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World J Transplant. Jun 18, 2026; 16(2): 115329
Published online Jun 18, 2026. doi: 10.5500/wjt.v16.i2.115329
Long-term renal function and complication profiles after ABO-incompatible vs compatible living-donor kidney transplantation: A single-center experience
Beatriz Gil Braga, Ana Cunha, Manuela Almeida, Bruno Dias, José Silvano, Catarina Ribeiro, Sofia Pedroso, La Salete Martins, Department of Nephrology, Unidade Local de Saúde de Santo António, Porto 4099-001, Portugal
Manuela Almeida, Bruno Dias, José Silvano, Catarina Ribeiro, La Salete Martins, UMIB-Unit for Multidisciplinary Research in Biomedicine, ICBAS-School of Medicine and Biomedical Sciences, University of Porto, Porto 4050-313, Portugal
Sofia Sousa, Department of Nephrology, Hospital Divino Espírito Santo, Ponta Delgada 9500-370, Azores, Portugal
Ana Filipa Trigo, Department of Nephrology, ULS Médio Tejo, Torres Novas 2304-909, Santarém, Portugal
António Inácio, Department of Nephrology, Unidade Local de Saúde da Arrábida, Setubal 2910-446, Portugal
Marco Sampaio, Marika Bini-Antunes, Department of Immunohemotherapy, Unidade Local de Saúde de Santo António, Porto 4099-001, Portugal
ORCID number: Beatriz Gil Braga (0009-0006-8924-0810).
Author contributions: Almeida M and Braga BG designed the study, were responsible for developing the methodology participated in the formal analysis and investigation; Braga BG and Cunha A wrote the original draft; Sousa S, Trigo AF, Inácio A, Dias B, Silvano S, Ribeiro C, Pedroso S, Sampaio M, Bini-Antunes M and Martins LS participated in the review and editing.
Institutional review board statement: This study was conducted in accordance with the Declaration of Helsinki and was approved by the Institutional Review Board of Unidade Local de Saúde de Santo António, authorization No. 147-21 (119-DEFI/122-CE).
Informed consent statement: Given its retrospective design, use of de-identified data, and absence of any intervention, the ethics committee waived the requirement for individual informed consent.
Conflict-of-interest statement: The authors declare no conflict of interest.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Data sharing statement: Due to patient confidentiality and institutional regulations, the data used in this study cannot be shared publicly.
Corresponding author: Beatriz Gil Braga, Department of Nephrology, Unidade Local de Saúde de Santo António, Largo do Prof. Abel Salazar, Porto 4099-001, Portugal. u14104@chporto.min-saude.pt
Received: October 16, 2025
Revised: November 13, 2025
Accepted: January 13, 2026
Published online: June 18, 2026
Processing time: 227 Days and 10.5 Hours

Abstract
BACKGROUND

ABO-incompatible (ABOi) kidney transplantation expands the living-donor pool but may increase immunologic and infectious risks. Advances in desensitization have improved outcomes, yet long-term comparative data remain limited. We hypothesized that ABOi living-donor kidney transplantation achieves renal function and complication rates comparable to ABO-compatible (ABOc) procedures under modern protocols.

AIM

To assess whether long-term renal function and complication profiles remain comparable between ABOi and ABOc living-donor kidney transplant recipients.

METHODS

A retrospective single-center cohort study was conducted in a Portuguese transplant program, including all adult living-donor kidney transplants from January 2014 to December 2022 (follow-up to June 2023). A total of 208 recipients were included: 22 ABOi and 186 ABOc, excluding human leukocyte antigen-incompatible or high immunologic risk cases. Continuous variables were compared using Mann-Whitney U or t-tests and categorical variables with Fisher’s exact test. Longitudinal changes were assessed by the Friedman test. Survival was analyzed with Kaplan-Meier and log-rank tests, with graft survival death-censored. Missing data were handled by available-case analysis.

RESULTS

Median follow-up was 57 months. Five-year patient survival was 92.9% [95% confidence interval (CI): 79.4-100] in ABOi and 90.3% (95%CI: 85.5-95.2) in ABOc (P = 0.81). Graft survival was also comparable. Estimated glomerular filtration rate trajectories and proteinuria did not differ significantly between groups. Rates of rejection, infections, and surgical or hemorrhagic complications were similar. No significant differences were found after adjustment.

