Expanding boundaries: The evolution and future of living donor kidney transplantation

Abstract

Living donor kidney transplantation (LDKT) has evolved into a globally adopted clinical practice, driven by improvements in donor selection, immunological compatibility, and perioperative care. These advances have contributed to enhanced donor safety and improved early graft outcomes. Still, its uptake remains limited worldwide, influenced by differences in clinical infrastructure, surgical expertise, and programmatic priorities. A central procedural consideration in LDKT is the choice of kidney for procurement, right or left. Left donor nephrectomy is generally preferred due to favorable vascular anatomy, yet right-sided procurement is often necessary in the presence of anatomical variations. While some studies report higher rates of early complications with right-sided nephrectomy, including delayed graft function and early graft loss, long-term outcomes appear comparable. The evaluation of laterality, however, varies significantly across centers and is often shaped more by institutional practice than by comparative evidence. In this editorial, we review key clinical and technical advances that have improved the safety and outcomes of LDKT, including immunological matching, donor selection, perioperative strategies, and early graft performance. We then critically examine the role of kidney laterality in donor nephrectomy, highlighting how anatomical complexity and procedural risk continue to shape clinical decision-making.

Key Words: Kidney transplantation; Living donors; Nephrectomy; Graft survival; Perioperative care

Core Tip: Living donor kidney transplantation (LDKT) offers favorable early graft outcomes and improved donor safety through advances in selection, immunologic matching, and perioperative care. Donor kidney laterality, right vs left, remains a key technical consideration, with right-sided nephrectomy linked to higher early complication rates but comparable long-term outcomes. Rather than using laterality as an isolated quality indicator, this editorial calls for its assessment within a broader surgical and clinical context, integrating anatomical complexity, procedural planning, and center-specific expertise to support informed, case-specific decision-making in LDKT.

INTRODUCTION

End-stage kidney disease (ESKD) is a growing global health challenge, with rising morbidity and mortality placing increasing pressure on healthcare systems[1]. Kidney transplantation (KT) remains the most effective treatment, offering better survival and quality of life than dialysis[2]. The persistent shortage of deceased donor kidneys has made living donor KT (LDKT) an essential strategy to expand access to transplantation[3].

Improvements in donor selection, surgical techniques, and perioperative management have enhanced both donor safety and recipient outcomes[4-6]. A central surgical consideration in LDKT is the choice of kidney to procure, right or left, a decision that remains subject to ongoing debate. Left donor nephrectomy (LDN) is generally preferred due to its longer renal vein and more favorable vascular anatomy[7]. Right donor nephrectomy (RDN), though less commonly selected, is often necessary when anatomical variations or donor-specific considerations make left nephrectomy unsuitable[8]. While some studies report comparable outcomes, others associate RDN with higher risks of vascular complications, delayed graft function (DGF), and early graft loss[9,10].

In this editorial, we review key clinical and technical advances that have improved the safety and outcomes of LDKT, including immunological matching, donor selection, perioperative strategies, and early graft performance. We then critically examine the role of kidney laterality in donor nephrectomy, highlighting how anatomical complexity and procedural risk continue to shape clinical decision-making.

LDKT: EVOLUTION AND CLINICAL ADVANCES

Since the first successful procedure in 1954, LDKT has transitioned from an experimental intervention to a globally adopted clinical practice, with over half a million transplants performed worldwide[11,12]. Despite its proven efficacy, LDKT remains less frequently performed than deceased donor KT, with an estimated global ratio of 1:3[13]. This disparity is largely driven by persistent concerns about long-term outcomes, particularly the risk of ESKD in donors and late complications in recipients.

Early evaluations of LDKT relied on small, single-center case series with inconsistent criteria and limited follow-up, making it difficult to quantify long-term donor risk or standardize clinical practices. In response, multicenter cohorts and, later, national registries were developed to improve data quality, enable better risk stratification, and guide clinical decision-making across KT programs[14-16]. However, persistent limitations remain, including incomplete follow-up, variability in reporting, and gaps in long-term outcome data for both donors and recipients[17].

