Gender in the allocation of organs in kidney transplants: meta-analysis

Erika Vieira Almeida e Santiago; Micheline Rosa Silveira; Vânia Eloisa de Araújo; Katia de Paula Farah; Francisco de Assis Acurcio; Maria das Graças Braga Ceccato

doi:10.1590/S0034-8910.2015049005822

. 2015 Sep 23;49:68. doi: 10.1590/S0034-8910.2015049005822

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Gender in the allocation of organs in kidney transplants: meta-analysis

Erika Vieira Almeida e Santiago ^I, Micheline Rosa Silveira ^I, Vânia Eloisa de Araújo ^II, Katia de Paula Farah ^III, Francisco de Assis Acurcio ^I, Maria das Graças Braga Ceccato ^I

PMCID: PMC4587823 PMID: 26465666

Abstract

OBJECTIVE

To analyze whether gender influence survival results of kidney transplant grafts and patients.

METHODS

Systematic review with meta-analysis of cohort studies available on Medline (PubMed), LILACS, CENTRAL, and Embase databases, including manual searching and in the grey literature. The selection of studies and the collection of data were conducted twice by independent reviewers, and disagreements were settled by a third reviewer. Graft and patient survival rates were evaluated as effectiveness measurements. Meta-analysis was conducted with the Review Manager^® 5.2 software, through the application of a random effects model. Recipient, donor, and donor-recipient gender comparisons were evaluated.

RESULTS

: Twenty-nine studies involving 765,753 patients were included. Regarding graft survival, those from male donors were observed to have longer survival rates as compared to the ones from female donors, only regarding a 10-year follow-up period. Comparison between recipient genders was not found to have significant differences on any evaluated follow-up periods. In the evaluation between donor-recipient genders, male donor-male recipient transplants were favored in a statistically significant way. No statistically significant differences were observed in regards to patient survival for gender comparisons in all follow-up periods evaluated.

CONCLUSIONS

The quantitative analysis of the studies suggests that donor or recipient genders, when evaluated isolatedly, do not influence patient or graft survival rates. However, the combination between donor-recipient genders may be a determining factor for graft survival.

Keywords: Kidney Transplantation, Sex Distribution, Gender and Health, Prognosis, Meta-Analysis

INTRODUCTION

Kidney transplants are considered to be the best therapeutic alternatives for persons suffering from advanced chronic kidney disease. ¹³ ^, ¹⁸ ^, ³² Gender differences regarding kidney transplants have been reported in the literature and observed in the clinical practice over the last decades. They affect transplant results, such as in acute and chronic rejections and graft and patient survival rates. Women have less access to transplants. They have increased risk of acute rejection and decreased risk of chronic rejection – those risks increase with age. ⁹ ^, ²² In turn, women are observed to account for around 65.0% of living kidney donors. ⁷ ^, ³⁷ The etiology of those differences is still unknown, but it probably reflects hormone, immunological, and aging differences, as well as prejudice. ⁷ ^, ²² ^, ²⁸

Survival rates are higher among women following kidney transplants, ⁹ ^, ¹¹ but the data are not confirmed by the literature. In a South African study, worse survival rates have been observed among women, but no significant differences were found between genders in graft survival. ²³ In another study, no differences were observed between genders in patient and graft survival rates. ²⁷

Knowing differences across genders is necessary to identify possible barriers in the achievement of ideal results and in the development of interventions that overcome those barriers. This review, by focusing on those gender-related differences in the clinical effectiveness of immunosuppressive therapies for kidney transplant maintenance, may promote better understanding, provide more efficient health care, contribute to the creation of clinical protocols, and promote better long-term results for patients.

The objective of this review was to analyze whether genders influence patient and graft survival rates in kidney transplants.

METHODS

This review was conducted according to the recommendations from the Cochrane Collaboration Handbook. ^a The article was prepared according to Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA). ²¹

Observational cohort studies were selected. The selection included studies with patients who received kidney transplants from living or deceased donors for the first time or more than once, mentioning gender differences concerning pre-transplant characteristics, and finding survival results for grafts, patients, or for both. Studies that did not involve immunosuppressants for maintenance of kidney transplants, pharmacokinetic studies, economic evaluation studies, review studies, and studies conducted on animals were excluded, as per the exclusion criteria.

An electronic search was performed for articles published until December 2013, on Medline (PubMed), Latin-American and Caribbean Center on Health Sciences Information (LILACS), Cochrane Controlled Trials Databases (CENTRAL), Embase databases. Manual searches were also conducted in the reference lists of all studies selected from the published systematic review. ⁴⁴ Studies from the grey literature were also sought after: in the thesis and essay database from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES – Coordination for the Improvement of Undergraduate Personnel), in Biblioteca Digital Brasileira de Teses e Dissertações (Brazilian Digital Library of Thesis and Dissertations), and in Universidade de São Paulo’s Digital Library of Theses and Dissertations. There were no restrictions regarding dates and languages of publications. Table 1 describes the search strategy used in each surveyed database.

Table 1. Bibliographical search strategies for observational studies conducted in each database, on 12/12/2013.

Database	Studies	Search strategy
Medline (via PubMed)	3,263	((((((((((((((Transplantation, Kidney) OR Kidney Transplantations) OR Transplantations, Kidney) OR Transplantation, Renal) OR Renal Transplantation) OR Renal Transplantations) OR Transplantations, Renal) OR Grafting, Kidney) OR Kidney Grafting)) OR (Kidney Transplantation) OR (“Kidney Transplantation”[Mesh) AND (((((male[Title/Abstract) OR female[Title/Abstract) OR gender[Title/Abstract)) OR (((((((((Factor, Sex) OR Factors, Sex) OR Sex Factor)) OR (Sex Factors)) OR (“Sex Factors”[Mesh)) OR (((((((Characteristic, Sex) OR Characteristics, Sex) OR Sex Characteristic) OR Sex Differences) OR Difference, Sex) OR Differences, Sex) OR Sex Difference)) OR (Sex Characteristics)) OR (“Sex Characteristics”[Mesh))) AND Humans[Mesh)) AND ((((“Cohort Studies”[Mesh) OR (cohort study) OR (studies, cohort) OR (study, cohort) OR (concurrent studies) OR (studies, concurrent) OR (concurrent study) OR (study, concurrent) OR (historical cohort studies) OR (studies, historical cohort) OR (cohort studies, historical) OR (cohort study, historical) OR (historical cohort study) OR (study, historical cohort) OR (analysis, cohort) OR (analysis, cohort) OR (cohort analyses) OR (cohort analysis) OR (closed cohort studies) OR (cohort studies, closed) OR (closed cohort study) OR (cohort study, closed) OR (study, closed cohort) OR (studies, closed cohort) OR (incidence studies) OR (incidence study) OR (studies, incidence) OR (study, incidence) OR (cohort studies) OR (cohort) OR (cohort analysis) OR (cohort study) OR (prospective cohort) OR (retrospective cohort) OR (retrospective cohort study) OR (prospective cohort study) OR (“Follow-Up Studies”[Mesh) OR (follow up studies) OR (follow-up study) OR (studies, follow-up) OR (study, follow-up) OR followup studies OR (followup study) OR (studies, followup) OR (study, followup) OR (“Epidemiologic Studies”[Mesh OR “Cross-Sectional Studies”[Mesh OR “Retrospective Studies”[Mesh OR “Longitudinal Studies”[Mesh OR “Prospective Studies”[Mesh))) OR ((case* AND and control*[Text Word))))
Embase	2,363	‘kidney transplantation’/exp ANDembase/lim AND ‘gender and sex’/exp ANDembase/lim OR ‘sex difference’/exp ANDembase/lim OR ‘gender’/exp ANDembase/lim OR ‘sex ratio’/exp ANDembase/lim AND (‘cohort analysis’/de OR ‘comparative study’/de OR ‘control group’/de OR ‘controlled study’/de OR ‘human’/de OR ‘observational study’/de OR ‘outcomes research’/de OR ‘prospective study’/de OR ‘retrospective study’/de)
CENTRAL	280	(“Transplantation, Kidney” OR “Kidney Transplantations” OR “Transplantations, Kidney” OR “Transplantation, Renal” OR “Renal Transplantation” OR “Renal Transplantations” OR “Transplantations, Renal” OR “Grafting, Kidney” OR “Kidney Grafting” OR “Kidney Transplantation” OR “MeSH descriptor:Kidney Transplantation 1 tree(s) exploded”) AND (“male” OR “female” OR “gender” OR “Factor, Sex” OR “Factors, Sex” OR “Sex Factor” OR “Sex Factors” OR “MeSH descriptor:Sex Factors explode all trees”) AND “Characteristic, Sex” OR “Characteristics, Sex” OR “Sex Characteristic” OR “Sex Differences” OR “Difference, Sex” OR “Differences, Sex” OR “Sex Difference” OR “Sex Characteristics” OR “MeSH descriptor:Sex Characteristics explode all trees”) AND (“graft rejection OR MeSH descriptor:Graft Rejection explode all trees”) AND (“survival rate” “MeSH descriptor:Survival Rate explode all trees”) AND “graft survival”
LILACS	87	(tw:(transplantation kidney)) OR (tw:(transplantation renal)) AND (tw:(gender differences)) OR (tw:(gender Characteristics)) OR (tw:(Sex Characteristics)) OR (tw:(sex differences)) AND (tw:(survival rate)) AND (tw:(survival graft))

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After duplicate studies were excluded, two independent reviewers selected the references in three phases: analysis of titles, abstracts, and full texts. The disagreements were settled by a third reviewer. The data – including methodological quality, subject information, treatment length, and patient and graft survival rates – were extracted and collected in duplicate in a Microsoft Excel 2010 spreadsheet.

Methodological quality evaluations were independently conducted by the reviewers, and related disagreements were settled through the consensus among reviewers. Newcastle-Ottawa scale ^b for observational studies was used. In this scale, each study is evaluated in three dimensions: selection of study groups; the comparability among groups; and the ascertainment of either the exposure or outcome of interest. Total score was up to nine stars – above six, studies are considered to be high quality.

In order to be analyzed, the studies were grouped according to the comparison of results among:

a)Donor genders – male donors (MD) and female donors (FD);

b)Recipient genders – male recipients (MR) and female recipients (FR);

c)Donor-recipient genders – male donor-male recipient transplants (MD-MR), male donor-female recipient transplants (MD-FR), female donor-female recipient transplants (FD-FR), female donor-male recipient transplants (FD-MR).

The study data were combined using randomized effects model in Metaview module of Review Manager software, version 5.3. The results were presented as relative risk for dichotomous variables, with a confidence interval of 95%. Analyses with I ² > 40.0% and p-value of Chi-squared test < 0.10 were considered to be significant heterogeneity. A sensitivity analysis was conducted to investigate heterogeneity causes, with the exclusion of one study at a time, with changes being verified in the values of I ² and p.

The outcomes that were evaluated in the meta-analysis were graft survival and patient survival per follow-up period (one, two, three, five, eight, 10 years or more).

RESULTS

A total of 5,993 publications were initially identified in the electronic databases, and seven through manual searches, all adding up to 6,000 publications. Of these, 500 publications were excluded because of the participant type, 5,251 due to study type and 177 due to the intervention. The main causes for excluded studies were: studies that did not analyze the outcome of interest (patient and graft survival rates), ones that did not include kidney transplants, review, pharmacokinetic, pharmacoeconomic studies, among others. After duplicate publications were eliminated and the reviewers conducted their analyses, 29 cohort studies were included, which involved 765.753 patients. Among those, six studies compared the measurements from results involving donor genders (MD and FD); eight studies, involving recipient genders (MR and FR), and for 20 others, results involving donor-recipient genders (MD-MR, MD-FR, FD-FR, FD-MR) (Figure). One study was included in donor, recipient, and donor-recipient gender comparisons; ⁵ another one ¹⁴ was included in the comparison between recipient and donor-recipient genders; and two studies, in the comparison between donor and donor-recipient genders. ³ ^, ²⁵

Out of the 29 observational studies included, 28 were retrospective and one was prospective. ³⁸ Most studies have not reported average follow-up periods, and the data from the cohorts were collected from 1978 to 2009. In the comparison between donor genders, 9,673 subjects were evaluated in the six studies. In the comparison between recipient genders, 84,070 subjects were evaluated in the eight studies included. In the comparison between donor-recipient genders, 672,010 subjects were evaluated in the 20 studies included. In regards to types of donors, 12 studies evaluated deceased donors, eight evaluated living donors, and nine evaluated both kinds (living and deceased) (Table 2).

Table 2. General characteristics of studies included in comparisons between genders.