CONCLUSION

ABOi transplantation achieved outcomes comparable to ABOc living-donor transplantation under contemporary desensitization protocols. These findings support the safety and efficacy of ABOi transplantation, while ongoing multicenter follow-up is needed to confirm long-term safety.

Key Words: ABO-incompatible kidney transplantation; Living donor transplantation; Graft survival; Patient survival; Estimated glomerular filtration rate; Proteinuria; Desensitization protocol

Core Tip: This single-center cohort study compared long-term outcomes after ABO-incompatible (ABOi) and ABO-compatible (ABOc) living-donor kidney transplantation performed under current desensitization protocols. Despite the higher immunologic and pharmacologic load required for ABOi recipients, patient and graft survival, renal function trajectories, and complication rates were comparable between groups during a median follow-up of nearly five years. These findings support ABOi living-donor kidney transplantation as a safe and effective option when ABOc donors are unavailable, expanding donor opportunities without compromising long-term graft performance.



INTRODUCTION

The prevalence of end-stage renal disease continues to rise globally, and kidney transplantation remains the preferred renal replacement therapy, associated with superior survival and quality of life when compared with dialysis[1]. However, organ shortage limits access to transplantation, leading many patients to remain on dialysis for long periods. Strategies to expand the donor pool include paired kidney exchange and ABO-incompatible (ABOi) living-donor kidney transplantation[2].

Historically, ABOi transplantation was associated with poor outcomes due to hyperacute rejection. The introduction of modern desensitization protocols, including rituximab, plasmapheresis or immunoadsorption, and intravenous immunoglobulin, has fundamentally changed its safety profile[3]. ABOi transplantation is now widely considered a viable option to increase living donor opportunities, particularly where kidney exchange programs are not readily available[4], and for some patients with blood group O who may wait longer for a compatible kidney in the Kidney Paired Exchange programs.

Recent large cohort studies and meta-analyses have demonstrated that patient and graft survival after ABOi transplantation are comparable to ABO-compatible (ABOc) procedures[5,6] after the first years, once in the first years they may develop more infectious complications. Nevertheless, concerns remain regarding long-term renal function, rejection risk, and infectious complications due to intensified immunosuppression[7,8].

This study aimed to determine whether long-term renal function and complication profiles remain comparable between ABOi and ABOc living-donor kidney transplant recipients[9], despite the increased immunological and pharmacological burden associated with desensitization. We also sought to provide real-world data from a Southern European center, contributing regional insight into infection patterns, surveillance protocols, and long-term outcomes.

MATERIALS AND METHODS

We conducted a retrospective comparative study of living-donor kidney transplants performed at our center between January 2014 and December 2022, with follow-up until 30th of June of 2023. Human leukocyte antigen (HLA)-incompatible recipients and HLA-compatible patients undergoing desensitization due to high immunological risk were excluded. Donor evaluation followed international guidelines, including demographic, clinical, and analytical data collection, renal function assessment by chronic kidney disease epidemiology collaboration (CKD-EPI) and nuclear renography, and anatomical evaluation by computed tomography. Exclusion criteria included uncontrolled hypertension, history of malignancy, obesity, diabetes, or estimated glomerular filtration rate (eGFR) < 80 mL/minute/1.73 m². Donor approval required multidisciplinary and ethical review. Laparoscopic left nephrectomy was preferred, with lifetime annual follow-up offered[10].

The desensitization protocol consisted of Rituximab two weeks pre-transplant, Tacrolimus and Mycophenolate initiation before surgery, and plasmapheresis with immunoglobulin until isoagglutinin titers reached ≤ 1:8. Induction included Methylprednisolone and Basiliximab, with immunosuppression tapered postoperatively according to protocol[11].

This study was conducted in accordance with the Declaration of Helsinki and was approved by the Institutional Review Board of Unidade Local de Saúde de Santo António, authorization No. 147-21 (119-DEFI/122-CE). Given its retrospective design, use of de-identified data, and absence of any intervention, the ethics committee waived the requirement for individual informed consent.

