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This issue is anchored by the immunology of the graft, with microvascular inflammation and how to classify and treat it running as the connecting thread. A phase I/II trial tests whether combined CD28 and IL-6 blockade can build a calcineurin-inhibitor-free, regulatory-T-cell-friendly regimen, while a multicentre registry reports early signals that CD38-targeted daratumumab may stabilise function in microvascular inflammation, and a gene-expression classifier offers a molecular read on the donor-specific-antibody-negative, C4d-negative phenotype that Banff 2022 carved out — together a coherent strand on rejection biology, biomarkers and novel immunosuppression. The supply side is represented by three donor-utilisation papers: a Cochrane review weighing therapeutic donor hypothermia, an Italian cohort showing that heavily scarred kidneys can succeed when used as dual grafts, and a multicentre description of why candidates themselves turn down deceased-donor offers. Cardiometabolic care features through a cohort of GLP-1 receptor agonists in post-transplant diabetes, and the issue closes on long-term graft survival with a Danish study of recurrent IgA nephropathy and its links to younger, faster-progressing recipients and living related donors. Across the selection, the levers are the same ones that decide whether a graft is offered, accepted, and kept: rejection control, donor utilisation, cardiometabolic risk, and disease recurrence.
1. Regulatory T cell modulation with selective CD28 blockade and IL-6 receptor antagonist in kidney transplant recipients: results of CTOT-24, a prospective clinical trial.
Chandran S, Tang Q, Leung JC, Armstrong BD, Friedewald JJ, Kirk AD, Laszik ZG, Goldstein J, Morsheimer M, Vincenti FG. Am J Transplant, 2026. PMID: 42486389.
This multicentre, prospective, phase I/II pilot trial (CTOT-24, NCT04066114) tested the hypothesis that simultaneously blocking CD28 and interleukin-6 would tip the balance toward regulatory T cells and control rejection within a calcineurin-inhibitor-free regimen. Living-donor kidney transplant recipients received lulizumab pegol, a novel anti-CD28 domain antibody, together with the anti-IL-6-receptor antibody tocilizumab for three months, followed by belatacept plus tocilizumab for a further three months, all on a backbone of anti-thymocyte globulin, steroids, and either mycophenolate mofetil or everolimus. The primary endpoint was freedom from biopsy-proven acute rejection at six months. Of eight treated recipients, five discontinued study therapy early — driven by acute T-cell-mediated rejection, severe neutropenia, and patient preference — while three completed the regimen rejection-free and remained on belatacept, mycophenolate and prednisone with a mean estimated glomerular filtration rate of 85.6 ml/min/1.73m² at two years. There were no episodes of antibody-mediated rejection and no deaths or graft losses. Mechanistically the strategy failed on its own terms: flow cytometry showed no rise in circulating regulatory T cells under the regimen and no difference between those who rejected and those who did not, so the anticipated tolerance signal never materialised. As a tiny pilot the study cannot support efficacy claims, and the T-cell-mediated rejection and neutropenia events temper enthusiasm for this particular combination. For UK practice, where belatacept-based, nephrotoxicity-sparing immunosuppression remains an attractive goal, it is a useful cautionary data point that layering CD28 and IL-6 blockade does not deliver reliable rejection control and that alternative routes to promoting regulatory T cells are still needed.
2. A multicenter registry study of the CD38 antibody daratumumab for the treatment of microvascular inflammation following kidney transplantation.
Drasch T, Mayer KA, Böhmig GA, Akifova A, Halleck F, Budde K, Rohlfing D, Hinze C, Kluger M, Grahammer F, Kowald J, Baatz S, Reuter S, Kemmner S, Seibt T, Pigorsch M, Beck J, Bornemann-Kolatzki K, Schütz E, Oellerich M, Banas B, Zecher D. Kidney Int, 2026. PMID: 42492852.
