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Saudi Journal of Kidney Diseases and Transplantation
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ORIGINAL ARTICLE  
Year : 2021  |  Volume : 32  |  Issue : 5  |  Page : 1273-1282
Comparison of short-term outcomes with and without induction therapy in low-risk renal transplant recipients


Department of Nephrology, Sir Ganga Ram Hospital, New Delhi, India

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Date of Web Publication4-May-2022
 

   Abstract 


With low rates of rejection with current immunosuppression consisting of steroids, mycophenolic acid and tacrolimus, the question arises whether induction offers any additional benefit in low-risk renal transplant recipients. This study evaluated outcomes with and without induction in low-risk renal transplant recipients. A prospective observational study in which 100 low-risk renal transplant recipients were included and divided into two groups – one that received induction (IND) and another that did not (NO IND). They were followed for 1.5 years. Three endpoints were compared - efficacy of induction, patient and graft survival, and adverse effects. Incidence of rejection in early posttransplant period did not differ (4% NO IND vs. 6% IND; P = 0.171). Rejection as cause of late graft dysfunction was seen in 16% in IND vs. 20% NO IND; (P = 0.603). No difference in serum creatinine at end of 1.5 years was seen. Graft survival was also similar. Relapsing and recurrent urinary tract infections (46% IND vs. 16% NO IND; P = 0.09), hospitalization requiring infections (76%IND vs. 64% NO IND; P = 0.119 NS) were more common in IND. Cytomegalovirus infection affected only IND (6% vs. none; P = 0.07). Patient survival at 1.5 years was comparable (94% IND vs. 96% NO IND; P = 0.646). The study showed comparable results between IND and NO IND with however an increased incidence of infections and hospitalizations in the IND group. The use of induction may be avoided in low-risk renal transplant recipients.

How to cite this article:
Yusuf S, Rana DS, Gupta A, Gupta A, Bhalla A K, Malik M, Bhargava V. Comparison of short-term outcomes with and without induction therapy in low-risk renal transplant recipients. Saudi J Kidney Dis Transpl 2021;32:1273-82

How to cite this URL:
Yusuf S, Rana DS, Gupta A, Gupta A, Bhalla A K, Malik M, Bhargava V. Comparison of short-term outcomes with and without induction therapy in low-risk renal transplant recipients. Saudi J Kidney Dis Transpl [serial online] 2021 [cited 2022 May 25];32:1273-82. Available from: https://www.sjkdt.org/text.asp?2021/32/5/1273/344746



   Introduction Top


The number of patients receiving induction therapy has increased considerably over the past years. UNOS data indicate that while 8.6% of kidney transplant recipients received an induction agent in 1992, the percentage increased to 59.7% by 2001 and continues to rise.[1] While induction therapy has become popular, several questions regarding the short-term effects of different agents as well as the long-term consequences of induction therapy remain to be answered.

Both recipient and donor populations have changed over recent years, with an increasing trend to transplant older patients who have more comorbidities. In addition, the number of previously transplanted, sensitized patients has increased. At the same time, more and more organs from older and less ideal donors are being utilized for transplantation.[2],[3] The use of induction therapy is associated with decreased rates of rejection and improved short term graft outcomes .[4] Also steroid free regimens or withholding calcineurin inhibitors may be permitted with use of induction in the early posttransplant period.[5] Sensitized and high-risk patients appear to fare better in terms of acute rejection episodes and graft survival with induction therapy. Despite these potential benefits, the risk of over-immunosuppression is always a concern with the use of induction. The increased use of induction therapy has been found to coincide with an increase in the rate of development of BK nephropathy in kidney transplant recipients. Equally serious is the concern that the use of induction therapy may result in higher rates of other infections as well as increased incidence of malignancies in the long term.