Cold ischemia time and early graft outcomes

The increasing adoption of LDKT is supported by its ability to minimize cold ischemia time (CIT), a key factor in reducing DGF and improving early graft outcomes[18,19]. A recent meta-analysis of 164179 patients confirmed that shorter CIT (< 4 hours) was significantly associated with lower DGF rates [odds ratio (OR) = 0.61, P < 0.01] and better graft survival at both one year (OR = 0.72, P < 0.001) and five years (OR = 0.88, P = 0.04)[20]. Although these findings are consistent across large datasets, most studies are observational in nature, raising concerns about selection bias, since LDKT recipients often have fewer comorbidities and receive organs under more favorable conditions. Propensity score-matching helps adjust for these confounders, but residual bias persists. Furthermore, heterogeneity in follow-up duration reduces the comparability of long-term outcomes, highlighting the need for prospective trials with standardized methodologies to clarify the impact of CIT on graft function over time.

Donor age and long-term graft performance

Donor age is a well-established predictor of graft durability, particularly in the context of long-term outcomes. Contemporary evidence shows that increasing age correlates with a higher risk of graft failure, even after adjusting for recipient and procedural variables[21]. A retrospective cohort study from Norway involving 1417 recipients found that deceased donor age ≥ 70 years was independently associated with increased graft loss compared to donors aged 60-69 [adjusted hazard ratios (aHR) = 1.23, 95%CI: 1.02-1.48, P = 0.029] and 45-54 years (aHR = 1.94, 95%CI: 1.54-2.45, P < 0.001)[22]. Complementing these results, a United States cohort study of 145470 KT recipients, including both living and deceased donors, showed a progressive increase in graft failure with donor age, with the lowest rates observed in living donors under 55 years[23]. In a propensity score–matched analysis, graft failure was significantly more likely in recipients of kidneys from brain-dead [hazard ratios (HR) = 2.19, P = 0.016] or circulatory death donors (HR = 3.38, P < 0.001) compared to living donors[24]. While these data support the advantage of younger living donors in long-term graft performance, donor age alone is an incomplete predictor of LDKT success. Older donors often have preserved function, and rigid age-based exclusion may reduce LDKT opportunities. A shift toward functional organ assessment and individualized risk stratification is needed to support equitable and clinically sound donor selection, particularly as programs increasingly rely on older living donors.

Immunological compatibility as a driver of LDKT success

The immunologic advantage of LDKT stems from both biologic and procedural factors. Controlled timing and reduced inflammatory exposure lower rejection risk, further strengthened by the higher likelihood of human leukocyte antigen (HLA) compatibility, particularly among related donors[25]. Ribeiro et al[26] reported that low HLA mismatch was observed in 13% of LDKT recipients, compared to 12% in deceased donor kidneys, indicating a modest immunologic advantage in the living donor setting. To broaden access, LDKT programs increasingly rely on paired kidney exchange and desensitization protocols to enable transplantation in recipients with immunologic incompatibilities[27,28]. While these strategies have expanded LDKT eligibility, outcomes vary depending on recipient sensitization levels, center-specific experience, and protocol intensity. These limitations highlight the need for more standardized reporting frameworks and comparative effectiveness data to guide optimal implementation in complex cases.

Advancements in perioperative management and their impact on LDKT outcomes

Advances in perioperative management, including surgical technique, have contributed directly to improving donor safety and procedural efficiency in LDKT. Laparoscopic donor nephrectomy is now standard in many centers, offering reduced postoperative pain, shorter hospitalization, and faster recovery[29]. Robotic-assisted approaches have been adopted in select programs, enhancing surgical precision, although broader use remains limited by infrastructure and training requirements[30]. Enhanced Recovery After Surgery (ERAS) protocols provide a structured, multimodal framework for perioperative care in LDKT[31]. As summarized in Table 1, each component targets specific aspects of physiological recovery in the context of LDKT. Saks et al[32] reported that ERAS implementation in LDKT improved overall recovery without increasing complication or readmission rates. Specifically, the protocol was associated with reduced opioid use, shorter hospital stays, earlier return of gastrointestinal function, and better postoperative pain scores. Despite its clinical benefits, ERAS integration in LDKT remains inconsistent. Implementation varies across centers due to differences in institutional capacity, perioperative protocols, and provider familiarity.

Table 1 Core components of Enhanced Recovery After Surgery protocols in living donor kidney transplantation.

Enhanced Recovery After Surgery domain	Intervention strategies	Intended benefit
Preoperative	Patient education, prehabilitation, carbohydrate loading	Reduce anxiety, enhance metabolic readiness
Intraoperative	Opioid-sparing anesthesia, goal-directed fluid therapy, normothermia	Minimize physiologic stress, maintain stability
Postoperative	Early mobilization, multimodal analgesia, early oral intake	Shorten recovery, reduce complications
Discharge planning	Standardized criteria for discharge, coordinated outpatient follow-up	Reduce length of stay, improve continuity of care

As perioperative practices in LDKT have become more standardized, attention has shifted toward refining surgical decisions that influence graft viability and procedural safety, chief among them, the selection of the donor kidney.

