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

doi:10.21203/rs.2.12091/v1

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

https://doi.org/10.21203/rs.2.12091/v1

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Background

Several factors are important in order to predict the graft survival in kidney transplant recipients like the age of recipient, BMI, serum cratinine, and having history of dialysis. One factor that can have impact of transplant outcomes but not considered can be the age of donor and recipients.

Patients and Methods

The numbers of 1113 kidney transplant recipients were considered through a retrospective cohort study. Several factors were taken into the account of 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 recipient the level of serum creatinine, and eGFR, have dialysis history before transplant, and low donor hemoglobin level can be a good prognosis factor that should considered for kidney transplant survival.

Conclusions

Our result suggested that the gender match is suggested for kidney transplant. On some exceptional occasion just kidney of male donor to female recipient may be successful and it would be better to hesitate female donors to male recipients especially in aged patients with history of dialysis.

Urology & Nephrology

kidney transplant

Gender match

Survival

Dialysis

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 the result of several improvements in early graft survival and long-term graft function (1). The first kidney transplantation was about half century ago in which transplant was from a live donor to his identical twin (2). After that the concept of living and non-living unrelated donor was leading to increasing the number of organ donation in ESRD and the number of kidney transplantation has escalated over the last ten years (3). More than two thousands of kidney transplants in Iran has been reported in which 50 % are deceased (brain death) cases (4).

Several factors may have an impact on patients and/or graft survival and transplant outcomes (5). 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 (6-8). Gender of both recipient and donor is one of the candidate elements that can be determining of the 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 (9, 10). 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 (11).

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.

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 recipient were choose for our research. All selected patients were same in living donor but they were different in having same donor gender and relative or non-relative donor. Patients with positive cross-match, incompatible blood group, younger than 18 years old, multiple organ transplantation history, having chronic viral B, C hepatitis, HIV , Pregnancy, and Diabetes, were excluded from the study. In addition, patients who had history of liver disease 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 in 24 hours), or need dialysis one week later than graft receipt. The biopsy was done over the patients who were at risk of rejection with more than 30% increase in basic level of creatinine. Anti-rejection medication was done by Methylprednisolone and on the occasion of its resistance, Anti-thymocyte globulin (ATG). The transplant rejection was defined by dialysis need more than 30 days, death, or graft excision. Included patients in this study were sub grouped in to the four distinct category of group 1 (donor: male, recipient male), group 2 (donor: male, recipient female), group 3 (donor: female, recipient male), and the last one but not the least group 4 (donor: female, recipient female). The clinical data like duration of dialysis before kidney transplantation, serum creatinine, and eGFR (Estimated Glomerular Filtration Rate) for transplant recipient were considered. In addition some demographic information of both recipient and donors were considered like; age, BMI in both donor and recipient and hemoglobin of donors. The graft rejection, again need dialysis, and death were checked for several factors by multiple logistic regression models.

Statistical Analysis

Actuarial survival was assessed by the 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 measured as the significant one. For the determination of factors that had an independent impact on graft survival, a Cox proportional hazard analysis was utilized.

The average creatinine level one week after receiving transplant was 1.65 ± 1.46 mg/deciliter (mean and standard deviation (SD)), one month after transplant was 1.63 ±1.29 mg/ deciliter, after six month was 1.37±0.69 mg/deciliter and after one year was 1.37±0.66 mg/deciliter. The mean of eGFR was 58.2 ± 22.2 cubic centimeters/minute at the first month after transplant, 62.0 ± 21.4 cubic centimeters/minute after six months, and 62.15 ± 21.1 cubic centimeters/minute one year after transplant. These decreasing trends in the amount of serum creatinine and increasing trend in serum eGFR was meaningful (p-value = 0.039). Table 1 is the characteristics of both graft donors and recipients. Additional data on serum creatinine, eGFR of transplant recipients and hemoglobin of donors are shown in table 2 over the several time of sampling after and before transplantation.

Table 1: Considering characteristics of both graft donors and recipients.

	Kidney transplant Donor	Kidney transplant Recipient
Mean age (year)	28.20 ± 5.34	35.02 ± 15.63
Female (percent)	202 (18.2%)	438 (39.4%)
BMI	24.02 ± 4.40	23.29 ± 5.41
Dialysis Before Graft	-	852 (76.6 %)
Arterial anastomosis	-	972 (87.4%)
Venous anastomosis	-	1101 (99.2%)
DGF	-	103 (9.3%)

Table 2: The fluctuation of serum creatinine and eGFR in recipients and hemoglobin in donors.