Since early randomized trials showed that rabbit anti-thymocyte globulin (rATG) or interleukin 2 receptor antagonist (IL2RA) induction reduces early acute rejection, it prompted recommendations by Kidney Disease Improving Global Outcomes that IL2RA induction be used routinely in first-line therapy after kidney transplantation, with lymphocyte-depleting induction reserved for high-risk cases.[6] Most of these trials are based on older immunosuppressive regimens. In the current era, on the other hand, most transplant centers administer triple maintenance therapy with steroids, tacrolimus and mycophenolic acid (MPA) as the standard maintenance treatment,[7] a shift that may explain the decrease in one-year acute rejection rates from ~50% in the early 1990s to ~10%–15% now.[7],[8],[9] With this low basal level of acute rejection risk, it is doubtful whether the addition of induction therapy still offers an additional benefit in standard or low-risk kidney transplant recipients. No large randomized trial has examined the effect of IL2RA or rATG induction versus no induction in patients receiving tacrolimus, mycophenolic acid, and steroids. Therefore with an increased armamentarium of immunosuppressants, including induction agents, we need to have a better understanding of their effects and efficacy, so that we will have the opportunity to tailor immunosuppression to the particular patient population. With this aim, the present study was designed to assess outcomes with and without induction therapy in low-risk renal transplant recipients.


   Materials and Methods Top


This was a prospective observational study conducted in Sir Ganga Ram Hospital in New Delhi, which is one of the largest centers for renal transplantation in the country. Patients were included in the study after they met the inclusion/exclusion criteria. Written informed consent for participation in the study was taken from every patient.

A total of 100 patients, 50 in each group, were included in the study. Criteria for inclusion were men or women 18–65 years of age undergoing a first kidney allograft transplantation from living donors, ≤3/6 human leukocyte antigens (HLA) mismatch, absence of donor-specific antibody (DSA), HIV negative, no evidence of drug addiction, psychiatric disorder or a condition of non-compliance, no previous or current malignancy. Luminex bead-based crossmatch assay was used to detect the presence of donor-specific antibodies. Patients with ABO incompatible transplants, more than 3/6 HLA mismatch, deceased donors, presence of DSA, or those who received another solid organ transplant or required multiple organ transplantation or had a positive crossmatch in their most recent serum specimen were excluded from the study.

Immunosuppressionprotocol

Triple drug therapy: basic immunosuppression for all recipients consisted of a calcineurin inhibitor (tacrolimus), MPA, and steroid. Tacrolimus and MPA were started according to body weight on the day (-2). Tacrolimus was administered orally as capsules in a total dose of 0.1 mg/kg/day in two divided doses. Subsequent adjustment to dosing was made based on maintenance of whole blood trough levels. Whole blood trough levels of tacrolimus were maintained between 10–12 ng/mL for the first month, 8–10 ng/mL for the next two months, 6–8 ng/mL between 3 to 6 months, and 4–6 ng/mL for the remaining study period. Tacrolimus whole blood trough level was assessed on days 2, 4, and 6 during hospitalization and at weeks 1, 2, 3, and months 2, 3, 6, and as clinically indicated. MPA was administered orally in a dose of 1 g (MMF)/720 mg (MPS) twice a day in those >50 kgs and 500 mg (MMF)/360 mg (MPS) thrice a day in those <50 kgs body weight. Methylprednisolone was started on the day (-1). It was administered intravenously at a dose of 125 mg on day (-1) followed by 125 mg twice a day on days 0, 1, and 2. Prednisolone equivalent was administered orally at 0.5 mg/kg from day 3.

Induction therapy

In the nephrology department of the hospital, there were two working units- one which used induction therapy in low-risk renal transplant recipients and the other that did not. Rest of the transplant protocol was similar in the two units. We selected 50 patients from each of the working units. Patients, therefore, fell into two groups-one that received triple-drug therapy alone and another that received triple-drug therapy with induction (Thymoglobulin). In those receiving thymoglobulin, the first dose of induction was given in the morning on the day of operation. Thymoglobulin was given in a dose of 1.0 mg/kg/day diluted in 250 mL of 5% D intravenously over 4–6 h after pre-medication with 100 mg hydrocortisone and 25 mg pheniramine to reduce cytokine release. The second and third doses of thyroglobulin were given on the postoperative days 1 and 2. Tacrolimus, MPA, and steroid were administered as in triple-drug therapy alone.