RIGHT VS LEFT LIVING DONOR NEPHRECTOMY: SURGICAL AND CLINICAL CONSIDERATIONS

In LDKT, the selection of the donor kidney, right or left, is determined by anatomical suitability, technical complexity, and expected graft performance. Table 2 summarizes the procedural and anatomical differences between RDN and LDN.

Table 2 Comparative surgical and anatomical considerations in right vs left nephrectomy in living donor kidney transplantation.

Transplant-relevant parameter	Left donor nephrectomy	Right donor nephrectomy
Renal vein anatomy	Longer renal vein, which facilitates easier venous anastomosis during graft implantation	Shorter renal vein, which increases technical complexity during vascular anastomosis
Surgical accessibility	Standard approach in most centers	Requires higher surgical expertise in select cases
Implantation challenges	Fewer technical modifications required	May require vascular extension or reconstruction
Risk of vascular complications	Lower (fewer IVC-related concerns)	Higher risk of IVC injury, venous thrombosis
Warm ischemia and handling time	Slightly longer due to more frequent laparoscopic use	May be shorter in open approaches
Utilization in practice	Approximately 80%-85% of living donor kidney transplantation cases	Approximately 15%-20%, used when left kidney is not suitable
Reported graft outcomes	Lower risk of DGF and early graft loss	Slightly higher risk of DGF and early graft loss
Preferred in vascular anomalies	More versatile with multiple arteries/veins	Occasionally favored with specific anatomical variants

DGF: Delayed graft function; IVC: Inferior vena cava.

A systematic review and meta-analysis by Calpin et al[33] included 312 studies and 79912 LDKT procedures. RDN was associated with higher rates of DGF [5.4% vs 4.2%; rate ratios (RR) = 1.29, 95%CI: 1.15-1.44], early graft loss (2.6% vs 1.1%; RR = 2.36, 95%CI: 1.85-3.01), and conversion to open surgery (1.4% vs 0.9%; RR = 1.56, 95%CI: 1.29-1.89). However, no significant differences were found in long-term graft function, recipient survival, or major postoperative complications, suggesting that laterality primarily affects early technical outcomes.

Similar patterns were reported in a paired cohort study by Kulkarni et al[34], which analyzed 87112 deceased donor transplants from the United Network for Organ Sharing database. RDN was linked to a higher risk of DGF (28.0% vs 25.8%; adjusted OR = 1.15, 95%CI: 1.12-1.17) and early graft failure (aHR = 1.07, 95%CI: 1.03-1.11), with no differences observed beyond six months. Death-censored graft loss followed the same trend, showing modest early disadvantage for right-sided grafts and equivalent long-term outcomes. Recipient survival was unaffected.

Additional data from the Australia and New Zealand Dialysis and Transplant Registry, analyzed by Doucet et al[35], included 10651 adult transplant recipients between 2000 and 2015, of whom 4102 received LDKT. In older recipients (n = 88), DGF was comparable to that in younger adults, while overall graft loss was more often related to recipient mortality than technical failure. Death-censored graft survival and acute rejection outcomes were favorable, indicating that long-term success was influenced more by recipient characteristics than by graft laterality.

Despite the association between RDN and slightly higher early complication rates, long-term graft function and recipient survival remain equivalent. The available evidence, however, is limited by inconsistent definitions and unadjusted analyses. Key variables such as donor anatomy, surgical expertise, and perioperative protocols are often unaccounted for, limiting comparability across studies. These constraints emphasize the need for standardized methodologies and reinforce that graft laterality alone should not dictate surgical strategy in LDKT.

CONCLUSION

LDKT continues to evolve through advances that span clinical, procedural, and system-level domains. Improvements in recipient stratification, donor selection, immunologic matching, and perioperative management have contributed to safer procedures and more consistent graft outcomes. Yet, further progress requires moving beyond isolated metrics and toward a more integrated understanding of how procedural complexity influences outcomes. Embedding standardized intraoperative data into national transplant registries would enable center-level benchmarking, support individualized clinical strategies, and inform quality improvement initiatives. This shift toward structured, outcome-linked reporting is essential to reinforce the evidence base and sustain accountable, high-quality care in LDKT.