Is there literature on the cumulative dose of rabbit antithymocyte globulin (rATG) for induction in kidney transplant patients and the risk of acute rejection? And if there is, how large are the sample size of these studies?

Is there literature on the cumulative dose of rATG for induction in kidney transplant patients and the risk of acute rejection? And if there is, how large are the sample size of these studies?

Comment by InpharmD Researcher

Available literature regarding the cumulative doses of rabbit antithymocyte globulin (rATG) is predominantly limited to retrospective analyses, with conflicting findings. rATG is commonly dosed as 1.5 mg/kg over the course of 4 to 7 days, with increases as needed based upon patient status and provider discretion. The most commonly identified maximum cumulative dose for rATG was ≥6 mg/kg. Low cumulative doses of rATG (2 to ≤5 mg/kg) demonstrated lower rates of acute rejection, decreased risk of infection, and maintained graft survival. However, some studies found no significant difference in rates of acute rejection or adverse events between low- and high-dose groups. Notably, sample sizes for rATG studies ranged from 83 to 261 patients. Overall, further large-scale prospective trials are needed to evaluate the effect of rATG cumulative dose on the incidence and risk of acute rejection following renal transplant.

Background

A 2021 systematic review and meta-analysis examined the association between cumulative doses of rabbit antithymocyte globulin (rATG) and various outcomes in kidney transplant recipients.Data from 23 cohort studies involving 3,457 patients and three randomized controlled trials (RCTs) with 154 patients were identified. The primary endpoints included biopsy-proven acute rejection (BPAR), delayed graft function (DGF), patient mortality, and death-censored graft loss. The findings highlighted that rATG doses of 3–4.5 mg/kg yielded lower rates of BPAR, cytomegalovirus (CMV) and BK virus infections, and malignancies, while maintaining comparable outcomes in DGF, patient mortality, and graft survival relative to higher doses of 4.5–6 mg/kg or >6 mg/kg. Comprehensive dose-response analyses revealed a non-linear association whereby BPAR rates decreased with rATG doses up to 3–4 mg/kg, but increased with higher doses. Similarly, infection rates, particularly CMV and BK virus, rose with higher rATG dosing, correlating positively with increased dose levels. Furthermore, the study observed that malignancy rates escalated with doses exceeding 6 mg/kg. Notably, the analysis confirmed that cumulative rATG doses in the range of 3–4.5 mg/kg optimized patient and graft outcomes while minimizing adverse effects, suggesting this dose range as effective for the induction of immunosuppressive therapy in kidney transplant patients. [1]

A 2019 analysis examined the effectiveness of rATG compared to interleukin-2 receptor antagonists (IL2RAs) for preventing acute rejection in kidney transplantation. Researchers conducted a pooled analysis of two international randomized controlled trials involving 508 kidney transplant recipients. The primary objective was to assess the noninferiority of rATG relative to IL2RAs with respect to a composite endpoint. This endpoint was defined as treatment failure encompassing biopsy-proven acute rejection, graft loss, death, or loss to follow-up. While comparative rATG and IL2RAs findings demonstrated noninferiority of rATG, the reported dosing of rATG varied acrossed trials and was often initiated intraoperatively prior to graft reperfusion, given at daily doses of 1.5 mg/kg for 4 to 7 days. Longer treatment durations with rATG were discussed, but further details were not provided. Overall, the recommended target cumulative dose of rATG is ≥6 mg/kg, with limited evaluation of cumulative doses <6 mg/kg in clinical trials. [2]

Relevant Prescribing Information

DOSAGE AND ADMINISTRATION [3]
Prophylaxis of Acute Rejection

The recommended dosage of THYMOGLOBULIN for prophylaxis of acute rejection in patients receiving a kidney transplant is 1.5 mg/kg of body weight administered daily with the first dose initiated prior to reperfusion of the donor kidney. The usual duration of administration is 4 to 7 days.

Literature Review

A search of the published medical literature revealed 6 studies investigating the researchable question:

Is there literature on the cumulative dose of rATG for induction in kidney transplant patients and the risk of acute rejection? And if there is, how large are the sample size of these studies?