Prophylaxis

All patients who received induction therapy were given prophylaxis for Cytomegalovirus and Pneumocystis carinii with valgancyclovir (for 3 months) and cotrimoxazole (for 1 year) respectively while those on triple-drug therapy alone were given prophylaxis for P. carinii only.

Study assessments

Patients were recruited for six months. Every patient was followed up for 1.5 years after recruitment in the study. All patients were assessed daily from the day of surgery till discharge, twice a week for one month, weekly for two months, fortnightly for three to six months and monthly for the rest of the study period. Blood pressure, weight, and routine laboratory assessments were performed at baseline and at each visit. Graft and patient survival were assessed continuously. Study endpoints were divided into three groups:

  1. Efficacy
  2. Patient and graft survival
  3. Adverse effects.


Efficacy

Efficacy was assessed by the occurrence of an acute rejection episode. The clinical diagnosis of acute rejection was made in cases of delayed graft function or in cases of a secondary rise in serum creatinine. Color duplex sonography, isotopic nephrography, whole blood trough levels of tacrolimus were used to eliminate any other causes of graft dysfunction. Any graft dysfunction not explained underwent biopsy. Protocol biopsies were not done in the study.

Patient and graft survival

Graft function was assessed using serum creatinine at each visit. Graft loss was defined by the need to return to dialysis. The number of patients requiring dialysis during the study period was recorded.

Adverse effects

All adverse events (death or life threatening events or those causing persistent significant disability or incapacity, hospitalization or prolongation of hospitalization or cancer) were recorded. All bacterial, fungal, viral, or protozoal infections occurring in patients were recorded. The episode of infection was defined as the necessity of antibiotic, antifungal, or antiviral treatment. Laboratory diagnosis of CMV infection was done by CMV PCR if clinical CMV disease was suspected any time. Patients were also assessed for the development of Denovo malignancies including PTLDs. The incidence of those with new-onset diabetes mellitus after transplant was assessed.


   Statistical Analysis Top


Data were analyzed using Statistical software Statistical Package for the Social Sciences (SPSS) version 16.0 (SPSS, Inc., Chicago, IL, USA). The descriptive statistics for qualitative variables were presented in terms of frequency (counts) and percentages (%) in different categories, and for quantitative variables as the range (minimum, maximum), mean, standard deviation/median, and standard error of the mean. The statistical significance of quantitative variables having paired observation was carried out by paired t-test or by non-parametric Wilcoxon signed rank-sum test, in case data did not follow the normal distribution. The statistical significance of qualitative variables was determined by Chi-square test and the McNemar-Bowker test. For all statistical tests, the level of significance was taken as 0.05 (5%).


   Results Top


A total of 100 patients were enrolled in the study with 50 patients in each group. One group included patients who did not receive induction (NO IND) and another included patients who were given induction therapy (IND). [Table 1] shows the baseline characteristics of patients in the two groups. Mean age of patients was higher in the group which received induction therapy compared to the group with no induction (P = 0.046). The percentage of donors in the ≥60 years age group was comparable between the two groups [Table 2]. Majority of the patients were male in both groups. About 85% of patients were on hemodialysis (HD) before renal transplant in both groups. While 22% of patients underwent a pre-emptive transplant in the induction group, 10% underwent pre-emptive transplant in the no induction group (P = 0.169 NS). The mean duration on HD (5–6 months) was almost similar in both groups (P = 0.588 NS). Chronic glomerulonephritis was the most common basic kidney disease among the study participants (in 25%) followed by diabetic kidney disease and CIN (in 11% each). In both groups, in >90% of patients kidney donor was a first-degree relatives [Table 3]. The mean donor age was 49.04 ± 9.4 years in the induction group and 47.10 ± 11.5 years in the no induction group (P = 0.359 NS). The number of patients with zero, one, two, and three HLA mismatches was comparable between the two groups [Table 4]. Majority of the patients were in the three mismatch category (~40% in each group) followed by the zero mismatch category (~30% in each group), (P = 0.980 NS).
Table 1: Baseline characteristics of the patients in the two study groups.

