Advocates for improved equity in kidney transplants in the United States have recently focused their efforts on initiatives to increase referral for transplant evaluation. However, because donor ...kidneys remain scarce, increased referrals are likely to result in an increasing number of patients proceeding through the evaluation process without ultimately receiving a kidney. Unfortunately, the process of referral and evaluation can be highly resource-intensive for patients, families, transplant programs, and payers. Patients and families may incur out-of-pocket expenses and be required to complete testing and treatments that they might not have chosen in the course of routine clinical care. Kidney transplant programs may struggle with insufficient capacity, inefficient workflow, and challenging programmatic finances, and payers will need to absorb the increased expenses of upfront pretransplant costs. Increased referral in isolation may risk simply transmitting system stress and resulting disparities to downstream processes in this complex system. We argue that success in efforts to improve access through increased referrals hinges on adaptations to the pretransplant process more broadly. We call for an urgent re-evaluation and redesign at multiple levels of the pretransplant system in order to achieve the aim of equitable access to kidney transplantation for all patients with kidney failure.
Determining candidacy for live kidney donation among obese individuals remains challenging. Among healthy non-donors, body mass index (BMI) above 30 is associated with a 16% increase in risk of ...end-stage renal disease (ESRD). However, the impact on the ESRD risk attributable to donation and living with only one kidney remains unknown. Here we studied the risk of ESRD associated with obesity at the time of donation among 119 769 live kidney donors in the United States. Maximum follow-up was 20 years. Obese (BMI above 30) live kidney donors were more likely male, African American, and had higher blood pressure. Estimated risk of ESRD 20 years after donation was 93.9 per 10 000 for obese; significantly greater than the 39.7 per 10 000 for non-obese live kidney donors. Adjusted for age, sex, ethnicity, blood pressure, baseline estimated glomerular filtration rate, and relationship to recipient, obese live kidney donors had a significant 86% increased risk of ESRD compared to their non-obese counterparts (adjusted hazard ratio 1.86; 95% confidence interval 1.05–3.30). For each unit increase in BMI above 27 kg/m2 there was an associated significant 7% increase in ESRD risk (1.07, 1.02–1.12). The impact of obesity on ESRD risk was similar for male and female donors, African American and Caucasian donors, and across the baseline estimated glomerular filtration rate spectrum. These findings may help to inform selection criteria and discussions with persons considering living kidney donation.
Kidney transplant recipients may be at a high risk of developing critical coronavirus disease 2019 (COVID‐19) illness due to chronic immunosuppression and comorbidities. We identified hospitalized ...adult kidney transplant recipients at 12 transplant centers in the United States, Italy, and Spain who tested positive for COVID‐19. Clinical presentation, laboratory values, immunosuppression, and treatment strategies were reviewed, and predictors of poor clinical outcomes were determined through multivariable analyses. Among 9845 kidney transplant recipients across centers, 144 were hospitalized due to COVID‐19 during the 9‐week study period. Of the 144 patients, 66% were male with a mean age of 60 (±12) years, and 40% were Hispanic and 25% were African American. Prevalent comorbidities included hypertension (95%), diabetes (52%), obesity (49%), and heart (28%) and lung (19%) disease. Therapeutic management included antimetabolite withdrawal (68%), calcineurin inhibitor withdrawal (23%), hydroxychloroquine (71%), antibiotics (74%), tocilizumab (13%), and antivirals (14%). During a median follow‐up period of 52 days (IQR: 16‐66 days), acute kidney injury occurred in 52% cases, with respiratory failure requiring intubation in 29%, and the mortality rate was 32%. The 46 patients who died were older, had lower lymphocyte counts and estimated glomerular filtration rate levels, and had higher serum lactate dehydrogenase, procalcitonin, and interleukin‐6 levels. In sum, hospitalized kidney transplant recipients with COVID‐19 have higher rates of acute kidney injury and mortality.
In this multinational cohort of 144 kidney transplanted patients from 11 transplant centers in the US and Europe who were hospitalized for COVID‐19, acute kidney injury occurred in 52% and respiratory failure requiring intubation occurred in 29%, with an overall mortality of 32%.
The 2020 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline on the Evaluation and Management of Candidates for Kidney Transplantation is intended to assist health care ...professionals worldwide who evaluate and manage potential candidates for deceased or living donor kidney transplantation. This guideline addresses general candidacy issues such as access to transplantation, patient demographic and health status factors, and immunological and psychosocial assessment. The roles of various risk factors and comorbid conditions governing an individual's suitability for transplantation such as adherence, tobacco use, diabetes, obesity, perioperative issues, causes of kidney failure, infections, malignancy, pulmonary disease, cardiac and peripheral arterial disease, neurologic disease, gastrointestinal and liver disease, hematologic disease, and bone and mineral disorder are also addressed. This guideline provides recommendations for evaluation of individual aspects of a candidate's profile such that each risk factor and comorbidity are considered separately. The goal is to assist the clinical team to assimilate all data relevant to an individual, consider this within their local health context, and make an overall judgment on candidacy for transplantation. The guideline development process followed the Grades of Recommendation Assessment, Development, and Evaluation (GRADE) approach. Guideline recommendations are primarily based on systematic reviews of relevant studies and our assessment of the quality of that evidence, and the strengths of recommendations are provided. Limitations of the evidence are discussed with differences from previous guidelines noted and suggestions for future research are also provided.
