The growing number of elderly patients with end-stage kidney disease awaiting transplantation has resulted in a corresponding rise in the number of elderly transplant recipients. In this paper, we ...review existing literature on age-related changes, transplant outcomes, and complications in the elderly in an attempt to propose a tailored approach to immunosuppression management in this group of patients. Despite the fact that the benefit of transplantation in the elderly is well established, clinical trials evaluating the safety and efficacy of immunosuppression regimens are lacking. Until such data exists, immunosuppression of the elderly transplant recipient should be based on the traditional principles which guide all transplant protocols and consideration of factors that are unique to the elderly. There are limited data regarding age-related changes in immune function and metabolism of immunosuppression agents in this population. Results of registry data analyses suggest that the risk of acute rejection decreases with age; however, the impact of acute rejection on long-term allograft function is greater in this population. There is also an increased risk of infection and adverse events posttransplantation among these patients. Elderly patients are more likely to receive organs from extended criteria donors and the impact of donor factors on transplant outcomes must therefore be considered. Taking these factors into consideration, we propose an approach to immunosuppression in the elderly based on individual risk stratification of treatment failure and the potential for adverse events.
BACKGROUNDBK virus infection remains an important cause of loss of allograft function after kidney transplantation. We sought to determine whether polyfunctional T cells secreting multiple cytokines ...simultaneously, which have been shown to be associated with viral control, could be detected early after start of BK viremia, which would provide insight into the mechanism of successful antiviral control.
METHODSPeripheral blood mononuclear cells collected during episodes of BK viral replication were evaluated by multiparameter flow cytometry after stimulation by overlapping peptide pools of BK virus antigen to determine frequency of CD8+ and CD4+ T cells expressing 1 or more cytokines simultaneously, as well as markers of T-cell activation, exhaustion, and maturation.
RESULTSBK virus controllers, defined as those with episodes of BK viremia of 3 months or less, had an 11-fold increase in frequency of CD8+ polyfunctional T cells expressing multiple cytokines, as compared with patients with prolonged episodes of BK viremia. Patients with only low level BK viremia expressed low frequencies of polyfunctional T cells. Polyfunctional T cells were predominantly of the effector memory maturation subtype and expressed the cytotoxicity marker CD107a.
CONCLUSIONSNoninvasive techniques for immune assessment of peripheral blood can provide insight into the mechanism of control of BK virus replication and may allow for future patient risk stratification and customization of immune suppression at the onset of BK viremia.
This popular handbook is a practical guide for physicians, surgeons, nurses, and other professionals who manage kidney transplant patients. It is concise, readable, and well-illustrated. Chapters ...outline the major concerns surrounding renal transplantation and the most successful approaches to problems arising in short-term and long-term patient care. Chapter topics include immunobiology and immunosuppression, as well as chapters on surgery, histocompatibility, and the first three months post-transplant surgery.
Simultaneous pancreas-kidney transplantation is considered a curative treatment for type 1 diabetes complicated by end-stage kidney disease. We report herein a case of mesangial sclerosis in a ...patient who underwent successful kidney-pancreas transplantation despite well-controlled glucose and excellent pancreatic allograft function.
A 76-year-old type 1 diabetic man who underwent a simultaneous pancreas-kidney transplantation 19 years prior presented with persistent nephrotic range proteinuria although creatinine was at his baseline (normal) level. Hemoglobin A1c and fasting glucose were well controlled without the use of insulin or oral antihyperglycemic agents. Serum lipase and amylase were within the reference range and there was no evidence of donor-specific antibodies. Kidney allograft biopsy was performed to evaluate proteinuria and showed diffuse capillary loop thickening and diffuse moderate to severe mesangial sclerosis resembling diabetic nephropathy.
This case demonstrates a case of mesangial sclerosis resembling diabetic nephropathy in a patient with good glucose control after simultaneous pancreas-kidney transplantation with excellent pancreatic allograft function.
An average of 3,280 recovered deceased donor kidneys are discarded annually in the United States. Increased cold ischemia time is associated with an increased rate of organ decline and subsequent ...discard. Here we examined the effect of prolonged cold ischemia time on kidney transplant outcomes.