Study	Comparison between genders	Number of patients	Country where the study was conducted	Type of donor	Donor age (years)	Recipient age (years)	Immunosuppressive therapy	Collection period	Average supervision type (months)	Newcastle Scale
Neugarten et al²⁵ (1996)	Donor and donor-recipient	651	USA	Both	NR	NR	Ciclosporin	1979 to 1994	NR	7
Buchler et al⁴ (1997)	Donor	354	France	Deceased	NR^a	49	Multiple	1985 to 1995	NR	6
Busson e Benoit⁵ (1997)	Recipient. donor. and donor-recipient	6,889	France	Deceased	NR^a	NR^a	NR	1989 to 1992	NR	7
Valdes et al⁴¹ (1997)	Donor	858	Spain	Deceased	NR^a	NR^a	NR	1981 to 1995	NR	7
Ben Hamida et al³ (1999)	Donor and donor-recipient	182	Tunisia	Living	39.3	28.1	Multiple	1986 to 1998	NR	7
Oien et al²⁹ (2007)	Donor	739	Norway	Living	NR^a	NR^a	Multiple	1994 to 2004	55.1	8
Sánches Garcia et al³⁵ (1989)	Recipient	760	Spain	Deceased	NR	NR	Ciclosporin	1978 to 1988	NR	7
Nyberg et al²⁷ (1997)	Recipient	1,000	Sweden	Both	NR^a	NR^a	Ciclosporin + prednisolone	1985 to 1993	73	8
Avula et al² (1998)	Recipient	431	India	Living	43.18	33.87	Multiple	NR	9	6
Meier-KriescheH et al²² (2001)	Recipient	73,477	USA	Both	NR^a	NR^a	Multiple	1988 to 1997	NR	8
Inoue et al¹⁴ (2002)	Recipient and donor-recipient	205	Japan	Both	NR^a	NR^a	Cisclosporin or FK506	1987 to 2000	NR	7
Moosa²³ (2003)	Recipient	542	South Africa	Deceased	NR^a	37	Multiple	1976 to 1999	75.6	7
Chen et al⁶ (2013)	Recipient	766	China	Both	NR^a	NR^a	Multiple	1988 to 2009	NR	7
Ellison etal⁸ (1994)	Donor-recipient	3,314	USA	Both	NR	NR	NR	1987 to 1992	NR	8
Shaheen et al³⁸ (1998)^b	Donor-recipient	406	Saudi Arabia	Living	31.3	34.3	Ciclosporin	NR	55.2	7
Vereerstraeten et al⁴² (1999)	Donor-recipient	741	Belgium	Deceased	34.8	36.9	Multiple	1983 to 1997	NR	7
Zeier et al⁴³ (2002)	Donor-recipient	119,195	49 countries	Both	38.3	44.3	NR	1985 to 2000	NR	8
Kayler et al¹⁶ (2003)	Donor-recipient	30,258	USA	Living	NR^a	NR^a	NR	1990 to 1999	NR	8
Kwon e Kwak¹⁹ (2004)	Donor-recipient	614	South Korea	Living	NR^a	NR^a	NR	1979 to 2002	NR	7
Pugliese et al³⁴ (2005)	Donor-recipient	3,233	Italy	Deceased	42.1	44.5	NR	1995 to 2000	NR	8
Jacobs et al¹⁵ (2007)	Donor-recipient	730	USA	Living	39.7	46.4	NR	1979 to 1994	NR	8
Gratwohl et al¹² (2008)	Donor-recipient	195,516	45 countries	Deceased	38	44.7	NR	1985 to 2004	67.2	8
Kim e Gill¹⁷ (2009)	Donor-recipient	117,877	USA	Deceased	NR^a	NR^a	NR	1990 to 2004	NR^a	7
Lankarani et al²⁰ (2009)	Donor-recipient	2,649	Iran	Living	NR^a	NR^a	NR	1992 to 2005	NR	8
Shaheen et al³⁹ (2010)	Donor-recipient	524	Saudi Arabia	Deceased	33.6	33.9	Múltipla	2003 to 2007	20.9	8
Głyda et al¹¹ (2011)	Donor-recipient	154	Poland	Deceased	NR^a	NR^a	Múltipla	NR	NR	7
Zukowski et al⁴⁵ (2011)	Donor-recipient	230	Poland	Deceased	33.1	37.6	NR	NR	NR	8
Abou-Jaoude et al¹ (2012)	Donor-recipient	135	Lebanon	Both	NR^a	NR^a	Múltipla	1998 to 2007	NR	7
Tan et al⁴⁰ (2012)	Donor-recipient	188,507	USA	Both	NR^a	NR^a	NR	1988 to 2006	NR	8

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NR: not reported; NR^a: not reported in the expected way

^b Prospective cohort.

The majority of subjects (donor, recipient, and donor-recipient) were males, for all gender comparisons. All studies included evaluated graft survival rates, but only eight of them evaluated patient survival rates. ¹ ^, ¹⁴ ^, ²⁰ ^, ²² ^, ²³ ^, ²⁷ ^, ³⁹ ^, ⁴³

Out of the 29 studies included, two of them were observed to have scores of six as per New-Castle Ottawa scale; ² ^, ⁴ 14 (48,3%) of them had score seven; and 13, eight (Table 2).

Out of the six studies included in the systematic review for donor gender comparison, five of them were included in the meta-analysis for graft survival outcome. ³ ^- ⁵ ^, ²⁹ ^, ⁴¹ The study by Neugarten et al ²⁵ was not found to have enough numerical data for the quantitative analysis. The studies included in the donor gender comparison did not evaluate patient survival.

Regarding graft survival, the relative risks (RR), as grouped chronologically according to follow-up periods of one, two, three, five, and ten years were, respectively, 1.02 (95%CI 0.97;1.07; p = 0.43; I² = 70.0%), 1.03 (95%CI 1.00;1.07; p = 0.07; I² = 27.0%), 1.02 (95%CI 0.94;1.12; p = 58; I² = 67.0%), 0.89 (95%CI 0.79;1.00; p = 0.06; I² = 0%), 0.86 (95%CI 0.73;1.02; p = 0.09; I² = 11.0%;), and 0.82 (95%CI 0.68;0.98; p = 0.03; I² = 0%). Only at the 10-year follow-up period was the difference significant for graft survival, favoring male donors. Heterogeneity was high and significant for follow-up periods of one and three years (Table 3).

Table 3. Summary of meta-analyses for survival of grafts according to donor genders (FD or MD) and recipient genders (FR or MR); and survival of patients according to kidney transplant recipient genders.

Outcome/Time	Studies	Subjects	RR	95%CI	p^a	I² (%)^b
Graft survival	FD versus MD
1 year	^3,5,30	7,478	1.02	0.97;1.07	0.43	70.0^c
2 years	^5,30,41	8,154	1.03	1.00;1.07	0.07	27.0
3 years	^5,30,41	8,154	1.02	0.94;1.12	0.58	67.0^c
5 years	^3,30	589	0.89	0.79;1.00	0.06	0
8 years	^4,30	761	0.86	0.73;1.02	0.09	11.0
10 years	^3,30	589	0.82	0.68;0.98	0.03	0
Graft survival	FR versus MR
1 year	^2,5,10	8,348	1.01	0.99;1.03	0.30	0
5 years	^2,6,15	1,402	0.99	0.88;1.12	0.88	75.0^c
10 years and older	^15,24	747	1.23	0.68;2.24	0.50	95.0^c
Patient survival	FR versus MR
10 years and older	^15,24	747	0.96	0.67;1.37	0.81	95.0^c

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RR: relative risk

^a Value of p < 0.10 of Z-test for all effects.

^b Value of I2 > 40.0% indicates statistical heterogeneity among studies.

^c Significant heterogeneity (p < 0.10).

Out of the eight studies included in the systematic review for recipient gender comparison, six were included in the meta-analysis for graft survival outcome. ² ^, ⁵ ^, ⁶ ^, ¹⁴ ^, ²³ ^, ³⁵ The studies by Nyberg et al ²⁷ and Meier-Kriesche et al ²² were not found to have numerical data in order to be included in the quantitative analysis. Thus, meta-analyses were conducted for monitored periods of one, five, and 10 years or more.

In the meta-analysis regarding graft survival for one year, four comparisons of three studies were included. In the study by Sánchez Garcia et al, ³⁵ (1989) the influence from immunosuppressive therapy was compared to genders in two groups: Sánchez Garcia et al ³⁵ (1989a), ciclosporin-treated; and Sánchez Garcia et al ³⁵ (1989b), ciclosporin-untreated.

Regarding graft survival, the relative risks (RR), as grouped chronologically according to follow-up periods of one, five, and 10 years or more were, respectively, 1.01 (95%CI 0.99;1.03; p = 0.30; I² = 0%), 0.99 (95%CI 0.88;1.12; p = 0.88; I² = 75.0%), 1.23 (95%CI 0.68;2.24; p = 0.50; I² = 95.0%). No significant differences were found for any of the follow-up periods, and no recipient genders were highlighted among the groups. Heterogeneity was high and significant for follow-up periods of five and 10 years or more (Table 3).

Regarding patient survival, two studies were included in the related meta-analysis. ¹⁴ ^, ²⁴ The meta-analysis was conducted for the follow-up period of 10 years or more, heterogeneity was high and the difference was not significant (RR = 0.96; 95%CI 0.67;1.37; p = 0.81; I² = 95.0%) (Table 3).

In order to evaluate donor-recipient genders, six comparisons were analyzed: MD-MR versus FD-MR, MD-MR versus FD-FR, MD-MR versus MD-FR, MD-FR versus FD-FR, MD-FR versus FD-MR, FD-FR versus FD-MR. Regarding graft survival outcome, 13 studies were included ¹ ^, ⁵ ^, ⁸ ^, ¹¹ ^, ¹⁵ ^- ¹⁷ ^, ¹⁹ ^, ²⁰ ^, ³⁸ ^- ⁴⁰ ^, ⁴³ in the meta-analyses (Table 4).

Table 4. Summary of meta-analyses for survival of grafts according to kidney transplant donor-recipient genders.

General characteristics		MD-MR versus MD-FR					MD-FR versus FD-FR
Time	Studies	Number of patients	RR	95%CI	p^a	I² (%)^b	Number of patients	RR	95%CI	p^a	I² (%)^b
1 year	^{1,5,8,15,16,17,20,39,40}	211,025	1.03	1.01;1.05	< 0.01	92.0^c	181,223	1.02	1.01. 1.04	< 0.01	83.0^c
2 years	^5,8,15,20	8,411	1.05	1.03;1.08	< 0.01	25.0	7,575	1.02	1.00;1.04	0.10	9.0
3 years	^{5,8,15,17,20,39}	79,979	1.06	1.02;1.09	< 0.01	72.0^c	69,993	1.05	1.01;1.09	0.02	73.0^c
5 years	^{11,16,17,19,20,38,40}	204,668	1.15	1.00;1.33	0.05	100^c	175,602	1.02	1.01;1.03	< 0.01	50.0^c
10 year	^17,40,43	258,63	1.08	1.05;1.11	< 0.01	91.0^c	223,404	1.02	0.97;1.07	0.43	97.0^c

General characteristics		MD-MR versus MD-FR					MD-FR versus FD-FR

Time	Studies	Number of patients	RR	95%CI^a	p^b	I² (%)^c	Number of patients	RR	95%CI^a	p^b	I² (%)^c

1 year	^{1,5,8,15,16,17,20,39,40}	196,191	1.01	1.01;1.02	< 0.01	67.0^c	139,859	1.01	0.99;1.02	0.30	77.0^c
2 years	^5,8,15,20	9,086	1.01	0.99;1.03	0.32	0	5,171	1.01	0.98;1.03	0.61	0
3 years	^{5,8,15,17,20,39}	80,495	1.03	1.00;1.06	0.07	76.0^c	51,994	1.01	1.00;1.02	< 0.01	0
5 years	^{11,16,17,19,20,38,40}	189,508	1.00	0.97;1.03	0.98	91.0^c	135,798	1.01	1.00;1.03	0.11	66.0^c
10 year	^17,40,43	246,909	0.96	0.86;1.06	0.38	99.0^c	166,817	1.04	1.02;1.06	< 0.01	80.0^c

General characteristics		MD-FR versus FD-MR					FD-FR versus FD-MR

Time	Studies	Number of patients	RR	95%CI^a	p^b	I² (%)^c	Number of patients	RR	95%CI^a	p^b	I² (%)^c

1 year	^{1,5,8,15,16,17,20,39,40}	169,666	1.01	1.00;1.03	0.15	90.0^c	154,693	1.01	0.99;1.02	0.45	80.0^c
2 years	^5,8,15,20	5,679	1.05	1.01;1.10	0.01	36.0	4,496	1.03	0.99;1.07	0.18	51.0^c
3 years	^{5,8,15,17,20,39}	61,980	1.03	1.00;1.05	0.04	44.0^c	51,478	1.01	0.98;1.04	0.53	44.0
5 years	^{11,16,17,19,20,38,40}	164,864	1.18	1.03;1.35	0.02	100^c	150,958	1.14	0.99;1.31	0.07	100^c
10 year	^17,40,43	202,176	1.10	1.01;1.21	0.03	99.0^c	176,671	1.06	0.98;1.14	0.14	98.0^c

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RR: relative risk

^a Value of p < 0.10 of Z-test for all effects.

