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Donor-derived cell free DNA (dd-cfDNA) is an established biomarker for detection of rejection in single organ transplants; data is limited in multi-organ transplant (MOT) recipients. “Use of dd-cfDNA in Multi-Organ Transplant Recipients” (MOTR) was a multicenter, prospective, cross-sectional study that assessed dd-cfDNA fraction (%) and donor quantity score (DQS, cp/mL) in pancreas-kidney (PKT), heart-kidney (HKT), and liver-kidney (LKT) recipients. We explored dd-cfDNA baseline levels across the different organ combinations, and compared them to kidney-only (KT) and heart-only (HT) transplant recipients. Among 347 MOT recipients from 18 sites (PKT = 183, HKT = 57, LKT = 107), most (88.2%) had simultaneous transplants. Median dd-cfDNA levels in PKT and HKT recipients were not significantly different from KT; median dd-cfDNA levels among HKT recipients were significantly higher than in HT recipients (p < 0.001). In LKT recipients, median dd-cfDNA was significantly higher compared to KT (p < 0.001). dd-cfDNA showed associations with organ impairment indicated by abnormal values of pancreatic and liver enzymes in PKT and LKT. As the largest multi-center study to date evaluating dd-cfDNA levels in MOT recipients, MOTR showed that organ-specific physiology affects dd-cfDNA levels across organ transplant combinations, laying the foundation for future efforts to use dd-cfDNA to assess organ-specific signatures of allograft injury in MOT recipients.

Proteinuria is associated with worse allograft outcomes in kidney transplant recipients (KTRs) and treatment strategies are limited. We examined the outcomes of calcineurin inhibitor (CNI) to belatacept conversion in proteinuric KTRs. In a pilot phase II single-arm multicenter prospective trial, we recruited adult KTRs >6 months post-kidney transplantation with an estimated glomerular filtration rate (eGFR) ≥30 ml/min/1.73m and proteinuria >1 g/day. Patients were converted from CNI to belatacept. The primary outcome was a 25% reduction in proteinuria at 12 months. A total of 15 KTRs were recruited who had pre-conversion median (interquartile range) proteinuria of 1.8 (IQR 1.4 - 3.5) g/g and estimated glomerular filtration rate (eGFR) of 48 (IQR 32 - 52.5) ml/min/1.73m . At 12 months post-conversion, median proteinuria was 1.4 (IQR 0.4 - 2.2) g/g ( = 0.068) and eGFR was maintained at 43 (34 - 54.5) ml/min/1.73m . The primary outcome of at least a 25% reduction in proteinuria occurred in 53% (8/15) at 12 months. Abbreviated IBOX scores predicting 7-year graft survival were also stable at 1-year post-conversion compared to baseline. At extended follow-up at 5 years, both proteinuria and eGFR remained stable at 0.69 (0.24 - 2.15) g/g and 39 (31 - 57) ml/min/1.73m , respectively. CNI to belatacept conversion was associated with preserved allograft function in KTRs with significant proteinuria. These findings need to be confirmed in a larger randomized clinical trial. https://clinicaltrials.gov/,

Since its discovery in 1971, BK Polyomavirus infection has been increasingly recognized, especially since the introduction of more effective immunosuppressive medications in the early 1990s. BK virus is believed to have a high seroprevalence in healthy individuals, entering a latent phase in the genitourinary that follows the primary infection. Reactivation may occur in immunocompromised hosts, with significant effects seen especially in kidney and hematopoietic stem cell transplant recipients. Screening methods have been developed and are implemented as early detection may allow for the prevention of irreversible tissue damage. Reduction of immunosuppression remains the cornerstone of therapy for BKV infection, and adjunctive therapies have shown variable results. Newer cellular-based therapeutics might provide a more targeted treatment for BKV infection but are still in need of more randomized human studies.

Discusses the use of belatacept for the prevention of acute rejection in adult kidney transplant recipients as part of a calcineurin inhibitor-free (CNI-free) maintenance immunosuppression regimen. Looks at costimulation blockade with belatacept. Summarises two phase III trials, Belatacept Evaluation of Nephroprotection and Efficacy as First-line Immunosuppression Trial (BENEFIT) and Belatacept Evaluation of Nephroprotection and Efficacy as First-line Immunosuppression Trial-EXTended criteria donors (BENEFIT-EXT). Deals with the incidence of rejection on belatacept. Addresses the development of post-transplant lymphoproliferative disorder (PTLD) in belatacept-treated patients as a major safety concern. Covers belatacept and cardiometabolic risk. Source: National Library of New Zealand Te Puna Matauranga o Aotearoa, licensed by the Department of Internal Affairs for re-use under the Creative Commons Attribution 3.0 New Zealand Licence.

Among patients with short bowel syndrome who commonly have kidney disease, kidney transplantation remains challenging. We describe the clinicopathologic course of a 59-year old man with short bowel syndrome secondary to Crohn’s disease who underwent a deceased donor kidney transplant that was complicated by recurrent acute kidney allograft injury due to volume depletion from diarrhea, ultimately requiring the placement of permanent intravenous access for daily volume expansion at home resulting in the recovery of allograft function. Teduglutide treatment at 1.8 years post-transplant led to a dramatic decrease in diarrhea. A literature review of similar cases yielded 18 patients who underwent 19 kidney transplants. Despite high rates of complications, at the time of last follow-up (median 2.1 years [0.04-7]), 94% of the patients were still alive and 89% had functioning allografts, with a median eGFR of 37.5 [14-122] ml/min/1.73m2. In conclusion, despite high rates of complications, kidney transplantation in patients with short bowel syndrome is associated with acceptable short- and midterm outcomes. Further, we report for the first time the effects of the glucagon-like peptide-2 analogue teduglutide for short bowel syndrome in a kidney transplant recipient.