Level of evidence

C - Multiple studies with limitations or conflicting results Read more→

Please see Tables 1-6 for your response.

Tailored Rabbit Antithymocyte Globulin Induction Dosing for Kidney Transplantation
Design	Single-center retrospective cohort study N= 224
Objective	To evaluate the safety and efficacy of reduced rabbit antithymocyte globulin (rATG) dosing in kidney transplant recipients, aiming to minimize acute rejection while reducing costs and adverse effects
Study Groups	Cumulative dose groups: rATG, 3 mg/kg (n= 96) rATG, 4.5 mg/kg (n= 102) rATG, 6 mg/kg (n= 26)
Inclusion Criteria	Adult kidney transplant recipients at Maine Medical Center between July 1, 2008, and December 31, 2013, with follow-up through January 1, 2015
Exclusion Criteria	No immunosuppression, identical twin transplant, kidney transplant from prior bone marrow donor, Interleukin-2 Receptor induction therapy, rATG therapy interrupted, graft thrombosis, death within 1 month of transplant
Methods	Recipients were divided into three groups based on cumulative rATG dosing: 3 mg/kg for nonsensitized living donor recipients, 4.5 mg/kg for nonsensitized deceased donor recipients, and 6 mg/kg for higher immunologic risk recipients. rATG dose was calcuated using actual body weight, with the first dose given intraoperatively; until November 2010, this intraoperative dose was given as 1.5 mg/kg, but was increased to 3 mg/kg to facilitate earlier discharge. The frequency of administration of subsequent doses of 1.5 mg/kg rATG was dictated by clinical progress and provider discretion. Maintenance immunosuppression included methylprednisolone, mycophenolate mofetil, and tacrolimus. Antimicrobial prophylaxis was provided with trimethoprim-sulfamethoxazole, clotrimazole or nystatin, and valganciclovir or acyclovir based on cytomegalovirus risk profile.
Duration	July 1, 2008, to December 31, 2013, with follow-up through January 1, 2015
Outcome Measures	Primary: Biopsy-proven acute rejection (BPAR) within the first year posttransplant Secondary: Patient survival, graft survival, costs, and length of stay (LOS)
Baseline Characteristics		All recipients (n= 224)	rATG, 3 mg/kg (n= 96)	rATG, 4.5 mg/kg (n= 102)	rATG, 6 mg/kg (n= 26)
	Mean age (± standard deviation [SD]), years	49.6 ± 12.7	49 ± 13.5	52 ± 11.2	45 ± 14
	Male sex	151 (67.4%)	63 (65.6%)	74 (72.5%)	14 (53.8%)
	White	215 (96%)	92 (95.8%)	98 (96.1%)	25 (96.2%)
	ESRD etiology Chronic glomerulonephritis Diabetes mellitus Hypertension Obstructive uropathy Polycystic kidney disease Other	79 (35.3%) 50 (22.3%) 25 (11.2%) 24 (10.7%) 26 (11.6%) 20 (8.9%)	38 (39.6%) 23 (24.0%) 8 (8.3%) 9 (9.4%) 8 (8.3%) 10 (10.4%)	33 (32.4%) 27 (26.5%) 16 (15.7%) 3 (2.9%) 16 (15.7%) 7 (6.9%)	8 (30.8%) 0 1 (3.8%) 12 (46.2%) 2 (7.7%) 3 (11.4%)