^b Value of I2 > 40.0% indicates statistical heterogeneity among studies.

^c Significant heterogeneity (p < 0.10).

The remaining studies were not found to have enough data for the quantitative analysis. ³ ^, ¹⁰ ^, ¹² ^, ¹⁴ ^, ²⁵ ^, ⁴² ^, ⁴⁵ For the patient survival outcome, two studies were included in the meta-analysis. ¹ ^, ²⁰

The studies by Ellison et al ⁸ and Tan et al ⁴⁰ separately evaluated transplants from living and deceased donors, and the total numbers of events and subjects in each study were included in the meta-analysis, considering living and deceased donors. In the study by Abou-Jaoude et al, ¹ rates regarding general graft survival and graft survival as interrupted by death with functioning graft were calculated. The uninterrupted graft survival rate was the one used in the meta-analysis.

In the MD-MR versus FD-MR comparison, the RRs as grouped for graft survival in a chronological order of follow-up periods of one, two, three, five, and 10 years were, respectively, 1,03 (95%CI 1.01;1.05; p = 0.0002; I² = 92.0%), 1.05 (95%CI 1.03;1.08; p < 0.0001; I² = 25.0%), 1.06 (95%CI 1.02;1.09; p = 0.0008; I² = 72.0%), 1.15 (95%CI 1.00;1.33; p = 0.05; I² = 100%), and 1.08 (95%CI 1.05;1.11; p < 0.00001; I² = 91.0%). The graft survival rate was significantly higher in all follow-up periods evaluated, and it favored MD-MR pair. Heterogeneity was high and significant for all periods, except for the two-year follow-up period. The patient survival analysis was only conducted for the one-year follow-up period, and no pairs were observed to be favored (RR = 0.99; 95%CI 0.96;1.02; p = 0.52; I² = 0.0%).

In the MD-MR versus FD-FR comparison, the RRs as grouped for graft survival in a chronological order of follow-up periods of one, two, three, five, and 10 years were, respectively, 1.02 (95%CI 1.01;1.04; p = 0.0008; I² = 83.0%), 1.02 (95%CI 1.00;1.04; p < 0.10; I² = 9.0%), 1.05 (95%CI 1.01;1.09; p = 0.02; I² = 73.0%), 1.02 (95%CI 1.01;1.03; p = 0.0004; I² = 50.0%), and 1.02 (95%CI 0.97;1.07; p = 0.43; I² = 97.0%). The graft survival rate was significantly higher in follow-up periods of one, three, and five years, and it favored MD-MR pair. Heterogeneity only was not significant for the two-year follow-up period. The patient survival meta-analysis was observed to favor none of the pairs (RR = 0.98; 95%CI 0.95;1.01; p = 0.21; I² = 0%).

In the MD-MR versus MD-FR comparison, the RRs as grouped for graft survival in a chronological order of follow-up periods of one, two, three, five, and 10 years were, respectively, 1.01 (95%CI 1.01;1.02; p = 0.0009; I² = 67.0%), 1.01 (95%CI 0.99;1.03; p = 0.32; I² = 0%), 1.03 (95%CI 1.00;1.06; p = 0.07; I² = 76.0%), 1.00 (95%CI 0.97;1.03; p = 0.98; I² = 91.0%), and 0.96 (95%CI 0.86;1.06; p = 0.38; I² = 99.0%). The graft survival rate was only significantly higher for the one-year follow-up period, favoring the MD-MR pair. Heterogeneity only was not significant for the two-year follow-up period. The patient survival meta-analysis was observed to favor none of the pairs (RR = 1.00; 95%CI 0.98;1.03; p = 0.86; I² = 0%).

In the MD-FR versus FD-FR comparison, the RRs as grouped for graft survival in a chronological order of follow-up periods of one, two, three, five, and 10 years were, respectively, 1.01 (95%CI 0.99;1.02; p = 0.30; I² = 77.0%), 1.01 (95%CI 0.98;1.03; p = 0.61; I² = 0%), 1.01 (95%CI 1.00;1.02; p = 0.0007; I² = 0%), 1.01 (95%CI 1.00;1.03; p = 0.11; I² = 66.0%), and 1.04 (95%CI 1.02;1.06; p = 0.0003; I² = 80.0%). The graft survival rate was significantly higher in follow-up periods of three and ten years, and it favored MD-FR pair. Heterogeneity only was not significant for the two and three-year follow-up periods. The patient survival meta-analysis was observed to favor none of the pairs (RR = 0.98; 95%CI 0.94;1.01; p = 0.19; I² = 0%).

In the MD-FR versus FD-FR comparison, the RRs as grouped for graft survival in a chronological order of follow-up periods of one, two, three, five, and 10 years were, respectively, 1.01 (95%CI 1.00;1.03; p = 0.15; I² = 90.0%), 1.05 (95%CI 1.01;1.10; p = 0.01; I² = 36.0%), 1.03 (95%CI 1.00;1.05; p = 0.04; I² = 44.0%), 1.18 (95%CI 1.03;1.35; p = 0.02; I² = 100%), and 1.10 (95%CI 1.01;1.21; p = 0.03; I² = 99.0%). The graft survival rate was significantly higher for all follow-up periods, except for the one-year one, favoring MD-FR pair. Heterogeneity was high and significant for all periods, except for the two-year follow-up period. The patient survival meta-analysis was observed to favor none of the pairs (RR = 0.99; 95%CI 0.95;1.02; p = 0.44; I² = 0%).

In the FD-FR versus FD-MR comparison, the RRs as grouped for graft survival in a chronological order of follow-up periods of one, two, three, five, and 10 years were, respectively, 1.01 (95%CI 0.99;1.02; p = 0.45; I² = 80.0%), 1.03 (95%CI 0.99;1.07; p = 0.18; I² = 51.0%), 1.01 (95%CI 0.98;1.04; p = 0.53; I² = 44.0%), 1.14 (95%CI 0.99;1.31; p = 0.07; I² = 100%), and 1.06 (95%CI 0.98;1.14; p = 0.14; I² = 98.0%). There were no significant differences regarding graft survival considering all follow-up periods. Heterogeneity was high and significant for all periods, except for the three-year follow-up period. The patient survival meta-analysis was observed to favor none of the pairs (RR = 1.01; 95%CI 0.97;1.06; p = 0.54; I² = 0%).

DISCUSSION

This meta-analysis evaluated the influences of donor genders, recipient genders, and the donor-recipient combination in regards to kidney transplant patient and graft survival rates.

In the comparison between donor genders, 9,022 subjects were evaluated in the meta-analysis. Donor genders were not found to favor gender rates in the evaluation of one, two, three, five, and eight-year follow-up periods (p < 0.05). Ten-year follow-up period was the only observed to differ significantly, favoring male donors (p = 0.03). The study by Muller ²⁴ concluded that kidney grafts from male patients work better than the ones from female donors in the long run. Several studies suggest that, in those cases, the grafts from female donors are more antigenic, which may explain the lower survival rates. ²² ^, ³⁰ ^, ³¹ ^, ³⁶

In the comparison between recipient genders in all follow-up periods, 9,593 subjects were evaluated in the meta-analysis, and no significant differences were observed regarding graft survival. Patient survival analysis considered 747 patients. No significant differences were found among the studies. The study by Busson and Benoit ⁵ evaluated the influence from recipient and donor genders and the donor-recipient combination. Recipient genders were the only ones for which significant differences were not found.

The comparison between donor-recipient genders included 471,252 patients. MD-MR pair should be highlighted for having been observed to have the best results in all comparisons (MD-MR versus FD-MR, MD-MR versus FD-FR, MD-MR versus MD-FR); that is, kidney transplants from male donors to male recipients were found to have the best graft survival rates. Nonetheless, FD-MR pair was found to have the worst results (FD-MR versus MD-MR, FD-MR versus MD-FR), except for the FD-MR versus FD-FR comparison. Those results are comparable with other reviews. ⁷ ^, ⁴⁴

The assessment of differences between genders is important to improve transplant results. Men and women have different biological factors, different body conditions, hormone circumstances, and immune responses, as well as different metabolic and functional demands, which can influence kidney transplant results. ⁴⁴ Gender incompatibilities in FD-MR pair are argued to negatively influence graft survival due to kidney sizes and their numbers of nephrons. The ratio between graft and recipient weights is an important one. ²⁶ ^, ³³

Giral et al ¹⁰ analyzed the consequences from kidney mass reduction following kidney transplants, and they concluded kidney graft mass to impact glomerular filtration and proteinuria rates. The authors suggest that great kidney-to-recipient weight ratios be avoided, once that might significantly influence long-term kidney function.

That meta-analysis only included cohort studies. One of the limitations from systematic reviews with meta-analyses of observational studies regards to the selection bias that is intrinsic to this study design and to uncontrolled confounding factors. Observational cohort studies are the ones conducted in the real world, under conditions uncontrolled for. In regards to that, differences were observed in the subject numbers among the groups, types of donors (living, deceased, or both), numbers of transplants, monitored periods, among others. Despite that, observational studies are observed to have the advantages of gathering a large number of patients and best representing the real world.

Another limitation in the interpretation of results was the statistical heterogeneity among studies, which was found in the meta-analyses. The small number of studies included in the comparisons, and the lack of complete, accurate information in the studies made it difficult to account for heterogeneity sources. Most studies were not observed to include immunosuppressive therapies, ages (donors and recipients), or monitored periods. The sensitivity analysis, in which studies were included and excluded for each comparison, in general, has not altered the directions of outcomes, having changes of small relevance in heterogeneity values. It has not provided information on the possible causes for heterogeneity either.

However, the results from this review can be considered for decision-making by medical teams responsible for transplants in the clinical practice, once it represents the best level of evidence regarding the topic.

Gender incompatibilities must be avoided whenever possible. Genders must be considered as criteria in the choices regarding allocation of organs from donors and to recipients. Gender combinations may make a difference in survival rates. Nonetheless, that reality is utopic in the clinical practice, due to the scarcity of donors and the increase in the number of patients on waiting lists for transplants. A change in that scenario is required in order to improve the allocation of organs.

In conclusion, recipient and donor genders, when evaluated isolatedly, do not influence patient or graft survival rates. However, combinations between donor-recipient genders may be a determining factor for graft survival, favoring MD-MR pair.

Funding Statement

Research was supported by the Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG – Process APQ-00770-12) and by the Research Dean’s Office of Universidade Federal de Minas Gerais.

Footnotes

Higgins JPT, Green S, editors. Cochrane handbook for systematic reviews of interventions: version 5.1.0. London: The Cochrane Collaboration; 2011 [cited 2014 Feb 6]. Available from: http://www.cochrane-handbook.org

Wells GA, Shea B, O’Connelll D, Peterson J, Welch V, Losos M, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Ottawa: Ottawa Hospital Research Institute; 2014 [cited 2014 Feb 6]. Available from: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp

Based on master dissertation by Erika Vieira de Almeida e Santiago, titled: “Gênero e Efetividade da terapia de manutenção entre pacientes transplantados renais, no Brasil, no período de 2001 a 2006: uma coorte histórica”, presented to the Postgraduate Program in Medications and Pharmaceutical Assistance of Faculdade de Farmácia of the Universidade Federal de Minas Gerais, in 2014.

Research was supported by the Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG – Process APQ-00770-12) and by the Research Dean’s Office of Universidade Federal de Minas Gerais.

