Living-donor kidney transplantation offers the highest survival benefit for patients with kidney failure, yet access remains limited by immunologic, biologic, geographic and logistical barriers. This review summarized recent developments in kidney-paired donation (KPD), highlights current challenges and outlines future directions to optimize program performance and equity. KPD has expanded rapidly in the Unites States and globally, with multicenter national and transnational programs demonstrating excellent allograft and patient outcomes. Increasing the use of altruistic donors, advanced donation models and molecular HLA-matching algorithms have improved match rates and compatibility. Despite these advances, significant challenges persist, including overrepresentation of Blood Group O and highly sensitized candidates, uneven program participation, financial and logistical barriers, and the need for robust ethical frameworks. Creating a national KPD program that is accessible to all transplant programs and incorporates compatible recipient-donor pairs would significantly improve the opportunities for living-donor kidney transplantation.

The Impact of Organ Blood Type Conversion on Kidney Paired Donation: A Simulation and Optimization Study.

Living donor kidney transplantation is an important avenue to address persistent shortage of deceased donor organs. Although transplantation offers superior survival and quality-of-life outcomes compared to dialysis, living donation rates have declined from their mid-2000s peak despite ongoing demand. Innovations in surgical techniques, expanded living donor acceptance criteria, and growth of paired kidney donation programs represent opportunities to improve and expand living donor kidney transplantation. The transition from open donor nephrectomy to minimally invasive laparoscopic approaches significantly reduced perioperative morbidity, postoperative pain, and recovery time. Robotic-assisted techniques offer enhanced visualization and ergonomics, with comparable clinical outcomes to conventional laparoscopy, though cost and resource constraints remain barriers to widespread adoption. Concurrently, transplant centers have broadened donor eligibility to include older individuals, donors with obesity, controlled hypertension, and more complex renal anatomy. Paired kidney donation has enabled incompatible donor-recipient pairs to undergo transplantation through multicenter exchanges and chain-based mechanisms. Despite logistical and resource challenges limiting universal participation, these programs now account for a growing proportion of living donor transplants. Continued innovation in surgical practice, donor selection, and exchange networks is essential to expand living kidney transplantation and mitigate organ shortage.

Left-sided kidneys are preferred for living donor kidney transplant (LDKT) because their longer renal vein leads to greater technical ease. Nevertheless, right-sided nephrectomies are performed when favorable for donors. We evaluated national and center-level trends in right living donor nephrectomy. We used SRTR data to identify all LDKTs from 1995-2024 and calculated annual proportions of right kidneys. Then analyzing the contemporary 10-year period (2015-2024), we calculated the Pearson correlation coefficient between center-level LDKT volume and proportion of right-sided nephrectomies. We also assessed the effect of Kidney paired donation (KPD) on proportion of right kidneys used at the center and national levels. We also compared the incidence of delayed graft function (DGF) and 90-day graft failure. The proportion of right-kidney LDKTs decreased from 27% in 1995 to 10%-12% in the contemporary period. Individual centers varied greatly in proportion of right LDKTs, ranging from 0%-37%, with no meaningful correlation between center-level LDKT volume and proportion of right-sided donor nephrectomies (r2 = 0.02). KPDs involved a greater proportion of right kidneys compared to direct donations (12%vs. 11%, p = 0.003). Additionally, even in the contemporary era, right-sided LDKTs had higher incidence of DGF (2.4%vs. 1.3%) and 90-day graft failure (8.7%vs. 5.2%) compared to left-sided LDKTs (both p<0.01). Center-level variation in right LDKTs likely reflects different thresholds in accepting anatomic complexity or split function and is independent from overall center volume. Further, despite advances in laparoscopic LDKT, right kidneys remain associated with early graft dysfunction in the contemporary era.

