Journal of Clinical and Experimental Transplantation
Open Access

Immunosuppression; Kidney transplantation; Immune system

Introduction

For kidney transplant patients, the transplant clinician can tailor a variety of immunosuppressive regimens to each patient’s specific requirements. Individualization based on specific patient profiles is now more feasible than ever before thanks to the inclusion of a variety of induction therapies, calcineurin inhibitors (CNIs), antiproliferative therapy (mycophenolic acid), and mammalian target of rapamycin (mTOR) inhibitors in the immunosuppressive arsenal [1]. The patient’s immunological risk status is the most important factor in determining a treatment plan, and immunosuppression should be tailored to the risk of graft rejection unless there are clear risk factors for drug-specific side effects. However, despite the fact that a patient’s risk status may be affected by a variety of factors, it is generally agreed that only the number of human leukocyte antigen (HLA) mismatches raises risk, and the relative importance of other variables frequently remains ambiguous [2]. Different entry criteria have been used in recent clinical trials that selectively recruited “high risk” patients

Consistently, only sensitization based on panel reactive antibodies (PRA) has been included, and HLA mismatch has not been. Luminex technology’s development of single antigen testing for donor specific antibodies (DSA) has also significantly improved risk assessment wherever it is available [3]. In order to assist clinicians in planning the most effective immunosuppressive regimen for individual recipients, this article takes into consideration the contributions made by recipient, donor, and transplant factors to the immunological risk status of kidney transplant patients at the time of transplant [4]. Since the middle of the 1990s, the rate of acute rejection following kidney transplantation has decreased significantly, stabilizing between 10% and 25% one year after transplantation, depending on the level of immunological risk. When compared to rejection-free transplants, acute rejection raises the risk of death-censored graft survival by more than 70%, according to a large US registry analysis from 2004 to 2007. However, this obscures the many distinct effects of various forms of acute rejection. The majority of episodes are mild cellular reactions (Banff grade I or IIA) that may have little or no effect on the results of the transplant. Midway through the 2000s, two large registry analyses revealed that subsequent graft survival is unaffected in patients whose graft function recovers after rejection (for example, by N85% compared to baseline). Instead, more severe episodes of cellular rejection without recovery of near-baseline function and late acute rejection (after month 3) have the greatest impact on graft survival [5].

Method

Regarding antibody-mediated rejection (AMR), which is highly predictive of kidney graft loss, a completely different picture emerges. AMR, or mixed AMR/cellular rejection, was found to be present in 75% of biopsies from 56 patients who went on to experience graft failure. Even subclinical AMR significantly lowers graft survival rates, and mixed rejection and late AMR (N 6 months post-transplant) are both difficult to treat and carry a particularly poor prognosis. It would appear that immunosuppressive regimens that come with a slightly higher risk of mild, reversible cellular rejection might be okay if they also have other advantages, like fewer complications in the long run.

Result

However, this trade-off is likely to be less successful in areas of high immunological risk. The significance of preventing AMR cannot be overstated for patients who are at increased risk for it. The scope of this article does not permit a comprehensive discussion of options for early immunosuppression as well as longer-term regimens based on the post-transplant course. Age-related changes in the T-cell effector immune response in older patients and lower adherence to the prescribed regimen are two factors that contribute to an increased risk of acute rejection in younger transplant recipients (see “Adherence to medication” below). a study by Tullius and colleagues Over 100,000 kidney transplant patients who were registered with the United Network for Organ Sharing (UNOS) registry from 1995 to 2008 found that acute rejection was significantly lower in the first year after the transplant for each successive decade of age above 39. Another large registry study, this one involving 27,707 transplant recipients in the United States from 1995 to 2002, found that recipients between the ages of 18 and 44 were 23% more likely than recipients between the ages of 44 and 59 to experience acute rejection by year 1.

Discussion

A younger age as a predictor of acute rejection risk has consistently been reported in other registry and large single-center analyses on the other hand, there is evidence that a graft from an older donor, possibly one with greater immunogenicity, increases rejection risk [6]. Tullius and colleagues’ extensive UNOS analysis revealed that donors over the age of 29 had higher acute rejection rates, but the difference was not statistically significant across all age groups. A well-established risk factor for graft loss following kidney transplantation is prolonged cold ischemia, with each additional hour of cold ischemia increasing the likelihood of graft failure[7]. Hypothermic preservation for 30 hours has been shown to have a 40% higher rate of graft loss than six hours. Although delayed graft function (DGF) is a well-established predictor of acute rejection, the impact of prolonged cold ischemia time on rejection risk can be directly attributed to exacerbated ischemia– perfusion injury and a higher risk of delayed graft function (DGF). When DGF was taken into consideration, significant single-center analyses have revealed small or non-significant increases in the risk of acute rejection with each additional hour of hypothermic preservation [8].

Conclusion

Long cold ischemia time had a small but significant effect (N 24 h versus 24 h:) according to a 2006 US registry analysis. adjusted risk ratio: 1.04, p = 0.03), but given that such long preservation times are now less common than they were in the past, this may not be relevant. Cold ischemia lasting longer than 8 hours has no effect on rejection rates for living-donor recipients. DGF appears to be a risk factor that is more directly relevant to the assessment of immunological rejection than ischemic time.

Whether or not machine perfusion reduces rejection risk is still an open question. Following randomization to either machine perfusion or cold storage, the outcomes of paired kidneys from the same donor were compared in a global study. Machine perfusion significantly reduced the likelihood of the primary DGF endpoint (odds ratio 0.57; 95% CI 0.36–0.88; p = 0.01), but acute rejection did not change by year 1. Another multicenter randomized trial of paired donor kidneys, this time from donors who had died of cardiac arrest, found that using either type of preservation resulted in the same amount of acute rejection at one year, despite a trend toward less rejection at three months with machine performance (7 percent versus 22 percent; p = 0.06). Overall, the literature does not support a clear link between the risk of rejection and the type of preservation system [104–106]. However, this intriguing finding has not been substantiated by other studies. A post-hoc analysis of three randomized trials found that donor kidneys with a shorter pump time had a significantly higher risk of acute rejection by one year than paired kidneys with a longer pump time (mean 22.7 h versus 31.2 h, p b 0.001).

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