REFERENCES

1.Abou-Jaoude MM, Abou-Jaoude WJ, Almawi WY. Sex matching plays a role in outcome of kidney transplant. 10.6002/ect.2011.0205Exp Clin Transplant. 2012;10(5):466–470. doi: 10.6002/ect.2011.0205. [DOI] [PubMed] [Google Scholar]
2.Avula S, Sharma RK, Singh AK, Gupta A, Kumar A, Agrawal S, et al. Age and gender discrepancies in living related renal transplant donors and recipients. 367410.1016/S0041-1345(98)01189-0Transplant Proc. 1998;30(7) doi: 10.1016/s0041-1345(98)01189-0. [DOI] [PubMed] [Google Scholar]
3.Ben Hamida F, Ben Abdallah T, Abdelmoula M, Mejri H, Goucha R, Abderrahim E, et al. Impact of donor/recipient gender, age, and HLA matching on graft survival following living-related renal transplantation. 10.1016/S0041-1345(99)00817-9Transplant Proc. 1999;31(8):3338–3339. doi: 10.1016/s0041-1345(99)00817-9. [DOI] [PubMed] [Google Scholar]
4.Buchler M, Al Najjar A, Duvallon C, Lanson Y, Bagros P, Nivet H, et al. Role of donor characteristics on long-term renal allograft survival. 234510.1016/S0041-1345(97)00394-1Transplant Proc. 1997;29(5) doi: 10.1016/s0041-1345(97)00394-1. [DOI] [PubMed] [Google Scholar]
5.Busson M, Benoit G. Is matching for sex and age beneficial to kidney graft survival? Societé Française de Transplantation and Association France Transplant. Clin Transplant. 1997;11(1):15–18. [PubMed] [Google Scholar]
6.Chen PD, Tsai MK, Lee CY, Yang CY, Hu RH, Lee PH, et al. Gender differences in renal transplant graft survival. 10.1016/j.jfma.2013.10.011J Formos Med Assoc. 2013;112(12):783–788. doi: 10.1016/j.jfma.2013.10.011. [DOI] [PubMed] [Google Scholar]
7.Csete M. Gender issues in transplantation. 10.1213/ane.0b013e318163feafAnesth Analg. 2008;107(1):232–238. doi: 10.1213/ane.0b013e318163feaf. [DOI] [PubMed] [Google Scholar]
8.Ellison MD, Norman DJ, Breen TJ, Edwards EB, Davies DB, Daily OP. No effect of H-Y minor histocompatibility antigen in zero-mismatched living-donor renal transplants. 10.1097/00007890-199408270-00020Transplantation. 1994;58(4):518–520. doi: 10.1097/00007890-199408270-00020. [DOI] [PubMed] [Google Scholar]
9.Gallieni M, Mezzina N, Pinerolo C, Granata A. Sex and gender differences in nephrology. In: Oertelt-Prigione S, Regitz-Zagrosek V, editors. Sex and gender aspects in clinical medicine. New York: ꞉ Springer Science & Business Media; 2011. pp. 83–100. [Google Scholar]
10.Giral M, Nguyen JM, Karam G, Kessler M, Ligny BH, Buchler M, et al. Impact of graft mass on the clinical outcome of kidney transplants. 10.1681/ASN.2004030209J Am Soc Nephrol. 2005;16(1):261–268. doi: 10.1681/ASN.2004030209. [DOI] [PubMed] [Google Scholar]
11.Głyda M, Czapiewski W, Karczewski M, Pięta R, Oko A. Influence of donor and recipient gender as well as selected factors on the five-year survival of kidney graft. 10.2478/v10035-011-0029-1Pol Przegl Chir. 2011;83(4):188–195. doi: 10.2478/v10035-011-0029-1. [DOI] [PubMed] [Google Scholar]
12.GratwohL A, Döhler B, Stern M, Opelz G. H-Y as a minor histocompatibility antigen in kidney transplantation: a retrospective cohort study. 10.1016/S0140-6736(08)60992-7Lancet. 2008;372(9632):49–53. doi: 10.1016/S0140-6736(08)60992-7. [DOI] [PubMed] [Google Scholar]
13.Howard K, Salked G, White S, MacDonald S, Chadban S, Craig JC, et al. The cost efectiveness of increasing kidney transplantation and home-based dialysis. 10.1111/j.1440-1797.2008.01073.xNephrology(Carlton) 2009;14(1):123–132. doi: 10.1111/j.1440-1797.2008.01073.x. [DOI] [PubMed] [Google Scholar]
14.Inoue S, Yamada Y, Kuzuhara K, Ubara Y, Hara S, Ootubo O. Are women privileged organ recipients? 10.1016/S0041-1345(02)03408-5Transplant Proc. 2002;34(7):2775–2776. doi: 10.1016/s0041-1345(02)03408-5. [DOI] [PubMed] [Google Scholar]
15.Jacobs SC, Nogueira JM, Phelan MW, Bartlett ST, Cooper M. Transplant recipient renal function is donor renal mass- and recipient gender-dependent. 10.1111/j.1432-2277.2007.00617.xTranspl Int. 2008;21(4):340–345. doi: 10.1111/j.1432-2277.2007.00617.x. [DOI] [PubMed] [Google Scholar]
16.Kayler LK, Rasmussen CS, Dykstra DM, Ojo AO, Port FK, Wolfe RA, et al. Gender imbalance and outcomes in living donor renal transplantation in the United States. 10.1034/j.1600-6143.2003.00086.xAm J Transplant. 2003;3(4):452–458. doi: 10.1034/j.1600-6143.2003.00086.x. [DOI] [PubMed] [Google Scholar]
17.Kim SJ, Gill JS. H-Y incompatibility predicts short-term outcomes for kidney transplant recipients. 10.1681/ASN.2008101110J Am Soc Nephrol. 2009;20(9):2025–2033. doi: 10.1681/ASN.2008101110. [DOI] [PMC free article] [PubMed] [Google Scholar]
18.Kontodimopoulos N, Niakas D. An estimate of lifelong costs and QALYs in renal replacement therapy based on patients’ life expectancy. 10.1016/j.healthpol.2007.10.002Health Policy. 2008;86(1):85–96. doi: 10.1016/j.healthpol.2007.10.002. [DOI] [PubMed] [Google Scholar]
19.Kwon OJ, Kwak JY. The impact of sex and age matching for long-term graft survival in living donor renal transplantation. 10.1016/j.transproceed.2004.07.046Transplant Proc. 2004;36(7):2040–2042. doi: 10.1016/j.transproceed.2004.07.046. [DOI] [PubMed] [Google Scholar]
20.Lankarani MM, Assari S, Nourbala MH. Improvement of renal transplantation outcome through matching donors and recipients. Ann Transplant. 2009;14(4):20–25. [PubMed] [Google Scholar]
21.Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. 10.7326/0003-4819-151-4-200908180-00136Ann Intern Med. 2009;151(4):W-65–W-94. doi: 10.7326/0003-4819-151-4-200908180-00136. [DOI] [PubMed] [Google Scholar]
22.Meier-Kriesche HU, Ojo AO, Leavy SF, Hanson JA, Leichtman AB, Magee JC, et al. Gender differences in the risk for chronic renal allograft failure. 10.1097/00007890-200102150-00016Transplantation. 2001;71(3):429–432. doi: 10.1097/00007890-200102150-00016. [DOI] [PubMed] [Google Scholar]
23.Moosa MR. Impact of age, gender and race on patient and graft survival following renal transplantation: developing country experience. S Afr Med J. 2003;93(9):689–695. [PubMed] [Google Scholar]
24.Muller V, Szabó A, Viklicky O, Gaul I, Portl S, Philipp T, et al. Sex hormones and gender related-differences: their influence on chronic renal allograft rejection. Kid Intern. 1999;55(5):2011–2020. doi: 10.1046/j.1523-1755.1999.00441.x. [DOI] [PubMed] [Google Scholar]
25.Neugarten J, Srinivas T, Tellis V, Silbiger S, Greenstein S. The effect of donor gender on renal allograft survival. J Am Soc Nephrol. 1996;7(2):318–324. doi: 10.1681/ASN.V72318. [DOI] [PubMed] [Google Scholar]
26.Nicholson ML, Windmill DC, Horsburgh T, Harris KP. Influence of allograft size to recipient body-weight ratio on the long-term outcome of renal transplantation. 10.1046/j.1365-2168.2000.01390.xBr J Surg. 2000;87(3):314–319. doi: 10.1046/j.1365-2168.2000.01390.x. [DOI] [PubMed] [Google Scholar]
27.Nyberg G, Blohmé I, Nordén G. Gender differences in a kidney transplant population. 10.1093/ndt/12.3.559Nephrol Dial Transplant. 1997;12(3):559–563. doi: 10.1093/ndt/12.3.559. [DOI] [PubMed] [Google Scholar]
28.Oertelt-Prigione S. Sex and gender in medical literature. In: Oertelt-Prigione S, Regitz-Zagrosek V, editors. Sex and gender aspects in clinical medicine. London: Springer; 2012. pp. 9–15. [Google Scholar]
29.Oien CM, Reisaeter AV, Leivestad T, Dekker FW, Line PD, OS I. Living donor kidney transplantation: the effects of donor age and gender on short-and long-term outcomes. 10.1097/01.tp.0000255583.34329.ddTransplantation. 2007;83(5):600–606. doi: 10.1097/01.tp.0000255583.34329.dd. [DOI] [PubMed] [Google Scholar]
30.Paavonen T. Hormonal regulation of immune responses. 10.3109/07853899409147900Ann Med. 1994;26(4):255–258. doi: 10.3109/07853899409147900. [DOI] [PubMed] [Google Scholar]
31.Panajotopoulos N, Ianhez LE, Neumann J, Sabbaga E, Kalil J. Immunological tolerance in human transplantation. The possible existence of a maternal effect. 10.1097/00007890-199009000-00016Transplantation. 1990;50(3):443–445. doi: 10.1097/00007890-199009000-00016. [DOI] [PubMed] [Google Scholar]
32.Perovic S, Jankovic S. Renal transplantation vs hemodialysis: cost-effectiveness analysis. 10.2298/VSP0908639PVojnosanit Pregl. 2009;66(8):639–644. doi: 10.2298/vsp0908639p. [DOI] [PubMed] [Google Scholar]
33.Poggio ED, Hila S, Stephany B, Fatica R, Krishnamurthi V, Del Bosque C, et al. Donor kidney volume and outcomes following live donor kidney transplantation. 10.1111/j.1600-6143.2005.01225.xAm J Transplant. 2006;6(3):616–624. doi: 10.1111/j.1600-6143.2005.01225.x. [DOI] [PubMed] [Google Scholar]
34.Pugliese O, Quintieri F, Mattucci DA, Venettoni S, Taioli E, Costa AN. Kidney graft survival in Italy and factors influencing it. 10.7182/prtr.15.4.lt8514u040417g86Prog Transplant. 2005;15(4):385–391. doi: 10.1177/152692480501500411. [DOI] [PubMed] [Google Scholar]
35.Sánchez Garcia F, Torres A, Magariño M, Wichmann I, Nuñez Roldán A. Influence of cyclosporine on sex-related differences observed in the outcome of cadaveric human-kidney allografts. Inmunologia. 1989;8(3):107–109. [Google Scholar]
36.Sanfey H. Gender-specific issues in liver and kidney failure and transplantation: a review. 10.1089/jwh.2005.14.617J Womens Health. 2005;14(7):617–626. doi: 10.1089/jwh.2005.14.617. [DOI] [PubMed] [Google Scholar]
37.Segev DL, Kucirka LM, Oberai PC, Parekh RS, Boulware LE, Powe NR, et al. Age and comorbidities are effect modifiers of gender disparities in renal transplantation. 10.1681/ASN.2008060591J Am Soc Nephrol. 2009;20(3):621–628. doi: 10.1681/ASN.2008060591. [DOI] [PMC free article] [PubMed] [Google Scholar]
38.Shaheen FAM, Al Sulaiman M, Mousa D, El Din ABS, Hawas F, Fallatah A, et al. Impact of donor/recipient gender, age, HLA matching, and weight on short-term graft survival following living related renal transplantation. 10.1016/S0041-1345(98)01179-8Transplant Proc. 1998;30(7):3655–3658. doi: 10.1016/s0041-1345(98)01179-8. [DOI] [PubMed] [Google Scholar]
39.Shaheen MF, Shaheen FAM, Attar B, Elamin K, Al Hayyan H, Al Sayyari A. Impact of recipient and donor nonimmunologic factors on the outcome of deceased donor kidney transplantation. 10.1016/j.transproceed.2009.12.052Transplant Proc. 2010;42(1):273–276. doi: 10.1016/j.transproceed.2009.12.052. [DOI] [PubMed] [Google Scholar]
40.Tan JC, Kim JP, Chertow GM, Grumet FC, Desai M. Donor-recipient sex mismatch in kidney transplantation. 10.1016/j.genm.2012.07.004Gend Med. 2012;9(5):335–347. doi: 10.1016/j.genm.2012.07.004. [DOI] [PMC free article] [PubMed] [Google Scholar]
41.Valdes F, Pita S, Alonso A, Rivera CF, Cao M, Fontan MP, et al. The effect of donor gender on renal allograft survival and influence of donor age on posttransplant graft outcome and patient survival. 10.1016/S0041-1345(97)01026-9Transplant Proc. 1997;29(8):3371–3372. doi: 10.1016/s0041-1345(97)01026-9. [DOI] [PubMed] [Google Scholar]
42.Vereerstraeten P, Wissing M, Pauw L, Abramowicz D, Kinnaert P. Male recipients of kidneys from female donors are at increased risk of graft loss from both rejection and technical failure. 10.1034/j.1399-0012.1999.130205.xClin Transplant. 1999;13(2):181–186. doi: 10.1034/j.1399-0012.1999.130205.x. [DOI] [PubMed] [Google Scholar]
43.Zeier M, Dohler B, Opelz G, Ritz E. The effect of donor gender on graft survival. 10.1097/01.ASN.0000030078.74889.69J Am Soc Nephrol. 2002;13(10):2570–2576. doi: 10.1097/01.asn.0000030078.74889.69. [DOI] [PubMed] [Google Scholar]
44.Zhou JY, Cheng J, Huang HF, Shen Y, Jiang Y, Chen JH. The effect of donor recipient gender mismatch on short- and- long term graft survival in kidney transplantation: a systematic review and meta analysis. 10.1111/ctr.12191Clin Transplant. 2013;27(5):764–771. doi: 10.1111/ctr.12191. [DOI] [PubMed] [Google Scholar]
45.Zukowski M, Kotfis K, Biernawska J, Zegan-Barańska M, Kaczmarczyk M, Ciechanowicz A, et al. Donor- recipient gender mismatch affects early graft loss after kidney transplantation. 10.1016/j.transproceed.2011.08.068Transplant Proc. 2011;43(8):2914–2916. doi: 10.1016/j.transproceed.2011.08.068. [DOI] [PubMed] [Google Scholar]