Kidney Paired Donation (KPD) is a transformative strategy in living kidney donor transplantation (LDKT), particularly for overcoming immunological barriers that preclude direct donation. In 2021, KPD accounted for one-fifth of adult LDKT and for half of LDKT for sensitized recipients in the United States. In Brazil, with a high prevalence of chronic kidney disease (CKD) and over 30,000 patients on transplant waiting lists, the demand for compatible donors far exceeds supply. This article presents a case report of KPD in the Brazilian context, illustrating its feasibility and highlighting challenges and considerations for broader implementation. The case demonstrates KPD's potential to increase transplant rates, improve outcomes, and reduce dialysis costs. Nevertheless, structural, ethical, and regulatory challenges remain. This report emphasizes the implications of expanding KPD as a sustainable, life-saving strategy in Brazil.

Kidney paired donation (KPD) is increasingly used to provide access to living donor kidney transplantation (LDKT), but concerns related to managing costs may pose barriers to transplant center participation. To help inform discussions of effective cost-management strategies, we surveyed U.S. LDKT program staff on experiences, practices, and needs for managing KPD-related costs. A survey instrument was designed by a multidisciplinary workgroup of professionals in transplant administration, finance, and clinical practice. We distributed the survey to staff at U.S. LDKT transplant programs by email and posting to professional society listservs in 2024 using the Qualtrics platform. Among 97 unique programs that responded, 88% report KPD participation, with 33% reporting >10 exchanges per year. Use of external exchanges among participating centers included the National Kidney Registry in 69%, Alliance for Paired Donation in 31%, and OPTN/UNOS in 31%. Reported resources for KPD include nurse coordinators (93%), physican champions (64%), financial expertise (47%), and contracting assistance (45%). Heterogeneous methods were used to cover registry fees and other costs, including evaluation, nephrectomy, and organ shipping. Although many centers rely on Medicare Cost Report (MCR) reimbursement or recipient insurance to manage expenses, more than one-quarter reported no formal cost-handling policies. Twenty-five percent of centers reported being uncomfortable discussing KPD costs with hospital administrators. Based on a survey of U.S. LDKT programs, a variety of approaches are used to cover the costs of KPD practice. Findings also underscore gaps in financial infrastructure, including limited formal volume analyses to guide investment in KPD resources.

Kidney transplantation is the best treatment for chronic kidney failure, but antibody-mediated rejection (AMR) is a major cause of kidney transplant loss. Human leukocyte antigen (HLA) molecular-compatibility-based organ allocation aims to reduce the risk of donor-specific antibody formation and thereby lower the risk of AMR. However, integrating molecular compatibility in organ allocation could introduce barriers to access, consequently raising ethical concerns. The objective of this study was to gather perspectives of HLA professionals on molecular matching in kidney transplantation. Individual semi-structured interviews. Canadian HLA laboratories. HLA laboratory directors or HLA professionals. Seven participants took part in semi-structured interviews between January and June 2024. The interviews were digitally recorded, transcribed, and analyzed using the qualitative description approach. Participants reported positive feelings regarding the current allocation system but highlighted that HLA matching could be improved. They differed on whether kidney allocation should prioritize medical utility or fairness. While acknowledging the potential benefits of precision medicine in improving transplant outcomes, experts emphasized that its implementation confronts both scientific uncertainties and practical challenges, identifying logistical, financial, technological, and occupational barriers. They expressed concerns regarding decreased access to kidney transplantation for marginalized groups, recommending the adoption of mitigation measures. Regarding the kidney-paired donation program, experts supported integrating molecular matching as an optimizing tool to complement the current algorithm. Participants recommended that future implementation of molecular matching in Canada should involve nationwide collaboration, establishing a maximum wait time and appropriate selection criteria, additional research, adequate staffing and funding for HLA laboratories, as well as education of transplant professionals and patients. The major limitation of this study is the small number of participants, all of whom were Canadian HLA professionals. Consequently, results may not be generalizable to transplant contexts in other countries. This study highlights the complexities of integrating molecular matching into organ allocation, raising concerns about equity, feasibility, and implementation. While HLA experts agree on the importance of ensuring equity and timely access, their perspectives also underscore the challenges of implementation, such as the availability of timely high-resolution HLA typing, stakeholder buy-in, and the need for dedicated tools and applications. To ensure an ethical and equitable implementation, future efforts must address access disparities through targeted mitigation strategies, such as the introduction of a maximum waiting time for a molecular-matched kidney.

