Low-Dose r-ATG vs Basiliximab in Low-Risk Living-Donor Kidney Transplantation: Outcomes in Acute Rejection, Graft Function, and Infections

Introduction

Kidney transplantation remains the preferred treatment for end-stage renal disease (ESRD), offering superior quality of life and survival compared to dialysis [1,2]. Despite advancements in immunosuppressive strategies, acute rejection remains a major threat to graft function and patient survival, even among low-risk recipients [3]. Induction immunosuppressive therapy – most commonly using basiliximab or rabbit anti-thymocyte globulin (r-ATG) – is widely used to control early alloimmune responses [4,5]. Basiliximab, an IL-2 receptor antagonist, is often favored in low-immunologic-risk patients due to its selective action and favorable safety profile [6,7], while r-ATG provides more potent immunosuppression but carries a higher infection risk [8,9]. Choosing an appropriate induction agent requires balancing immunologic efficacy against potential complications [10–12].

Previous studies, such as Brennan et al [13] and Gaber et al [14], demonstrated that r-ATG can reduce acute rejection rates more effectively than basiliximab, but these findings largely are from deceased donor and higher-risk populations using moderate-to-high r-ATG doses (5–7.5 mg/kg). Lower-dose r-ATG regimens have been proposed to maintain efficacy while minimizing infectious complications, but clinical data in low-risk living-donor transplantation remain limited.

This study aimed to compare biopsy-proven acute rejection (BPAR), graft function, and infection outcomes between basiliximab and low-dose r-ATG (4 mg/kg) in low-immunologic-risk recipients undergoing living-donor kidney transplantation.

Material and Methods

STUDY DESIGN:

This retrospective observational cohort study was conducted at the 108 Military Central Hospital, a national tertiary transplant center in Vietnam. All kidney transplants were performed between January 2022 and January 2025, with patients followed from the date of transplantation for a minimum of 30 days and up to the end of the study period. Clinical data were extracted from electronic medical records. The study was approved by the institutional ethics committee and conducted in accordance with the Declaration of Helsinki. Informed consent was waived due to the retrospective nature of the study, and all patient data were anonymized prior to analysis.

PATIENT SELECTION:

Eligible patients were adults (>18 years old) undergoing their first kidney transplant from a living donor with low immunologic risk, defined by ABO compatibility, absence of donor-specific antibodies (DSA), panel-reactive antibody (PRA) <30% at the time of transplantation, and a historical peak PRA <50%. Patients were excluded if they had undergone multi-organ transplantation, had a positive HLA crossmatch, or had incomplete clinical or immunologic data.

INDUCTION THERAPY:

Patients were divided into 2 induction immunosuppression groups: low-dose r-ATG and basiliximab. In the low-dose r-ATG group, patients received rabbit anti-thymocyte globulin (r-ATG, Glafalon, Neovii Biotech GmbH) at a dose of 1 mg/kg per dose, for a total of 4 doses (total dose 4 mg/kg). The first dose was administered intravenously during surgery before reperfusion, with the remaining doses given daily for the next 3 days. In the basiliximab group, patients received intravenous basiliximab 20 mg (Simulect®, Novartis Pharmaceuticals) according to the manufacturer’s instructions, with the first dose given before reperfusion and second dose on post-transplant day 4.

MAINTENANCE IMMUNOSUPPRESSION:

All patients were treated with a triple-drug immunosuppressive regimen: calcineurin inhibitor (CNI, tacrolimus), mycophenolate mofetil (MMF), and prednisone. For the first 2 weeks after transplant, CNI trough levels were maintained at 10–12 ng/mL for tacrolimus, then tapered. MMF was administered orally at 1000 mg twice daily. Corticosteroids included 250 mg intravenous methylprednisolone before reperfusion, reduced to 125 mg on postoperative day 1, followed by 15 mg oral prednisolone daily.

CMV SCREENING AND MANAGEMENT:

A prophylactic antiviral strategy was used, including routine screening and therapeutic adjustments. High-risk patients (CMV-IgG-negative recipients from CMV-IgG-positive donors) received intravenous ganciclovir during hospitalization, followed by oral valganciclovir for 6 months. Patients in the r-ATG group also received intravenous ganciclovir for 2 weeks. CMV-PCR was monitored weekly postoperatively and monthly after discharge for 12 months.

