Induction therapy in kidney transplant recipients: A consensus statement of Indian Society of Organ Transplantation

Table 1 Rabbit anti-thymocyte globulin dose used in different kidney recipient populations (n = 254 completed survey)

Type of recipients with specialists using rATG as preferred dose unless otherwise specified	Lowest dose (mg/kg in single dose or given twice if required)	Highest dose (mg/kg in single dose)	Using 1.5 mg/kg dose (in single dose or fraction of cumulative dose)1, %
High immunological risk	0.2	6	10.6 (27/254)
Low immunological risk3	0.25	3	4.7 (12/254)
ABOiKT	0.5	6	7.9 (20/254)
Adults with low immunological risk3	0.25	5	7.5 (19/254)
Adults with high immunological risk	0.25	6	11.4 (29/254)
Elderly	0.5	4	5.1 (13/254)
Adolescents	0.4	5	7.1 (18/254)
Paediatric	0.2	5	9.1 (23/254)
Kidney from living donor with diabetes	0.25	10	11.4 (29/254)
Kidney from SCD	0.2	7-8	8.3 (21/254)
Kidney from ECD	0.2	6	7.9 (20/254)
Kidney from deceased donor with AKI	0.5	5	9.1 (23/254)
Kidney from deceased donor with infection	0.5	32	6.7 (17/254)

¹Includes 1.5 mg as single/3 mg in 2 divided doses/4.5 mg in 3 divided doses.

²Three doses of 3 mg/kg.

³IL-R2A was the preferred therapy.

AKI: Acute kidney injury; ABOiKT: ABO incompatible kidney transplant; ATG: Anti-thymocyte globulin; ECD: Expanded criteria donor; SCD: Standard criteria donor; rATG: Rabbit anti-thymocyte globulin.

Table 2 High risk stratification according to the Kidney Disease: Improving Global Outcomes guidelines[2]

Universal agreement (A)	Majority agreement (B)	Evidence from single study (C)
> 1 HLA mismatches	Younger recipient age – no age threshold; older donor age – no age threshold; Black ethnicity (in the United States); PRA > 0%; presence of DSA; blood group incompatibility; delayed onset of graft function, especially with ECD	Cold ischemia time > 24 hours

HLA: Human leucocyte antigen; DSA: Donor-specific antibody; ECD: Expanded criteria donor; PRA: Panel reactive antibodies.

Table 3 India-specific risk stratification[4]

	Strong	Moderate	Mild	No effect
Donor-related factors	Donor-recipient age matching	Older donor age	-	Deceased donor; ECD/cause of death/non-heart beating1; diabetes/hypertension, polycystic kidney disease; HCV status
Recipient-related factors	Donor-recipient age matching; HLA mismatch; presence of anti-HLA antibodies; presence of pre-transplant DSA and DSA titer	PRA	Re-transplantation	-
Transplant-related factors	Delayed graft function	-	Cold ischemia time	CMV/HIV/HCV infection1; gender; high BMI

¹Based on weak or poor-quality evidence.

BMI: Body mass index; CMV: Cytomegalovirus; DSA: Donor specific antibody; ECD: Expanded criteria donor; HCV: Hepatitis C virus; HLA: Human leucocyte antigen; HIV: Human immunodeficiency virus; PRA: Panel reactive antibody.

Table 4 Relative importance of pretransplant risk factors for acute rejection after kidney transplants[19]

Risk factor	Reason for considering	Importance
Younger recipient age	Stronger immune response	++
Adolescent recipient	Higher risk for nonadherence	+++
Donor age	Older organs: Higher immunogenicity	+
Recipient gender	Males: Fewer rejections	+
Ethnicity	African Americans: Significantly higher risk	+++
Deceased vs living donor	Insignificant differences. DD: Insignificant differences between donation after cardiac vs brain death, or ECD vs SCD	+
Previous-transfusion	low immunologic responder: If unsensitized despite previous transfusion	+
Previous-transplantation	Unsensitized recipient: No significant increase in risk; early loss of previous graft to immunological causes → increased risk of next graft rejection	++1
Previous-pregnancy	Increasing risk with successive pregnancies	++
PRA > 0% (HLA antibodies)	Includes both historic and current PRA level HLA antibodies class I and/or class II	+++
Preformed HLA, DSA (> 500 MFI)	Having no preformed HLA DSA at transplant: Low immunological risk. Low noncytotoxic HLA antibodies level: Intermediate risk. Required de novo HLA DSA posttransplant monitoring	++++
Sensitized patients after desensitization	Increased AMR risk, which may persist after desensitization in DSA-positive patients: Negative cytotoxicity and negative flow cross-match (low risk); flow cross-match (moderate increase in risk); positive cytotoxicity (profound increase in risk)	++/+++
HLA mismatch	Marked and well-documented effect on cellular and antibody-mediated rejection. Particularly pronounced for HLA DR mismatch	+++
CMV1 mismatch	No association between CMV mismatch and acute rejection due to CMV prophylaxis	–
EBV1 mismatch	No effect per se on acute rejection	–
Cold ischemia time	Less important with current shorter ischemic times	+
Delayed graft function	Delayed function may prompt changes to the planned protocol in the first few days posttransplant	+++

¹Important consideration in India due to increased risk[20,21].

AMR: Antibody mediated rejection; AT1: Angiotensin II receptor type 1; CMV: Cytomegalovirus; DSA: Donor-specific antibodies; EBV: Epstein-Barr virus; ECD: Expanded criteria donor; HLA: Human leucocyte antigen; MFI: Mean fluorescence intensity; PRA: Panel reactive antibody; SCD: Standard criteria donor.

Table 5 Anti-thymocyte globulin dose modification (standard dose: Body weight × 1.25 mg/day)[49]

	Lab value	ATG dose
WBC	2000/mm3 to 3000/mm3	Dose halved
	< 2000/mm3	ATG stopped
Platelet	< 75000/mm3 but > 50000/mm3	Dose halved
	< 50000/mm3	ATG stopped

ATG: Anti-thymocyte globulin; WBC: White blood cell.