Statistical analyses

Data were analyzed with IBM SPSS Statistics, version 23 (IBM Corp., Armonk, NY, United States). Statistical review of the study was performed by a biomedical statistician. Categorical variables are summarized as n (%) and compared using Fisher’s exact test. Continuous variables were assessed for normality with the Kolmogorov-Smirnov and Shapiro-Wilk tests. Normally distributed variables are reported as mean ± SD and compared between groups with the independent-samples t-test. Variables that did not follow a normal distribution are presented as median (interquartile range) and compared using the Mann-Whitney U test.

For longitudinal analyses within groups (repeated measures), the Friedman test was applied when normality was not met. Parametric approaches such as repeated-measures ANOVA or mixed-effects models were not used, as assumptions of normality and homogeneity of variances were violated in most variables and the AB0-incompatible group had a small sample size, which limited model reliability.

Statistical significance was set at P < 0.05. When applicable, propensity score adjustment was performed using a logistic regression model including viable baseline variables associated with both ABO incompatibility and outcomes (duration of kidney replacement therapy, recipient age, sex, and hypertension). The resulting score was incorporated as a covariate in logistic regression models to obtain adjusted odds ratios (OR) and 95% confidence intervals (CI). This adjustment was applied only to outcomes for which the model was statistically feasible [hemorrhagic and surgical complications, surgical reintervention, and urinary tract infection (UTI) at discharge and at 1 year].

Survival probabilities were estimated using the Kaplan-Meier method. For patient survival, individuals were censored at the date of last follow-up if alive. For graft survival, patients were censored at the time of death with a functioning graft, loss to follow-up, or at the study end date if no graft failure had occurred. Graft survival was therefore analyzed as death-censored, with graft failure considered the event of interest. Analyses were performed on available data without imputation; cases with missing values at specific time points were excluded listwise.

RESULTS

Baseline characteristics of ABOi and ABOc living-donor kidney transplant recipients are presented in Table 1. We obtained a median follow up time of 57.2 months [(34.3-82.2) (min: 0.4, max: 105.1)]. Rates of cardiovascular comorbidities, including cardiac disease, peripheral artery disease, cerebrovascular disease, and prior history of cancer, were similarly low and comparable between groups. Overall, ABOi and ABOc groups were comparable at baseline.

Table 1 General population characteristics and comparison between ABO-incompatible and ABO-compatible groups, n (%).

ABOi (n = 22)
ABOc (n = 186)
P value
Age at transplantation, years, mean ± SD (min-max)45.8 ± 9 (28.7-60.0)45.3 ± 13.5 (7.8-74.1)0.088
Recipient BMI, kg/m², median (IQR) [min-max]23.9 (20.0-24.8) [17.9-30.7]23.4 (22.4-25.7) [16.3-34.3]0.96
Time on KRT, months, median (IQR)[min-max]10.0 (0-28.0) [0-158.2]6.3 (2.0-34.0) [0-370.5]0.225
Gender, male17 (77.3)118 (63.4)0.335
DM1 (4.5)16 (8.6)1
Active smoking6 (27.3)43 (23.1)0.664
Hypertension19 (86.4)144 (77.4)0.422
Cardiac disease2 (9.1)17 (9.1)1
    Peripheral artery disease0 (0)3 (1.6)1
    Cerebrovascular disease0 (0)5 (2.7)1
Previous history of cancer0 (0)4 (2.2)1
Previous type of KRT0.174
Hemodialysis10 (45.5)86 (46.2)
Peritoneal dialysis8 (36.4)34 (18.3)
    Preemptive4 (18.2)61 (32.8)
    Transplant01 (0.5)
History of previous kidney transplant2 (9.1)23 (12.4)1
Induction therapy
Basiliximab22 (100)171 (91.9)0.377
Thymoglobulin0 (0)15 (8.1)
HCV positive0 (0)3 (2.2)1
Recipient CMV seropositive18 (85.7)155 (84.2)1
Donor CMV seropositive14 (87.5)129 (91.5)0.638
HLA-A mismatches
    05 (22.7)48 (25.9)0.947
    112 (54.5)96 (51.9)
    25 (22.7)41 (22.2)
HLA-B mismatches
    03 (13.6)27 (14.6)0.625
    19 (40.9)93 (50.3)
    210 (45.5)65 (35.1)
HLA-DR mismatches
    03 (13.6)37 (20.0)0.774
    112 (54.5)94 (50.8)
    27 (31.8)54 (29.2)
Graft and patient survival