BK POLYOMAVIRUS SCREENING AND MANAGEMENT:

BK virus was monitored biweekly during the first 16 weeks, then monthly through year 2, unless persistent or recurrent viremia was observed beyond year 1. Screening continued monthly for 12 months after the last positive detection. Testing was also performed when unexplained serum creatinine increases occurred or renal biopsies were conducted.

OTHER INFECTION SURVEILLANCE, PROPHYLAXIS, AND TREATMENT:

Patients in the basiliximab group received intravenous ceftriaxone (2 g every 24 hours) for 5 days after transplant to prevent perioperative bacterial infection. The r-ATG group received intravenous meropenem (1 g every 12 hours) for 5 days. For Pneumocystis jirovecii prophylaxis, 1 tablet of Bactrim™ daily was prescribed for 6 months, beginning on post-transplant day 5.

DATA COLLECTION:

Recipient characteristics, including age, sex, body mass index (BMI), duration of dialysis prior to transplantation, and causes of end-stage renal disease (diabetes, hypertension, polycystic kidney disease, glomerulonephritis, systemic lupus erythematosus), were collected and evaluated. Immunological status was assessed by HLA mismatches. Additionally, cold ischemia time (CIT), warm ischemia time (WIT), and pre-transplant CMV status were analyzed.

The primary outcomes included graft failure, graft and patient survival, delayed graft function (DGF), and biopsy-proven acute rejection (BPAR) in the 2 groups receiving low-dose r-ATG and basiliximab. Graft failure was defined as severe deterioration of the transplanted kidney function requiring dialysis or re-transplantation due to worsening uremia. This diagnosis was made by a nephrologist based on clinical evaluation, excluding cases of acute kidney injury (AKI) requiring short-term dialysis. DGF was defined as the need for dialysis within 1 week after transplantation before the graft became functional. Renal biopsies were performed for unexplained increases in serum creatinine. BPAR episodes were reviewed and classified according to the Banff 2019 criteria [15]. Routine post-transplant screening for de novo DSAs was not performed; testing was limited to clinically indicated cases where antibody-mediated rejection was suspected.

The secondary outcomes included changes in renal function and incidence of post-transplant infections, including CMV viremia, BK viremia, bacterial infections (%), viral pneumonia (%), fungal infections (%), and tuberculosis (%).

STATISTICAL ANALYSIS:

Statistical analyses were conducted using SPSS version 27 and R version 4.3.2 (R Core Team, Vienna, Austria, 2022). Categorical variables are expressed as frequencies and percentages, while continuous variables are presented as means±standard deviation (SD) or medians with ranges, depending on distribution. Comparisons between the low-dose r-ATG and basiliximab groups were made using the chi-square test or Fisher’s exact test for categorical variables, and the Student’s t-test or Wilcoxon rank-sum test for continuous variables. Time-to-event outcomes, including acute rejection and graft failure, were evaluated using Kaplan-Meier survival analysis, with group differences assessed via the log-rank test. Multivariable Cox proportional hazards regression models were constructed to adjust for potential confounders, including age, sex, and covariates with a P value <0.1 in univariate analysis. Due to the limited sample size in the r-ATG group, case-control matching was not applied. Instead, HLA Class I and II mismatches were included as covariates in the Cox regression models to account for immunologic risk.

Results

BASELINE CHARACTERISTICS:

The study flow chart is presented in Figure 1. Characteristics of the 150 patients included in the study are presented in Table 1. Of these, 37 patients (24.67%) were in the low-dose r-ATG group, and 113 patients (75.33%) were in the basiliximab group. The average recipient age was 40 years. The most common cause of ESRD was glomerulonephritis, followed by hypertension. Age, BMI, dialysis duration, sex, warm ischemia time, and cold ischemia time were comparable between the 2 groups. HLA mismatch status before transplantation did not differ significantly between the groups. Both groups were classified as moderate CMV-infected risk, with no patients categorized as high or low risk (Table 1).

