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This issue is anchored by the donor and the donation pathway. A Lancet first-in-human report pushes the surgical frontier with combined bladder-kidney transplantation, while two US studies reframe living donation: a JAMA Internal Medicine cohort linking APOL1 high-risk genotypes to worse long-term kidney function in donors, and a 25-year registry analysis showing how voucher-based “Good Samaritan” donation has reshaped non-directed living donation. Sensitisation and multi-organ complexity feature in a UNOS analysis of positive-crossmatch heart-kidney transplantation. A second thread runs through immune monitoring and infection: donor-derived cell-free DNA paired with molecular microscope diagnostics to refine T-cell-mediated rejection management, Torque Teno Virus as a candidate marker of net immunosuppression, and a meta-analysis of cytomegalovirus and BK virus risk under belatacept. The issue closes on paediatrics, where genetic testing stratifies recurrence risk in steroid-resistant nephrotic syndrome after transplantation. Together they reflect a field tightening risk stratification at both ends of the transplant pathway — who donates safely, and how rejection and infection are detected and dosed.
1. Combined bladder-kidney transplantation: first-in-human feasibility trial.
Nassiri N, Gill IS. Lancet, 2026. PMID: 42335920.
This is the first report from an ongoing phase 0 feasibility trial of deceased-donor bladder or combined bladder-kidney transplantation across two US academic centres, testing vascularised composite bladder allograft transplantation as an alternative to intestinal reconstruction for terminal bladder dysfunction. Eligible recipients are adults aged 18–70 with non-functional, poorly compliant bladders, with patients already requiring immunosuppression considered ideal candidates; the co-primary endpoints are technical feasibility (completing the operation with restored urinary continuity and graft perfusion) and safety. The index case, performed in May 2025, was a 41-year-old anephric man with end-stage kidney disease from hypertension who had spent seven years on peritoneal dialysis, receiving kidney and bladder from an ABO-compatible 35-year-old donor after anoxic brain injury. The eight-hour operation achieved excellent perfusion of both organs with no intraoperative complications. On postoperative day 25 he developed a urine leak from the suprapubic tube tract with wound breakdown (Clavien-Dindo grade 4), managed surgically with good recovery. Beyond six months, he maintained an eGFR of 52–55 mL/min/1.73 m², a bladder capacity of 600 mL, complete continence, spontaneous voiding (maximum flow 17 mL/s) with negligible post-void residual, and intact bladder sensation, on tacrolimus, mycophenolate mofetil and prednisone, with serial bladder biopsies free of cell- or antibody-mediated rejection. As a single-patient feasibility account it establishes proof of concept rather than effectiveness. For UK practice it signals a potential reconstructive option for highly selected patients with terminal lower urinary tract failure who already need immunosuppression, but one that remains experimental and far from routine.
2. Apolipoprotein L1 Gene Genotype and Kidney Outcomes After Living Kidney Donation.
Hsu CY, Gao Y, Freedman BI, Lunn MR, Muiru AN, Schnitzler MA, Divers J, Mannon RB, Palmer ND, Karger AB, Lentine KL, Park M. JAMA Intern Med, 2026. PMID: 42329639.
This retrospective cohort study examined whether APOL1 high-risk genotypes are associated with worse long-term kidney function after living kidney donation, addressing a central uncertainty in donor selection. Black and White US residents who donated between January 2000 and December 2008 were traced through the Scientific Registry of Transplant Recipients and invited to home-based research visits conducted between March 2020 and March 2024. A total of 445 Black donors (66% female, mean age 38 years) and 208 White donors (68% female, mean age 44 years) enrolled, with visits occurring a median of 18.5 years after donation; 68 Black donors (15.3%) carried APOL1 high-risk genotypes (G1/G1, G2/G2 or G1/G2). Overall, 46 participants (7.0%) had an eGFR below 45 mL/min/1.73 m². Black donors with high-risk genotypes had more than double the risk of reaching that threshold compared with Black donors without (relative risk 2.31, 95% CI 1.16–4.61; P=.02), though the association attenuated and lost significance after adjustment for predonation eGFR (relative risk 1.91, 95% CI 0.90–4.03; P=.09). The authors conclude that APOL1 genotype is a risk factor for reduced postdonation kidney function and recommend genotyping all Black living-donor candidates in the US. The modest high-risk subgroup and the attenuated adjusted estimate temper firm causal claims. For UK practice this strengthens the case for incorporating APOL1 genotyping into the evaluation of prospective donors of African ancestry, while underscoring that absolute risk and local selection thresholds need careful counselling.
3. The Changing Paradigm of Good Samaritan Kidney Donation in the United States.
Hil G, Fonk J, Thomas AG, Veale JL. Transplant Direct, 2026. PMID: 42325822.
