Indian Journal of Transplantation

EXPERT OPINION
Year
: 2022  |  Volume : 16  |  Issue : 2  |  Page : 145--154

Clinical perspectives towards improving risk stratification strategy for renal transplantation outcomes in Indian patients


Vijay Kher1, Vivek B Kute2, Sarbeswar Sahariah3, Deepak S Ray4, Dinesh Khullar5, Sandeep Guleria6, Shyam Bansal1, Sishir Gang7, Anil Kumar Bhalla8, Jai Prakash9, Abi Abraham10, Sunil Shroff11, Madan M Bahadur12, Pratik Das4, Urmila Anandh13, Arpita Ray Chaudhury14, Manoj Singhal15, Jatin Kothari16, Sree Bhushan Raju17, Dilip Kumar Pahari18, G Vishwanath Siddini19, G Sudhakar19, Santosh Varughese20, Tarun K Saha21,  
1 Department of Nephrology, Medanta Institute of Kidney and Urology, Medanta-The Medicity, Gurugram, Haryana, India
2 Department of Nephrology, Institute of Kidney Diseases and Research Centre, Dr. HL Trivedi Institute of Transplantation Sciences, Ahmedabad, Gujarat, India
3 Department of Transplantation Surgery, KIMS Hospital, Hyderabad, India
4 Department of Nephrology, Rabindranath Tagore International Institute of Cardiac Sciences, Kolkata, West Bengal, India
5 Department of Nephrology, Max Saket Complex, Max Super Speciality Hospital, Saket, Delhi, India
6 Department of Transplantation Surgery, Indraprastha Apollo Hospital, Varanasi, Uttar Pradesh, India
7 Department of Nephrology, Muljibhai Patel Urological Hospital, Nadiad, Gujarat, India
8 Department of Nephrology, Sir Ganga Ram Hospital, New Delhi, India
9 Department of Nephrology, Banaras Hindu University, Varanasi, Uttar Pradesh, India
10 Department of Nephrology, VPS Lakeshore Hospital, Kochi, Kerala, India
11 Managing Trustee, MOHAN Foundation, Chennai, Tamil Nadu, India
12 Department of Nephrology, Jaslok Hospital and Research Centre, Mumbai, Maharastra, India
13 Department of Nephrology, Yashoda Hospitals, Secunderabad, Telangana, India
14 Department of Nephrology, Institute of Post-Graduate Medical Education and Research, Kolkata, West Bengal, India
15 Department of Nephrology, Max Super Specialty Hospital, Vaishali, Ghaziabad, India
16 Department of Nephrology, Nanavati Max Hospital, Mumbai, Maharastra, India
17 Department of Nephrology, Nizam's Institute of Medical Sciences, Hyderabad, Telangana, India
18 Department of Nephrology, Medica Super Specialty Hospital, Kolkata, West Bengal, India
19 Department of Nephrology, Manipal Hospital, Bengaluru, Karnataka, India
20 Department of Nephrology, Christian Medical College, Vellore, Tamil Nadu, India
21 Department of Nephrology, Apollo Hospital, Secunderabad, Telangana, India