Table 2 presents the results of the association analysis between ABOi and ABOc living donor kidney transplantation and graft loss. No cases of graft loss were observed in the ABOi group (0.0%), whereas a higher proportion was found in the ABOc group (n = 17; 9.1%); however, this difference was not statistically significant (P > 0.05).

Table 2 Outcomes regarding graft and patient death, n (%).

ABOi (n = 22)
ABOc (n = 186)
P value
Graft death0 (0)17 (9.1)10.226
Patient death0 (0)6 (3.2)11

Regarding patient survival (Table 2), no statistically significant difference was observed according to ABO living-donor kidney transplantation (P = 1.000). There were no deaths in the ABOi group (0.0%), and only 3.2% in the ABOc group.

Patient survival (Figure 1A) at 1, 3, and 5 years was 98.9% (95%CI: 97.3-100.0), 95.8% (95%CI: 92.8-98.9), and 95.8% (95%CI: 92.8-98.9) in ABOc recipients, compared with 100%, 100%, and 92.9% (95%CI: 79.4-100.0) in ABOi recipients. No statistically significant difference was observed (log-rank P = 0.822).

Figure 1
Figure 1 Kaplan Meier curves after regarding outcomes in kidney transplantation. A: Patient survival; B: Death-censored graft survival.

Death-censored graft survival (Figure 1B) at 1, 3, and 5 years was 95.7% (95%CI: 92.8-98.6), 93.1% (95%CI: 89.3-96.9), and 90.3% (95%CI: 85.5-95.2) in the ABOc group, and 100%, 100%, and 92.9% (95%CI: 79.4-100.0) in the ABOi group. Overall survival did not differ significantly (log-rank P = 0.808).

At the end of follow-up, all 22 ABOi recipients had functioning grafts and were alive. However, due to shorter individual follow-up times, only one remained at risk beyond 96 months in the Kaplan-Meier analysis.

Immediate complications after kidney transplantation

Regarding the need for post-transplant dialysis, no patients in the ABOi group required dialysis compared with 10 (5.4%) in the ABOc group (P = 0.604). Hemorrhagic complications occurred in three (13.6%) of ABOi recipients and twenty-nine (15.6%) of ABOc recipients (OR = 0.85, 95%CI: 0.24-3.06; P = 0.803) and, after adjustment for propensity score, the association remained similar (adjusted OR = 0.96, 95%CI: 0.26-3.5; P = 0.945). Similarly, fewer surgical complications were observed in the ABOi group (n = 2; 9.1%) compared with the ABOc group (n = 32, 17.2%) (OR = 0.48, 95%CI: 0.1-2.1; P = 0.336) and, after adjustment for propensity score, the association remained similar (adjusted OR = 0.57, 95%CI: 0.1-2.6; P = 0.466).

Regarding reoperations, less reoperations were observed in the ABOi vs ABOc (n = 2, 9.1% vs n = 25, 13.4%) (OR = 0.64, 95%CI: 0.1-2.9; P = 0.563) and, after adjustment for propensity score the association remained similar (adjusted OR = 0.7, 95%CI: 0.1-3.3; P = 0.670). None of these differences reached statistical significance.

Table 3 presents the results of the analyses of infectious outcomes immediately after ABO living-donor kidney transplantation. Cytomegalovirus (CMV) infection was numerically more frequent (13.6% vs 8.6%) and BK infection less frequent (4.5% vs 16.1%) in the ABOi group compared with the ABOc group. The ABOi group showed higher rates of sepsis (4.5% vs 2.2%) and UTI (22.7% vs 18.3%). None of these differences reached statistical significance (all P > 0.05).

Table 3 Infections in the immediate post-transplant period, n (%).