Optimal glycemic control in kidney transplant recipients with diabetes is associated with improved morbidity and better patient and allograft survival. Transplant options for patients with diabetes ...requiring insulin therapy and chronic kidney disease who are suitable candidates for kidney transplantation should include consideration of β-cell replacement therapy: pancreas or islet transplantation. International variation related to national regulatory policies exists in offering one or both options to suitable candidates and is further affected by pancreas/islet allocation policies and transplant waiting list dynamics. The selection of appropriate candidates depends on patient age, coexistent morbidities, the timing of referral to the transplant center (predialysis versus on dialysis) and availability of living kidney donors. Therefore, early referral (estimated glomerular filtration rate < 30 mL/min/1.73 m2) is of the utmost importance to ensure adequate time for informed decision making and thorough pretransplant evaluation. Obesity, cardiovascular disease, peripheral vascular disease, smoking, and frailty are some of the conditions that need to be addressed before acceptance on the transplant list, and ideally before dialysis becoming imminent. This review offers insights into selection of pancreas/islet transplant candidates by transplant centers and an update on posttransplant outcomes, which may have practice implications for referring nephrologists.
Transportable normothermic kidney perfusion for 24 hours or longer could enable viability assessment of marginal grafts, increased organ use, and improved transplant logistics. Eleven clinically ...declined kidneys were perfused normothermically, with 6 being from donors after brain death (median cold ischemia time 33 ± 36.9 hours) and 5 being from donors after circulatory death (36.2 ± 38.3 hours). Three kidneys were perfused using Ringer’s lactate to replace excreted urine volume, and 8 kidneys were perfused using urine recirculation to maintain perfusate volume without fluid replenishment. In all cases, normothermic perfusion either maintained or slightly improved the histopathologically assessed tubular condition, and there was effective urine production in kidneys from both donors after brain death and donors after circulatory death (2367 ± 1798 mL vs 744.4 ± 198.4 mL, respectively; P = .44). Biomarkers, neutrophil gelatinase–associated lipocalin, and kidney injury molecule‐1 were successfully detected and quantified in the perfusate. All kidneys with urine recirculation were readily perfused for 24 hours (n = 8) and exhibited physiological perfusate sodium levels (140.7 ± 1.2 mmol/L), while kidneys without urine recirculation (n = 3) achieved a reduced normothermic perfusion time of 7.7 ± 1.5 hours and significantly higher perfusate sodium levels (159.6 ± 4.63 mmol/:, P < .01). Normothermic machine perfusion of human kidneys for 24 hours appears to be feasible, and urine recirculation was found to facilitate the maintenance of perfusate volume and homeostasis.
Normothermic machine perfusion of human kidneys for 24 hours is feasible, and urine recirculation facilitates maintenance of perfusate volume and homeostasis.
Xenografts from genetically modified pigs have become one of the most promising solutions to the dearth of human organs available for transplantation. The challenge in this model has been hyperacute ...rejection. To avoid this, pigs have been bred with a knockout of the alpha-1,3-galactosyltransferase gene and with subcapsular autologous thymic tissue.
We transplanted kidneys from these genetically modified pigs into two brain-dead human recipients whose circulatory and respiratory activity was maintained on ventilators for the duration of the study. We performed serial biopsies and monitored the urine output and kinetic estimated glomerular filtration rate (eGFR) to assess renal function and xenograft rejection.
The xenograft in both recipients began to make urine within moments after reperfusion. Over the 54-hour study, the kinetic eGFR increased from 23 ml per minute per 1.73 m
of body-surface area before transplantation to 62 ml per minute per 1.73 m
after transplantation in Recipient 1 and from 55 to 109 ml per minute per 1.73 m
in Recipient 2. In both recipients, the creatinine level, which had been at a steady state, decreased after implantation of the xenograft, from 1.97 to 0.82 mg per deciliter in Recipient 1 and from 1.10 to 0.57 mg per deciliter in Recipient 2. The transplanted kidneys remained pink and well-perfused, continuing to make urine throughout the study. Biopsies that were performed at 6, 24, 48, and 54 hours revealed no signs of hyperacute or antibody-mediated rejection. Hourly urine output with the xenograft was more than double the output with the native kidneys.
Genetically modified kidney xenografts from pigs remained viable and functioning in brain-dead human recipients for 54 hours, without signs of hyperacute rejection. (Funded by Lung Biotechnology.).
Objectives
To evaluate functional results, graft survival and late complications in patients who underwent robot‐assisted kidney transplantation (RAKT) and who had a minimum of 1 year of follow‐up ...data, and to analyse the correlations between surgical data and functional results at a minimum of 1‐year postoperatively and between renal function in the immediate postoperative period and after 1 year.