	Preemptive	27 (12.1%)	25 (26.0%)	1 (1%)	1 (3.8%)
	Deceased donor	118 (52.7%)	4 (4.2%)	93 (91.2%)	21 (80.8%)
	History of previous transplant	37 (16.5%)	1 (0.1%)	13 (12.7%)	23 (88.5%)
	Mean human leukocyte antigen (HLA) mismatch ± SD	3.9 ± 1.6	3.4 ± 1.7	4.5 ± 1.1	3.2 ± 2.1
	Mean Cumulative rATG dosage delivered (±SD), mg/kg	4.0 ± 1.0	3.0 ± 0	4.5 ± 0	6.1 ± 0.3
	Maintenance immunosuppression Calcineurin inhibitor Antimetabolite Steroid	224 (100%) 211 (94.2%) 224 (100%)	96 (100%) 88 (91.7%) 96 (100%)	102 (100%) 97 (95.1%) 102 (100%)	26 (100%) 26 (100%) 26 (100%)
	Mean follow-up (±SD), months	42.3 ± 20.0	43 ± 18.8	42 ± 20.7	39 ± 22.2
Results		All recipients (n= 224)	rATG, 3 mg/kg (n= 96)	rATG, 4.5 mg/kg (n= 102)	rATG, 6 mg/kg (n= 26)
	Mean serum creatinine at 1 year (±SD), mg/dL	1.5 ± 0.6	1.5 ± 0.5	1.5 ± 0.5	1.8 ± 0.9
	No. biopsies	87 (39%)	33 (34%)	34 (33%)	20 (76%)
	No. patients with one or more biopsies, n (%)	71 (31.7%)	29 (30.2%)	27 (26.5%)	15 (57.7%)
	Mean time to first biopsy (± SD), days	118 ± 102	144 ± 110	116 ± 100	71 ± 69
	Donor-specific antibody (DSA) screen	97 (43.3%)	46 (47.9%)	34 (33.3%)	17 (65.4%)
	DSA positivity Class I Class II	16 (7.1%) 18 (8.0%) -	7 (7.3%) 10 (10.4%) -	6 (5.9%) 4 (3.9%) -	3 (11.4%) 4 (15.4%) -
	No. patients with biopsy-proven acute rejection (BPAR)	21 (9.4%)	8 (8.3%)	9 (8.8%)	4 (15.4%)
	No. BPAR episodes	29 (12.9%)	9 (9.3%)	13 (12.7%)	7 (26.9%)
	Death-censored graft survival 1-year End-of-study	224 (100%) 212 (94.6%)	96 (100%) 90 (93.8%)	102 (100%) 99 (97.1%)	26 (100%) 23 (88.5%)
	Deaths at 1 y	8 (3.6%)	2 (2.1%)	4 (3.9%)	2 (7.7%)
	Deaths at the end of study	15 (6.7%)	4 (4.2%)	9 (8.8%)	2 (7.7%)
Adverse Events	Infection rates were comparable with those reported to the Scientific Registry of Transplant Recipients. There were no episodes of phlebitis.
Study Author Conclusions	The study concludes that tailored rATG dosing is safe and effective for kidney transplant recipients, providing excellent allograft outcomes and substantial cost savings without increasing adverse effects. Peripheral administration and reduced dosing are novel findings that contribute to favorable safety and reduced length of stay.
Critique	The study's strengths include a large sample size (N= 224), long follow-up period, and clear cost savings. However, its retrospective design and predominantly Caucasian population may limit generalizability. The small size of the higher immunologic risk group and lack of diversity in the study population are noted limitations.

