Objectives: Living kidney donation is a critical option to overcome the global organ shortage, yet many potential donors are excluded during evaluation. Understanding the reasons is important for optimizing donor selection, improving candidate outcomes, and increasing the living donor pool. We aimed to identify principal factors for exclusion of potential living kidney donors and compare baseline demographic and clinical characteristics between accepted donors and excluded candidates.
Materials and Methods: We performed a retrospective analysis of 82 consecutive potential living kidney donors evaluated for 70 recipients with end-stage renal disease between January 2020 and December 2024. Donor evaluations followed clinical practice guidelines of Kidney Disease: Improving Global Outcomes. Exclusion criteria were medical (obesity [body mass index >30], diabetes, impaired renal function, hypertension, and undiagnosed renal structural anomalies), immunological, and uncategorized causes.
Results: Of 82 donor candidates, 36 (43.9%) were excluded. Medical contraindications were the leading cause (26 cases; 72.2% of exclusions). The most frequent medical subcategories were undiagnosed renal structural anomalies (9 cases, 34.6%), which included 7 vascular anatomic variants (26.9%), 1 horseshoe kidney (3.8%), and 1 renal artery stenosis (3.8%); other exclusions were obesity (5 cases; 19.2%), diabetes (3; 11.5%), impaired renal function (2; 7.7%), and hypertension (1; 3.8%). Immunological incompatibilities contributed 8 cases (22.2%); uncategorized reasons accounted for 2 cases (5.5%). No significant sex-based difference in exclusion rates was observed (P = .⁵⁸). Excluded and approved candidates were comparable in age and baseline estimated glomerular filtration rate, indicating rejection was predominantly driven by other factors, particularly comorbidities (P = .⁰⁴⁶). Donor-recipient relationships were predominantly fraternal (45.1%), parental (34.1%), and spousal (14.6%).
Conclusions: Medical contraindications constituted the major barriers to living kidney donation. These findings highlight the need for early screening and management of modifiable comorbidities to safely increase donor eligibility and expand the living donor pool in resource-limited settings.

Key words : Donor exclusion, Immunological incompatibility, Medical contraindications, Obesity, Vascular renal variants

Introduction
Living kidney donation represents the preferred form of renal replacement therapy due to superior graft and patient survival compared with deceased donor transplant or dialysis.¹ However, rigorous evaluation protocols are required to secure long-term health of donors and ensure optimal transplant outcomes. Despite these precautionary measures, a significant proportion of prospective donors are excluded during the evaluation process, often due to medical comorbidities or immunological barriers.^2,3 Single-center and registry-based studies have consistently identified medical factors (such as hypertension, obesity, diabetes, and reduced renal reserve) and immunological incompatibilities as the leading causes of exclusion, with reported rates varying widely depending on population characteristics and institutional criteria.^4-6 In settings with limited deceased donor availability, such as Tunisia, understanding the specific patterns of exclusion is essential to clarify donor selection processes, execute targeted pre-evaluation interventions, and ultimately increase the number of safe living donor transplants.⁷ We aimed to systematically identify and quantify the primary factors responsible for exclusion of living kidney donor candidates at our center and to compare baseline demographic and clinical characteristics between accepted donors and excluded candidates.

Materials and Methods
This retrospective observational study examined medical records of 82 consecutive potential living kidney donors evaluated for 70 recipients with end-stage renal disease at the nephrology day care unit, from January 2020 to December 2024. The study was approved by the institutional ethics and conducted in accordance with the 1975 Declaration of Helsinki (revised 2013). Informed consent was waived due to the retrospective nature of our study and use of anonymized data. Evaluation of donors was conducted in accordance with the 2017 Clinical Practice Guideline on the Evaluation and Care of Living Kidney Donors established by Kidney Disease: Improving Global Outcomes (KDIGO).⁸ The assessment protocol included the following items: detailed medical history and physical examination, laboratory tests (serum creatinine, estimated glomerular filtration rate [eGFR] via Chronic Kidney Disease Epidemiology Collaboration equation, urinalysis, infectious serologies, and immunological profiling), structural imaging (computed tomography angiography or magnetic resonance angiography), psychosocial assessment by a dedicated psychiatrist, and a final multidisciplinary transplant committee approval. Donor candidates were categorized into 3 groups based on evaluation outcome, that is, approved for donation, excluded from donation, or required further workup (neither approved nor excluded). Comorbidities were systematically searched and documented only in the excluded and approved groups. In the subgroup of donor candidates that required further workup, no additional follow-up or detailed assessment of comorbidities was conducted, as their evaluation remained incomplete at the time of data collection. Exclusion reasons were prospectively classified into 3 categories. (1) Medical exclusions were obesity (body mass index [BMI] >30), diabetes mellitus, impaired renal function (eGFR <80 mL/min/1.73 m²), hypertension, and undiagnosed renal structural anomalies (vascular anatomic variants, horseshoe kidney, and renal artery stenosis). (2) Immunological exclusions were ABO blood group incompatibility, positive complement-dependent cytotoxicity or flow cytometry crossmatch, and presence of donor-specific antibodies. (3) Uncategorized causes for exclusion were details such as withdrawal of consent or psychosocial contraindications. Collected variables included age, sex, BMI, donor-recipient relationship, eGFR, and relevant medical history. We recorded BMI when it was available in the medical records; however, this parameter was not consistently documented for all candidates and is therefore presented for a limited subset of cases. We used SPSS software version 26 (IBM) for all statistical analyses. We expressed continuous variables as mean ± SD and categorical variables as absolute frequencies (with percentages). We used χ2 tests to compare exclusion rates across categorical variables. P < .⁰⁵ was considered statistically significant.