Correspondence Address:
Dr. Vivek B Kute
IKDRC-ITS, Ahmedabad, Gujarat
India

Abstract

Graft loss and rejections (acute/chronic) continue to remain important concerns in long-term outcomes in kidney transplant despite newer immunosuppressive regimens and increased use of induction agents. Global guidelines identify the risk factors and suggest a framework for management of patients at different risk levels for rejection; however, these are better applicable to deceased donor transplants. Their applicability in Indian scenario (predominantly live donor program) could be a matter of debate. Therefore, a panel of experts discussed the current clinical practice and adaptability of global recommendations to Indian settings. They also took a survey to define risk factors in kidney transplants and provide direction toward evidence- and clinical experience-based risk stratification for donor/recipient and transplant-related characteristics, with a focus on living donor transplantations. Several recipient related factors (dialysis, comorbidities, and age, donor-specific antibodies [DSAs]), donor-related factors (age, body mass index, type – living or deceased) and transplantation related factors (cold ischemia time [CIT], number of transplantations) were assessed. The experts suggested that immunological conflict should be avoided by performing cytotoxic cross match, flow cross match in all patients and DSA-(single antigen bead) whenever considered clinically relevant. HLA mismatches, presence of DSA, along with donor/recipient age, CIT, etc., were associated with increased risk of rejection. Furthermore, the panel agreed that the risk of rejection in living donor transplant is not dissimilar to deceased donor recipients. The experts also suggested that induction immunosuppression could be individualized based on the risk stratification.



How to cite this article:
Kher V, Kute VB, Sahariah S, Ray DS, Khullar D, Guleria S, Bansal S, Gang S, Bhalla AK, Prakash J, Abraham A, Shroff S, Bahadur MM, Das P, Anandh U, Chaudhury AR, Singhal M, Kothari J, Raju SB, Pahari DK, Siddini G V, Sudhakar G, Varughese S, Saha TK. Clinical perspectives towards improving risk stratification strategy for renal transplantation outcomes in Indian patients.Indian J Transplant 2022;16:145-154


How to cite this URL:
Kher V, Kute VB, Sahariah S, Ray DS, Khullar D, Guleria S, Bansal S, Gang S, Bhalla AK, Prakash J, Abraham A, Shroff S, Bahadur MM, Das P, Anandh U, Chaudhury AR, Singhal M, Kothari J, Raju SB, Pahari DK, Siddini G V, Sudhakar G, Varughese S, Saha TK. Clinical perspectives towards improving risk stratification strategy for renal transplantation outcomes in Indian patients. Indian J Transplant [serial online] 2022 [cited 2022 Oct 3 ];16:145-154
Available from: https://www.ijtonline.in/text.asp?2022/16/2/145/349329


Full Text



 Introduction



Acute cellular rejection (ACR) and acute and chronic antibody-mediated rejection (ABMR) are important determinants of long-term outcome in kidney transplant.[1] Although the rates of ACR and acute ABMR have come down significantly with newer immunosuppressive regimens, increased use of induction agents and better immunological evaluation prior to transplant,[2],[3] chronic ABMR remains the most common cause of death censored graft loss after first year of transplant.[4] Several factors such as type of donor (living or deceased), duration of dialysis, recipient characteristics influence graft outcome.

The type of donor organ is an important factor predicting the graft survival. While only ~40% of renal allografts in the US are obtained from living donors,[5] in Indian transplant centers, the proportion is >80%.[6] Living donor transplantations reduce the delays associated with long waiting times for deceased donors, while providing the advantage of an elective procedure, thereby reducing the time on dialysis.[2],[6],[7] Living donor transplantations are also perceived to have a relatively lower immunological risk compared to deceased donor transplantation.[8],[9] However, contrary to this perception among nephrologists, the incidence of acute rejection rates are comparable for living and deceased donor recipients.[10]

The Kidney Disease: Improving Global Outcomes (KDIGO) 2009 guidelines, while listing risk factors in renal transplantation and providing a framework for therapies to be used for patients at different risk levels, the application of these guidelines globally are lacking.[9],[11] In addition, the guideline has not been updated since 2009.[12],[13] The utility of KDIGO guidelines in Indian population also needs to be assessed, as the criteria used for risk assessment in the guidelines were based on data from studies conducted in the Caucasian population, and the guidelines were established in the cyclosporine era while the immunosuppression today is mostly tacrolimus based. Revised guidelines are awaited and expected to be available soon.