References:
[1] [1] Singh N, Rossi AP, Savic M, Rubocki RJ, Parker MG, Vella JP. Tailored Rabbit Antithymocyte Globulin Induction Dosing for Kidney Transplantation. Transplant Direct. 2018;4(2):e343. Published 2018 Feb 2. doi:10.1097/TXD.0000000000000765

Comparative Efficacy and Safety of Low-Dose Versus Standard-Dose Rabbit Antithymocyte Globulin Induction Strategy in Kidney Transplant Recipients: Insights From a Single-Center Experience in North India
Design	Single-center, retrospective, observational study N= 208
Objective	To evaluate the efficacy and tolerability of varying rabbit antithymocyte globulin (rATG) doses in kidney transplant recipients (KTRs)
Study Groups	Group A (rATG dose 2/2.5 mg/kg, n= 122) Group B (rATG dose ≥3 mg/kg, n= 86)
Inclusion Criteria	KTRs who received two to three consecutive doses of rATG as part of their planned induction protocol between 2009 and 2014, with follow-up data available for five years
Exclusion Criteria	KTRs under 10 years of age, ABO-incompatible transplants, dual-organ transplants, and those with incomplete follow-up data; highly sensitized transplants with a positive cross-match status
Methods	Retrospective analysis of KTRs receiving rATG induction therapy. Group A received a cumulative dose of 2 or 2.5 mg/kg, while Group B received ≥3 mg/kg. rATG was administered with appropriate dilution in normal saline following premedication with steroids and antihistamines. Tacrolimus, mycophenolate mofetil, and prednisolone were used as part of the immunosuppressive regimen. Follow-up included monitoring for infections and graft function.
Duration	2009 to 2014, with five-year follow-up data
Outcome Measures	Primary: Incidence of acute rejection episodes Secondary: Incidence of delayed graft function (DGF), graft loss, death, infectious complications
Baseline Characteristics		Group A (n= 122)	Group B (n= 86)	p-value
	Mean age, years ± standard deviation (SD)	41.31 ± 12.23	42.13 ± 12.08	0.634
	Recipient Gender, males	98 (80.32%)	64 (74.42%)	0.312
	Mean weight, kg ± SD	64.13 ± 15.62	61.43 ± 12.63	0.188
	Mean donor age, years ± SD	48.36 ± 10.97	45.17 ± 10.34	0.034
	Number of human leukocyte antigen (HLA) mismatch ± SD	3.55 ± 1.06	4.13 ± 1.04	0.000
	Mean rATG dose in mg/kg ± SD	2.18 ± 0.24	3.14 ± 0.35	0.000
Results		Total (N= 208)	Group A (n= 122)	Group B (n= 86)
	Acute rejection episodes	8 (3.84%)	5 (4.09%)	3 (3.49%)
	Total graft loss	15 (7.21%)	9 (7.37%)	6 (6.98%)
	Death	9 (4.32%)	5 (4.09%)	4 (4.65%)
	Death-censored graft loss	6 (2.88%)	4 (3.27%)	2 (2.33%)
Adverse Events	Two malignancies and 141 infectious complications were noted. No significant difference between groups regarding infectious complications and incidence of acute rejection episodes.
Study Author Conclusions	The dosage for rATG induction therapy for KTRs should be tailored based on immunological and other factors impacting graft survival, along with a comprehensive risk assessment for potential infectious complications. A cumulative dose of 2.0 or 2.5 mg/kg could be optimal, offering effective induction therapy in KTRs with excellent graft survival rates and potentially fewer infectious complications
Critique	The study provides valuable insights into the efficacy of lower rATG doses, suggesting potential benefits in reducing adverse effects and costs. However, as a single-center retrospective study, it may be subject to biases and lacks generalizability. Larger, multicenter studies are needed to confirm these findings and explore dosing in high-risk populations.

References:
[1] [1] Khullar D, Panigrahi DK, Bagai S, et al. Comparative Efficacy and Safety of Low-Dose Versus Standard-Dose Rabbit Antithymocyte Globulin Induction Strategy in Kidney Transplant Recipients: Insights From a Single-Center Experience in North India. Cureus. 2024;16(9):e69770. Published 2024 Sep 20. doi:10.7759/cureus.69770