Highly sensitized kidney transplant candidates, particularly those with calculated panel reactive antibody (CPRA) ≥99.9%, face significant immunologic barriers to transplantation. This review highlights recent clinical strategies that have improved transplant access and outcomes in this population, with a focus on allocation policy, kidney-paired donation, and desensitization. Updates from national allocation systems and kidney-paired donation programs have demonstrated substantial gains in transplant access for many highly sensitized candidates. However, those with CPRA at least 99.9% remain difficult to match. Novel desensitization approaches, such as imlifidase, proteasome inhibitors, anti-CD38 mAbs, and early-phase CAR T-cell therapies have shown promise in selected patients. Increasingly, immunologic phenotyping or gene expression profiling may help tailor desensitization strategies to individual recipients. Most highly sensitized candidates now achieve transplant through allocation policy or paired donation. For those with CPRA at least 99.9%, desensitization will likely remain an important tool to facilitate transplantation. Emerging therapies and immunologic profiling may help individualize treatment and expand transplant access for this challenging group.

Kidney paired donation (KPD) programs are organized in various countries to facilitate the donation of kidneys from willing but incompatible donors by matching them with pairs in similar situations. These programs often struggle with an accumulation of difficult-to-match recipients and small pools of incompatible pairs. To address this, several international collaborations have emerged to expand the pool sizes and increase the number of transplants by "exchanging" donors' kidneys across countries. We identified 4 established international KPD programs, each supported by protocols and agreements signed by the participating parties. Each program is presented separately, detailing its historical establishment, operational aspects, and statistics on pool characteristics and performance. Following this, we provide a comparative analysis of key aspects across the 4 programs. Each program has its unique context and specificities. Even though 3 of 4 collaborations started just before the COVID-19 pandemic, they have collectively facilitated >450 transplants. This underscores the importance of further developing these collaborations to share practices and experiences, and to facilitate more transplants, particularly for difficult-to-match recipients. Three of the 4 presented collaborations are either fully operated or led by European countries. This highlights the crucial role of ongoing international cooperation in the development of KPDs, in particular in Europe. By further promoting collaboration among countries, we can facilitate pan-European exchanges and improve access to live kidney transplants for patients in need.

Living Paired Exchange Donation: Unlocking New Horizons in Kidney Transplantation.

Practical and ethical considerations in kidney paired donation and emerging liver paired exchange.

Kidney transplant rejection despite zero eplet DR / DQ mismatch: A case report.

India continues to face a significant gap between organ demand and supply, primarily due to low deceased organ donation rates and limited public awareness. The deceased donor rate remains 0.77 per million population (PMP), contributing to only 15% of transplants, with only anecdotal reports of donation after circulatory death. In contrast, living donor transplants have increased to 9.4 PMP. Globally, India ranks first in living donor transplants, third in total transplants, and 68th in deceased donor transplants. A total of 682 kidney transplant centers are registered under the National Organ and Tissue Transplant Organization (NOTTO), with a predominant concentration in the private sector (87%) and only 13% in government hospitals. Gender disparities in transplantation remain striking, underpinned by longstanding socio-economic and cultural inequities. Between 2019 and 2023, female recipients constituted only 30% of all living donor kidney transplants, even as women represented 66.2% of donors. The overall proportion of female recipients rose modestly from 28% in 2019 to 36.8% in 2023. Globally, men accounted for 64% of all recipients, with India ranked 59th among 78 countries for male dominance among living donors. Infrastructural limitations persist, with nearly 80% of immunology laboratories in metropolitan areas. Access to transplant pathology, infectious disease specialists, and advanced diagnostics remains sparse in tier 2 and 3 cities. Policy reforms-including amendments to the Transplantation of Human Organs and Tissues Act, establishment of State and Regional Organ and Tissue Transplant Organizations, and centralized coordination by NOTTO-aim to enhance access and equity. The NOTTO Chintan Shivir 2024 emphasized digital registries and protocol standardization. While innovations such as ABO-incompatible and multicenter kidney-paired donation are advancing, broader systemic reforms are essential for long-term equity and sustainability.