Rev Saude Publica. 2015 Sep 23;49:68. [Article in Portuguese]

Gênero na alocação de órgãos no transplante renal: metanálise

Erika Vieira Almeida e Santiago ^I, Micheline Rosa Silveira ^I, Vânia Eloisa de Araújo ^II, Katia de Paula Farah ^III, Francisco de Assis Acurcio ^I, Maria das Graças Braga Ceccato ^I

Abstract

OBJETIVO

Analisar se o gênero influencia os resultados da sobrevida do enxerto e do paciente no transplante renal.

MÉTODOS

Revisão sistemática com metanálise de estudos de coorte disponíveis nas bases de dados Medline (PubMed), Lilacs, Central e Embase, incluindo busca manual e na literatura cinzenta. A seleção dos estudos e a coleta dos dados foram realizadas em duplicata por revisores independentes e as discordâncias foram resolvidas por um terceiro revisor. A sobrevida do enxerto e do paciente foram avaliadas como medidas de efetividade. A metanálise foi conduzida no softwareReview Manager ^® 5.2, aplicando o modelo de efeitos aleatórios. Foram avaliadas as comparações entre gênero de receptor, doador e doador-receptor.

RESULTADOS

Foram incluídos 29 estudos envolvendo 765.753 pacientes. Em relação à sobrevida do enxerto, aqueles provenientes de doadores masculinos apresentaram maior sobrevida quando comparado com aqueles de doadores femininos, somente no tempo de acompanhamento de 10 anos. A comparação entre gênero de receptor não apresentou diferença significativa em nenhum tempo de acompanhamento avaliado. Na avaliação entre gênero de doador-receptor houve favorecimento estatisticamente significante para doador masculino-receptor masculino. Não houve diferença, estatisticamente significante, na sobrevida do paciente para as comparações entre gênero em todos os períodos de acompanhamento avaliados.

CONCLUSÕES

A análise quantitativa dos estudos sugere que o gênero do doador ou do receptor, avaliado isoladamente, não influencia na sobrevida do enxerto e paciente. Contudo, a combinação entre gênero de doador-receptor pode ser fator determinante para a sobrevida do enxerto.

Keywords: Transplante de Rim, Distribuição por Sexo, Gênero e Saúde, Prognóstico, Metanálise

INTRODUÇÃO

O transplante renal é considerado a melhor alternativa terapêutica para os portadores de doença renal crônica avançada. ¹³ ^, ¹⁸ ^, ³² Diferenças entre gênero em relação ao transplante renal são relatadas na literatura, observadas na prática clínica nas últimas décadas, e afeta os resultados do transplante, como nas rejeições agudas e crônicas e nas sobrevidas do enxerto e dos pacientes. As mulheres têm menor acesso ao transplante, apresentam risco aumentado para rejeição aguda e diminuído para rejeição crônica, sendo esses riscos acentuados pelo envelhecimento. ⁹ ^, ²² Em contrapartida, as mulheres representam cerca de 65,0% dos doadores vivos de rins. ⁷ ^, ³⁷ A etiologia dessas diferenças ainda é desconhecida, mas, provavelmente, reflete diferenças hormonais, imunológicas, envelhecimento e preconceitos. ⁷ ^, ²² ^, ²⁸

A sobrevida após o transplante renal é maior entre as mulheres, ⁹ ^, ¹¹ mas os dados são discordantes na literatura. Em estudo na África do Sul, observou-se pior sobrevida entre as mulheres, mas não houve diferenças significativas entre gênero na sobrevida do enxerto. ²³ Em outro estudo, não foram observadas diferenças entre gênero na sobrevida do paciente e do enxerto. ²⁷

Conhecer as diferenças entre gênero é necessário para identificar possíveis barreiras para obtenção dos resultados ideais e desenvolvimento de intervenções que as superem. Esta revisão, ao focalizar essas diferenças entre gênero na efetividade clínica da terapia imunossupressora de manutenção do transplante renal, poderá promover melhor compreensão, proporcionar cuidados à saúde mais eficientes, contribuir para a elaboração de protocolos clínicos e promover melhores resultados em longo prazo para os pacientes.

O objetivo desta revisão foi analisar se gênero influencia a sobrevida de enxerto e paciente no transplante renal.

MÉTODOS

Esta revisão foi realizada de acordo com as recomendações da Cochrane Collaboration Handbookv. ^a O artigo foi preparado segundo o Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA). ²¹

Foram selecionados estudos observacionais, do tipo coorte, realizados em pacientes que receberam transplantes renais de doadores vivos ou cadáver, pela primeira vez ou por mais vezes, que abordaram as diferenças entre gênero relacionadas às características pré-transplantes e que apresentaram resultados de sobrevida do enxerto, do paciente ou de ambos. Os critérios de exclusão foram estudos não relacionados aos imunossupressores de manutenção do transplante renal, estudos farmacocinéticos, de avaliação econômica, de revisão e estudos realizados em animais.

Foi realizada busca eletrônica de artigos publicados até dezembro de 2013 nas bases de dados Medline (PubMed), Literatura Latino-Americana e do Caribe em Ciências da Saúde (Lilacs), Cochrane Controlled Trials Databases (Central), Embase. Também foi feita busca manual nas listas de referências de todos os estudos selecionados da revisão sistemática publicada. ⁴⁴ Foi também realizada busca por estudos da literatura cinzenta: no banco de teses e dissertações da Coordenação de Aperfeiçoamento de Pessoal de nível superior (Capes), da Biblioteca Digital Brasileira de Teses e Dissertações e da Biblioteca Digital de Teses e Dissertações da Universidade de São Paulo. Não houve restrições quanto à data e ao idioma das publicações. A Tabela 1 descreve a estratégia de busca utilizada em cada base de dados consultada.

Tabela 1. Estratégia de busca bibliográfica para estudos observacionais realizada em cada base eletrônica, em 12/12/2013.

Base eletrônica	Estudos	Estratégia de busca
Medline (via PubMed)	3.263	((((((((((((((Transplantation, Kidney) OR Kidney Transplantations) OR Transplantations, Kidney) OR Transplantation, Renal) OR Renal Transplantation) OR Renal Transplantations) OR Transplantations, Renal) OR Grafting, Kidney) OR Kidney Grafting)) OR (Kidney Transplantation) OR (“Kidney Transplantation”[Mesh) AND (((((male[Title/Abstract) OR female[Title/Abstract) OR gender[Title/Abstract)) OR (((((((((Factor, Sex) OR Factors, Sex) OR Sex Factor)) OR (Sex Factors)) OR (“Sex Factors”[Mesh)) OR (((((((Characteristic, Sex) OR Characteristics, Sex) OR Sex Characteristic) OR Sex Differences) OR Difference, Sex) OR Differences, Sex) OR Sex Difference)) OR (Sex Characteristics)) OR (“Sex Characteristics”[Mesh))) AND Humans[Mesh)) AND ((((“Cohort Studies”[Mesh) OR (cohort study) OR (studies, cohort) OR (study, cohort) OR (concurrent studies) OR (studies, concurrent) OR (concurrent study) OR (study, concurrent) OR (historical cohort studies) OR (studies, historical cohort) OR (cohort studies, historical) OR (cohort study, historical) OR (historical cohort study) OR (study, historical cohort) OR (analysis, cohort) OR (analysis, cohort) OR (cohort analyses) OR (cohort analysis) OR (closed cohort studies) OR (cohort studies, closed) OR (closed cohort study) OR (cohort study, closed) OR (study, closed cohort) OR (studies, closed cohort) OR (incidence studies) OR (incidence study) OR (studies, incidence) OR (study, incidence) OR (cohort studies) OR (cohort) OR (cohort analysis) OR (cohort study) OR (prospective cohort) OR (retrospective cohort) OR (retrospective cohort study) OR (prospective cohort study) OR (“Follow-Up Studies”[Mesh) OR (follow up studies) OR (follow-up study) OR (studies, follow-up) OR (study, follow-up) OR followup studies OR (followup study) OR (studies, followup) OR (study, followup) OR (“Epidemiologic Studies”[Mesh OR “Cross-Sectional Studies”[Mesh OR “Retrospective Studies”[Mesh OR “Longitudinal Studies”[Mesh OR “Prospective Studies”[Mesh))) OR ((case* AND and control*[Text Word))))
Embase	2.363	‘kidney transplantation’/exp ANDembase/lim AND ‘gender and sex’/exp ANDembase/lim OR ‘sex difference’/exp ANDembase/lim OR ‘gender’/exp ANDembase/lim OR ‘sex ratio’/exp ANDembase/lim AND (‘cohort analysis’/de OR ‘comparative study’/de OR ‘control group’/de OR ‘controlled study’/de OR ‘human’/de OR ‘observational study’/de OR ‘outcomes research’/de OR ‘prospective study’/de OR ‘retrospective study’/de)
Central	280	(“Transplantation, Kidney” OR “Kidney Transplantations” OR “Transplantations, Kidney” OR “Transplantation, Renal” OR “Renal Transplantation” OR “Renal Transplantations” OR “Transplantations, Renal” OR “Grafting, Kidney” OR “Kidney Grafting” OR “Kidney Transplantation” OR “MeSH descriptor:Kidney Transplantation 1 tree(s) exploded”) AND (“male” OR “female” OR “gender” OR “Factor, Sex” OR “Factors, Sex” OR “Sex Factor” OR “Sex Factors” OR “MeSH descriptor:Sex Factors explode all trees”) AND “Characteristic, Sex” OR “Characteristics, Sex” OR “Sex Characteristic” OR “Sex Differences” OR “Difference, Sex” OR “Differences, Sex” OR “Sex Difference” OR “Sex Characteristics” OR “MeSH descriptor:Sex Characteristics explode all trees”) AND (“graft rejection OR MeSH descriptor:Graft Rejection explode all trees”) AND (“survival rate” “MeSH descriptor:Survival Rate explode all trees”) AND “graft survival”
Lilacs	87	(tw:(transplantation kidney)) OR (tw:(transplantation renal)) AND (tw:(gender differences)) OR (tw:(gender Characteristics)) OR (tw:(Sex Characteristics)) OR (tw:(sex differences)) AND (tw:(survival rate)) AND (tw:(survival graft))

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Excluídas todas as duplicações, dois revisores independentes selecionaram as referências, em três fases: análise de títulos, dos resumos e dos textos completos. As discordâncias foram resolvidas por um terceiro revisor. Os dados, incluindo qualidade metodológica, informações do participante, período de duração do tratamento e sobrevida do enxerto e do paciente, foram extraídos e coletados em duplicata em planilha do Microsoft Excel 2010.

