXA5 association in diabetes warrants further investigation in a larger population.

Association of Physical Function and Survival in Older-Adult Renal Transplant Recipients.

There is an increase in older-adult renal transplant recipients in United States. The objective of this study was to assess the association between physical function (PF) and patient survival in renal transplant recipients who are aged 65 years or older. Using United Network for Organ Sharing (UNOS) data from 2007 to 2016, renal transplant recipients aged 65 years or older were included. Multivariable Cox regression was used to assess associations between survival and functional status adjusted for age, sex, race, donor quality, diabetes, and dialysis vintage. The study identified 26,721 patients. Patient survival was significantly higher in recipients who needed no assistance and lowest in patients in need of total assistance (P < .0001). In deceased donor (DD) transplants, the relative risk for mortality was 2.06 (1.74-2.43) for total assistance and 1.17 (1.08-1.28) for moderate assistance compared to no assistance (P < .0001). In living donor (LD) transplants, the relative risk of mortality was 1.38 (0.78-2.42) for patients needing total assistance and 1.37 (1.14-1.65) for patients needing moderate assistance compared to patients who did not need assistance (0.003). PF is an independent predictor of post-transplant mortality. Assessment of older potential renal transplant recipients should include assessment and standardization of functional status to counsel about post-transplant survival.

Association between nitrated lipoproteins and vascular function in type 2 diabetes.

Higher levels of nitrated lipoproteins (NT-HDL and NT-LDL) were found in blood and atherosclerotic plaques of patients with coronary artery disease. We aimed to examine the relationship between plasma NT-HDL and NT-LDL and diabetic vascular dysfunction. The study included 125 African-American patients with T2DM. NT-HDL and NT-LDL were quantified by ELISA. Microvascular function was assessed by vascular reactivity index (VRI). Large artery stiffness was assessed by carotid-femoral pulse wave velocity (PWV). Carotid intima-media thickness (CIMT) was assessed by B-mode ultrasound imaging. In univariate analysis, NT-HDL was associated with VRI in total population and in patients with HbA1c more than or equal to 7.0 percent (beta= -0.178, p= 0.034; beta = -0.265, p= 0.042; respectively). In contrast, NT-LDL was associated with CIMT in total population and in patients with HbA1c more than 7.0 percent (beta = -0.205, p= 0.022; beta = -0.244, p= 0.042; respectively). Multivariable-adjusted regression analysis demonstrated that NT-HDL independently predicted VRI outcome in total population and in well-controlled patients (beta = -0.282, p= 0.014; beta = -0.400, p= 0.035, respectively). These results suggest that NT-HDL could be used as marker to identify diabetic patients at risk of developing early microvascular complications.

Chylothorax and chylopericardial tamponade in a hemodialysis patient with catheter-induced superior vena cava stenosis.

Chylothorax and chylopericardium refer to the presence of milky, triglyceride-rich chylous fluid in the thoracic and pericardial spaces, respectively. Both conditions are extremely uncommon in end-stage renal disease patients on dialysis. We report the first known case of combined chylothorax and chylous pericardial tamponade in a dialysis patient associated with catheter-induced superior vena cava (SVC) stenosis. A successful outcome was achieved with drainage of both chylous effusions in combination with angioplasty of the SVC stenosis.

Posttransplant diabetes and hypertension: pathophysiologic insights and therapeutic rationale.

New-onset diabetes after transplantation and hypertension are very common after renal transplantation and are associated with adverse graft and cardiovascular outcomes. A thorough understanding of the unique factors that operate in renal transplant recipients is essential for the proper evaluation and management of these important disorders. This review outlines the pathogenesis, diagnostic workup, and therapeutic rationale for diabetes and hypertension after transplantation.

Prevalence of Central Vein Stenosis in Patients Referred for Vein Mapping.