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Table 2: Comparison of the donor age (<60 or ≥60 years) in the two groups.

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Table 3: Relationship between the donors and recipients in each group.

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Table 4: Distribution of various degrees of HLA mismatch in the two groups.

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The most common in-hospital complication in either group was urinary tract infection (UTI) which affected 22% of patients in NO IND and 34% of patients in IND (P = 0.197). The most common causative organism for UTI was  Escherichia More Details coli (E. coli) in NO IND (accounting for 36% cases) and Klebsiella in IND (accounting for 41% cases). Delayed graft function was seen in one patient in each group with graft biopsy showing cortical necrosis in one patient (IND) and ATN in another patient (NO IND) which was attributed to the complex vascular anatomy of the donor. Acute graft dysfunction, on the other hand, occurred in six patients (12%) in the group which received induction therapy and two patients (4%) in the group with no induction (P = 0.337 NS) [Table 5]. Causes of acute graft dysfunction included UTI with severe sepsis (n = 2, induction group), biopsy-proven acute rejection (n = 3, induction group and n = 2, no induction group), and acute tubular necrosis (n=1, induction group). Rejections consisted of one antibody-mediated rejection in each group, the rest being borderline cellular rejections in both groups. All the rejections which occurred in the early post-transplant period in either group were sensitive to treatment with recovery of normal renal function in all. Mean creatinine at discharge was 1.042 ± 0.44 in the induction group and 1.064 ± 0.29 in the induction group (P = 0.238 NS).
Table 5: Comparison of the occurrence and causes of acute graft dysfunction between the two groups.

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Late graft dysfunction (occurring more than 3 months after transplant) was seen in 28% patients in NO IND and 20% patients in IND (P = 0.349). Comparison of events causing late graft dysfunction in two groups is shown in [Table 6]. In both groups, borderline cellular rejection formed the most common type of rejection followed by acute cellular rejection. Acute antibody-mediated rejection occurred in one patient in NO IND, and mixed cellular and antibody-mediated rejection was seen in one patient in IND. Four percent of patients in NO IND had more than one rejection episode compared to none in IND (P = 0.153 NS). Rejections were treatment sensitive in both groups with only one case of treatment-resistant rejection in each group.
Table 6: Causes of late graft dysfunction in the two groups.

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Infection episodes after discharge from the hospital occurred in 24% of patients in NO IND and 40% of patients in the IND group [Table 7]. UTI was responsible for the majority of episodes in both groups. Majority of the patients in NO IND (83.3%) had only a single episode of UTI with no one having recurrent episodes and only one having a relapsing infection. On the other hand, nearly 47% patients in IND had either a recurrent or relapsing UTI as depicted in [Table 8]. Klebsiella species were responsible for the majority of the episodes in both groups (nearly 50%). While 70% of patients in the induction group had UTIs severe enough to require hospitalization with almost 20% needing multiple admissions, only 33% of patients required hospitalization for UTI in the no induction group with none of them requiring multiple admissions.
Table 7: Incidence and nature of infections in the two groups

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Table 8: The incidence and frequency of urinary tract infections in the two groups.

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The occurrence and severity of LRTI did not differ between the groups. Patients in both groups required hospitalization for severe sepsis caused by LRTI. Mortality rates for LRTI were also high in both groups (causing death in all except in one patient in no induction group). While CMV infection affected 6% of patients in the induction group, it affected none in the no induction group (P = 0.07). The occurrence of BKV infection did not differ between the groups. Overall bacterial infections constituted the majority of infections in both groups (50% NO IND and 65% IND). However fungal and mycobacterial infections were seen only in the group which received induction therapy. Also more hospitalization requiring infections were seen in the induction group (76%) compared to no induction group (64%) (P = 0.11). While one patient (2%) developed Hodgkin’s lymphoma at the end of 1.5 years in the induction group, none of the patients developed malignancy in the no induction group. The occurrence of new onset diabetes after transplantation did not differ between the two groups (16% IND vs. 20% NO IND) (P = 0.603).