Serum Creatinine In Graft Recipient
One week after transplant	1.65 ± 1.46
One month after transplant	1.63 ± 1.29
Six months after transplant	1.37 ± 0.69
One year after transplant	1.37 ± 0.66
eGFR In Graft Recipient
One month after transplant	58.02 ± 22.2
Six months after transplant	62.00 ± 21.4
One year after transplant	62.15 ± 21.1
Hemoglobin of Graft Donor
Before surgery	15.11 ± 7.87
After surgery	14.04 ± 7.66
Two days after surgery	13.50 ± 2.92

Side effects and complications after surgery were just seen in 4.6 % of patient. The graft rejection was reported in about 51 cases (4.6%) of graft recipients, and 130 (11.7%) of patients were made to have dialysis after transplantation. The death rate after transplantation was equal to 41 cases (3.7%). The consequences of surgery, side effects, graft rejection, dialysis return, and death in transplant recipients is presented in table 3 based on the donor- recipient gender.

Table 3: The consequences of surgery like side effects, graft rejection, dialysis return, and death in transplant recipients.

Consequence	Frequency	p-value
Side Effects
Male to Male	2.3 %	0.068
Male to Female	4.0 %
Female to Male	3.8 %
Female to Female	4.5 %
Graft Rejection
Male to Male	4.0 %	0.087
Male to Female	6.4 %
Female to Male	3.8 %
Female to Female	4.0 %
Dialysis Return
Male to Male	10.5 %	0.009*
Male to Female	15.0 %
Female to Male	8.4 %
Female to Female	12.1 %
Death
Male to Male	3.4 %	0.517
Male to Female	4.3 %
Female to Male	3.6 %
Female to Female	3.2 %

*p-value less than 0.05 is considered as the meaningful one.

The Kaplan-Meier test the survival percentage after one year was 97.3%, after two years was 95.7%, after three years was 95.1%, after four years was 94.8%, after five years was 94.4%, and after 10 years was 93.7% (figure 1). The distribution of patients in our four defined groups based on donor-recipient gender was 606 (54.4%) in group1, 304 (27.4%) cases in group 2, 105 (99.4%) cases in group 3, and 98 (8.8%) cases in group 4.

Considering predictive factors for mortality, graft rejection, and returning the need of dialysis were gender of donor and recipient, age (special in transplant recipient), serum creatinin, eGFR, the level of donor hemoglobuline, history and duration of dialysis before kidney transplant. The result of multiple logistic regression analysis of graft rejection, dialysis return, and death recipients are presented in table 4. The multiple logistic regression model for graft rejection indicated to being female recipient (p-value: 0.035), delayed graft function (DGF) (p-value: 0.001), age of recipients (p-value: 0.050), primary serum level of creatinine and eGFR (p-value: 0.001), and donor hemoglobin (p value: 0.043) as critical elements of graft rejection.

Table 4: Multiple logistic regression models for several factors and graft rejection again need dialysis, and death.

	Candidate Variable	Beta coefficient	p-value	Probability Ratio
Graft Rejection	Recipients Gender	-0.437	0.040	0.646
	Age of Recipient	0.019	0.010*	1.019
	Creatinine/eGFR	-0.341	0.001*	0.711
	Donor hemoglobin	0.019	0.001*	1.019

Again Need Dialysis	Recipients Gender	-0.602	0.002*	0.548
	Age of Recipient	0.038	0.001*	1.039
	Creatinine/eGFR	-0.275	0.001*	0.760
	Donor hemoglobin	0.148	0.016*	1.159
	Arterial Anastomosis	0.171	0.650	1.187
	DGF	0.564	0.146	1.758
	Donor Age	-0.022	0.177	0.978

Death	History of Having Dialysis	0.417	0.453	1.518
	Age of recipient	-0.042	0.010*	1.959
	Creatinine/eGFR	-0.305	0.001*	0.749
	BMI of Recipient	0.009	0.009*	0.959
	Creatinine/eGFR	-0.067	0.642	0.935

The multiple regression models showed that in kidney transplant recipients who had history of dialysis, older age, higher Creatinine/eGFR and higher hemoglobin in their donors are more susceptible to return to dialysis again 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.