Evaluation of a Weight-based Rabbit Anti-thymocyte Globulin Induction Dosing Regimen for Kidney Transplant Recipients
Design	Single-center retrospective cohort study N= 261
Objective	To evaluate the potential consequences of rounding and capping rabbit anti-thymocyte globulin (rATG) doses in patients receiving steroid-containing maintenance immunosuppression when calculating the dose based on actual body weight
Study Groups	rATG dose ≥5 mg/kg (n= 138) rATG dose <5 mg/kg (n= 123)
Inclusion Criteria	Adult kidney transplant recipients between July 1, 2010, and December 31, 2012, who received rATG induction and were maintained on tacrolimus, mycophenolate, and prednisone
Exclusion Criteria	Patients who received a prior or simultaneous nonrenal transplant, underwent desensitization, experienced primary graft nonfunction, expired within 7 days of transplantation, and those who received a positive crossmatch graft, investigational medications, or rATG for nonprotocol indications
Methods	Patients received rATG induction with a cumulative dose of 5 mg/kg based on actual body weight, rounded to the nearest vial size and capped at 500 mg. Induction consisted of 1.5 mg/kg on post-operative day (POD) 0 and POD 1, followed by 2 mg/kg on POD 2. Maintenance immunosuppression included tacrolimus, mycophenolate, and prednisone.
Duration	July 1, 2010, to December 31, 2012
Outcome Measures	Primary: Incidence of biopsy-confirmed acute rejection (BCAR) grade 1A or greater within 12 months posttransplant Secondary: Patient and graft survival, graft function, hematologic effects
Baseline Characteristics		Group I (n= 138)	Group II (n= 123)
	Mean age, years ± standard deviation (SD)	50.3 ± 14.1	50.5 ± 11.9
	Male	82 (59.4%)	76 (61.8%)
	Mean actual body weight, kg ± SD	80.3 ± 13.8	94.6 ± 24.4
	Mean ideal body weight, kg ± SD	64.4 ± 11.5	66.8 ± 10.9
	Body mass index, kg/m², mean ± SD	27.6 ± 4.8	31.3 ± 6.9
Results		Group I (n= 138)	Group II (n= 123)	p-value
	BCAR grade ≥1A	12 (8.7%)	11 (8.9%)	0.994
	BCAR grade Grade 1 Grade 2 Grade 3	6 (4.3%) 5 (3.6%) 1 (0.7%)	9 (7.3%) 1 (0.8%) 1 (0.8%)	0.304 0.13 0.935
	Recurrent BCAR grade ≥1A	10 (7.2%)	3 (2.4%)	0.075
	Antibody-mediated rejection	5 (3.6%)	2 (1.6%)	0.319
Adverse Events	No significant differences in the incidences of cytomegalovirus, BK viremia, or BK virus nephropathy between groups. Lymphopenia, thrombocytopenia, and leukopenia incidences were similar between groups.
Study Author Conclusions	Modest differences in the cumulative rATG dose were not associated with increased risk of acute rejection when combined with triple maintenance immunosuppression. Optimizing rATG utilization can offer cost-saving opportunities without sacrificing efficacy.
Critique	The study's retrospective design and single-center setting may limit generalizability. The absence of patients receiving higher doses of rATG (>6 mg/kg) restricts conclusions about higher dosing strategies. The study provides valuable insights into cost-saving dosing strategies without compromising efficacy.