This multicentre retrospective registry examined whether the anti-CD38 monoclonal antibody daratumumab can stabilise grafts affected by microvascular inflammation, a lesion tied to reduced allograft survival and, until now, without an established treatment. The authors assembled data on estimated glomerular filtration rate, albuminuria, allograft histology, donor-specific antibodies and donor-derived cell-free DNA from 70 recipients, captured both before and after daratumumab was started. Fifty-nine had antibody-mediated rejection and eleven had the donor-specific-antibody-negative, C4d-negative microvascular inflammation phenotype; the median interval from transplantation to diagnosis was 36 months, and treatment began a median of 1.6 months after diagnosis. In a mixed linear model the trajectory of graft function reversed, from a decline of −1.6 ml/min/1.73m² per month in the year before diagnosis to a gain of +0.3 ml/min/1.73m² per month after starting daratumumab. Median albuminuria and donor-derived cell-free DNA both fell early during treatment, whereas the effect on donor-specific antibodies was heterogeneous, and neither the number of doses nor the treatment duration measurably changed outcome. Six recipients nonetheless lost their graft during follow-up, and the authors frame their findings explicitly as preliminary. As an uncontrolled retrospective series it cannot separate drug effect from regression to the mean or concurrent care, and safety was documented rather than systematically compared. For UK practice it adds to a growing signal that CD38-directed therapy may be worth formal trial evaluation in microvascular inflammation and chronic antibody-mediated rejection, conditions where clinicians currently have little to offer.
3. Molecular Classification Predicts Clinical Outcomes of Kidney Transplant Recipients With Microvascular Inflammation, Donor-specific Antibodies-negative and C4d-negative.
Aziz F, Zhang H, Chuang P, Tian W, Zeng J, Lu J, Shen L, Gulbahce N, Kobrle J, Tobin L, Woodward R, Coley S, Napier J, Djamali A, Garg N. Transplantation, 2026. PMID: 42490311.
This study asked whether molecular profiling can bring prognostic clarity to isolated microvascular inflammation, the donor-specific-antibody-negative and C4d-negative phenotype that Banff 2022 recognised as distinct but whose behaviour remains hard to predict from histology alone. The authors built a multiclass, gene-expression-based classifier trained to assign formalin-fixed paraffin-embedded allograft biopsies to molecular categories of rejection, then applied it to an independent set of 138 biopsies from a large US transplant centre, of which 42 carried the microvascular-inflammation, antibody-negative, C4d-negative diagnosis. Against histology, the molecular calls showed strong concordance for no rejection, antibody-mediated rejection and T-cell-mediated rejection, with concordance rates ranging from 85% to 93% across groups. Within the microvascular-inflammation subgroup, molecular classification tracked with meaningful clinical differences, being significantly associated with divergent renal function and graft survival. In other words, biopsies that look alike under the microscope separated into molecular subsets with different prognoses, some resembling antibody-mediated rejection at the transcript level and others not. As a single-centre validation of a proprietary classifier it establishes association rather than a management pathway, and prospective evidence that acting on the molecular label improves outcomes is still lacking. For UK practice it complements this issue’s daratumumab data by suggesting a way to identify which microvascular-inflammation cases carry rejection-like biology and the worst trajectory — precisely the patients in whom aggressive therapy might be justified.
4. Therapeutic donor hypothermia following brain death to improve the quality of transplanted organs.
Amarnath DR, Tingle SJ, Hoather TJ, Thompson ER, Wilson CH. Cochrane Database Syst Rev, 2026. PMID: 42495907.
This Cochrane systematic review and meta-analysis assessed whether cooling brain-dead donors — a simple, low-cost intervention intended to blunt the organ injury of brain death — improves outcomes in the recipients of their organs. The reviewers searched the Cochrane Kidney and Transplant register, CENTRAL, MEDLINE, Embase and two trial registries to 3 September 2025 for randomised and quasi-randomised trials of donor hypothermia versus normothermia, using Cochrane’s risk-of-bias tool and GRADE, and pooled four studies enrolling 2,096 donors. For kidney recipients, hypothermia may not reduce delayed graft function (risk ratio 0.87, 95% CI 0.71–1.08; I²=57%; four studies, 3,015 participants; low certainty) and showed no clear association with one-year graft survival (hazard ratio 0.77, 95% CI 0.51–1.14; three studies, 2,075 participants) or one-year patient survival (hazard ratio 0.81, 95% CI 0.42–1.57; one study, 526 participants), all at low certainty. Organ utilisation was essentially unchanged, with a kidney utilisation risk ratio of 0.99 (95% CI 0.95–1.03; four studies, 4,265 participants; moderate certainty) and high-certainty evidence of no effect on liver utilisation. Reassuringly, donor hypothermia was not associated with more donor adverse events (risk ratio 1.28, 95% CI 0.45–3.62), and no safety concerns emerged. The overall picture is low-to-moderate certainty, limited by imprecision and reporting bias, and no data addressed primary non-function, acute rejection or quality of life. For UK practice it argues against expecting donor cooling to lift kidney outcomes or expand utilisation on current evidence, while confirming it is safe — leaving the question open for better-powered trials.