Results
The cohort included 82 potential living kidney donors evaluated during the study period.

Outcomes of donor evaluation
Thirty-six of 82 candidates (43.9%) were excluded from donation. The remaining 11 candidates (13.4%) proceeded to donor nephrectomy and transplant, whereas 35 candidates (42.7%) required additional diagnostic investigations.

Baseline characteristics
The overall cohort had a median age of 51 years (interquartile range [IQR], 37-57 years), with female donors comprising 61%. Donor-recipient relationships were predominantly fraternal (45.1%), parental (34.1%), spousal (14.6%), or other (6.1%). Mean eGFR was 103.7 ± 18.6 mL/min/1.73 m². Compared with approved donors, excluded candidates had similar median age (56 [IQR, 45-62] vs 50 [IQR, 36.5-56.5] years, respectively; P = .¹⁶⁵) and comparable baseline eGFR (102.4 ± 17.1 vs 104.1 ± 19.2 mL/min/1.73 m², respectively; P = .⁷⁸). In a subgroup of 10 candidates with available BMI data (3 approved and 7 excluded), mean BMI was higher in excluded candidates (30.6 ± 4.7) versus approved donors (26.3 ± 1.5), although the difference was not significant (P = .⁰⁶⁵). No significant sex-based difference in exclusion rates was observed (P = .⁵⁸) (Table 1). Recipients were younger, with a median age of 31 years, ranging from 17 to 50 years, and 54.3% were male patients.

Association between comorbidities and donor approval
Comorbidities were assessed only in the excluded and approved groups; no systematic search for comorbidities was performed in the pending workup group. Among the 47 donor candidates with recorded comorbidity data, 11 (23.4%) had at least 1 documented comorbidity. All 11 candidates with comorbidities were excluded, whereas among the 36 without comorbidities only 11 were approved (30.6%), with the remaining 25 (69.4%) excluded for other reasons. This association was significant (P = .⁰⁴⁶).

Reasons for exclusion
Medical contraindications were the predominant reasons for exclusion (26 cases, 72.2%), followed by immunological incompatibilities (8 cases, 22.2%) and uncategorized causes (2 cases, 5.5%; withdrawal of consent) (Figure 1). Within the medical exclusion group (n = 26), the most common subcategories were undiagnosed renal structural anomalies (9 cases, 34.6%), which included vascular anatomic variants (7 cases; 26.9%), horseshoe kidney (1 case; 3.8%), and renal artery stenosis (1 case; 3.8%); as well as obesity (5 cases; 19.2%), diabetes mellitus (3 cases; 11.5%), neoplasia (3 cases; 11.5%), impaired renal function (2 cases; 7.7%), and hypertension (1 case; 3.8%). Immunological exclusions were primarily due to positive crossmatch or donor-specific antibodies (Table 2).