Our observational study indicated to the gender match between kidney donor and recipient as an important graft survival determinant. More than sex match the transplant survival was dependent on the younger age of recipient and having history of dialysis before transplant. Several factors are suggested by some studies that can change long-term survival in renal transplant recipients with graft function (12-15). For example, the incidence of post-transplant hyperglycemia and its cardiovascular disease as the Pre-transplant characteristics and, particularly, the glycemia during the first month post-transplant identified patients at risk of post-transplant diabetes (16). Our result showed that the age of recipient younger than 35 is more critical than the age of donor. For cardiac and hepatic grafts, no significant effect of donor gender on the proportion of patients treated for rejection episodes was seen and adverse effects of female donor gender for different organs is much less uniform (17). The donor age can be the potential confounder because a gender effect on graft survival was also observed for cardiac allograft. The age of donor older than 60 years or other algorithms to simplify identification of organs with elevated risk of transplant failure (18). Our result showed that the age of recipient younger than 35 is more critical than the age of donor. Age matching can possibly increase the positive results of transplantation, particularly when kidneys from older donors are used (19). Consideration of age and gender as principles for the optimal donors and recipients selection may be considered in organ allocation (20, 21). Some structural and functional change that happens in kidney with age increasing can change the efficacy of transplantation (22).

It is suggested by Peter Stenvinkel and his colleagues that as inflamed female 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 (23). This can be the logic that female recipients even from male donors showed higher transplant outcome in comparison with male recipients from female donors. Additional studies must conclude whether sex- and age-specific immunosuppressant is warranted for kidney graft recipients (24-26). Despite 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 (27). 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 (28). However there are some suggestion that the impressive long-term graft survival benefit of male donor-female recipient versus female donor-male recipient and of male donor-female recipient versus matched groups (male-male, female-female) in transplant can be the result of some donor quality and recipient characteristics as the confounding elements (29-31). Time of being in waiting list of transplantation and duration of dialysis can be confounders like the age of donor and recipients. Our data suggested that in addition to age of recipients and gender matching, having history of dialysis can be prognostic element of transplant survival. Several previous studies indicated to the natural history of permanent renal dysfunction and severe liver failure in liver transplant recipients that can be helpful in the progress of non-nephrotoxic immunosuppressive regimens for high- risk liver transplant recipients (32-34).

A paired donor kidney analysis indicated that waiting time on dialysis can be the strongest modifiable risk factor for renal transplant outcomes (35). The advantage of living-donor versus cadaveric-donor transplantation can be the logic of waiting time. Cadaveric renal transplant recipient with an end-stage renal disease time ≤6 months has the equivalent graft survival of living donor transplant recipients compare to who wait on dialysis for ≥2 years (36, 37). In fact, increased time on dialysis previous than kidney transplantation is linked to the decreased survival of transplant recipients (38, 39).

By far the most successful transplant based on donor-recipient gender was seen in male donor to male recipient and then male donor to female recipient. Contradictory, the most unsuccessful transplant was seen when the donor was female and the recipient was male which means should be hesitate from that. In female transplant recipient the level of serum creatinine, and eGFR, have dialysis history before transplant, and low donor hemoglobin level can be a good prognosis factor kidney transplant survival.

Ethics approval and consent to participate: Patient consent undertook before surgery based on the ethical code of Tehran University of Medical Sciences Ethics committee.

Consent for publication: The information are published without the name of patients (both kidney donors and kidney recipients)

Availability of data and material: Information, data, and photos will be provided if they requested.

Competing interests: All authors claim that there is not any potential competing or conflict of interest

Funding: Urology Research center of Tehran University of medical sciences.

Authors' contributions: SMK.A. was the principal investigator. GH. N. was the professor who the surgery was under his supervision; F.KH., SR. Y. write the manuscript. A.A. run the project.

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Review #2 received at journal
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Editorial decision: Major revision
08 Aug, 2019
Review #1 received at journal
07 Aug, 2019
Reviewer #3 agreed at journal
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Reviewers invited by journal
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Reviewer #1 agreed at journal
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Submission checks completed at journal
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Editor invited by journal
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First submitted to journal
03 Jul, 2019

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

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Abstract

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Introduction

Patients and Methods

Results

Discussion

Conclusion

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References

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