Impact of the donor-recipient gender matching graft survival from live donors donor-recipient gender matching on the graft survival from live donors

Background: Several factors like age of recipient, BMI, serum cratinine, and positive history of dialysis are important in predicting graft survival in kidney transplant recipients. One factor that can affect transplant outcomes and is usually ignored is the gender of donor and recipients. Methods: A total of 1113 kidney transplant recipients were studied in a retrospective cohort study. Several factors were taken into account for graft survival and outcomes like gender and age of donor and recipients in addition to common recipient factors like cratinine, eGFR, BMI, and positive history of dialysis. Results: The most successful transplant based on donor-recipient gender was seen in male donor to male recipient and then male donor to female recipient. In female transplant recipients, level of serum cratinine, and eGFR, positive dialysis history before transplant, and low donor hemoglobin level can be good prognostic factors recommended to be considered for kidney transplant survival. Conclusions: Our results suggested that gender matching for kidney transplant. Only on some exceptional occasions, male donor to female recipient kidney transplant may be successful and female donors to male recipients are not suggested, especially in aged patients with history of dialysis.


Introduction
For most patients with end-stage renal disease (ESRD), the only treatment strategy is renal transplantation. Kidney transplantation has become a more cost-effective alternative to dialysis as a result of several improvements in early graft survival and long-term graft function. The first kidney transplantation was about half a century ago in which the transplant was performed from a live donor to his identical twin. After that, the concept of living and non-living unrelated donor led to increasing the number of organ donation in ESRD and the number of kidney transplantations has escalated over the last ten years. More than two thousands kidney transplants has been reported in Iran, among which, 50 % are deceased (brain death) cases.
Several factors may have an impact on patients and/or graft survival and transplant outcomes. Donor factors such as age, female gender, brain death of cerebrovascular cause and prolonged criteria donor status had a noteworthy effect on the renal graft function (1)(2)(3). Gender of both recipient and donor is one of the candidate elements that can determine better graft outcomes and gender match is suggested. Similar graft survival rates for males and females has been reported and a systematic review on gender differences in kidney transplantation identified 14 studies with contradicting results (4,5). However, more recently, a study from the Collaborative Transplant Study confirmed that female recipients of male donor kidneys had the worst graft survival after the first year and up to ten years post-transplant (6).
In this study, we aimed at checking the impact of gender match between kidney donor and recipients.
Moreover, we want to evaluate predictive markers of graft survival

Patients And Methods
In this retrospective cohort study, among 2000 graft recipient patients registered in transplant center of Shariati Hospital transplant data bank from 2002-2018, 1113 renal graft recipients were chosen for our research. All selected patients were the same in being living donors but were different in having the same donor gender and relative or non-relative donor. Patients with positive cross-match, incompatible blood group, age<18 years old, multiple organ transplantation history, positive chronic viral B, C hepatitis, HIV, pregnancy and Diabetes were excluded from the study. In addition, patients with positive history of liver diseases like Cirrhosis, Autoimmune hepatitis (including Gamma globulin serum & FANA), primary biliary cirrhosis, biliary obstruction, hemochromatosis, alpha-1-antitrypsin deficiency, Wilson's disease (including serum ceruloplasmin, transferrin saturation percentage), Chronic disabling diseases (severe cardiac dysfunction, Chronic obstructive pulmonary disease, malignancy) and known cancers were excluded from study.
Delayed graft function was defined by decrease in urine volume (≤400 ml/24 hours) or needing dialysis one week after graft receipt. The biopsy was done for patients at risk of rejection with more than 30% increase in basic levels of cratinine. Anti-rejection medication was Methylprednisolone and on the occasion of its resistance, Anti-thymocyte globulin (ATG) was the alternative. Transplant rejection was defined by dialysis need for more than 30 days, death, or graft excision. Patients included in this study were sub grouped into the four distinct category of group 1 (donor: male, recipient: male), group 2 (donor: male, recipient: female), group 3 (donor: female, recipient: male), and finally group 4 (donor: female, recipient: female). Clinical data like duration of dialysis before kidney transplantation, serum cratinine, and eGFR (Estimated Glomerular Filtration Rate) for transplant recipients were considered. In addition, some demographic information of both recipients and donors like age, BMI in both donor and recipient and hemoglobin of donors were considered.
Graft rejection, needing dialysis again, and death were checked for several factors by multiple logistic regression models.

Statistical Analysis
Actuarial survival was assessed by Kaplan-Meier test and the log derivation of the survival percentage was employed for the half-life predicting of grafts and/or patients. Differences in survival were done through log-rank test and p-value less than 0.05 was taken as significant. For the determination of factors that had an independent impact on graft survival, a Cox proportional hazard analysis was utilized.

Results
The average creatinine levels (mean and standard deviation (SD)) were 1.65 ± 1.46 mg/dl, 1.      The multiple regression models showed that kidney transplant recipients with history of dialysis, older age, higher Creatinine/eGFR and higher hemoglobin levels in their donors are more susceptible to return of dialysis after transplantation. In addition, higher Creatinine/eGFR, BMI and older age of recipients (≥35 years) can decrease the risk of transplant survival and increase the risk of death in graft recipients. Figure 2 represent the frequency of death, back to dialysis, graft rejection and other complications based on gender math.

Discussion
Our observational study indicated that gender match between kidney donor and recipient is an Donor's age can be the potential confounder because a gender effect on graft survival was also observed for cardiac allograft. The age of donors> 60 years or other algorithms to simplify identification of organs with elevated risk of transplant failure (9). Our findings showed that the age of recipients<35 is more critical than the age of donors. Age matching can possibly increase the positive results of transplantation, particularly when kidneys from older donors are used (10). Consideration of age and gender as principles for the optimal donor/recipient selection may be considered in organ allocation (11,12). Some structural and functional changes happening in kidney with age increase can change the efficacy of transplantation .
Peter Stenvinkel et al suggested that as inflamed females patients have a better outcome than inflamed males because sex hormones may have important cardioprotective effects that limit the effect of inflammation on vascular injury in female end-stage renal disease (ESRD) patients . This can be the logic that female recipients, even from male donors, showed higher transplant outcomes in comparison to male recipients (from female donors). Additional studies must conclude whether sexand age-specific immunosuppressant is warranted for kidney graft recipients (13)(14)(15). Despite the conflicting data regarding the influence of gender on chronic kidney disease, it was shown by Idan Goldberg and Ilan Krause that the prevalence of chronic kidney disease tends to be higher in women, whereas the disease in men is more severe (16). In the pre-lung allocation score era, female gender was not connected with better survival. Female recipients showed considerably improved survival over five years compared to males (17

Conclusion
By far, the most successful transplants, based on donor-recipient gender, were seen in male donors to male recipients and then male donors to female recipients. Contradictory, the most unsuccessful transplant was seen when the donor was female and the recipient was male. In female transplant recipients, the level of serum cratinine, and eGFR, positive dialysis history before transplant, and low donor hemoglobin levels can be good prognostic factors in kidney transplant survival. Judging based on hemoglobin yields these results, but if we take Gender into account, we get inconsistent results.
Further studies are therefore needed to complete this section." Declarations Ethics approval and consent to participate: An informed consent was taken before surgery based on the ethical code of Tehran University of Medical Sciences ethics committee.

Consent for publication:
The information is published without the name of patients (both kidney donors and kidney recipients) Availability of data and material: Information, data, and photos will be provided upon request.
Competing interests: All authors claim that there is not any potential competing or conflict of  Frequency of death, back to dialysis, graft rejection and other complications based on gender math.