There is dearth of publication on long-term outcome data of kidney transplant recipients in India. The study from AIIMS has reported 10-year graft survival in 30% of the cohort –most of whom were below 30 years of age, had chronic glomerulonephritis as a cause of end-stage kidney disease and were on cyclosporine and azathioprine. This contrasts with the state of practice in the western world as well as in India.[14] Thus an expert forum was identified to revisit the guidelines and adapt the immunosuppressive regimens tailored toward Indian patients requiring renal transplantation. This is especially important as induction therapy is largely applied in both deceased and living donor transplantations in India.[15],[16] Taken together, there is a need for a comprehensive risk stratification strategy[17] to ensure the use of precise immunosuppressive regimens in Indian clinical practice.

In this article, we aim to define risk factors in kidney transplants and provide direction toward evidence- and clinical experience- based risk stratification for donor/recipient and transplant-related characteristics, with a focus on living donor transplantations.

 Defining Risk in Renal Transplantation: Donor, Recipient, Transplant-Related Factors



Importance of risk stratification in renal transplantation

Risk stratification based on donor, recipient, and transplant-related factors is an important method to select the appropriate immunosuppression regimen for a patient; it can help strike a balance between avoiding acute rejection and excessive immunosuppression (reducing infection risk) and reduce other adverse events such as new-onset diabetes mellitus, dyslipidemia, and nephrotoxicity. Risk stratification is also the key to individualized therapy following kidney transplantation.[18],[19] [Table 1] provides an overview of the impact of various donor, recipient, and transplant-related risk factors on renal transplantation outcomes. Based on a questionnaire-based survey, followed by discussions on the survey results, Indian experts in the field of renal transplantation unanimously agreed on the need for risk stratification criteria for kidney transplantations which will be applicable to India.{Table 1}

Factors influencing the outcomes of renal transplantation

The outcome of renal transplantation depends on various clinical and immunologic risk factors. Identification and management of such factors may improve the overall outcomes of the transplantation procedure.

Clinical risk factors (donor/recipients): Age, gender, body mass index, race, viral infections such as cytomegalovirus (CMV), BK virus and human immunodeficiency virus (HIV), immunosuppressive drug noncompliance.Immunological risk factors: Degree of human leukocyte antigen (HLA) mismatch, pre-transplant donor-specific antibodies (DSAs), panel reactive antibodies (PRAs) mostly in deceased donation, alloantigen specific memory B cells, presence of cross reactive and donor-specific memory T cells and presence of antibodies against non-HLA antigens like auto antigens or MHC class 1-related chain A (MICA). Pre-transplant levels of soluble CD30 (sCD30) has also been studied as a risk factor; however, there is no compelling evidence for it.

Although the independent risk factors have been discussed before, a holistic risk stratification scoring system is needed to understand the effect of these on the outcomes of renal transplant. Owing to several challenges in utilizing KDIGO 2009 guideline in the Indian transplant settings, there are differences in perspective regarding its implementation. KDIGO definition of high-risk factors for acute rejection has been described in the Supplementary Section.

 Methodology of Developing Questionnaire and Conduct of Survey



To discuss the current clinical practice in renal transplantation and assess the concordance of Indian practice with Western guidelines and recommendations, 3 expert committee meetings were conducted between April 2017 and February 2018. A total of 29 subject matter experts from across India participated in these meetings. At the end of these meetings, a questionnaire was prepared based on experts' clinical experience in kidney transplantation centers across India, as well as evidence from randomized clinical studies, and relevant prospective and retrospective studies.

Topics discussed by experts

Question 1: Do you consider younger recipient age as a risk factor for acute rejection?Question 2: Do you consider recipients of Asian ethnicity to have a higher risk for acute rejection?Question 3: Do you consider HLA mismatches as a risk factor for acute rejection? If so, how important is it and do you quantify it?Question 4: Do you consider low DSA titers as a risk factor for rejection?Question 5: Do you consider PRA positive as a risk factor for acute rejection?Question 6: Do you consider deceased donor transplant riskier than living donor transplants if cold ischemia time is not very high?Question 7: Do you consider older donor as a risk factor for acute rejection?Question 8: Do you consider transplants with high risk for delayed graft function (DGF) as high risk for acute rejection?Question 9: Should induction agents be used in high-risk transplants?Question 10: Are KDIGO 2009 guidelines applicable to the Indian setting?