ABOi (n = 22)
ABOc (n = 188)
P value
OR (95%CI)
CMV infection3 (13.6)16 (8.6)0.432-
BK infection1 (4.5)30 (16.1)0.211-
Sepsis1 (4.5)4 (2.2)0.431-
Pneumonia0 (0.0)2 (1.1)1-
Urinary tract infection5 (22.7)34 (18.3)0.5721.3 (0.5-3.8)
Surgical wound infection0 (0.0)2 (1.1)1.000-

For UTI, propensity score-adjusted logistic regression was feasible (OR = 1.5: 95%CI: 0.5-4.5; P = 0.443) ABO incompatibility was not significantly associated with UTI.

The incidence of rejection was comparable between groups (4.8%; n = 9) in ABOc vs (4.5%; n = 1) in ABOi (P = 1.000).

Infections at 1 year of kidney transplantation

We also evaluated the prevalence of infectious complications 1 year after transplant (Table 4). CMV infection was more frequent (13.6% vs 8.1%) and BK infection less frequent (4.5% vs 16.1%) in the ABOi group compared with the ABOc. The ABOi group showed higher rates of sepsis (4.5% vs 1.7%).

Table 4 Comparison between groups regarding infections 1 year after transplant, n (%).

ABO incompatible (n = 22)
ABO compatible (n = 186)
P value
OR (95%CI)
Sepsis1 (4.5)3 (1.7)0.37512.8 (0.3-27.9)
Pneumonia0 (0.0)2 (1.1)1.000-
Urinary tract infection3 (13.6)26 (13.8)0.89510.92 (0.3-3.3)
CMV infection3 (13.6)15 (8.1)0.43111.7 (0.5-6.4)
BK infection1 (4.5)30 (16.1)0.16510.2 (0.0-1.8)

Similarly, the incidence of pneumonia, and UTI did not differ between groups. None of these associations reached statistical significance (all P > 0.05).

Graft function and proteinuria

Table 5 presents the evolution of eGFR in specific periods of time. We analyzed longitudinal renal function using eGFR, CKD-EPI 2012 to capture potential statistical differences in graft performance. As shown in Table 5, ABOi recipients showed lower eGFR at 3-6 months, followed by partial recovery at 12-24 months, and a subsequent decline after 36 months. In contrast, ABOc recipients maintained relatively stable values throughout follow-up. Despite these fluctuations, no statistically significant differences were observed between groups at any timepoint up to 60 months, and overall trends were broadly comparable.

Table 5 Comparison between estimated glomerular filtration rate at 1, 3, 6, 12, 24, 36, 48 and 60 months.

ABO incompatible (n = 22)
ABO compatible (n = 186)
P value
eGFR at 1-month, median (IQR)66.1 (43.0-70.6)66.3 (53.5-82.4)0.485
eGFR at 3 months, median (IQR)60.9 (37.7-75.7) 58.6 (46.4-76.8)0.838
eGFR at 6 months, median (IQR)52.6 (39.6-79.8) 62.0 (45.8-80.3)0.926
eGFR at 12 months, median (IQR)54.8 (47.6-66.5) 58.2 (47.0-77.1)0.086
eGFR at 24 months, median (IQR)65.5 (58.2-93.0) 58.5 (42.7-75.1)0.188
eGFR at 36 months, median (IQR)80.7 (44.1-94.5)60.4 (49.2-81.3)0.825
eGFR at 48 months, median (IQR)63.1 (42.0-87.9)66.7 (42.0-87.9)0.675
eGFR at 60 months, median (IQR)62.2 (43.2-94.2)62.5 (45.3-78.4)0.734

Table 6 represents the evolution for proteinuria, also not reaching statistical significance.

Table 6 Comparison between proteinuria at 1, 3, 6, 12, 24, 36, 48 and 60 months.