This study traced 25 years of non-directed (“Good Samaritan”) living kidney donation in the US, analysing how voucher-based models have changed its volume and character, using National Kidney Registry data (103 centres, from 2008) and the Scientific Registry of Transplant Recipients with linear-regression trend estimates. Across 2000–2024 the authors identified 4,662 Good Samaritan donations; among the 2,131 registry-facilitated cases characterised in detail, donors had a median age of 43 years and were predominantly White (93%) and female (60%), while recipients (median age 52) were more diverse (63% White, 14% Black, 10% Hispanic). Annual Good Samaritan donations rose from 17 in 2000 to 439 in 2024, a 14.5% growth rate, and voucher-based (“Family Voucher”) non-directed donations climbed from 2 in 2015 to 314 in 2024, comprising 72% of all Good Samaritan donations that year and overtaking traditional non-directed donation from 2022. The share performed at registry centres rose from 36% in 2015–2016 to 77% in 2023–2024, even as non-registry Good Samaritan donations fell by roughly half after 2019. The full text emphasises that a voucher confers only contingent future transplant priority for a named family member rather than monetary value, and cites long-horizon simulations suggesting the programme can honour future redemptions. As a descriptive registry analysis it shows correlation rather than causation, and the donor pool remains overwhelmingly White. For UK practice — where vouchered advanced donation is not currently used — it offers evidence that structured non-directed and chain-enabling models can substantially expand living donation, informing future paired-exchange policy discussion.
4. Outcomes of Simultaneous Heart-Kidney Transplant With a Positive Crossmatch in the United States.
Wilson A, Ohira S, Misawa R, Dhand A, Okumura K. J Surg Res, 2026. PMID: 42335616.
This registry study assessed whether a positive crossmatch (+XM) compromises outcomes in the growing practice of simultaneous heart-kidney transplantation (SHKT), analysing adult recipients in the United Network for Organ Sharing database from January 2014 to December 2023 and comparing +XM with negative-crossmatch (−XM) cohorts. One-year patient survival was comparable between groups (88.5% vs 89%, P=0.83), as were heart graft survival (88.9% vs 88.5%, P=0.88) and kidney graft survival (84.6% vs 85.1%, P=0.67). However, +XM recipients had significantly higher rejection rates before initial discharge in both the heart (17% vs 8.1%, P<0.001) and kidney allografts (8.3% vs 3.9%, P<0.01), and in the kidney at one year (5.8% vs 2.2%, P<0.05). On multivariable analysis a positive crossmatch was not associated with patient mortality, heart allograft failure, or kidney allograft failure, and among +XM candidates SHKT conferred better survival than heart transplantation alone (88.8% vs 70.4%, P<0.05). The authors conclude that a positive crossmatch alone should not contraindicate SHKT in selected sensitised patients. As a registry analysis it lacks granular donor-specific antibody and desensitisation detail and is subject to residual confounding. For UK practice it provides reassurance that sensitised patients needing combined heart and kidney transplantation can achieve comparable one-year graft and patient survival, albeit with closer vigilance for early rejection.
5. Complementary Roles of Tissue-based Gene Expression and Donor-derived Cell-free DNA for Therapy of Mild and Moderate T-cell-mediated Rejection in Kidney Transplants.
Kumar D, Azzouz L, Moinuddin I, Philogene MC, Paulus A, Kamal L, Muthusamy S, Sinhmar P, Shah S, Seelam SR, Gupta G. Transplantation, 2026. PMID: 42325162.
This single-cohort study of 141 adult kidney transplant recipients tested whether donor-derived cell-free DNA (dd-cfDNA) and the Molecular Microscope Diagnostic System (MMDx) can refine the management of mild-to-moderate T-cell-mediated rejection (TCMR). Recipients were grouped as untreated histologic TCMR with molecular quiescence (H+M−Rx−), treated histologic and molecular TCMR (H+M+Rx+, with high-dose steroids and/or anti-thymocyte globulin), and controls without rejection, and followed for a 12-month composite of graft loss, death, recurrent rejection, or a ≥30% eGFR decline. At biopsy, median dd-cfDNA was substantially higher in the treated molecular-positive group (0.94%, IQR 0.38–2.30) than in the molecularly quiescent (0.30%, IQR 0.17–0.40) or control groups (0.26%, IQR 0.18–0.51; P<0.001), with parallel separation in MMDx TCMR and molecular acute kidney injury scores. Over 12 months, dd-cfDNA fell with treatment in the molecular-positive group and remained low in the others, and in a Cox model molecular acute kidney injury (HR 3.20, 95% CI 1.54–6.66; P=0.002), chronic interstitial fibrosis/tubular atrophy (HR 1.39 per unit, 95% CI 1.09–1.77; P=0.008) and index-biopsy dd-cfDNA (HR 1.28, 95% CI 1.04–1.57; P=0.02) predicted the composite outcome. Notably, histologic TCMR with molecular quiescence left untreated had outcomes comparable to cases without rejection. As an observational cohort with non-randomised treatment decisions, it cannot prove that withholding therapy is safe. For UK practice it adds to the case for combining molecular phenotyping and dd-cfDNA to avoid over-treating biopsies that look like rejection but are molecularly silent — a direction not yet embedded in routine UK pathways.