The risk stratification scoring system discussed by our expert committee is presented in [Figure 1].[20],[21],[22],[23],[24]{Figure 1}

 Results from the Survey and its Comparison with the Rest of the World Guidelines



Donor-related factors

Deceased donor

Renal transplantation from deceased donor is considered to be an alternative to matched live donor transplants.[25],[26] Having a deceased donor was thought to be an independent risk factor by 10%–12% of the experts. In line with the reports available in literature, the experts further suggested that as an individual factor type of donor (living or deceased) may not be a significant risk; however, DGF which is much higher in the deceased donor may pose this type of transplantation at a higher risk of rejection. In cases of deceased donations, the cause of death does not have substantial impact on renal transplant outcomes if blood circulation is maintained at the time of donation. Hypertension, diabetes mellitus, and other comorbidities may be important considerations as they may alter the blood supply to the kidney. An exception to this is cases of death due to sepsis, where higher chances of acute rejection have been noted.

The experts stated that in cases of donation after cardiac death (DCD), there is a higher risk of DGF which provokes the formation of anti-HLA antibodies. This increases the risk of rejection. Similar reports are available in literature that indicate that DCD kidneys have higher rates of primary nonfunction,[27] DGF, and rejection,[28],[29] than donation after brain death (DBD). Around 4.17% expert in the survey, considered this to be a very high risk for rejection. Though in India, live donor transplants are most performed, rate of graft and patient survival rate of transplant from deceased donor in a study conducted at tertiary care Centre in India was equally satisfactory. The authors suggested that there is a need to sensitize and expand the rate of deceased transplantation to upsurge the donor pool.[26]

Live donor

Live donor transplants in the western world have gained significant importance in recent times due to organ shortage. Continued research and growth in medical science has enabled successful donation from unrelated individuals and even individuals with ABO-incompatibilities.[30] Live donor transplants were considered safe by the group of participating experts, irrespective of whether the donor is an immediate family member or not; with the only exception being spousal donor transplant. They form the largest group of living kidney donors in India and are at a higher risk because of HLA mismatch and antigen sensitization and more so when the donor is the husband.

Living donor who is not an immediate family member may impose some risk. Conflicting results are evidenced in literature; a few studies indicated that grafts received from live related donors and live unrelated donors had comparable patient and graft survival outcomes,[31] however, poorer outcomes with live unrelated donor transplants compared to live related donor transplants have been also reported.[32]

Other donor characteristics

Donor age and body mass index (BMI) do not impose additional risk in cases of renal transplantation. A study by Sekito et al. demonstrated that kidney grafts from elderly living donors (≥60 years) were not associated with a decline in renal function, and their pathologic findings were comparable with those of young donors for up to 2 years' post-transplantation.[33] Preimplantation renal histology in elderly donors may be helpful for predicting renal outcomes.[34] Obese donors do not change the graft outcomes, however, it is advisable to not choose such individuals as donors as the risk is more for the donor than the recipient.[35],[36] Nevertheless, to increase the donor pool, obese individuals are now being considered both in case of living and deceased donors.[37] If selected, when the donor work-up is done, underlying risk of obesity related kidney disease should be ruled out. A study by Alhamad et al. suggested that donor BMI 30 to 35 kg/m2, does not impact kidney allograft failure.[38] CMV is regarded as the most common viral infection in adults after renal transplantation and its rate is significantly more frequent in older recipients. Other risk factors for CMV include positive donor serostatus, T-cell depleting induction, and other co-infections.[39] Risk associated with D+/R-; D+/R+; and D-/R + as well as D-/R-; D+/R-serostatus is different and development of CMV infection in the recipient not only impacts the mortality but increases the risk of rejection. factors.[40],[41] Hepatitis C-infected (HCV+) deceased donors were underutilized for renal transplantation before the introduction of direct-acting antiviral agents.[42],[43],[44] With high cure rates with newer therapies, a donor with HCV positive status is also considered for transplantation in current times.[45] In a use of HCV+ donor and the HCV-uninfected recipients, we might be transferring the risk of infection and strategies to prevent HCV infection in HCV − recipients should be followed stringently.[46]