BACKGROUND AND OBJECTIVES: Central vein stenosis is considered to be common in patients on hemodialysis but its exact prevalence is not known. In this study, we report the prevalence of central vein stenosis in patients with CKD referred for vein mapping. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a retrospective study of adult patients who had bilateral upper extremity venographic vein mapping from September 1, 2011 to December 31, 2015. Patients with and without stenosis were compared for differences in clinical or demographic characteristics. Multiple logistic regression was used to identify independent associations between patient characteristics and central vein stenosis. RESULTS: There were 525 patients who underwent venographic vein mapping during the study period, 27% of whom were referred before initiation of hemodialysis. The mean age (±SD) and body mass index were 59 (±15) years and 28 (±7), respectively. Women accounted for 45% of patients; 82% were black. The prevalence of central vein stenosis was 10% (95% confidence interval [95% CI], 8% to 13%) for the whole group, and 13% (95% CI, 10% to 17%) among patients with tunneled central venous dialysis catheters. Current use of tunneled hemodialysis catheters (odds ratio [OR], 14.5; 95% CI, 3.25 to 65.1), presence of cardiac rhythm devices (OR, 5.07; 95% CI, 1.82 to 14.11), previous history of fistula or graft (OR, 3.28; 95% CI, 1.58 to 6.7), and history of previous kidney transplant (OR, 18; 95% CI, 4.7 to 68.8) were independently associated with central vein stenosis. CONCLUSIONS: In this population, the prevalence of central vein stenosis was 10% and was clustered among those with tunneled hemodialysis catheters, cardiac rhythm device, and previous history of dialysis access or transplant.

Antihypertensive Medications and Change in Stages of Chronic Kidney Disease.

OBJECTIVES: The goal of this study is to estimate the change in the relationships between use of five classes of antihypertensive medications and stages of Chronic Kidney Disease (CKD) in American adults treated for hypertension. METHODS: The US National Health and Nutrition Examination Survey (NHANES) data sets 1999-2012 were used with the final analytical sample of 3,045 participants. Population prevalence estimates were calculated using the NHANES survey design weights. Inferential analyses were done with binomial logistic regression models. RESULTS: The odds of advanced (3, 4, and 5 combined) versus early CKD stages (1 and 2 combined) were significantly higher among patients treated with Angiotensin Receptor Blockers (ARB) versus those not treated with ARB in 2009-2012 (adjusted odds ratio (95% confidence interval) = 2.52 (1.32-4.80)). From 1999 to 2012, the increase in this relationship was significant (p = 0.0023) for users of ARB polytherapy and in users of ARB in patients with albuminuria (p = 0.0031). CONCLUSION: Aggressive pharmacological management of hypertension with ARB as add-on therapy may have accelerated kidney damage in American adults. However, prospective longitudinal studies are needed to establish proper temporal sequence in this relationship.

Hypertension after renal transplant.

Hypertension is common after renal transplant and is associated with adverse graft and patient outcomes. A thorough understanding of the unique factors that operate in renal transplant recipients is essential for the proper evaluation and management of this disorder. In this review, the authors outline the pathogenesis, diagnostic workup, and treatment of hypertension after renal transplant.

A Pilot Randomized Controlled Trial to Promote Immunosuppressant Adherence in Adult Kidney Transplant Recipients.

BACKGROUND: Nonadherence to immunosuppressant medication is a prevalent practice among kidney transplant recipients and has been associated with increased risk for graft failure and economic burden. The aim of this pilot study was to test whether a culturally sensitive cognitive-behavioral adherence promotion program could significantly improve medication adherence to tacrolimus prescription as measured by telephone pill counts among kidney transplant recipients. METHODS: Thirty-three adult transplant recipients were less than 98% adherent to tacrolimus prescription based on 3 telephone pill counts and were randomized either to the 2-session cognitive-behavioral adherence promotion program or to standard care. The curriculum was developed from an iterative process with transplant recipients into a 2-session group program that provided psychoeducation, addressed barriers to adherence, fostered motivation to improve adherence behavior, and discussed cultural messages on adherence behavior. RESULTS: The intervention group displayed significantly higher levels of adherence when compared to the control group (t = 2.2, p = 0.04) and. similarly, when the amount of change was compared between the groups, the intervention group showed more change than the control condition (F (22,1) = 12.005, p = 0.003). Tacrolimus trough concentration levels were used as a secondary measure of adherence and, while there were no significant between-group differences for mean trough concentration levels, the variability in the trough levels did significantly decrease over time indicating more consistent pill-taking behavior in the intervention group. CONCLUSIONS: There is preliminary support for the pilot program as a successful intervention in helping patients with their immunosuppressant medication.