GRAFT FUNCTION AND PATIENT SURVIVAL:

The average follow-up time was 26.65 months (28.86 months for the low-dose r-ATG group and 24.6 months for the basiliximab group). The overall patient survival rate was 100% (Table 2). The rate of delayed graft function was 0% in both groups. There were 3 (2%) cases of graft failure: 1 (2.7%) in the low-dose r-ATG group and 2 (1.77%) in the basiliximab group. The difference between the 2 groups was not statistically significant. Due to the very small number of graft failure cases, we did not perform a Cox regression analysis to evaluate risk factors for graft rejection.

ACUTE REJECTION:

A total of 19 (12.67%) patients were diagnosed with acute rejection confirmed by kidney biopsy, including 4 (10.81%) in the low-dose r-ATG group and 15 (13.27%) in the basiliximab group. There was no statistically significant difference between the 2 groups (Table 2). The rejection-free survival rate was 88.6% in the low-dose r-ATG group and 86.7% in the basiliximab group, with no significant difference according to the log-rank test (P=0.794, Figure 2). Univariate Cox regression analysis showed that sex, age, induction therapy (low-dose r-ATG or basiliximab), BMI, dialysis duration, CMV status, warm ischemia time (WIT), and cold ischemia time (CIT) had no impact on rejection status. However, multivariate analysis showed that HLA Class I mismatch increased the risk of rejection by 3.06 times (95% CI: 1.25–7.52, P=0.014), and HLA Class II mismatch increased the risk by 5.59 times (95% CI: 1.37–8.9, P=0.002) (Table 3).

KIDNEY FUNCTION AFTER TRANSPLANTATION:

Analysis of kidney function over time showed that estimated glomerular filtration rate (eGFR) remained stable throughout the 36-month follow-up. The average eGFR across all study participants ranged from 71.78 to 76.35 mL/min/1.73 m2, with the lowest at post-transplant month 3 and the highest at month 24 (Table 4). The low-dose r-ATG and basiliximab groups maintained stable eGFR values over 36 months (73–77 mL/min/1.73 m2). There were no significant differences in mean eGFR values at various time points (Figure 3).

INFECTIONS:

A comparative analysis of post-transplant infection rates between the low-dose r-ATG group (n=37) and the basiliximab group (n=113) showed no statistically significant differences in any type of infection assessed (all P>0.05). The CMV infection rate was 10.81% (4/37) in the r-ATG group and 14.15% (16/113) in the basiliximab group (P=0.783). Similarly, the BK viremia rate was not significantly different between the 2 groups (13.51% vs 16.81%, P=0.798). Bacterial infection rates were low and comparable between groups (r-ATG: 5.41%, basiliximab: 6.19%). No cases of viral pneumonia or tuberculosis infection were recorded in either group. Fungal infections were rare and occurred at similar frequencies in both groups (2.70% vs 2.65%) (Table 5).

Discussion

This retrospective study aimed to compare the efficacy and safety of low-dose r-ATG (total 4 mg/kg) versus basiliximab as induction immunosuppressive therapy in kidney transplant patients from living donors with low immunological risk. The results showed no significant differences in graft failure, patient survival, DGF, BPAR, or eGFR between the 2 groups. Similarly, infection rates were not significantly different, including CMV viremia, BK viremia, and other infections such as viral pneumonia, fungal infections, and tuberculosis.

The graft failure and survival rates at 26.65 months in our study align with prior reports in low-risk living-donor kidney transplantation. Laftavi et al (2011) reported 8-year graft survival rates of 100% with low-dose r-ATG and 98% with basiliximab in a U.S. cohort [16]. Similarly, studies from Korea by Lee et al (2018) and Kim et al (2020) demonstrated 5-year graft survival rates exceeding 95% with either induction agent in comparable low-risk populations [17,18]. Most recently, Masset et al (2023) confirmed no significant differences in 1-year graft survival between low-dose r-ATG and basiliximab in a European cohort [19]. These results reinforce the safety and efficacy of low-dose r-ATG in appropriately selected low-risk recipients. Mechanistically, basiliximab inhibits T-cell proliferation via IL-2 receptor blockade, while r-ATG depletes T cells through complement-mediated cytotoxicity and apoptosis. A low r-ATG dose (4 mg/kg) appears sufficient in patients without DSAs and moderate HLA mismatch, aligning with Sawinski et al (2021), who highlighted the immunologic advantages of living donation [2]. While our findings are consistent with this literature, the follow-up duration was relatively short, and longer-term studies are needed to confirm the durability of these outcomes.