As avaliações da qualidade metodológica foram realizadas de forma independente por dois revisores e as divergências, por consenso. Foi utilizada a escala de Newcastle-Ottawa ^b para estudos observacionais. Nesta escala, cada estudo é avaliado em três dimensões: seleção dos grupos de estudo, comparabilidade dos grupos e apuração da exposição ou resultado de interesse. A pontuação total foi de até nove estrelas, sendo que acima de seis, o estudo é considerado de alta qualidade.

Para serem analisados, os estudos foram agrupados de acordo com a comparação de resultados entre:

a) Gênero de doador – doador masculino (DM) e doador feminino (DF);

b) Gênero de receptor – receptor masculino (RM) e receptor feminino (RF);

c) Gênero de doador-receptor – doador masculino-receptor masculino (DM-RM), doador masculino-receptor feminino (DM-RF), doador feminino-receptor feminino (DF-RF), doador feminino-receptor masculino (DF-RM).

Os dados dos estudos foram combinados usando o modelo de efeitos randômicos no módulo Metaview do softwareReview Manager versão 5.3. Os resultados foram apresentados por risco relativo para as variáveis dicotômicas com intervalo de confiança de 95%. Análises com I²> 40,0% e p-valor do teste do Qui-quadrado < 0,10 foram consideradas como heterogeneidade significante. Análise de sensibilidade foi conduzida para investigar as causas da heterogeneidade, excluindo um estudo de cada vez e verificadas as mudanças nos valores de I² e p.

Os desfechos avaliados na metanálise foram sobrevida do enxerto e sobrevida do paciente por tempo de seguimento (um; dois; três; cinco; oito; 10 ou mais anos).

RESULTADOS

Inicialmente foram identificadas 5.993 publicações nas bases eletrônicas e sete pela busca manual, totalizando 6.000 publicações. Foram excluídas 500 devido ao tipo do participante, 5.251 pelo tipo de estudo e 177 devido à intervenção. As principais causas das exclusões foram: estudos que não analisavam desfecho de interesse (sobrevida do enxerto e do paciente), que não contemplavam transplante renal, estudos de revisão, farmacocinéticos e farmacoeconômico, entre outros. Após a eliminação de duplicatas e análise pelos revisores, 29 estudos de coortes foram incluídos, envolvendo 765.753 pacientes. Desses, seis estudos compararam as medidas de resultados entre gênero de doador (DM e DF); oito estudos entre gênero de receptor (RM e RF); e 20 entre combinações de gênero de doador-receptor (DM-RM, DM-RF, DF-RF, DF-RM) (Figura). Foram incluídos um estudo nas comparações entre gênero de doador, receptor e doador-receptor, ⁵ um estudo ¹⁴ na comparação entre gênero de receptor e doador-receptor e dois estudos na comparação entre gênero de doador e doador-receptor. ³ ^, ²⁵

Dos 29 estudos observacionais incluídos, 28 eram retrospectivos e um prospectivo. ³⁸ A maioria dos estudos não relatou tempo médio de acompanhamento e o período de coleta de dados das coortes foi de 1978 a 2009. Na comparação entre gênero de doador, foram avaliados 9.673 participantes nos seis estudos. Na comparação entre gênero de receptor foram avaliados 84.070 participantes nos oito estudos incluídos e, na comparação entre gênero doador-receptor foram avaliados 672.010 participantes nos 20 estudos incluídos. Em relação ao tipo de doador, 12 estudos avaliaram doador cadáver, oito avaliaram doador vivo e nove, ambos (vivo e cadáver) (Tabela 2).

Tabela 2. Características gerais dos estudos incluídos nas comparações entre gênero.

Estudo	Comparação entre gênero	N^o de pacientes	País de realização do estudo	Tipo de doador	Idade do doador (anos)	Idade do receptor (anos)	Terapia imunossupressora	Período de Coleta	Tempo médio de acompanhamento (meses)	Escala Newcastle
Neugarten et al²⁵ (1996)	Doador e doador-receptor	651	EUA	Ambos	NR	NR	Ciclosporina	1979 a 1994	NR	7
Buchler et al⁴ (1997)	Doador	354	França	Cadáver	NR^a	49	Múltipla	1985 a 1995	NR	6
Busson e Benoit⁵ (1997)	Receptor, doador e doador-receptor	6.889	França	Cadáver	NR^a	NR^a	NR	1989 a 1992	NR	7
Valdes et al⁴¹ (1997)	Doador	858	Espanha	Cadáver	NR^a	NR^a	NR	1981 a 1995	NR	7
Ben Hamida et al³ (1999)	Doador e doador-receptor	182	Tunísia	Vivo	39,3	28,1	Múltipla	1986 a 1998	NR	7
Oien et al²⁹ (2007)	Doador	739	Noruega	Vivo	NR^a	NR^a	Múltipla	1994 a 2004	55,1	8
Sánches Garcia et al³⁵ (1989)	Receptor	760	Espanha	Cadáver	NR	NR	Ciclosporina	1978 a 1988	NR	7
Nyberg et al²⁷ (1997)	Receptor	1.000	Suécia	Ambos	NR^a	NR^a	Ciclosporina + prednisolona	1985 a 1993	73	8
Avula et al² (1998)	Receptor	431	Índia	Vivo	43,18	33,87	Múltipla	NR	9	6
Meier-KriescheH et al²² (2001)	Receptor	73.477	EUA	Ambos	NR^a	NR^a	Múltipla	1988 a 1997	NR	8
Inoue et al¹⁴ (2002)	Receptor e doador-receptor	205	Japão	Ambos	NR^a	NR^a	Cisclosporina ou FK506	1987 a 2000	NR	7
Moosa²³ (2003)	Receptor	542	África do Sul	Cadáver	NR^a	37	Múltipla	1976 a 1999	75,6	7
Chen et al⁶ (2013)	Receptor	766	China	Ambos	NR^a	NR^a	Múltipla	1988 a 2009	NR	7
Ellison etal⁸ (1994)	Doador-receptor	3.314	EUA	Ambos	NR	NR	NR	1987 a 1992	NR	8
Shaheen et al³⁸ (1998)^b	Doador-receptor	406	Arábia Saudita	Vivo	31,3	34,3	Ciclosporina	NR	55,2	7
Vereerstraeten et al⁴² (1999)	Doador-receptor	741	Bélgica	Cadáver	34,8	36,9	Múltipla	1983 a 1997	NR	7
Zeier et al⁴³ (2002)	Doador-receptor	119.195	49 países	Ambos	38,3	44,3	NR	1985 a 2000	NR	8
Kayler et al¹⁶ (2003)	Doador-receptor	30.258	EUA	Vivo	NR^a	NR^a	NR	1990 a 1999	NR	8
Kwon e Kwak¹⁹ (2004)	Doador-receptor	614	Coreia do Sul	Vivo	NR^a	NR^a	NR	1979 a 2002	NR	7
Pugliese et al³⁴ (2005)	Doador-receptor	3.233	Itália	Cadáver	42,1	44,5	NR	1995 a 2000.	NR	8
Jacobs et al¹⁵ (2007)	Doador-receptor	730	EUA	Vivo	39,7	46,4	NR	1979 a 1994	NR	8
Gratwohl et al¹² (2008)	Doador-receptor	195.516	45 países	Cadáver	38	44,7	NR	1985 a 2004	67,2	8
Kim e Gill¹⁷ (2009)	Doador-receptor	117.877	EUA	Cadáver	NR^a	NR^a	NR	1990 a 2004	NR^a	7
Lankarani et al²⁰ (2009)	Doador-receptor	2.649	Iran	Vivo	NR^a	NR^a	NR	1992 a 2005	NR	8
Shaheen et al³⁹ (2010)	Doador-receptor	524	Arábia Saudita	Cadáver	33,6	33,9	Múltipla	2003 a 2007	20,9	8
Głyda et al¹¹ (2011)	Doador-receptor	154	Polônia	Cadáver	NR^a	NR^a	Múltipla	NR	NR	7
Zukowski et al⁴⁵ (2011)	Doador-receptor	230	Polônia	Cadáver	33,1	37,6	NR	NR	NR	8
Abou-Jaoude et al¹ (2012)	Doador-receptor	135	Líbano	Ambos	NR^a	NR^a	Múltipla	1998 a 2007	NR	7
Tan et al⁴⁰ (2012)	Doador-receptor	188.507	EUA	Ambos	NR^a	NR^a	NR	1988 a 2006	NR	8

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NR: não relata; NR^a: não relata da forma desejada.

^b Coorte prospectiva.

Para todas as comparações entre gênero, a maioria dos participantes dos estudos (doadores, receptores e doadores-receptores) era do sexo masculino. Todos os estudos incluídos avaliaram sobrevida do enxerto, mas apenas oito avaliaram sobrevida do paciente. ¹ ^, ¹⁴ ^, ²⁰ ^, ²² ^, ²³ ^, ²⁷ ^, ³⁹ ^, ⁴³

Dos 29 estudos incluídos, dois obtiveram a pontuação seis na escala de New-Castle Ottawa; ² ^, ⁴ 14 (48,3%) obtiveram sete; e 13, oito (Tabela 2).

Dos seis estudos incluídos na revisão sistemática para a comparação de gênero do doador, cinco foram incluídos na metanálise para o desfecho sobrevida do enxerto. ³ ^- ⁵ ^, ²⁹ ^, ⁴¹ O estudo de Neugarten et al ²⁵ não apresentou dados numéricos suficientes para a análise quantitativa. Os estudos incluídos na comparação gênero do doador não avaliaram sobrevida do paciente.

Para a sobrevida do enxerto, os riscos relativos (RR) agrupados em ordem por tempo de acompanhamento de um, dois, três, cinco, oito e 10 anos foram, respectivamente, 1,02 (IC95% 0,97;1,07; p = 0,43; I² = 70,0%), 1,03 (IC95% 1,00;1,07; p = 0,07; I² = 27,0%), 1,02 (IC95% 0,94;1,12; p = 0,58; I² = 67,0%), 0,89 (IC95% 0,79;1,00; p = 0,06; I² = 0%), 0,86 (IC95% 0,73;1,02; p = 0,09; I² = 11,0%;) e 0,82 (IC95% 0,68;0,98; p = 0,03; I² = 0%). Apenas aos 10 anos de acompanhamento a diferença foi significativa para sobrevida do enxerto, favorecendo doadores do gênero masculino. A heterogeneidade foi alta e significante para os tempos de acompanhamento de um e três anos (Tabela 3).

Tabela 3. Resumo das metanálises para sobrevida do enxerto segundo o gênero do doador (DF ou DM) e do receptor (RF ou RM); e sobrevida do paciente segundo o gênero do receptor de transplante de renal.

Desfecho/tempo	Estudos	Participantes	RR	IC95%	p^a	I² (%)^b
Sobrevida do enxerto	DF versus DM
1 ano	^3,5,30	7.478	1,02	0,97;1,07	0,43	70,0^c
2 anos	^5,30,41	8.154	1,03	1,00;1,07	0,07	27,0
3 anos	^5,30,41	8.154	1,02	0,94;1,12	0,58	67,0^c
5 anos	^3,30	589	0,89	0,79;1,00	0,06	0
8 anos	^4,30	761	0,86	0,73;1,02	0,09	11,0
10 anos	^3,30	589	0,82	0,68;0,98	0,03	0
Sobrevida do enxerto	RF versus RM
1 ano	^2,5,10	8.348	1,01	0,99;1,03	0,30	0
5 anos	^2,6,15	1.402	0,99	0,88;1,12	0,88	75,0^c
10 anos e mais	^15,24	747	1,23	0,68;2,24	0,50	95,0^c
Sobrevida do paciente	RF versus RM
10 anos e mais	^15,24	747	0,96	0,67;1,37	0,81	95,0^c

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RR: risco relativo

^a Valor de p < 0,10 do teste Z para todos os efeitos.

^b Valor de I² > 40,0% indica heterogeneidade estatística entre os estudos.

^c Heterogeneidade significante (p < 0,10).

Dos oito estudos incluídos na revisão sistemática para a comparação de gênero do receptor, seis foram incluídos na metanálise para o desfecho sobrevida do enxerto. ² ^, ⁵ ^, ⁶ ^, ¹⁴ ^, ²³ ^, ³⁵ Os estudos de Nyberg et al²⁷ e Meier-Kriesche et al²² não apresentaram dados numéricos para serem incluídos na análise quantitativa. Assim, as metanálises foram realizadas nos tempos de seguimento (um; cinco; e 10 ou mais anos).

Na metanálise referente à sobrevida do enxerto para um ano foram incluídas quatro comparações de três estudos. No estudo de Sánchez Garcia et al,³⁵ (1989) comparou-se a influência da terapia imunossupressora sobre o gênero, dividido em dois grupos: Sánchez Garcia et al ³⁵ (1989a), tratados com ciclosporina, e Sánchez Garcia et al ³⁵ (1989b), não tratados com ciclosporina.