Retrospective observational study
Recipients of deceased donor kidney transplants in the United States from 2000 to 2018.
Recipients of deceased donor kidneys were divided based on documented cold ischemia time: ≤16, 16-24, 24-32, 32-40, and>40 hours.
The incidence of delayed graft function, primary nonfunction, and 10-year death-censored graft survival.
The Kaplan-Meier method was used to generate survival curves, and the log rank test was used to compare graft survival.
The rate of observed delayed graft function increased with cold ischemia time (20.9%, 28.1%, 32.4%, 37.5%, and 35.8%). Primary nonfunction also showed a similar increase with cold ischemia time (0.6%, 0.9%, 1.3%, 2.1%, and 2.3%), During a median follow-up time of 4.6 years, 37,301 recipients experienced death-censored graft failure. Analysis based on kidney donor profile index (KDPI) demonstrated significant differences in 10-year death-censored graft survival, with a death-censored graft survival in recipients of a kidney with a KDPI<85% of 71.0% (95% CI, 70.5%-71.5%), 70.5% (95% CI, 69.9%-71.0%), 69.6% (95% CI, 68.7%-70.4%), 65.5% (95% CI, 63.7%-67.3%), and 67.2% (95% CI, 64.6%-69.6%), compared to 53.5% (95% CI, 51.1%-55.8%), 50.7% (95% CI, 48.3%-53.1%), 50.3% (95% CI, 46.6%-53.8%), 50.7% (95% CI, 45.1%-56.1%), and 48.3% (95% CI, 40.0%-56.1%), for recipients of a kidney with a KDPI>85%.
Heterogeneity of acceptance patterns among transplant centers, presence of confounding variables leading to acceptance of kidneys with prolonged cold ischemia times.
Cold ischemia time was associated with an increased risk of delayed graft function and primary nonfunction. However, the effect of increased cold ischemia time is modest and has less impact than the KDPI. Transplant programs should not consider prolonged cold ischemia time alone as a predominant reason to decline an organ, especially with a KDPI<85%.
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BACKGROUND.Combined liver–kidney transplantation (CLKT) improves survival for liver transplant recipients with renal dysfunction; however, the tenuous perioperative hemodynamic and metabolic milieu ...in high-acuity CLKT recipients increases delayed graft function and kidney allograft failure. We sought to analyze whether delayed KT through pumping would improve kidney outcomes following CLKT.
METHODS.A retrospective analysis (University of California Los Angeles n = 145, Houston Methodist Hospital n = 79) was performed in all adults receiving CLKT at 2 high-volume transplant centers from February 2004 to January 2017, and recipients were analyzed for patient and allograft survival as well as renal outcomes following CLKT.
RESULTS.A total of 63 patients (28.1%) underwent delayed implantation of pumped kidneys during CLKT (dCLKT) and 161 patients (71.9%) received early implantation of nonpumped kidneys during CLKT (eCLKT). Most recipients were high-acuity with median biologic model of end-stage liver disease (MELD) score of, 35 for dCLKT and 34 for eCLKT (P = ns). Pretransplant, dCLKT had longer intensive care unit stay, were more often intubated, and had greater vasopressor use. Despite this, dCLKT exhibited improved 1-, 3-, and 5-year patient and kidney survival (P = 0.02) and decreased length of stay (P = 0.001), kidney allograft failure (P = 0.012), and dialysis duration (P = 0.031). This reduced kidney allograft futility (death or continued need for hemodialysis within 3 mo posttransplant) for dCLKT (6.3%) compared with eCLKT (19.9%) (P = 0.013).
CONCLUSIONS.Delayed implantation of pumped kidneys is associated with improved patient and renal allograft survival and decreased hospital length of stay despite longer kidney cold ischemia. These data should inform the ethical debate as to the futility of performing CLKT in high-acuity recipients.