ABO incompatible (n = 22)
ABO compatible (n = 186)
P value
Proteinuria (g/L) at 1 month, median (IQR)0.4 (0.1-0.7)0.2 (0.1-0.3)0.535
Proteinuria (g/L) at 3 months, median (IQR)0.1 (0.1-0.8)0.1 (0.1-0.2)0.111
Proteinuria (g/L) at 6 months, median (IQR)0.1 (0.1-0.5)0.1 (0.1-0.2)0.985
Proteinuria (g/L) at 12 months, median (IQR)0.1 (0.1-0.3)0.1 (0.1-0.1)0.475
Proteinuria (g/L) at 24 months, median (IQR)0.1 (0.0-0.3)0.1 (0.1-0.2)0.432
Proteinuria (g/L) at 36 months, median (IQR)0.1 (0.1-0.8)0.1 (0.1-0.2)0.326
Proteinuria (g/L) at 48 months median (IQR)0.1 (0.1-0.5)0.1 (0.1-0.1)0.482
Proteinuria (g/L) at 60 months, median (IQR)0.1 (0.1-0.4)0.1 (0.1-0.1)0.518

Applying Friedman test, (eGFR, CKD-EPI 2012) did not significantly change over time in either group (ABOc χ² = 4.055, df = 7, P = 0.773; ABOi: χ² = 6.917, df = 7, P = 0.438). Proteinuria significantly varied over time in the AB0-compatible group (χ² = 37.920, df = 7, P < 0.001), whereas no significant change was observed in the ABOi group (χ² = 8.486, df = 7, P = 0.292). Nonetheless, median proteinuria remained very low throughout follow-up, with medians of 0.1 g/L both at 3-12 months and 36-60 months, indicating stabilization at low levels rather than a clinically meaningful increase.

DISCUSSION
Clinical significance of ABOi transplantation

Our study suggests that ABOi living-donor kidney transplantation can achieve patient and graft survival outcomes comparable to those of ABOc procedures, without a measurable increase in rejection, infectious, or surgical complications.

ABOi kidney transplantation has become increasingly relevant as a strategy to expand the donor pool and reduce waiting times, especially in regions with limited deceased donor programs or paired-exchange opportunities[4,5]. Historically associated with poor outcomes due to hyperacute rejection, the advent of effective desensitization regimens has transformed ABOi into a feasible and generally safe procedure[4]. Our observations are consistent with previous registry and meta-analytic data supporting comparable short- to medium-term outcomes[5-7].

Desensitization and immunosuppression

The favorable results of ABOi transplantation are largely attributable to modern desensitization protocols[12,13]. Early approaches relied on splenectomy and intensive plasmapheresis, which carried high morbidity[14]. The introduction of rituximab, plasmapheresis, and intravenous immunoglobulin markedly reduced both rejection risk and infectious complications[13-15]. In our cohort, all ABOi patients underwent desensitization, which may explain the absence of significant differences in rejection rates relative to compatible recipients. These findings align with data from Europe, Japan, and the United States showing that rituximab-based regimens can eliminate the need for splenectomy while maintaining efficacy[3,15,16].

Infections and complications

Infectious complications remain a central concern in ABOi transplantation given the augmented immunosuppressive burden. Earlier studies reported increased rates of CMV and BK virus infections[16], but recent evidence indicates no significant difference compared with ABOc[3-5]. Our study found no significant increase in CMV, BK polyomavirus, or bacterial infections in ABOi recipients, consistent with contemporary European and Asian reports. Interestingly, we observed numerically fewer BK infections in ABOi patients. However, the low number of ABOi recipients reduces the power to detect differences in infrequent events such as BK virus replication. This limitation should be considered when interpreting the infection rates, as BK virus nephropathy remains a clinically relevant concern in ABOi transplantation.

Rates of hemorrhage, surgical complications, and need for reintervention were also comparable, suggesting that modern ABOi protocols do not substantially increase perioperative morbidity[3,7].

Graft and patient survival

Several large studies confirm that graft and patient survival after ABOi transplantation are equivalent to ABOc outcomes. The Collaborative Transplant Study by de Weerd and Betjes[6] found no survival disadvantage at 3 and 5 years, while the meta-analysis by Scurt et al[5] comprehending over 12000 patients confirmed non-inferiority up to 5 years.

In our single center cohort, both patient and graft survival were excellent and did not differ significantly between groups. All ABOi patients were alive with functioning grafts at the end of follow-up, supporting the short- to medium-term safety of this approach. The apparent reduction in numbers beyond 96 months reflects shorter follow-up rather than true events; therefore, long-term inferences should be made cautiously.