Reduced Dose Rabbit Anti-Thymocyte Globulin Induction for Prevention of Acute Rejection in High-Risk Kidney Transplant Recipients
Design	Retrospective analysis N= 83
Objective	To determine the impact of reduced-exposure rabbit anti-thymocyte (rATG) in the prevention of acute rejection in high-risk kidney transplant recipients
Study Groups	3-dose rATG (n= 39) 4-dose rATG (n= 44)
Inclusion Criteria	Recipients of a single-organ kidney transplant with repeat transplant, African American race, or panel reactive antibody (PRA) ≥20%
Exclusion Criteria	Patients with multiorgan transplants and patients with delayed graft function requiring dialysis within the first 48 hr of transplant
Methods	Retrospective analysis of kidney transplant recipients treated with rATG 1.5 mg/kg per day for 3 or 4 doses (cumulative dose: 4.5 mg/kg and 6 mg/kg, respectively). All patients received triple maintenance immunosuppression, including a calcineurin inhibitor (tacrolimus [TAC] or cyclosporin [CsA]), prednisone (Pred), and a mycophenolate agent (MPA; mycophenolate mofetil or enteric-coated mycophenolate sodium) or sirolimus. Patients requiring dialysis within 48 hr after transplant were excluded from analysis.
Duration	July 2004 to July 2007
Outcome Measures	Primary: Acute rejection rates at 1 year Secondary: Patient and graft survival, length of hospital stay, estimated glomerular filtration rate (eGFR)
Baseline Characteristics		Total (n= 83)	3-dose (n= 39)	4-dose (n= 44)	p-value
	Mean age, years	48	50	46	0.12
	Gender Male Female	42 (51%) 41 (49%)	17 (44%) 22 (56%)	25 (57%) 19 (43%)	0.23 0.23
	Donor status Living Deceased	25 (30%) 58 (70%)	13 (33%) 26 (67%)	12 (27%) 32 (73%)	0.55 0.55
	Expanded criteria donor, n (% of deceased donors)	3 (5%)	2 (8%)	1 (3%)	0.58
	Race African American White Other	15 (18%) 51 (61%) 17 (21%)	10 (26%) 21 (54%) 8 (20%)	5 (11%) 30 (68%) 9 (21%)	0.22 0.22 0.22
	PRA ≥20%	63 (76%)	29 (74%)	34 (77%)	0.76
	PRA ≥80%	37 (45%)	18 (46%)	19 (43%)	0.79
	Previous transplant	45 (54%)	17 (44%)	28 (64%)	0.07
	Mean serum creatinine, postoperative day 2, mg/dL ± standard deviation (SD)	3.6 ± 2.8	2.7 ± 1.9	4.4 ± 3.2	0.005
	Mean reduction in serum creatinine from postoperative day 1–2, mg/dL ± SD	1.8 ± 1.7	1.9 ± 1.7	1.7 ± 1.7	0.52
	Immunosuppression Tacrolimus (TAC)/MPA/Pred TAC/SRL/Pred CsA/SRL/Pred	49 (59%) 33 (40%) 1 (1%)	29 (74%) 10 (26%) 0	20 (45%) 23 (53%) 1 (2%)	0.01 0.01 0.01
Results		Total (n= 83)	3-dose (n= 39)	4-dose (n= 44)	p-value
	Acute rejection At 6 months At 12 months	8 (10%) 9 (11%)	4 (10%) 4 (10%)	4 (9%) 5 (11%)	1.00 1.00
	Graft survival At 6 months At 12 months	100% 100%	100% 100%	100% 100%	1.00 1.00
	Patient survival At 6 months At 12 months	100% 100%	100% 100%	100% 100%	1.00 1.00
	Mean eGFR, mL/min ± SD At 6 months At 12 months	60.2 ± 16.3 58.7 ± 18.1	64.2 ± 16.2 63.4 ± 20.3	56.7 ± 15.7 54.6 ± 14.9	0.03 0.03
	Median transplant hospitalization length of stay, days (range)	4 (3–12)	3 (3–8)	4 (3–12)	0.004
Adverse Events	Infectious complications were not statistically different between subgroups. Bacterial infections were common, with 25.6% in the 3-dose group and 15.9% in the 4-dose group. Cytomegalovirus disease occurred in 5.1% of the 3-dose group, while BKV viremia was more frequent in the 4-dose group (18.2%) compared to the 3-dose group (5.1%)
Study Author Conclusions	A 3- or 4-dose course of rATG (1.5 mg/kg/dose) provides excellent protection against acute rejection in high-risk patients, with potential cost savings from reduced hospital stay and medication administration.
Critique	The study provides promising data on reduced-dose rATG in high-risk renal transplant recipients, but its retrospective nature limits the ability to control for confounding variables. The exclusion of patients with delayed graft function may have influenced the low acute rejection rates. Differences in maintenance immunosuppression regimens between groups could have impacted eGFR outcomes. Further prospective studies are needed to confirm these findings and explore the economic benefits of reduced dosing.

References:
[1] [1] Klem P, Cooper JE, Weiss AS, et al. Reduced dose rabbit anti-thymocyte globulin induction for prevention of acute rejection in high-risk kidney transplant recipients. Transplantation. 2009;88(7):891-896. doi:10.1097/TP.0b013e3181b6f38c