Discussion
The exclusion rate of 43.9% observed in this cohort reflects the strict application of donor safety criteria, consistent with findings from other single-center experiences for which exclusion proportions have ranged from 20% to greater than 50%.^1-6,9 Medical contraindications predominated as the leading cause of exclusion in our cohort (72.2% of exclusions), aligning with most of the published single-center studies where medical contraindications accounted for 40% to 50% or more of disqualifications (47.9% in a Saudi Arabian cohort,² 50.7% in a German series,¹ and 40.1% in a South African study¹⁰). The Stanford experience provides the closest match to our observations, as 79% of medical exclusions in their cohort were attributable to a cluster of obesity, hypertension, nephrolithiasis, and/or abnormal glucose tolerance, mirroring the prominent role of cardiometabolic comorbidities in our excluded candidates.⁹ Among anatomic factors, undiagnosed renal structural anomalies and renal vascular variants represented a substantial challenge, particularly in cases of complex multiplicity or accessory vessels, contributing in our study to 34.6% and 26.9% of exclusions, respectively, due to surgical complexity and increased perioperative risks, as reported in computed tomography angiography-based evaluations.^10,11 Although such variants are increasingly viewed as a relative contraindication rather than an absolute contraindication in modern practice, our results highlight the critical role of cross-sectional imaging to identify surgically relevant anomalies that may increase perioperative risk or compromise long-term donor renal function.¹² Obesity (19.2%) and diabetes mellitus (11.5%) were the most frequent comorbidities in our excluded candidates, which aligns with multiple reports that have identified metabolic comorbidities as major barriers to donation.^2,3,9 For example, a German single-center study has reported medical contraindications in 50.7% of disqualified pairs, with reduced renal function (30.2%), obesity (BMI >35; 16.5%), and hypertension (12.9%) as leading factors.¹ Similarly, a study on a Saudi Arabian cohort has documented medical reasons in 47.9% of exclusions, with obesity and diabetes frequently cited.² Impaired renal function (7.7%) and hypertension (3.8%) were also acting as a barrier, as mentioned in previously published observations from centers in South Africa, Japan, and the United States where low baseline GFR and lifestyle-related diseases are common exclusion criteria.^2,4,13 Moreover, our study showed that incidental neoplasia discovered during the evaluation process accounted for 3 of 26 medical exclusions (11.5%), serving as an absolute contraindication consistent with KDIGO guidelines and single-center data for which such findings have represented 15% of medical disqualifications in some cohorts.^1,8 Taken together, these observations suggest that many exclusions may be preventable through earlier screening and targeted lifestyle interventions (eg, weight reduction programs, glycemic control).¹⁴ Immunological barriers accounted for 22.2% of exclusions in our study, primarily positive crossmatch or donor-specific antibodies, and comparable rates have been reported from Germany (18.9%) and Saudi Arabia (19.5%).^1,2 Some studies have highlighted ABO incompatibility as a key reason for donor nonselection or exclusion (14.3%-39.9% in reported cohorts, frequently the most common immunological factor).^5,10 In contrast, our center’s approach identified ABO incompatibility early, prior to initiating the donor evaluation, thus avoiding unnecessary detailed assessments and preventing its inclusion among the evaluated exclusion reasons. Uncategorized reasons, such as withdrawal of consent (5.5%), were uncommon, consistent with global data for which psychosocial or consent-related barriers remain secondary.⁶ Baseline comparisons revealed no sex-based differences between excluded candidates and approved donors in our study (P = .⁵⁸), which aligned with several previously published studies but contrasted with other studies that have reported slight male predominance in medical exclusions.^2,4,13 Notably, the lack of significant differences in age and baseline eGFR between the 2 groups, consistent with findings from other centers,^1,2,6 suggests that exclusion was primarily driven by comorbidities and other medical contraindications rather than these baseline demographic or renal parameters.^1,13 In our study, excluded candidates tended to have higher BMI, although this difference was not significant (P = .⁰⁶⁵). Due to the very small sample size, particularly in the approved group, our results should be interpreted with caution. This pattern reinforces the role of comorbidities, particularly obesity, in the exclusion process.^1,9 Some previous reports have associated advanced age and borderline renal reserve with increased likelihood of exclusion.¹⁵ The presence of comorbidities was strongly associated with exclusion (P = .⁰⁴⁶) with all 11 candidates with documented comorbidities excluded (100%) versus 30.6% approval among the 36 candidates without comorbidities. The remaining 69.4% of comorbidity-free candidates were excluded for other reasons (immunological, anatomic, or uncategorized reasons). This pattern indicates that, although medical factors (particularly comorbidities) were the dominant barrier, additional obstacles persisted even in otherwise healthier candidates, consistent with multifaceted exclusion profiles reported in the previously published literature.^5,9,10 Donor-recipient relationships were predominantly familial, with fraternal links most common (45.1%). Some studies have shown that donor-recipient relationship differed significantly between the 2 groups, typically with unrelated or spousal donors more commonly excluded, unlike our findings for which no significant difference in donor-recipient relationship was observed between accepted donors and excluded candidates. This lack of difference may reflect our center’s consistent evaluation protocols across relationship types or the relatively small proportion of unrelated donors in our cohort.^1,2 Recipients were younger and 54.3% were male patients, consistent with typical patterns in living donation for which recipients are often younger individuals with end-stage renal disease while donors are older family members. This age difference underscores the reliance on living donors in our country, where deceased donor wait times are prolonged.

Limitations
Our study was limited by its retrospective design, single-center setting, and relatively modest sample size, which may restrict generalizability. Prospective multicenter studies would provide more powerful evidence regarding exclusion patterns and the effect of targeted interventions.

Conclusions
This single-center retrospective analysis revealed an exclusion rate of 43.9% among 82 evaluated living kidney donor candidates. Medical contraindications were the leading cause of exclusion, with obesity, diabetes mellitus, impaired renal function, and hypertension as the most frequent subcategories, in addition to renal vascular anatomic variants. These details emphasize the need for enhanced collaboration with urologists to improve vascular assessment strategies and potentially increase donor eligibility. In settings with limited deceased donor availability such as Tunisia, where living donation remains the primary source of kidney grafts due to the scarcity of deceased donors, these patterns highlight opportunities for pre-evaluation optimization, including weight management and metabolic screening programs, enhanced vascular imaging protocols, and advanced immunological testing to minimize avoidable exclusions while preserving donor safety.