The 0% rate of delayed graft function (DGF) observed in both groups is consistent with the inherently low risk of DGF in living-donor kidney transplantation. Therefore, while this finding is reassuring, it is expected and should not be overemphasized.

The overall BPAR rate in our study was 12.67%, with no significant difference between groups (10.81% with r-ATG vs 13.27% with basiliximab). This is consistent with Webster et al (2010), who found no significant difference in acute rejection between the 2 agents across 16 trials, although r-ATG was associated with a modest reduction in 1-year BPAR (RR 1.30) [7]. Several recent studies in low-risk living-donor recipients have reported similar results. Martinez-Mier et al (2021) found comparable rejection rates between low-dose r-ATG and basiliximab (6.9% vs 5.1%) [20]. Gavela Martínez et al (2008), Singh et al (2018), and Jalalonmuhali et al (2020) also reported no significant differences in BPAR rates [21–23]. In contrast, Brennan et al (2006) observed a lower rejection rate with high-dose r-ATG (15.6%) versus basiliximab (25.5%) in high-risk deceased donor transplants [13]. In our multivariable analysis, HLA mismatch was the strongest predictor of BPAR (Class I: HR 3.06; Class II: HR 5.59), while induction type had no independent effect (P=0.383). This aligns with findings from Opelz et al (2007), who showed increasing HLA mismatches significantly raised rejection risk [24].

Regarding renal function, eGFR remained stable (71.78–76.35 mL/min/1.73 m2) over 36 months and showed no differences between the 2 groups. These results are consistent with Patel et al (2014), who reported eGFRs of 65–70 mL/min/1.73 m2 for both groups, with no significant differences [25]. Laftavi et al (2011) found higher year-3 eGFRs in the low-dose r-ATG group (60–70) vs the basiliximab group (50–60, P=0.02), possibly due to reduced acute rejection (7.8% vs 35%) [16].

CMV and BK polyomavirus are major post-transplant infections arising from immunosuppressive therapy that compromises T-cell responses. In our study, CMV and BK viremia rates were lower in the low-dose r-ATG group compared to basiliximab, although not statistically significant. CMV viremia occurred in 10.81% of r-ATG patients, which is lower than the 16.2% reported by Kim et al (2020) using a higher r-ATG dose (4.5 mg/kg). Similarly, BK viremia was lower in our r-ATG group (13.51%) compared to 37.8% in Kim’s study, while the basiliximab group had comparable rates (~16%) [18]. These findings suggest that low-dose r-ATG can reduce viral infection risks while maintaining immunosuppressive efficacy, particularly when combined with CMV prophylaxis such as valganciclovir. Overall, this supports the use of reduced-dose r-ATG in low-risk recipients to minimize infectious complications.

It is worth noting that the 2 groups received different prophylactic antibiotic regimens per institutional protocol, based on local resistance patterns. The r-ATG group received broad-spectrum antibiotics (eg, meropenem), while the basiliximab group received narrower-spectrum agents (eg, ceftriaxone); both regimens were administered for 5 days after transplant. Although this difference may have influenced early infection risk, the minimum follow-up period was 30 days, and no significant difference in overall infection rates was observed. Therefore, the short duration of antibiotic use is unlikely to have significantly affected long-term infection outcomes. Nevertheless, this variation is acknowledged as a potential confounding factor in short-term analyses.

Low-dose r-ATG appears to be a safe alternative to basiliximab in low-risk living-donor kidney transplantation, with comparable efficacy and potentially fewer infections. However, its use should be individualized based on immunologic risk factors. The retrospective design, small sample size in the r-ATG group, single-center nature, and relatively short follow-up (mean 26.65 months) limit generalizability and the ability to assess long-term outcomes.

Conclusions

In low-immunologic-risk living-donor kidney transplantation, low-dose r-ATG and basiliximab induction therapies result in comparable outcomes in graft failure, survival, rejection, renal function, and infection rates. HLA mismatch remains the key predictor of BPAR, highlighting the importance of immunologic compatibility. These findings underscore the feasibility of using either agent safely in selected low-risk recipients. Larger, prospective multicenter studies with cost-effectiveness evaluations are warranted to guide clinical decision-making.