The appropriate dose of thymoglobulin induction therapy in kidney transplantation
Design	Single-center randomized open-labeled clinical trial N= 90
Objective	To delineate the safest effective dose of thymoglobulin induction therapy in kidney transplantation
Study Groups	Arm A (4.5 mg/kg in 3 days) (n= 30) Arm B (4.5 mg/kg single bolus dose) (n= 30) Arm C (6 mg/kg in 3 days) (n= 30)
Inclusion Criteria	Positive panel reactive antibodies (PRA) (>0%) at the time of transplantation, history of previous transplantation, aged 18-65 years old; Extended criteria donor (ECD), Cold ischemia time >6 hours
Exclusion Criteria	Multiple organ transplants, serological evidence of human immunodeficiency virus or active hepatitis B and C in recipients or donors
Methods	Patients received quadruple immunosuppression with thymoglobulin followed by tacrolimus, mycophenolic acid, and prednisolone. Thymoglobulin was administered as 4.5 mg/kg in 3 days, 4.5 mg/kg single bolus, or 6 mg/kg in 3 days. First dose was administered over 6 hours beginning intraoperatively; subsequent doses were given over at least four hours. Premedications included diphenhydramine or acetaminophen. Tacrolimus was initiated within 72 hours of transplantation, with targeted trough levels. Mycophenolate mofetil and methylprednisolone were also administered.
Duration	January 2014 to February 2015
Outcome Measures	Primary: Rate and severity of acute rejection (biopsy-proven) during the first post-transplantation year Secondary: Length of hospital stay, rate of readmission, renal function (serum creatinine and glomerular filtration rate [GFR])
Baseline Characteristics		Arm A (n= 30)	Arm B (n= 30)	Arm C (n= 30)	p-value
	Donor age, mean ± standard deviation (SD)	35 ± 3	34 ± 4	36 ± 2	0.6
	Recipient age mean ± SD	54 ± 4	56 ± 5	51 ± 4	0.311
	Weight, mean ± SD	63.7 ± 12	71 ± 6	66.5 ± 9	0.214
	Male	39 (42%)	45 (45%)	40 (43%)	0.324
	Preemptive transplantation	6 (20%)	5 (16%)	5 (16%)	0.23
	Previous transplant	10 (33%)	8 (26%)	8 (26%)	0.5
	PRA-positive patients	14 (46%)	12 (40%)	11 (36%)	0.11
	Cadaveric donor	14 (48%)	16 (51%)	17 (52%)	0.382
Results		Arm A (n= 30)	Arm B (n= 30)	Arm C (n= 30)	p-value
	Acute rejection Cellular Humoral	1 1	1 1	1 1	0.1
	Histologic evidence of acute rejection g ptc	2 (7%) 2 (7%)	1 (4%) 0	1 (4%) 1 (4%)	0.3
	Serum creatinine at 12 months, mg/dL	1.5 ± 0.3	1.5 ± 0.8	1.6 ± 0.5	0.331
	GFR at 12 months, mg/mL	64.5 ± 7	63.5 ± 7	64 ± 8	0.631
	Length of stay, days	7.4 ± 1.8	10 ± 2.2	10.1 ± 2.5	0.002
	Readmission	11 (33%)	13 (42%)	12 (40%)	0.034
Adverse Events	The one-year incidence of serious infection was lower in Arm A (23%) compared to Arm B (33%) and Arm C (30%). The incidence of cytomegalovirus (CMV) infection was also lower in Arm A (16%) compared to Arm B (26%) and Arm C (33%). Arm C had a higher incidence of BK nephropathy (23%) compared to Arms A and B (7% each). Significant leukopenia was observed in Arm C and thrombocytopenia in Arm B.
Study Author Conclusions	Although all regimens showed the same efficacy regarding the rate of rejection episodes, 3-day 4.5 mg/kg Thymoglobulin had significantly fewer complications. Lower thymoglobulin dose causes less immunosuppression, but it may be more advantageous to use for the potential long-term gain given the lower infectious and CMV rate.
Critique	The study was limited by its small sample size and lack of protocol biopsy in all patients. The absence of CD3+ T-cell count as a marker of T-cell depletion was also a limitation. Despite these limitations, the study provided valuable insights into the dosing of thymoglobulin, showing that lower doses are effective and associated with fewer complications. Larger studies are needed to confirm these findings and evaluate long-term outcomes.

References:
[1] [1] Nafar M, Dalili N, Poor-Reza-Gholi F, Ahmadpoor P, Samadian F, Samavat S. The appropriate dose of thymoglobulin induction therapy in kidney transplantation. Clin Transplant. 2017;31(6):10.1111/ctr.12977. doi:10.1111/ctr.12977