Para a sobrevida do enxerto, os RR agrupados em ordem por tempo de acompanhamento de um, cinco, 10 anos e mais foram, respectivamente, 1,01 (IC95% 0,99;1,03; p = 0,30; I² = 0%), 0,99 (IC95% 0,88;1,12; p = 0,88; I² = 75,0%), 1,23 (IC95% 0,68;2,24; p = 0,50; I² = 95,0%). Não houve diferença significante em nenhum dos tempos de acompanhamento, sem favorecimento para o gênero de receptor entre os grupos. A heterogeneidade foi alta e significante para cinco e 10 ou mais anos de acompanhamento (Tabela 3).

Para a sobrevida do paciente foram incluídos na metanálise dois estudos. ¹⁴ ^, ²⁴ A metanálise foi realizada para o tempo de acompanhamento de 10 anos ou mais, a heterogeneidade foi alta e a diferença não foi significativa (RR = 0,96; IC95% 0,67;1,37; p = 0,81; I² = 95,0%) (Tabela 3).

Para avaliar gênero do doador-receptor, foram analisadas seis comparações: DM-RM versus DF-RM, DM-RM versus DF-RF, DM-RM versus DM-RF, DM-RF versus DF-RF, DM-RF versus DF-RM, DF-RF versus DF-RM. Para o desfecho sobrevida do enxerto, foram incluídos 13 estudos ¹ ^, ⁵ ^, ⁸ ^, ¹¹ ^, ¹⁵ ^- ¹⁷ ^, ¹⁹ ^, ²⁰ ^, ³⁸ ^- ⁴⁰ ^, ⁴³ nas metanálises (Tabela 4).

Tabela 4. Resumo das metanálises para sobrevida do enxerto segundo o gênero do doador-receptor de transplante renal.

Características gerais		DM-RM versus DF-RM					DM-RM versus DF-RF
Tempo	Estudos	N^o pacientes	RR	IC95%	p^a	I² (%)^b	N° pacientes	RR	IC95%	p^a	I² (%)^b
1 ano	^{1,5,8,15,16,17,20,39,40}	211.025	1,03	1,01;1,05	< 0,01	92,0^c	181.223	1,02	1,01, 1,04	< 0,01	83,0^c
2 anos	^5,8,15,20	8.411	1,05	1,03;1,08	<0,01	25,0	7.575	1,02	1,00;1,04	0,10	9,0
3 anos	^{5,8,15,17,20,39}	79.979	1,06	1,02;1,09	< 0,01	72,0^c	69.993	1,05	1,01;1,09	0,02	73,0^c
5 anos	^{11,16,17,19,20,38,40}	204.668	1,15	1,00;1,33	0,05	100^c	175.602	1,02	1,01;1,03	< 0,01	50,0^c
10 anos	^17,40,43	258.63	1,08	1,05;1,11	< 0,01	91,0^c	223.404	1,02	0,97;1,07	0,43	97,0^c

Características gerais		DM-RM versus DM-RF					DM-RF versus DF-RF

Tempo	Estudos	N^o pacientes	RR	IC95%^a	p^b	I² (%)^c	N° pacientes	RR	IC95%^a	p^b	I² (%)^c

1 ano	^{1,5,8,15,16,17,20,39,40}	196.191	1,01	1,01;1,02	< 0,01	67,0^c	139.859	1,01	0,99;1,02	0,30	77,0^c
2 anos	^5,8,15,20	9.086	1,01	0,99;1,03	0,32	0	5.171	1,01	0,98;1,03	0,61	0
3 anos	^{5,8,15,17,20,39}	80.495	1,03	1,00;1,06	0,07	76,0^c	51.994	1,01	1,00;1,02	< 0,01	0
5 anos	^{11,16,17,19,20,38,40}	189.508	1,00	0,97;1,03	0,98	91,0^c	135.798	1,01	1,00;1,03	0,11	66,0^c
10 anos	^17,40,43	246.909	0,96	0,86;1,06	0,38	99,0^c	166.817	1,04	1,02;1,06	< 0,01	80,0^c

Características gerais		DM-RF versus DF-RM					DF-RF versus DF-RM

Tempo	Estudos	N^o pacientes	RR	IC95%^a	p^b	I² (%)^c	N° pacientes	RR	IC95%^a	p^b	I² (%)^c

1 ano	^{1,5,8,15,16,17,20,39,40}	169.666	1,01	1,00;1,03	0,15	90,0^c	154.693	1,01	0,99;1,02	0,45	80,0^c
2 anos	^5,8,15,20	5.679	1,05	1,01;1,10	0,01	36,0	4.496	1,03	0,99;1,07	0,18	51,0^c
3 anos	^{5,8,15,17,20,39}	61.980	1,03	1,00;1,05	0,04	44,0^c	51.478	1,01	0,98;1,04	0,53	44,0
5 anos	^{11,16,17,19,20,38,40}	164.864	1,18	1,03;1,35	0,02	100^c	150.958	1,14	0,99;1,31	0,07	100^c
10 anos	^17,40,43	202.176	1,10	1,01;1,21	0,03	99,0^c	176.671	1,06	0,98;1,14	0,14	98,0^c

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RR: risco relativo

^a Valor de p < 0,10 do teste Z para todos os efeitos.

^b Valor de I² > 40,0% indica heterogeneidade estatística entre os estudos.

^c Heterogeneidade significante (p < 0,10).

Os outros estudos não apresentaram dados suficientes para a análise quantitativa. ³ ^, ¹⁰ ^, ¹² ^, ¹⁴ ^, ²⁵ ^, ⁴² ^, ⁴⁵ Para o desfecho sobrevida do paciente, dois estudos foram incluídos na metanálise. ¹ ^, ²⁰

Os estudos de Ellison et al ⁸ e Tan et al ⁴⁰ avaliaram transplantes de doadores vivos e falecidos, separadamente, sendo incluída na metanálise a somatória do número de eventos e de participantes de cada estudo considerando doadores vivos e falecidos. No estudo de Abou-Jaoude et al ¹ foi avaliada a sobrevida do enxerto geral e a sobrevida do enxerto censurada pela morte com enxerto funcionante, sendo utilizada na metanálise a sobrevida sem censura.

Na comparação DM-RM versus DF-RM, os RR agrupados para a sobrevida do enxerto em ordem por tempo de acompanhamento de um, dois, três, cinco e 10 anos foram, respectivamente, 1,03 (IC95% 1,01;1,05; p = 0,0002; I² = 92,0%), 1,05 (IC95% 1,03;1,08; p < 0,0001; I² = 25,0%), 1,06 (IC95% 1,02;1,09; p = 0,0008; I² = 72,0%), 1,15 (IC95% 1,00;1,33; p = 0,05; I² = 100%) e 1,08 (IC95% 1,05;1,11; p < 0,00001; I² = 91,0%). A taxa de sobrevida do enxerto foi significativamente maior em todos os tempos de acompanhamento avaliados, favorecendo o par DM-RM. A heterogeneidade foi alta e significante para todos os períodos, exceto aos dois anos de acompanhamento. A análise de sobrevida do paciente foi realizada apenas para o tempo de acompanhamento de um ano e não houve favorecimento de nenhum par (RR = 0,99; IC95% 0,96;1,02; p = 0,52; I² = 0,0%).

Na comparação DM-RM versus DF-RF, os RR agrupados para a sobrevida do enxerto em ordem por tempo de acompanhamento de um, dois, três, cinco e 10 anos foram, respectivamente, 1,02 (IC95% 1,01;1,04; p = 0,0008; I² = 83,0%), 1,02 (IC95% 1,00;1,04; p < 0,10; I² = 9,0%), 1,05 (IC95% 1,01;1,09; p = 0,02; I² = 73,0%), 1,02 (IC95% 1,01;1,03; p = 0,0004; I² = 50,0%) e 1,02 (IC95% 0,97;1,07; p = 0,43; I² = 97,0%). A taxa de sobrevida do enxerto foi significativamente maior nos tempos de acompanhamento de um, três e cinco anos, favorecendo o par DM-RM. A heterogeneidade não foi significante apenas para dois anos de acompanhamento. A metanálise de sobrevida do paciente não mostrou favorecimento para nenhum par (RR = 0,98; IC95% 0,95;1,01; p = 0,21; I² = 0%).

Na comparação DM-RM versus DM-RF, os RR agrupados para a sobrevida do enxerto, em ordem por tempo de acompanhamento de um, dois, três, cinco e 10 anos foram, respectivamente, 1,01 (IC95% 1,01;1,02; p = 0,0009; I² = 67,0%), 1,01 (IC95% 0,99;1,03; p = 0,32; I² = 0%), 1,03 (IC95%1,00;1,06; p = 0,07; I² = 76,0%), 1,00 (IC95% 0,97;1,03; p = 0,98; I² = 91,0%) e 0,96 (IC95% 0,86;1,06; p = 0,38; I² = 99,0%). A taxa de sobrevida do enxerto foi significativamente maior apenas no tempo de acompanhamento de um ano, favorecendo o par DM-RM. A heterogeneidade não foi significante apenas para dois anos de acompanhamento. A metanálise de sobrevida do paciente não mostrou favorecimento para nenhum par (RR = 1,00; IC95% 0,98;1,03; p = 0,86; I² = 0%).

Na comparação DM-RF versus DF-RF, os RR agrupados para a sobrevida do enxerto, em ordem por tempo de acompanhamento de um, dois, três, cinco e 10 anos foram, respectivamente, 1,01 (IC95% 0,99;1,02; p = 0,30; I² = 77,0%), 1,01 (IC95% 0,98;1,03; p = 0,61; I² = 0%), 1,01 (IC95% 1,00;1,02; p = 0,0007; I² = 0%), 1,01 (IC95% 1,00;1,03; p = 0,11; I² = 66,0%) e 1,04 (IC95% 1,02;1,06; p = 0,0003; I² = 80,0%). A taxa de sobrevida do enxerto foi significativamente maior nos tempos de acompanhamento de três e 10 anos, favorecendo o par DM-RF. A heterogeneidade não foi significante apenas para dois e três anos de acompanhamento. A metanálise de sobrevida do paciente não mostrou favorecimento para nenhum par (RR = 0,98; IC95% 0,94;1,01; p = 0,19; I² = 0%).

Na comparação DM-RF versus DF-RM, os RR agrupados para a sobrevida do enxerto em ordem por tempo de acompanhamento de um, dois, três, cinco e 10 anos foram, respectivamente, 1,01 (IC95% 1,00;1,03; p = 0,15; I² = 90,0%), 1,05 (IC95% 1,01;1,10; p = 0,01; I² = 36,0%), 1,03 (IC95% 1,00;1,05; p = 0,04; I² = 44,0%), 1,18 (IC95% 1,03;1,35; p = 0,02; I² = 100%) e 1,10 (IC95% 1,01;1,21; p = 0,03; I² = 99,0%). A taxa de sobrevida do enxerto foi significativamente maior em todos os tempos de seguimento, exceto em um ano, favorecendo o par DM-RF. A heterogeneidade foi alta e significante para todos os períodos, exceto aos dois anos de acompanhamento. A metanálise de sobrevida do paciente não mostrou favorecimento para nenhum par (RR = 0,99; IC95% 0,95;1,02; p = 0,44; I² = 0%).

Na comparação DF-RF versus DF-RM, os RR agrupados para a sobrevida do enxerto em ordem por tempo de acompanhamento de um, dois, três, cinco e 10 anos foram, respectivamente, 1,01 (IC95% 0,99;1,02; p = 0,45; I² = 80,0%), 1,03 (IC95% 0,99;1,07; p = 0,18; I² = 51,0%), 1,01 (IC95% 0,98;1,04; p = 0,53; I² = 44,0%), 1,14 (IC95% 0,99;1,31; p = 0,07; I² = 100%) e 1,06 (IC95% 0,98;1,14; p = 0,14; I² = 98,0%). Não houve diferença significante na taxa de sobrevida do enxerto nos tempos de acompanhamento. A heterogeneidade foi alta e significante para todos os períodos, exceto aos três anos de acompanhamento. A metanálise de sobrevida do paciente não mostrou favorecimento para nenhum par (RR = 1,01; IC95% 0,97;1,06; p = 0,54; I² = 0%).

DISCUSSÃO

Esta metanálise avaliou a influência do gênero de doadores, receptores e combinação doador-receptor na sobrevida do enxerto e do paciente no transplante renal.