Chronic kidney disease (CKD) in South Africa (SA) is a growing public health crisis, driven by the intersecting burdens of HIV, tuberculosis, hypertension, diabetes and obesity. In Black African populations, high-risk apolipoprotein L1 (APOL1) variants add a genetic predisposition to non-diabetic kidney diseases, compounding risk. Global recognition of CKD has recently advanced, marked by the 2025 World Health Organization (WHO) non-communicable disease resolution, which urges the integration of kidney care into national health strategies. This resolution emphasises prevention, early detection and treatment, while strengthening primary healthcare and addressing social determinants of health, particularly in low-income countries. However, in SA, domestic capacity has not kept pace. Public-sector dialysis slots have remained static since 1994, while the private sector has expanded rapidly, deepening inequities by province and income. In the public sector, dialysis is rationed to patients eligible for transplantation, yet transplant access is limited by organ shortages, logistical barriers and variable provincial resources. Expanding deceased donation and implementing kidney paired donation (KPD) programmes are essential to increase transplant opportunities, particularly for incompatible donor- recipient pairs, and to improve equity in access. Children and adolescents face additional barriers, including limited age-specific pathways and the absence of structured transition to adult care. Workforce shortages, inadequate regulatory oversight, inconsistent procurement processes and incomplete registry reporting undermine service quality, limit expansion and perpetuate inequities in access. Without urgent reform, CKD will continue to drive preventable morbidity, premature mortality and escalating costs. Scaling equitable dialysis and transplantation services, integrating KPD and investing in prevention, workforce and infrastructure are critical to reversing current trends and fulfilling the WHO's call for action.

Kidney transplantation is one of the most effective treatments for patients with end-stage renal disease. However, many regions face low deceased donor rates and limited ABO-compatible transplant availability, which increases reliance on living donors. These regional challenges necessitate the implementation of kidney paired donation (KPD) programs to overcome incompatibilities such as ABO mismatch or positive cross-matching, even when suitable and willing donors are available. To evaluate the effectiveness of a single-center domino KPD model in both operational planning and clinical management processes and to assess its impact on clinical outcomes. Between April 2020 and January 2024, we retrospectively evaluated patients enrolled in our center's domino kidney transplantation program. Donor-recipient pairs unable to proceed due to ABO incompatibility or positive cross-matching with their own living donors were included. Donors and recipients were assessed based on blood group compatibility, HLA tissue typing, and negative cross-match results. A specialized computer algorithm grouped patients into three-way, four-way, and five-way chains. All surgical procedures were performed on the same day at a single center. A total of 169 kidney transplants were performed, forming 52 domino chains. These domino KPD transplants accounted for a notable proportion of our center's overall transplant activity, which included both living donor kidney transplants and deceased donor transplants. Among these chains, the primary reasons for participation were ABO incompatibility (74%), positive cross-matching (10%), and the desire to improve HLA mismatch (16%). Improved HLA mismatch profiles and high graft survival (96% at 1 year, 92% at 3 years) and patient survival (98% at 1 year, 94% at 3 years) rates were observed, as well as low acute rejection episodes. The single-center domino KPD model enhanced transplant opportunities for incompatible donor-recipient pairs while maintaining excellent clinical outcomes. By providing a framework that addresses regional challenges, improves operational efficiency, and optimizes clinical management, this model offers actionable insights to reduce waiting lists and improve patient outcomes.