Low dose rabbit antithymocyte globulin is non-inferior to higher dose in low-risk pediatric kidney transplant recipients
Design	Single-center, retrospective cohort study N= 166
Objective	To compare the safety and efficacy of lower-dose versus higher-dose rATG for induction in pediatric kidney transplant recipients at low immunologic risk for acute rejection
Study Groups	Low risk patients, higher cumulative rATG dose (n= 47) Low risk patients, lower cumulative rATG dose (n= 52) High risk patients (n= 67)
Inclusion Criteria	Pediatric patients who underwent kidney transplantation at Stanford University's Lucile Packard Children's Hospital (LPCH) from May 1, 2013 to May 1, 2018 with at least 12 months of follow-up post-transplant
Exclusion Criteria	Patients who received basiliximab due to an allergic reaction thought to be caused by rATG, inadequate CD3+ T cell depletion, lack of protocol biopsies
Methods	Eligible patient data was retrospectively extracted from the electronic medical record system at LPCH and the Stanford Histocompatibility, Immunogenetics, and Disease Profiling Laboratory electronic database at LPCH. Patients received the first dose of rATG intravenously in the operating room prior to graft perfusion. Total cumulative rATG dose was determined based on immunologic risk of acute rejection; high risk defined as repeat transplant, preformed donor-specific antibody (DSA), current panel-reactive antibodies (PRA) ≥20%, 0 antigen match and/or African American heritage. Low-risk patients received 1.5 mg/kg daily for 3 days (cumulative dose 4.5 mg/kg) until 2016, which was updated to 1 mg/kg daily for 5 days (cumulative dose 5 mg/kg). High-risk patients received 1.5 mg/kg daily for 5 days (cumulative dose 7.5 mg/kg) until 2016, which was updated to 1 mg/kg daily for 5 days (cumulative dose 5 mg/kg). For analysis, patients were divided into 3 groups based on immunologic risk and rATG dose. Low immunologic risk patients were divided into 2 groups, those who received the lower cumulative rATG dose of equal to or less than 3.5 mg/kg, versus the higher cumulative dose of more than 3.5 mg/kg, respectively. All high-risk patients were analyzed as a single group. Patients were maintained on tacrolimus and mycophenolate mofetil, with or without prednisone, initiated prior to or following discharge.
Duration	May 2013 to May 2018
Outcome Measures	Primary: Incidence of biopsy-proven acute rejection, graft function at 12 months, graft loss or death in the first 12 months
Baseline Characteristics		All patients (N= 166)
	Median age at transplant, years (interquartile range [IQR])	12.6 (10)
	Female	84 (50.6%)
	White	64 (38.6%)
Results	Endpoint	Low-risk, higher dose (n= 47)	Low-risk, lower dose (n= 52)	High-risk (n= 67)	p-value
	Median total dose, mg/kg (IQR)	4.4 (0.8)	3.1 (0.3)	5.7 (1.7)	<0.001
	Median total number of doses (IQR)	3 (0)	3 (0)	5 (0)	-
	Biospy proven rejection	6 (12.8%)	7 (13.5%)	12 (17.1%)	1.0
	Banff grade ≥2B	0	0	3	-
	Patient survival at 1 year	47	52	67	-
	Graft failure at 1 year	1	0	0	0.4
Adverse Events	Patients were admitted for infection in 29.8% of low risk, low dose patients, 25% of low risk, high dose patients, and 16.4% of high risk patients. CD3 depletion did not significantly differ between groups. No cases of malignancy were identified within the first year.
Study Author Conclusions	Reduced rATG dosing (≤ 3.5 mg/kg) when compared to higher dosing (> 3.5 mg/kg) is safe and effective in low-risk pediatric kidney transplant recipients without increasing risk of rejection.
InpharmD Researcher Critique	This study is limited by its retrospective analysis, with potential for misreporting or lack of adequate documentation regarding patient characteristics and subsequent effect on medication use. Notably, this evaluation of rATG is specific to pediatric patients and may not be generalizable to larger, adult patient populations. The use of low-dose rATG demonstrated comparable efficacy in reduction of risk of acute rejection to higher doses, but overall demonstrated better safety profiles overall. Further prospective trials are necessary to determine the validity of these findings.

References:
[1] [1] Sigurjonsdottir VK, Maestretti L, McGrath A, et al. Low dose rabbit antithymocyte globulin is non-inferior to higher dose in low-risk pediatric kidney transplant recipients. Pediatr Nephrol. 2022;37(9):2091-2098. doi:10.1007/s00467-021-05407-y