HIV in the recipient may be a risk factor for acute rejection, a fact contrary to a general opinion.[47] A multicenter case–control study compared outcome of renal transplant in HIV-positive (n = 20) patients with those who were HIV-negative (n = 40). Although there was no difference in the survival rate, HIV-positive recipients demonstrated lower incidence of immediate renal function and more acute rejection.[48] However, another study from France suggested that post-transplant infections and not the HIV status, have detrimental effects on patient and graft survival.[49] Locke et al. opined that proper donor selection and transplant recipient management, including the avoidance of prolonged cold ischemic time, use of living donors, and determination of optimal immunosuppression dosing before transplant, are key factors that determine the long-term graft survival HIV-positive patients.[50]

Recipient-related factors

Dialysis history

A recipient having dialysis vintage of <1 year before transplantation is a favorable situation and does not pose any risk for rejection in renal transplantation. The risk may increase slightly as the dialysis vintage increases. While a patient with 3–5 years of dialysis may impose a moderate risk, having a dialysis history of >5 years is a significant risk factor for rejection due to sensitization as perceived by more than 30% experts who participated in the survey.[51]

This is particularly relevant in the patients who remain on the deceased donation waiting list for a long time. On the other hand, living donation happens usually within a year of starting dialysis. Few experts believe that the duration of dialysis as a risk is only valid if sensitization has happened; the chances of sensitization are high in patients with long-term dialysis. If they have not received blood transfusions, the risk is comparable with other patients. This is in line with the results of a case-control study conducted by Masaki et al. which compared graft and patient survivals between the recipients who are on dialysis for >20 years and those with <20 years of dialysis vintage. The outcomes were comparable in both groups.[52]

The long-term outcomes also do not vary based on the type of dialysis; graft survival being similar in both the patients undergoing peritoneal dialysis and hemodialysis. However, DGF and rejection rate may be higher in patients undergoing hemodialysis.[53]

Previous transplantation

Advances in the understanding of renal transplantation techniques and outcomes have made renal re-transplantation possible, but the outcome of third and fourth transplant remains controversial. Han et al. established that graft survival of second renal transplantation was not significantly different from that of first renal transplantation.[54] The experts agreed that the first transplantation in isolation is safe, and number of transplantations only increase the risk of rejection if the recipient has received more than 2 transplantations.

A retrospective analysis assessed outcomes of patients who underwent third and fourth transplantation in 16 patients and showed that cases of third kidney transplantation showed satisfactory patient and graft survival. However, in cases of fourth transplant, the graft survival was on 33.3% at the end of 1 year.[55] It is interesting to note that quality of the donor is an important determinant for graft survival in re-transplantation cases and living donor re-transplants are associated with similar outcomes as with the first transplant.[56] Our survey results also indicated that third or fourth transplantation are associated with significant risk as suggested by around 30% of the experts.

Age and weight of the recipient

Although the survey categorized age as >60 years and ≤60 years, the experts believed that we cannot compare the risk of rejection between a 59-year-old and a 20-year-old recipient. Although both are <60 years of age; the immunologic and comorbid risk in these patients is different. Evidence suggests that recipient's age does not have a significant predictive value on outcomes of renal transplant.[57] However, experts suggest that the rejection rate varies with age and a pediatric patient has a different rejection rate than the adolescent and a person in his 30s or 40s. The rejection risk is low in older recipients. The significance of donor-recipient age difference as a prognostic indicator on short- and long-term graft and patient survival has also been investigated.[58],[59],[60] Although the transplantation is not contraindicated due to high donor-recipient age difference, it is notable that younger the recipient and older the donor, the rate of rejection is high.