6. Torque Teno Virus in Kidney Transplant Recipients: Perspectives on Its Role as a Complementary Marker in Monitoring Net Immunosuppression.
Wawrzonkowski P, Mizera J, Zachciał J, Banasik M. J Clin Med, 2026. PMID: 42355850.
This narrative review appraised the evidence for using Torque Teno Virus (TTV) load as a complementary biomarker of the net state of immunosuppression in kidney transplant recipients, on the premise that conventional therapeutic drug monitoring captures pharmacokinetic drug exposure but not overall functional immune competence. The authors examined TTV’s correlation with standard drug measures, the analytical performance of quantitative PCR assays, and its predictive value for clinical outcomes. They report that TTV load correlates only weakly and inconsistently with individual drug concentrations such as tacrolimus troughs, supporting a complementary rather than substitutive role. Quantitative PCR assays show generally good sensitivity and reproducibility, but inter-assay variability and the absence of standardisation remain important limitations. Clinically, higher TTV loads have been associated with a greater risk of opportunistic infection, whereas lower loads have been linked to acute rejection, consistent with TTV viraemia tracking the degree of immune suppression. The authors stress that prospective and interventional studies are still needed to validate standardised thresholds and to show that TTV-guided dosing improves outcomes over conventional monitoring. As a review without new primary data, its conclusions are inevitably qualitative. For UK practice TTV monitoring represents a promising adjunct for individualising immunosuppression, but it is not yet ready for routine use pending assay harmonisation and trial evidence.
7. Cytomegalovirus and BK polyomavirus in belatacept-treated kidney transplant recipients: a systematic review and meta-analysis.
Tawhari I, Yamani F, Alotaibi M, Hennawy HE, Tawhari M, Alqahtani M, Asiri K. BMC Nephrol, 2026. PMID: 42337500.
This systematic review and meta-analysis compared the risk of cytomegalovirus (CMV) and BK virus infection between belatacept-based and calcineurin inhibitor (CNI)-based immunosuppression in kidney transplant recipients. Seven studies — six randomised controlled trials and one cohort study, totalling 1,625 patients — were pooled. There was little to no evidence of a difference in CMV infection risk between belatacept and CNI regimens (odds ratio 1.24, 95% CI 0.80–1.94; P=0.34), and a sensitivity analysis restricted to the randomised trials was similar (OR 1.16, 95% CI 0.57–2.37; P=0.69). For BK virus the pooled estimate likewise did not reach significance, though the point estimate suggested a possible increase (OR 2.11, 95% CI 0.71–6.33; P=0.18). Heterogeneity across studies was low (I²=0%). The authors conclude that, while belatacept offers renal and metabolic advantages over CNIs, the wide confidence interval around the BK estimate means careful viral surveillance remains prudent, particularly in higher-risk recipients. The small number of studies and imprecise BK estimate are the principal limitations, alongside variable infection definitions. For UK practice, as belatacept use expands, this offers reassurance that CMV risk is not clearly elevated while supporting structured CMV and BK surveillance rather than a relaxation of monitoring.
8. Monogenic variants drive low recurrence risk in pediatric steroid-resistant nephrotic syndrome after kidney transplantation: a high-consanguinity cohort.
ALQattan F, Azzam A, Alkanani H, Alharthi W, Bahbah H, Hammed A, Almaghrabi M, Alshami A. Pediatr Nephrol, 2026. PMID: 42350677.
This retrospective single-centre cohort study examined whether genetic testing predicts post-transplant disease recurrence in children with steroid-resistant nephrotic syndrome (SRNS), drawing on a high-consanguinity population at a Saudi referral hospital and including all first paediatric kidney transplants performed between 2008 and 2023 for SRNS, focal segmental glomerulosclerosis, congenital nephrotic syndrome, or a known monogenic cause. Among 208 paediatric recipients, 60 (28.8%) had stage 5 chronic kidney disease attributable to SRNS/FSGS; next-generation sequencing was performed in 59 of 60 and identified pathogenic variants in 44 (74.6%), most commonly NPHS2 (28.8%). Post-transplant recurrence occurred in 6 of 60 patients (10%), but the risk diverged sharply by aetiology: 5 of 15 in the non-genetic group (33%) versus 1 of 44 in the genetic group (2.3%; P<0.001). All six recurrences were treated with plasmapheresis and five also received rituximab, achieving complete remission in five (83%) and partial remission in one. Five-year graft survival was 98% overall (100% genetic vs 93% non-genetic; log-rank P=0.21), and eGFR at five years was higher in the genetic group (73.5 vs 60.6 mL/min/1.73 m²; P=0.049). The single-centre design and the regionally high consanguinity, which inflates the monogenic fraction, limit generalisability. For UK practice it reinforces the value of pre-transplant genetic testing to stratify recurrence risk: a confirmed monogenic cause predicts very low recurrence, while non-genetic SRNS carries substantial risk that nonetheless often responds to plasmapheresis and rituximab.
Generated 2026-06-27 from PubMed search results for kidney transplantation published 2026-06-13 to 2026-06-27. 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.