Overall graft and patient survival at the end of the study period did not reveal any statistically significant difference between the two groups [Figure 1]. One case of graft loss occurred in each group, both due to rejection and three deaths (with functioning graft) in the induction group compared to two in no induction group. Mean serum creatinine at the end of six months, one year and 1.5 years was comparable [Table 9].Various risk factors were analyzed independently to identify an association with the occurrence of rejection (>3 months) after transplant. These included recipient age, donor age, relationship with donor, degree of HLA mismatch, and acute graft dysfunction or delayed graft function. The only risk factor which was found to be significantly associated with rejection causing late graft dysfunction was acute graft dysfunction in the early posttransplant period (P = 0.042 S).
Figure 1: Kaplan Meier analysis of patient survival.

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Table 9: The mean serum creatinine at the end of six months, one year and 1.5 years in the patients in two groups.

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   Discussion Top


This study was a prospective observational study in which the risks and benefits associated with the use of induction therapy in low-risk renal allograft recipients were analyzed. The occurrence of infections, which has been considered the main downside to the use of induction therapy, was compared between the two groups of low-risk renal transplant recipients - one that received induction and another that did not. Overall the incidence and severity of infections was more in IND than NO IND. In the early post-transplant period, the most common infection was UTI which affected 34% of patients in IND compared to 22% in NO IND. Moreover, in two (12%) patients affected with UTI in induction group, UTI was severe enough to cause acute graft dysfunction, while none of the patients in the no induction group developed acute graft dysfunction as a result of UTI. In the late posttransplant period, the incidence of infectious complications was 40% in IND and 24% in NO IND (P = 0.253 NS). UTI still remained the most common infection in both groups. Forty-six percent of patients had relapsing or recurrent UTIs in IND compared to only 16% in NO IND (P = 0.094). While only 33% of patients required hospitalization for UTI in the no induction group, more than 70% required hospitalization for UTI in the induction group with nearly 20% needing multiple hospitalizations.

Fungal and mycobacterial infections were seen only in the group which was given induction, incidences being 4% and 2% respecttively. Trend toward increased incidence of CMV infection (6%) was seen in the induction group in which three cases were identified compared to none in NO IND (P = 0.079). The occurrence of BKV infection in urine or blood did not differ significantly between the two groups and none of the patients developed BKV nephropathy. Though the overall outcome of infections in terms of cure rate and mortality was similar in the two groups, the morbidity conferred by the increased incidence and severity of infections in the induction group was significantly higher.

Various studies have been conducted previously to study the effect of induction therapy on the incidence of infectious complications in renal allograft recipients. In the study by Brennan et al[10] in which short courses of ATG and basiliximab were compared in patients at high risk for acute rejection who received a renal transplant from a deceased donor, incidence of infection was 85.8% in the ATG group and 75.2% in the basiliximab group. Both groups had a greater frequency of UTIs (39.0% in ATG group, vs. 27.0% in the basiliximab group) and non-CMV viral infections (21.3% vs. 11.7%) than seen in our study (30% and 2%). The incidence of CMV disease was 7.8% in the ATG group compared to 6% in the induction group in our study. Fungal infections occurred at a rate of 14% in both groups in this study. The higher incidence of infections in this study by Brennan can be explained by the higher dose and duration of ATG use. In yet another study undertaken by Charpentier et al[11] to assess the safety of ATG induction, it was seen that in the groups receiving ATG induction, there was a significantly greater incidence of leukopenia, thrombocytopenia, serum sickness, fever, and CMV infection compared to the Tac triple group which did not receive induction. Only 58.4% of patients receiving Tac triple recorded infection events compared with 67.7% in the ATG-Tac group and 75.0% in the ATG-CsA group (P = 0.003). In yet another landmark study by Mourad et al[12] which compared safety of induction treatment with ATG followed by tacrolimus therapy with immediate tacrolimus therapy found statistically significant differences in the incidence of adverse events for CMV infection (induction, 32.5% vs. non induction, 19.0%, P = 0.009), leukopenia (37.3% vs. 9.5%, P <0.001), fever (25.2% vs. 10.1%, P = 0.001), herpes simplex (17.9% vs. 5.7%, P = 0.001), and thrombocytopenia (11.3% vs. 3.2%, P = 0.007) between the two groups. Taken together, however, in all these studies including our own study those patients who were given induction therapy showed a higher incidence of various infections as compared to our no induction group.