A recipient with a BMI <25 kg/m2 is comparatively at a lower risk than a recipient with a BMI >35 kg/m2. A retrospective study conducted by Liese et al. also confirmed that increased recipient BMI at the time of renal transplantation is a prognosticator of adverse outcomes, including DGF.[61] A systematic review and meta-analysis exploring the correlation between recipient obesity and mortality, death-censored graft loss and DGF subsequent to kidney transplantation, concluded that even though there seems to be an increased possibility of DGF, obese transplant recipients have only a slightly higher risk of graft loss. They have similar graft survival when compared to recipients with normal BMI.[62] However, a significant mismatch in donor-recipient weight (donor<recipient) may be associated with a higher risk of death-censored graft loss in kidney transplantation.[63]

Donor specific antibodies

DSA has been recognized as a standard biomarker in predicting transplant outcomes, and its presence has been associated with a higher incidence of antibody-mediated rejection, graft dysfunction, and lower graft survival.[64] Patients with high titers of preformed DSAs (mean fluorescence intensity >1000) need desensitization prior to transplant to prevent acute antibody-mediated rejection.[65],[66] Around 13%–30% of formerly non-sensitized patients develop de novo DSAs, primarily targeted to donor HLA class 2 mismatches, after renal transplant.[67],[68],[69],[70],[71],[72],[73],[74] Non-HLA antibodies such as preformed hemagglutinin A and/or B antibody, MICA and angiotensin II type 1 receptor[75] can also cause antibody-mediated rejection and graft loss.[64]

Through HLA typing and identification of ABO blood types and titers, autologous HLA and non-HLA antibodies and complement dependent cytotoxicity (CDC) crossmatch techniques, identifying patients at higher risk of rejection is possible. All the participating experts agreed that presence of DSA increases the risk of rejection. The risk ranges from moderate to very high, on the other hand, the absence of DSA is important to prevent rejection. Interestingly, pretransplant DSA may recede immediately after transplantation in several patients without any clinical effect, whereas in others, even weak pretransplant DSA persist and result in severe consequences leading to rejection.[76],[77]

Transplant-related factors

The basis of selecting immunosuppressive therapy for living donor renal transplantation needs to be guided by comprehensive assessment of immunological risks for individual patients.

HLA and risk of rejection in renal transplant patients

Antibodies to HLA molecules, the polymorphic antigens that comprise an immunodominant alloreactive trigger for the immune response, are known to be associated with late graft loss, lower graft survival, poor transplant function, and proteinuria.[75],[76],[78] HLA class 1 antigens (A, B, and C) are expressed on all nucleated cells, whereas HLA class 2 antigens (DR, DQ, and DP) are normally confined to antigen-presenting cells (dendritic cells, B cells, and macrophages).[64] The formation of pretransplant HLA class I and II alloantibodies can be induced through exposures to blood transfusions, prior transplants, and pregnancy.[79]

Flow cytometric cross match increases the sensitivity of antibody detection and is useful when solid phase assays are not available or possible due to financial constraints. It helps to select patients who need to do solid phase assays (i.e., CDC negative, flow positive).[80] Solid phase immunoassays such as enzyme linked immunoassays and single antigen bead assays on the Luminex platform have significantly improved the precision of detecting antibodies. For stratification of risk in this survey, the HLA matching score was categorized into three different groups: <3, =3, and >3 [Figure 2]. Although a definite consensus was not achieved, the experts suggested that only assessing HLA mismatch is not sufficient; it is also important to consider at what locus the mismatch occurs. Secondly, the type of mismatch is also important, for example, determining whether it is a DR mismatch and whether an epitope matching should also be considered.{Figure 2}