ABSTRACTSince 2012, the Organ Procurement and Transplantation Network (OPTN)/United Network for Organ Sharing (UNOS) has required transplant centers to record the citizenship residency status of ...patients undergoing transplantation in the United States. This policy replaced the 5% threshold of the non–US citizen/nonresidents (NC/NR) undergoing organ transplantation that could result in an audit of transplant center activity. Since April 1, 2015, the country of residence for the NC/NR on the waitlist has also been recorded. We analyzed the frequency of NC/NR deceased donor organ transplants and waitlist registrations at all US transplant centers by data provided by UNOS for that purpose to the UNOS Ad Hoc International Relations Committee. During the period of 2013 to 2016, 1176 deceased donor transplants (of all organs) were performed in non–US citizen/non–US resident (NC/NR) candidates (0.54% of the total number of transplants). We focused on high-volume NC/NR transplant centers that performed more than 5% of the deceased donor kidney or liver transplants in NC/NR or whose waitlist registrants exceeded 5% NC/NR. This report was prepared to fulfill the transparency policy of UNOS to assure a public trust in the distribution of organs. When viewed with a public awareness of deceased donor organ shortages, it suggests the need for a more comprehensive understanding of current NC/NR activity in the United States. Patterns of organ specific NC/NR registrations and transplantations at high-volume centers should prompt a review of transplant center practices to determine whether the deceased donor and center resources may be compromised for their US patients.
Pulmonary toxicity has recently been recognized as a potentially serious complication associated with sirolimus therapy. We further detail this condition on the basis of our own cases and those ...reported in the literature.
We report three cases of suspected sirolimus-induced pulmonary toxicity that occurred in three renal transplant recipients and searched PubMed for all previously reported cases.
Including our current cases, 43 patients with sirolimus-induced pulmonary toxicity have now been reported. Clinical data were incomplete in 28 cases. Analysis of available data for 15 patients revealed that the most commonly presenting symptoms were dyspnea on exertion and dry cough followed by fatigue and fever. Chest radiographs and high-resolution computed tomography scans commonly revealed bilateral patchy or diffuse alveolo-interstitial infiltrates. Bronchoalveolar fluid analysis and lung biopsy in selected case reports revealed several distinct histologic features, including lymphocytic alveolitis, lymphocytic interstitial pneumonitis, bronchoalveolar obliterans organizing pneumonia, focal fibrosis, pulmonary alveolar hemorrhage, or a combination thereof. The diagnosis of sirolimus-associated pulmonary toxicity was made after an exhaustive work-up to exclude infectious causes and other pulmonary disease. Sirolimus discontinuation or dose reduction resulted in clinical and radiologic improvement in all 15 patients within 3 weeks.
The temporal relationship between sirolimus exposure and onset of pulmonary symptoms in the absence of infectious causes and other alternative pulmonary disease and the associated clinical and radiologic improvement after its cessation suggests a causal relationship. Because the use of sirolimus in organ transplantation has become more widespread, clinicians must remain vigilant to its potential pulmonary complication.
Renal thrombotic microangiopathy (TMA) involves diverse causes and clinical presentations. Genetic determinants causing alternate pathway complement dysregulation underlie a substantial proportion of ...cases. In a significant proportion of TMAs, no defect in complement regulation is identified. Mutations in the major mammalian 3′ DNA repair exonuclease 1 (TREX1) have been associated with autoimmune and cerebroretinal vasculopathy syndromes. Carboxy-terminal TREX1 mutations that result in only altered localization of the exonuclease protein with preserved catalytic function cause microangiopathy of the brain and retina, termed retinal vasculopathy and cerebral leukodystrophy (RVCL). Kidney involvement reported with RVCL usually accompanies significant brain and retinal microangiopathy. We present a pedigree with autosomal dominant renal TMA and chronic kidney disease found to have a carboxy-terminal frameshift TREX1 variant. Although symptomatic brain and retinal microangiopathy is known to associate with carboxy-terminal TREX1 mutations, this report describes a carboxy-terminal TREX1 frameshift variant causing predominant renal TMA. These findings underscore the clinical importance of recognizing TREX1 mutations as a cause of renal TMA. This case demonstrates the value of whole-exome sequencing in unsolved TMA.
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