Kidney-paired donation programs assist patients in need of a kidney to swap their incompatible donor with another incompatible patient–donor pair for a suitable kidney in return. The kidney exchange problem (KEP) is a mathematical optimization problem that consists of finding the maximum set of matches in a directed graph representing the pool of incompatible pairs. Depending on the specific framework, these matches can come in the form of (bounded) directed cycles or directed paths. This gives rise to a family of KEP models that have been studied over the past few years. Several of these models require an exponential number of constraints to eliminate cycles and chains that exceed a given length. In this paper, we present enhancements to a subset of existing models that exploit the connectivity properties of the underlying graphs, thereby rendering more compact and tractable models in both cycle-only and cycle-and-chain versions. In addition, an efficient algorithm is developed for detecting violated constraints and solving the problem. To assess the value of our enhanced models and algorithm, an extensive computational study was carried out comparing with existing formulations. The results demonstrated the effectiveness of the proposed approach. For example, among the main findings for edge-based cycle-only models, the proposed (*PRE(i)) model uses a new set of constraints and a small subset of the full set of length-k paths that are included in the edge formulation. The proposed model was observed to achieve a more than 98% reduction in the number of such paths among all tested instances. With respect to cycle-and-chain formulations, the proposed (*ReSPLIT) model outperformed Anderson’s arc-based (AA) formulation and the path constrained-TSP formulation on all instances that we tested. In particular, when tested on a difficult sets of instances from the literature, the proposed (*ReSPLIT) model provided the best results compared to the AA and PC-based models.

Pushing the Boundaries of Living Donation Through Kidney Paired Donation.

The Role of Race and Socioeconomic Status in Live Donor Kidney Transplant Interest and Evaluation

High-risk cytomegalovirus (CMV) and Epstein-Barr virus (EBV) mismatches (ie, seropositive donors to seronegative recipients) among kidney transplant recipients lead to increased healthcare utilization, inferior allograft outcomes, and high mortality. We assessed the interest among prospective kidney donor and recipient candidates to participate in kidney paired donation (KPD) for averting CMV/EBV high-risk mismatches. We surveyed 51 potential living donors and 102 kidney recipient candidates presenting for their evaluation visit at the University of Pittsburgh Medical Center between October 2022 and May 2023. We evaluated their general inclination toward KPD and their interest in KPD under various risk-benefit scenarios, particularly emphasizing the mitigation of high-risk mismatches associated with EBV and CMV. This was done using a 5-point Likert scale (1-low interest; 5-high interest) customized survey. There was high interest in KPD among both donor and recipient candidates (median score 4 versus 4; P = 0.09). However, donor candidates had a lower interest in KPD if they were compatible with their intended recipient (median score 2 versus 4; P < 0.001). Most donor (80.4%; N = 41) and recipient candidates (89.2%; N = 91) expressed a strong willingness to participate in KPD to prevent high-risk CMV and EBV mismatches, but this interest declined with longer transplant delays. Interest also varied on the basis of participants' income and employment status. Interest in KPD for avoiding CMV and EBV was high among both donor and recipient candidates. Additional research is required to assess the capacity and desirability for KPD expansion, particularly among ABO and HLA-compatible pairs.

Kidney disease is a rapidly growing non-communicable ailment, with Delhi-National Capital Territory (NCT) emerging as a key hub for nephrology services in India. The field’s evolution in Delhi-NCT has seen significant milestones, starting with the establishment of the nephrology department at AIIMS in 1969 and the expansion of dialysis and transplantation services across the region. Currently, Delhi-NCT hosts over 300 nephrologists and more than 70 nephrology centers, serving over 13,500 patients on hemodialysis and around 550 on peritoneal dialysis. The region leads in the number of kidney transplant, having conducted over 23,000 transplants till 2023, with 97% of these involving living donors, mainly close relatives. A gender disparity exists, with 80% of transplants performed on males and females constituting the majority of donors. The limited scope of deceased donor programs underscores the need for greater awareness of cadaver donation. To address this, Delhi Nephrology Society is promoting paired kidney donation through software aimed at expanding the donor pool. Delhi-NCT also excels in academic and community engagement, offering nephrology training programs and conducting public awareness and outreach initiatives. Despite these advancements, challenges persist, including limited access to specialized care in the peripheral areas, financial constraints, and a shortage of nephrologists. Governmental efforts, such as the Pradhan Mantri National Dialysis Programme (PMNDP) and the Delhi Arogya Kosh, support kidney care but face gaps in coverage and implementation. The absence of a state-run CKD registry and standardized policies highlights the need for strategic improvements. Enhancing resource allocation, integrating technology, and expanding governmental programs are essential steps toward advancing kidney care services in Delhi-NCT.