PRA and risk of rejection in renal transplant patients

Recipients who have previously formed DSAs (anti-HLA antibodies) and non-HLA antibodies and/or a historical positive crossmatch by CDC and/or flow cytometry are cases with high risk of hyperacute or accelerated acute rejections.[81],[82] The estimation of PRA prior to transplantation forms the basis of deceased donor organ allocation and is an important step to identify sensitized patients. The present survey grouped PRAs as 0%–20%, 20%–40% and >40%; while most of the experts felt that having PRA in between 0–20% is a mild risk factor for acute rejection, 50% believed that 20%–40% PRA score was moderate to high risk and all the participating experts considered a score >40% as a high to extremely high risk for rejection [Figure 3]. PRA does not add value to risk stratification in living donor transplantation.{Figure 3}

Cold ischemia time and risk of rejection in renal transplant patients

Increased cold ischemia time (CIT) is the most important risk factor for DGF and suboptimal graft outcomes after kidney transplant.[83] Delayed graft function in turn is associated with higher rejection rates and worse outcomes in renal transplant patients.[84],[85] Immunological investigations before deceased donor transplant leads to prolonged CIT and delays the process especially in highly sensitized patients and patients receiving kidney from marginal donors.[86],[87] Hansson et al. established that the risk of graft loss increased, with a CIT cutoff of ≥14 h as compared with CIT <14 h.[83] Another study stated that CIT >20 h is a risk factor for DGF.[88] In the present survey, we used a cut-off of 24 h and all the experts agreed that a CIT of <24 h is an important factor in decreasing the risk of rejection.

 Summary of Clinical Insights



Risk evaluation strategies should consider recipient related factors (dialysis, comorbidities, and age), donor related factors (age, BMI, type – living or deceased) and other factors (cold ischemia time, mismatch, DSA)Immunological conflict should be avoided by performing cytotoxic cross match, flow cross match and DSA (if possible)HLA mismatches, presence of DSA, and DGF, along with donor/recipient age, CIT etc., are associated with increased risk of rejectionThe risk of rejection in living donor transplant is similar to deceased donor recipients.

 Risk Stratification Strategy



In an economically diverse country like India, risk stratification strategy should consider whether a test is absolutely necessary for stratifying riskPrecision tests should be done only where there are doubts regarding risk stratification

 Conclusion



There is a long waiting list of patients requiring deceased donor transplantation across India. Applicability of KDIGO guidelines and risk stratification in renal transplantation has been a challenge in Indian setting given the country's socio-economic status, limitations in physician and patient awareness of the disease state and resource availability. Therefore, adaptation/modification of the KDIGO guidelines in Indian settings is necessary. Based on risk stratification strategy, tailored immunosuppression regimens can be selected to avoid the risk of acute rejection. The use of induction therapy for appropriate patient risk profile can be corroborated with the current clinical practice. Induction immunosuppression could be tailored based on the risk stratification (considering demographic factors of recipients as well as donor, immunological characteristics of recipient and transplant-related factors). Potent induction agent may help in reducing both incidence and severity of acute rejections after renal transplantation with good safety profile.

Financial support and sponsorship

Medical writing and open access-related charges were paid for by Sanofi India. The authors received no honoraria from Sanofi directly or indirectly related to the development of this publication.

Conflicts of interest

There are no conflicts of interest.

 Supplementary Section



KDIGO definition of highrisk factors for acute rejection

The number of HLA mismatches (A)Younger recipient age (B)Older donor age (B)African American ethnicity (in the United States) (B)Panel Reactive Antibody (PRA) >0% (B)Presence of a donor-specific antibody (DSA) (B)Blood group incompatibility (B)Delayed onset of graft function (B)Cold ischemia time >24 hours (C)

(where A is the universal agreement, B is the majority agreement and C is a single study)

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