Kidney transplantation from donors with human immunodeficiency virus (HIV) to recipients with HIV is an emerging practice. It has been performed since 2016 under the U.S. congressional HIV Organ Policy Equity Act and is currently approved for research only. The Department of Health and Human Services is considering expanding the procedure to clinical practice, but data are limited to small case series that did not include donors without HIV as controls. In an observational study conducted at 26 U.S. centers, we compared transplantation of kidneys from deceased donors with HIV and donors without HIV to recipients with HIV. The primary outcome was a safety event (a composite of death from any cause, graft loss, serious adverse event, HIV breakthrough infection, persistent failure of HIV treatment, or opportunistic infection), assessed for noninferiority (margin for the upper bound of the 95% confidence interval, 3.00). Secondary outcomes included overall survival, survival without graft loss, rejection, infection, cancer, and HIV superinfection. We enrolled 408 transplantation candidates, of whom 198 received a kidney from a deceased donor; 99 received a kidney from a donor with HIV and 99 from a donor without HIV. The adjusted hazard ratio for the composite primary outcome was 1.00 (95% confidence interval [CI], 0.73 to 1.38), which showed noninferiority. The following secondary outcomes were similar whether the donor had HIV or not: overall survival at 1 year (94% vs. 95%) and 3 years (85% vs. 87%), survival without graft loss at 1 year (93% vs. 90%) and 3 years (84% vs. 81%), and rejection at 1 year (13% vs. 21%) and 3 years (21% vs. 24%). The incidence of serious adverse events, infections, surgical or vascular complications, and cancer was similar in the groups. The incidence of HIV breakthrough infection was higher among recipients of kidneys from donors with HIV (incidence rate ratio, 3.14; 95%, CI, 1.02 to 9.63), with one potential HIV superinfection among the 58 recipients in this group with sequence data and no persistent failures of HIV treatment. In this observational study of kidney transplantation in persons with HIV, transplantation from donors with HIV appeared to be noninferior to that from donors without HIV. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT03500315.).

A 49-year-old man with HIV infection and chronic kidney disease was evaluated in the kidney transplantation clinic because of declining kidney function. Management decisions were made.

The last three decades have witnessed significant advances in the development of immunosuppressive medications used in kidney transplantation leading to a remarkable gain in short-term graft function and outcomes. Despite these major breakthroughs, improvements in long-term outcomes lag behind due to a stalemate between drug-related nephrotoxicity and chronic rejection typically due to donor-specific antibodies. Regulatory T cells (Tregs) have been shown to modulate the alloimmune response and can exert suppressive activity preventing allograft rejection in kidney transplantation. Currently available immunosuppressive agents impact Tregs in the alloimmune milieu with some of these interactions being deleterious to the allograft while others may be beneficial. Variable effects are seen with common antibody induction agents such that basiliximab, an IL-2 receptor blocker, decreases Tregs while lymphocyte depleting agents such as antithymocyte globulin increase Tregs. Calcineurin inhibitors, a mainstay of maintenance immunosuppression since the mid-1980s, seem to suppress Tregs while mammalian targets of rapamycin (less commonly used in maintenance regimens) expand Tregs. The purpose of this review is to provide an overview of Treg biology in transplantation, identify in more detail the interactions between commonly used immunosuppressive agents and Tregs in kidney transplantation and lastly describe future directions in the use of Tregs themselves as therapy for tolerance induction.

Many patients with hepatorenal syndrome (HRS) end up receiving a combined liver and kidney transplant (CKLT) with preservation of native kidneys, specially type 1 HRS since is characterizes by a very rapid deterioration of renal function. Eventually, most of the patients regain renal function, but it is unknown if this is due to the transplanted kidney, the recovery of native renal function, or both. The aim of this study is to evaluate if there is recovery of native renal function in patients with HRS following CKLT. 22 patients (16 men; 6 women) with history of HRS and status post CKLT were studied. Mercapto-acetyltriglycine-3 renograms in the anterior and posterior views with the three kidneys in the field of view were simultaneously acquired. The renograms were analyzed by creating regions of interest around the transplanted and native kidneys. Relative contribution to the renal function, clearance, and effective renal plasma flow for the transplanted and native kidneys were obtained. 1/22 (4.5%) patients presented with a very poor functioning transplanted kidney, in 15/22 (68%) cases the combined native renal function was markedly poorer than the transplanted renal function and in 6/22 (27%) native kidneys showed a contribution to the renal function similar to the transplanted kidney. In conclusion, our series show that around 32% of the HRS patients recovered their native renal function after CKLT. Identification of common factors that affect recovery of native renal function may help to avoid unnecessary renal transplants, significantly reducing morbidity and cost, while facilitating a reallocation of scarce donor resources.