5. Outcomes of Dual Kidney Transplantation from Donors with High Pre-implantation Biopsy Scores.
Comai G, Provenzano M, Gessaroli E, Grandinetti V, Vetrano D, Napoletano A, Abenavoli C, Bini C, Cuna V, Demetri M, Chiappo F, Leone F, Fabbrizio B, Del Gaudio M, Maroni L, Ravaioli M, La Manna G, Corradetti V. Am J Nephrol, 2026. PMID: 42485259.
This single-centre Italian retrospective cohort tested whether kidneys carrying heavy chronic damage on pre-implantation biopsy — organs that are frequently discarded — can be used successfully when transplanted as dual grafts to increase nephron mass. Among 262 adult deceased-donor recipients biopsied before implantation between 2014 and 2021, patients were stratified into single transplantation with a Karpinski score below 9 (n=142), dual transplantation with a combined score below 9 (n=35), and dual transplantation with a combined score of 9 or above (n=85), the last representing the most heavily scarred organs. Dual-graft donors were older and had higher kidney donor profile and risk indices, yet recipients of the high-chronicity dual grafts did not show inferior function, achieving comparable estimated glomerular filtration rate and proteinuria at both 12 and 36 months. Primary non-function, delayed graft function, biopsy-proven acute rejection and major complications were similar across the three groups, although post-transplant thrombotic microangiopathy occurred more often in dual-graft recipients. Kaplan–Meier analyses showed no significant differences in overall graft failure, all-cause mortality or death-censored graft failure, and in multivariable Cox regression allocation group was not independently associated with graft failure. As a retrospective single-centre experience with modest numbers and a real-world allocation process, it demonstrates feasibility rather than proving equivalence, and the thrombotic microangiopathy signal warrants attention. For UK practice, where marginal-kidney utilisation and discard rates are a live concern, it supports dual transplantation as a way to safely use organs that high histological chronicity might otherwise condemn, provided the decision integrates clinical and functional donor assessment.
6. Patterns and Reasons for Patient-Level Refusal of Deceased Donor Kidney Offers: A Multicenter Descriptive Study.
Mylarapu N, Kadri H, McMahon A, Stewart C, Sycheva M, Casingal V, Choudhury R, Denny R, Eskind L, Jay C, McCracken E, Levi D, Soto JR, Vrochides D, Schold JD, Baimas-George M. Am J Transplant, 2026. PMID: 42486388.
This multicentre retrospective study looked at an under-characterised contributor to organ non-use — the point at which the candidate, rather than the transplant team, declines a deceased-donor kidney offer. Across three transplant centres over two years, 841 offers reached the stage of patient contact, and 108 (13%) ended in a patient-level refusal. Donation-after-circulatory-death kidneys made up 51% of offers and a slightly higher 54% of refusals, with donation-after-brain-death kidneys accounting for the remainder, and the refused offers were not uniformly marginal, carrying a median kidney donor profile index of 50.5 and arising early in the match run (median sequence position 5, IQR 3–14). The stated reasons clustered around donor-related quality and longevity concerns (33.3%), infectious or behavioural risk (23%), patient preference or readiness (15%), logistical constraints (14%), and psychosocial or caregiver limitations (7%). Importantly, refusal was rarely a dead end: candidates received a further offer at a median of 7.5 days, 59% went on to transplantation at a median of 46.5 days, and 83% of the refused kidneys were transplanted elsewhere with acceptable outcomes — though 23% of the refusing candidates experienced waitlist inactivation or removal within 24 months. As a descriptive study from three US centres it cannot establish how many refusals were avoidable or quantify the harm of waiting, and practice will differ under the UK offering scheme. For UK units it nonetheless highlights that candidate-side education, timely preference reassessment, and attention to logistical and psychosocial barriers could reduce avoidable refusals while still respecting patient-centred choice.