Renal function and subclinical injury

Our cohort did not show persistent statistical differences in renal function between groups. eGFR, CKD-EPI 2012 remained stable over time in both ABOc and ABOi recipients. Although eGFR values tended to be slightly lower in the ABOi group during much of the follow-up, this difference did not reach statistical significance and may reflect limited power to detect small but clinically relevant effects. ABOi recipients exhibited greater variability in the early months, but this was not sustained, and long-term function converged with that of compatible recipients. These findings suggest that, beyond the early post-transplant period, renal function is largely maintained regardless of ABO compatibility. While some series have reported persistently higher creatinine or lower eGFR in ABOi recipients, sometimes attributed to subclinical microvascular injury or incomplete “accommodation”[4,16], our results did not demonstrate such a persistent disadvantage in this cohort.

Proteinuria followed a different pattern. In the ABOc group, we observed significant longitudinal variation, with levels increasing modestly after the first year and remaining higher in later follow-up, while in the ABOi group no statistically significant changes were detected. However, this increase in proteinuria should be interpreted cautiously: The very low levels at 3-12 months and may represent a stabilization rather than a concerning upward trend.

Taken together, the absence of a significant decline in eGFR and the generally low proteinuria levels support the short- to medium-term safety of ABOi kidney transplantation. However, without protocol biopsies or donor-specific antibody monitoring, subclinical injury could not be evaluated. Future multicenter studies incorporating histologic and immunologic data are needed to clarify whether subtle functional trends translate into late graft dysfunction.

Strengths and limitations

This study provides a comprehensive outcome assessment, uniform use of desensitization in ABOi recipients, and a relatively long follow-up period compared with similar single-center reports[9,17]. However, the small number of ABOi recipients (n = 22) compared with the larger ABOc cohort (n = 186) limits statistical power, especially for rare events such as graft loss or death, and increases the risk of type II error, particularly for rare outcomes such as graft loss, death, or severe infection. Longitudinal changes were analyzed using the Friedman test, as data were non-normally distributed and the small sample size of the ABOi group limited the use of mixed-effects models.

The retrospective single-center design entails the possibility of residual confounding, and the exclusion of HLA-incompatible or high-risk immunologic recipients-although methodologically justified to isolate the effect of ABO incompatibility-may have introduced selection bias by yielding a comparatively lower-risk compatible cohort. Furthermore, the shorter median follow-up in the ABOi group weakens any inference about long-term outcomes. Finally, the absence of protocol biopsies and donor-specific antibody data limits mechanistic interpretation of subclinical or chronic antibody-mediated injury.

The role of ABOi transplantation is expected to continue expanding with the refinement of desensitization strategies and the introduction of novel agents such as imlifidase (IgG endopeptidase), which has shown encouraging results in highly sensitized and ABOi recipients[8]. Further multicenter prospective studies are required to define the long-term functional impact of ABOi transplantation and to optimize protocols that balance graft protection with minimization of infectious and immunologic risks.

CONCLUSION

In our single-center Portuguese cohort, ABOi living-donor kidney transplantation achieved patient and graft survival outcomes comparable to ABOc procedures, without an evident increase in rejection, infectious, or surgical complications. Although ABOi recipients exhibited some early variability in renal function, long-term eGFR remained stable and proteinuria did not differ significantly between groups. These findings support the continued use of ABOi transplantation as a viable strategy to expand the living-donor pool, while underscoring the need for sustained functional monitoring and larger multicenter studies to confirm long-term safety.

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Footnotes

Peer review: Externally peer reviewed.

Peer-review model: Single blind

Specialty type: Transplantation

Country of origin: Portugal

Peer-review report’s classification

Scientific quality: Grade A, Grade C

Novelty: Grade A, Grade C

Creativity or innovation: Grade A, Grade C

Scientific significance: Grade B, Grade C

P-Reviewer: Sessa C, MD, Consultant, Italy; Tu ZH, MD, Consultant, Professor, Vice Director, China S-Editor: Qu XL L-Editor: A P-Editor: Zhang YL

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