In our study, we found that there was no statistically significant difference (P = 0.337) in the incidence of acute graft dysfunction (due to rejection and other causes) between the induction and no induction groups. All rejections in both groups were sensitive to treatment. Mean creatinine at discharge from the hospital was similar between the two groups. Late graft dysfunction (>3 months after transplant) occurred in 20% of patients in the induction group compared to 28% patients in no induction group (P = 0.349 NS). Rejection was the main cause of late graft dysfunction in both groups. However, the incidence of rejection did not differ significantly between the groups (16% IND vs. 20% NO IND, P = 0.603 NS). Although two patients (4%) in the no induction group experienced more than one rejection episode as compared to none in the induction group, this was not found to be statistically significant (P = 0.153). Treatment sensitivity of rejections was also similar in the two groups with an equal percentage of resistant rejections (10% in the induction group and 12.5% in no induction group) seen in the two groups (P = 0.652).

Very few studies have examined the effect of IL2RA or ATG induction versus no induction in low-risk renal transplant recipients, and the available evidence is mostly retrospective. Although the rejection rates are slightly higher in our study, the lack of difference in terms of incidence or severity of rejections between the induction and no induction groups is similar to what was seen in these trials. In the study by Gralla and Wiseman[13] which was a retrospective analysis using US registry data comparing patients who received initial immunosuppression consisting of tacrolimus, MPA, and prednisone with or without IL2RA induction the one-year acute rejection rate was 11.6% with IL2RA induction versus 13.0% with no induction. In the retrospective study, by Willoughby et al[14] which compared outcomes between kidney transplant patients who received rATG, basiliximab, or no induction the six-month acute rejection rates were <15% in all groups, with no impact on graft or patient survival. Retrospective analysis by Tanriover et al[15] of US registry data from patients who underwent living donor transplantation between 2000 and 2012 and who received tacrolimus, MPA, and steroids also showed that IL2RA induction was not associated with any improvement in outcomes compared with no induction (acute rejection at 1 year 11.7% vs. 12.4% (P = 0.55 NS); similar graft survival at five years (P = 0.92). Contrary to this, in the study by Mourad et al,[12] at 12 months, biopsy-confirmed acute rejections were lower in the induction group as compared to noninduction (P = 0.001). This can be however explained by the fact that his study included patients undergoing cadaveric kidney allograft transplantation or retransplantation also, both of which comprise the high immunological risk groups. Patient and graft survival at 12 months was similar in both treatment groups (97.4% vs. 96.8% and 92.1% vs. 91.1%, respectively) in this study also.

In our part of the world, ours is the first of its kind which has tried to assess the use of induction therapy in low-risk renal transplant recipients on standard modern triple-drug immunosuppressive therapy consisting of tacrolimus, MPA and steroids. While the use of induction therapy in this group of patients did not alter the incidence of rejections, graft, and patient survival, it certainly increased the risk and frequency of infections leading to an appreciable increase in morbidity with increased rates of hospitalization and hence an increased health expenditure posttransplant. In a country like India where financial and physical resources are limited this could have serious implications. However, given the limited number of patients included in our study, it may not be prudent to over generalize the conclusion of our study pointing to no beneficial outcome of induction therapy in low risk renal transplant recipients. Hence larger studies are required to further confirm our findings.