7. GLP-1 receptor agonists in kidney transplant recipients with post-transplant diabetes: efficacy and safety outcomes from a retrospective cohort study.
Navarrete RET, Freitas JC, Fonseca I, Cunha A, Martins S, Sa JR. Arch Endocrinol Metab, 2026. PMID: 42485571.
This retrospective single-centre cohort evaluated the efficacy and safety of glucagon-like peptide-1 receptor agonists added to existing therapy in 24 kidney transplant recipients with post-transplant diabetes mellitus, treated between August 2013 and April 2024. Over a mean follow-up of 3.2 ± 2.1 years, the metabolic effects were mixed: there were non-significant trends toward weight loss (−3.6 ± 8.5 kg, p=0.051) and lower body mass index (−1.4 ± 3.3 kg/m², p=0.056), while glycaemic control barely moved, with HbA1c falling only 0.2% (p=0.362) and fasting plasma glucose actually rising by 12.1 mg/dL (p=0.232). The clearer benefits were cardiometabolic rather than glycaemic — total cholesterol dropped by 41.5 mg/dL (p<0.001) and systolic blood pressure by 8.5 mmHg (p=0.041) — and renal function stayed stable, with serum creatinine and estimated glomerular filtration rate essentially unchanged (−0.09 mg/dL, p=0.305; +3.2 ml/min/1.73m², p=0.206). Tolerability was acceptable, with nausea in 21% (n=5) and no other severe adverse events reported. As a small, uncontrolled, single-centre series the study cannot isolate the drug’s contribution or exclude confounding, and the muted glycaemic signal may reflect the add-on setting and small numbers. For UK practice, where GLP-1 receptor agonists are increasingly reached for to manage weight, cardiovascular risk and diabetes after transplantation, it offers modest reassurance on renal safety and points to lipid and blood-pressure benefit, while underscoring that prospective data are needed to confirm durable cardiorenal gains.
8. Incidence and risk factors for recurrent IgA nephropathy after kidney transplantation: A multicenter cohort study from Denmark.
Øhrstrøm MT, Schultz MD, Bistrup C, Birn H. PLoS One, 2026. PMID: 42475362.
This Danish multicentre cohort quantified the recurrence of IgA nephropathy after transplantation and its risk factors, drawing on all adults with biopsy-proven disease who received a first kidney-only transplant at two centres between 1990 and 2020. Among 118 recipients followed for a median of 5.5 years (798 patient-years), biopsy-confirmed recurrence occurred in 14% (17 patients), with a cumulative incidence rising from 4% at one year to 12% at five years and 16% at ten years, and a median time to recurrence of 2.9 years — all based on clinically indicated rather than protocol biopsies, which the authors note probably underestimates true recurrence. Recipients who recurred were younger at kidney failure and had progressed faster from diagnosis to failure, and donor type mattered: living donation carried a markedly higher unadjusted risk (hazard ratio 5.15, 95% CI 1.48–17.94), as did a genetically related donor (hazard ratio 3.92, 95% CI 1.38–11.17), with the living-donor association persisting after adjustment for sex and age at kidney failure (hazard ratio 3.75, 95% CI 1.06–13.20). Maintenance post-transplant steroid use showed no protective effect on recurrence. The clinical cost was substantial: recurrent disease was independently associated with graft failure (unadjusted hazard ratio 3.8; adjusted hazard ratio 6.7, 95% CI 1.7–26.8), and death-censored graft survival at five and ten years was 70% and 51% with recurrence versus 91% and 77% without. As a retrospective study with few recurrence events, wide confidence intervals and susceptibility to immortal-time bias, its estimates are best read as directional. For UK practice it supports frank counselling of younger, rapidly progressing IgA nephropathy candidates — including those weighing a living related donor — about recurrence risk and its threat to the graft, while indication-only biopsy means clinicians should keep a low threshold for allograft biopsy when function declines.
Generated 2026-07-25 from PubMed search results for kidney transplantation published 2026-07-11 to 2026-07-25. Articles already recorded in prior issues were excluded. PubMed is the source of all metadata and abstracts.
How this digest is made: From a literature-search skill to a self-running evidence digest.