Materials and Methods
A common prospectively collected RAKT database was created by the European Robotic Urological Section (ERUS) RAKT working group, which included eight different European centres. In each centre RAKTs were performed with kidneys from living donors. Data on demographic variables, surgical results, graft survival, functional outcomes (creatinine and estimated glomerular filtration rate eGFR) on postoperative days 7 and 30 and at 1 year, and late complications were extracted from the common database.
Results
A total of 147 RAKTs were performed by the ERUS RAKT working group. Of the 147 patients, 83 had at least 1‐year follow‐up (mean range 21 13–27 months). Of these 83 patients, 30 were women. The patients’ median (range) age was 43 (30–75) years, body mass index was 25.3 (20–40) kg/m2, pre‐transplantation serum creatinine was 517 (198–1 414) μmol/L and estimated GFR (eGFR) was 10 (3–29) mL/min per 1.73 m2. Of the 83 cases, 46 were pre‐emptive. The median (range) overall ischaemia time was 116 (53–377) min. The median (range) rewarming time was 60 (35–110) min. At 1‐year follow‐up, the median (range) serum creatinine was 131 (66–244) μmol/L, with a median (range) eGFR of 57.4 (28–97) mL/min per 1.73 m2. There was no statistically significant difference between functional data at postoperative day 30 and those at 1 year for creatinine (P = 0.78) or eGFR (P = 0.91). Regarding the correlation between the surgical data and the functional outcomes, the data showed that overall operating time and rewarming time did not affect the graft function at 1 year. Three cases of graft loss occurred as a result of massive arterial thrombosis within the first postoperative week. Late complications comprised one case of ureteric stenosis and one case of graft pyelonephritis. No late vascular complications or cases of incisional hernia were recorded.
Conclusion
Findings at 1‐year follow‐up indicate RAKT from a living donor to be a safe procedure in a properly selected group of recipients. RAKT was associated with a low complication rate and there was maintenance of excellent graft survival and function. This is the first and largest study to report functional results after RAKT from a living donor with a minimum follow‐up of 1 year.
De Novo Malignancies after Kidney Transplantation Al-Adra, David; Al-Qaoud, Talal; Fowler, Kevin ...
Clinical journal of the American Society of Nephrology,
03/2022, Volume:
17, Issue:
3
Journal Article
Peer reviewed
Open access
Cancer is an important outcome after kidney transplantation because it is the second leading cause of death in most Western countries. The excess risk of cancer after transplantation is approximately ...two to three times higher than the age- and sex-matched general population, driven largely by viral- and immune-related cancers. Once cancer develops, outcomes are generally poor, particularly for those with melanoma, renal cell carcinoma, and post-transplant lymphoproliferative disease. More importantly, effective screening and treatment strategies are limited in this high-risk population. In this review, we begin with a patient's journey that maps the experience of living with a kidney transplant and understand the patient's knowledge, education, and experience of cancer in the context of transplantation. The epidemiology and burden of cancer in recipients of kidney transplants, along with the up-to-date screening and treatment strategies, are discussed. We also focus on the current understanding of optimal care for recipients of kidney transplants who are living with cancer from the patients' perspectives.
The aim of this study was to compare the outcomes of simultaneous and delayed implantation of kidney grafts in combined liver-kidney transplantation (CLKT).
Delayed function of the renal graft (DGF), ...which can result from hypotension and pressor use related to the liver transplantation (LT), may cause worse outcomes in CLKT.
A total of 130 CLKTs were performed at Indiana University between 2002 and 2015 and studied in an observational cohort study. All kidneys underwent continuous hypothermic pulsatile machine perfusion until transplant: 69 with simultaneous kidney transplantation (KT) (at time of LT, group 1) and 61 with delayed KT (performed at a later time as a second operation, group 2). All patients received continuous veno-venous hemodialysis during the LT. Propensity score match analysis in a 1:1 case-match was performed.
Mean kidney cold ischemia time was 10 ± 3 and 50 ± 15 hours, for groups 1 and 2 (P < 0.0001), respectively. The rate of DGF was 7.3% in group 1, but no DGF was seen in group 2 (P = 0.0600). Kidney function was significantly better in group 2, if the implantation of kidneys was delayed >48 hours (P < 0.01). Patient survival was greater in group 2 at 1 year (91%), and 5 year (87%) post-transplantation (P = 0.0019). On multivariate analysis, DGF hazard ratio (HR), 165.7; 95% confidence interval (CI), 9.4-2926, extended criteria donor kidneys (HR, 15.9; 95% CI 1.8-145.2), and recipient hepatitis C (HR, 5.5; 95% CI 1.7-17.8) were significant independent risk factors for patient survival.
Delayed KT in CLKT (especially if delayed >48 h) is associated with improved kidney function with no DGF post-KT, and improved patient and graft survival.
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