Conflict of interest: None declared.



 
   References Top

1.
Health Resources and Services Administration, Department of Health and Human Services: 2002 Annual Report. In: edited, UNOS pp 278. Table 5.6a.  Back to cited text no. 1
    
2.
Tullius SG, Volk HD, Neuhaus P. Transplantation of organs from marginal donors. Transplantation 2001;72:1341-9.  Back to cited text no. 2
    
3.
Martins PN, Pratschke J, Pascher A. Age and immune response in organ transplantation. Transplantation 2005;79:127-32.  Back to cited text no. 3
    
4.
Szczech LA, Berlin JA, Aradhye S, Grossman RA, Feldman HI. Effect of anti-lymphocyte induction therapy on renal allograft survival: A meta-analysis. J Am Soc Nephrol 1997;8: 1771-7.  Back to cited text no. 4
    
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Knight RJ, Kerman RH, Schoenberg L, et al. The selective use of basiliximab versus thymoglobulin in combination with sirolimus for cadaveric renal transplant recipients at low risk versus high risk for delayed graft function. Transplantation 2004;78:904-10.  Back to cited text no. 5
    
6.
Kidney Disease: Improving Global Outcomes (KDIGO) Transplant Work Group. KDIGO clinical practice guideline for the care of kidney transplant recipients. Am J Transplant 2009;9Suppl 3:S1-155.  Back to cited text no. 6
    
7.
OPTN/SRTR Annual Report 2012; 2012. Available from: http://srtr.transplant.hrsa.gov/ annual_reports/2012/pdf/2012_SRTR_ADR.p df. [Last accessed on 2016 Jun 15].  Back to cited text no. 7
    
8.
Ekberg H, Tedesco-Silva H, Demirbas A, et al. Reduced exposure to calcineurin inhibitors in renal transplantation. N Engl J Med 2007;357: 2562-75.  Back to cited text no. 8
    
9.
Meier-Kriesche HU, Schold JD, Srinivas TR, Kaplan B. Lack of improvement in renal allograft survival despite a marked decrease in acute rejection rates over the most recent era. Am J Transplant 2004;4:378-83.  Back to cited text no. 9
    
10.
Brennan DC, Daller JA, Lake KD, Cibrik D, DelCastillo D; ThymoglobulinInduction Study Group. Rabbit antithymocyte globulin versus basiliximab in renal transplantation. N Engl J Med 2006;355:1967-77.  Back to cited text no. 10
    
11.
Charpentier B, Rostaing L, Berthoux F, et al. A three-arm study comparing immediate tacrolimus therapy with antithymocyte globulin induction therapy followed by tacrolimus or cyclosporine A in adult renal transplant recipients. Transplantation 2003;75:844-51.  Back to cited text no. 11
    
12.
Mourad G, Garrigue V, Squifflet JP, et al. Induction versus noninduction in renal transplant recipients with tacrolimus-based immunosuppression. Transplantation 2001;72: 1050-5.  Back to cited text no. 12
    
13.
Gralla J, Wiseman AC. The impact of IL2ra induction therapy in kidney transplantation using tacrolimus- and mycophenolate-based immunosuppression. Transplantation 2010;90: 639-44.  Back to cited text no. 13
    
14.
Willoughby LM, Schnitzler MA, Brennan DC, et al. Early outcomes of thymoglobulin and basiliximab induction in kidney transplantation: Application of statistical approaches to reduce bias in observational comparisons. Transplantation 2009;87:1520-9.  Back to cited text no. 14
    
15.
Tanriover B, Zhang S, MacConmara M, et al. Induction therapies in live donor kidney transplantation on tacrolimus and mycophenolate with or without steroid maintenance. Clin J Am Soc Nephrol 2015;10:1041-9.  Back to cited text no. 15
    

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Correspondence Address:
Sabina Yusuf
Department of Nephrology, Sir Ganga Ram Hospital, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1319-2442.344746

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  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8], [Table 9]



 

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