Para a comparação entre gênero de doador, foram avaliados 9.022 pacientes na metanálise. O gênero do doador não favoreceu a sobrevida do enxerto na avaliação de um, dois, três, cinco e oito anos de acompanhamento (p > 0,05). Apenas no tempo de acompanhamento de 10 anos houve diferença significativa favorecendo os doadores do gênero masculino (p = 0,03). O estudo de Muller²⁴ concluiu que enxertos renais de pacientes do gênero masculino funcionam melhor que aqueles de pacientes do gênero feminino, em longo prazo. Vários estudos sugerem que, nesses casos, os enxertos de doadoras são mais antigênicos, o que pode explicar a menor sobrevida. ²² ^, ³⁰ ^, ³¹ ^, ³⁶

Para a comparação entre gênero de receptor, em todos os períodos de acompanhamento, foram avaliados 9.593 pacientes na metanálise e não foi observada diferença significativa na sobrevida do enxerto. Na análise de sobrevida do paciente foram avaliados 747 pacientes e não foram encontradas diferenças significativas entre os estudos. O estudo de Busson e Benoit ⁵ avaliou a influência do gênero entre receptores, doadores e da combinação doadores-receptores e não encontrou diferenças significativas apenas para o gênero do receptor.

Na comparação entre gênero de doador-receptor, participaram 471.252 pacientes. Evidencia-se que no par DM-RM houve melhores resultados em todas as comparações (DM-RM versus DF-RM, DM-RM versus DF-RF, DM-RM versus DM-RF), ou seja, os transplantes de rins de doadores masculinos em receptores masculinos apresentaram melhores taxas para sobrevida do enxerto. Entretanto, no par DF-RM houve os piores resultados (DF-RM versus DM-RM, DF-RM versus DM-RF), exceto na comparação DF-RM versus DF-RF. Esses resultados são comparáveis com outras revisões. ⁷ ^, ⁴⁴

A avaliação das diferenças entre gênero é importante para melhorar os resultados no transplante. Homens e mulheres possuem fatores biologicamente desiguais, bem como condições diferentes do corpo, circunstâncias hormonais e respostas imunes, além de demandas metabólicas e funcionais, que podem influenciar nos resultados do transplante renal. ⁴⁴ Estudos discutem que a incompatibilidade entre gênero no par DF-RM influencia negativamente a sobrevida do enxerto devido ao volume do rim e número de néfrons, sendo importante a relação do peso do enxerto com o peso do destinatário. ²⁶ ^, ³³

Giral et al ¹⁰ analisaram as consequências da redução da massa renal em resultados após transplante renal e concluíram que a massa do enxerto renal impacta a taxa de filtração glomerular e proteinúria. Os autores sugerem evitar grande inadequação do peso do rim e do destinatário, uma vez que isso pode influenciar significativamente na função do transplante em longo prazo.

Esta metanálise incluiu somente estudos de coorte. Uma das limitações de revisões sistemáticas com metanálise de estudos observacionais refere-se ao viés de seleção intrínseco a esse delineamento de estudo e a fatores de confusão não controlados. Estudos observacionais de coorte são estudos realizados no mundo real em condições não controladas. Com isso, foram observadas diferenças no número de participantes entre os grupos, tipo de doadores (vivos, falecidos ou ambos), número de transplantes, período de seguimento, entre outros. Apesar disso, os estudos observacionais têm a vantagem de reunir um número grande de pacientes e melhor representar o mundo real.

Outra limitação na interpretação dos resultados foi a heterogeneidade estatística entre os estudos encontrada nas metanálises. O pequeno número de estudos incluídos nas comparações e a falta de informações completas e precisas nos estudos dificultaram a explicação para as fontes de heterogeneidade. A maioria dos estudos não apresentou a terapia imunossupressora, idade (doador e receptor) e tempo de seguimento. A análise de sensibilidade com inclusão e exclusão de estudos em cada comparação, no geral, não alterou a direção dos desfechos, com alterações pouco relevantes no valor da heterogeneidade, além de não fornecer informação sobre as possíveis causas para a heterogeneidade.

Entretanto, os resultados desta revisão podem ser considerados para a tomada de decisão na prática clínica pelas equipes transplantadoras, uma vez que representa o melhor nível de evidência sobre o assunto.

A incompatibilidade entre gênero deve ser evitada sempre que possível. O gênero deve ser considerado como um critério na escolha da alocação de órgãos dos doadores e receptores, sendo que a combinação de gênero pode fazer a diferença nas taxas de sobrevida. Entretanto, essa é uma realidade comprometida na prática clínica, devido à escassez de doadores e ao aumento do número de pacientes na lista de espera para transplante, tornando-se necessária uma mudança nesse cenário a fim de melhorar a alocação dos órgãos.

Em conclusão, gênero do receptor e do doador avaliado isoladamente não influencia a sobrevida do enxerto e do paciente. Contudo, a combinação gênero doador-receptor pode ser um fator determinante para a sobrevida do enxerto, favorecendo o par DM-RM.

Footnotes

Higgins JPT, Green S, editors. Cochrane handbook for systematic reviews of interventions: version 5.1.0. London: The Cochrane Collaboration; 2011 [citado 2014 fev 6]. Disponível em: http://www.cochrane-handbook.org

Wells GA, Shea B, O’Connelll D, Peterson J, Welch V, Losos M, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Ottawa: Ottawa Hospital Research Institute; 2014 [citado 2014 fev 6]. Disponível em: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp

Baseado na dissertação de Erika Vieira de Almeida e Santiago, intitulada: “Gênero e Efetividade da terapia de manutenção entre pacientes transplantados renais, no Brasil, no período de 2001 a 2006: uma coorte histórica”, apresentada ao Programa de Pós-Graduação em Medicamentos e Assistência Farmacêutica da Faculdade de Farmácia da Universidade Federal de Minas Gerais, em 2014.

Pesquisa financiada pela Fundação de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG – Processo APQ-00770-12) e pela Pró-Reitoria de Pesquisa da Universidade Federal de Minas Gerais.

[B1] 1.Abou-Jaoude MM, Abou-Jaoude WJ, Almawi WY. Sex matching plays a role in outcome of kidney transplant. 10.6002/ect.2011.0205Exp Clin Transplant. 2012;10(5):466–470. doi: 10.6002/ect.2011.0205. [DOI] [PubMed] [Google Scholar]

[B2] 2.Avula S, Sharma RK, Singh AK, Gupta A, Kumar A, Agrawal S, et al. Age and gender discrepancies in living related renal transplant donors and recipients. 367410.1016/S0041-1345(98)01189-0Transplant Proc. 1998;30(7) doi: 10.1016/s0041-1345(98)01189-0. [DOI] [PubMed] [Google Scholar]

[B3] 3.Ben Hamida F, Ben Abdallah T, Abdelmoula M, Mejri H, Goucha R, Abderrahim E, et al. Impact of donor/recipient gender, age, and HLA matching on graft survival following living-related renal transplantation. 10.1016/S0041-1345(99)00817-9Transplant Proc. 1999;31(8):3338–3339. doi: 10.1016/s0041-1345(99)00817-9. [DOI] [PubMed] [Google Scholar]

[B4] 4.Buchler M, Al Najjar A, Duvallon C, Lanson Y, Bagros P, Nivet H, et al. Role of donor characteristics on long-term renal allograft survival. 234510.1016/S0041-1345(97)00394-1Transplant Proc. 1997;29(5) doi: 10.1016/s0041-1345(97)00394-1. [DOI] [PubMed] [Google Scholar]

[B5] 5.Busson M, Benoit G. Is matching for sex and age beneficial to kidney graft survival? Societé Française de Transplantation and Association France Transplant. Clin Transplant. 1997;11(1):15–18. [PubMed] [Google Scholar]

[B6] 6.Chen PD, Tsai MK, Lee CY, Yang CY, Hu RH, Lee PH, et al. Gender differences in renal transplant graft survival. 10.1016/j.jfma.2013.10.011J Formos Med Assoc. 2013;112(12):783–788. doi: 10.1016/j.jfma.2013.10.011. [DOI] [PubMed] [Google Scholar]

[B7] 7.Csete M. Gender issues in transplantation. 10.1213/ane.0b013e318163feafAnesth Analg. 2008;107(1):232–238. doi: 10.1213/ane.0b013e318163feaf. [DOI] [PubMed] [Google Scholar]

[B8] 8.Ellison MD, Norman DJ, Breen TJ, Edwards EB, Davies DB, Daily OP. No effect of H-Y minor histocompatibility antigen in zero-mismatched living-donor renal transplants. 10.1097/00007890-199408270-00020Transplantation. 1994;58(4):518–520. doi: 10.1097/00007890-199408270-00020. [DOI] [PubMed] [Google Scholar]

[B9] 9.Gallieni M, Mezzina N, Pinerolo C, Granata A. Sex and gender differences in nephrology. In: Oertelt-Prigione S, Regitz-Zagrosek V, editors. Sex and gender aspects in clinical medicine. New York: ꞉ Springer Science & Business Media; 2011. pp. 83–100. [Google Scholar]

[B10] 10.Giral M, Nguyen JM, Karam G, Kessler M, Ligny BH, Buchler M, et al. Impact of graft mass on the clinical outcome of kidney transplants. 10.1681/ASN.2004030209J Am Soc Nephrol. 2005;16(1):261–268. doi: 10.1681/ASN.2004030209. [DOI] [PubMed] [Google Scholar]

[B11] 11.Głyda M, Czapiewski W, Karczewski M, Pięta R, Oko A. Influence of donor and recipient gender as well as selected factors on the five-year survival of kidney graft. 10.2478/v10035-011-0029-1Pol Przegl Chir. 2011;83(4):188–195. doi: 10.2478/v10035-011-0029-1. [DOI] [PubMed] [Google Scholar]

[B12] 12.GratwohL A, Döhler B, Stern M, Opelz G. H-Y as a minor histocompatibility antigen in kidney transplantation: a retrospective cohort study. 10.1016/S0140-6736(08)60992-7Lancet. 2008;372(9632):49–53. doi: 10.1016/S0140-6736(08)60992-7. [DOI] [PubMed] [Google Scholar]

[B13] 13.Howard K, Salked G, White S, MacDonald S, Chadban S, Craig JC, et al. The cost efectiveness of increasing kidney transplantation and home-based dialysis. 10.1111/j.1440-1797.2008.01073.xNephrology(Carlton) 2009;14(1):123–132. doi: 10.1111/j.1440-1797.2008.01073.x. [DOI] [PubMed] [Google Scholar]

[B14] 14.Inoue S, Yamada Y, Kuzuhara K, Ubara Y, Hara S, Ootubo O. Are women privileged organ recipients? 10.1016/S0041-1345(02)03408-5Transplant Proc. 2002;34(7):2775–2776. doi: 10.1016/s0041-1345(02)03408-5. [DOI] [PubMed] [Google Scholar]

[B15] 15.Jacobs SC, Nogueira JM, Phelan MW, Bartlett ST, Cooper M. Transplant recipient renal function is donor renal mass- and recipient gender-dependent. 10.1111/j.1432-2277.2007.00617.xTranspl Int. 2008;21(4):340–345. doi: 10.1111/j.1432-2277.2007.00617.x. [DOI] [PubMed] [Google Scholar]

[B16] 16.Kayler LK, Rasmussen CS, Dykstra DM, Ojo AO, Port FK, Wolfe RA, et al. Gender imbalance and outcomes in living donor renal transplantation in the United States. 10.1034/j.1600-6143.2003.00086.xAm J Transplant. 2003;3(4):452–458. doi: 10.1034/j.1600-6143.2003.00086.x. [DOI] [PubMed] [Google Scholar]

[B17] 17.Kim SJ, Gill JS. H-Y incompatibility predicts short-term outcomes for kidney transplant recipients. 10.1681/ASN.2008101110J Am Soc Nephrol. 2009;20(9):2025–2033. doi: 10.1681/ASN.2008101110. [DOI] [PMC free article] [PubMed] [Google Scholar]

[B18] 18.Kontodimopoulos N, Niakas D. An estimate of lifelong costs and QALYs in renal replacement therapy based on patients’ life expectancy. 10.1016/j.healthpol.2007.10.002Health Policy. 2008;86(1):85–96. doi: 10.1016/j.healthpol.2007.10.002. [DOI] [PubMed] [Google Scholar]

[B19] 19.Kwon OJ, Kwak JY. The impact of sex and age matching for long-term graft survival in living donor renal transplantation. 10.1016/j.transproceed.2004.07.046Transplant Proc. 2004;36(7):2040–2042. doi: 10.1016/j.transproceed.2004.07.046. [DOI] [PubMed] [Google Scholar]

[B20] 20.Lankarani MM, Assari S, Nourbala MH. Improvement of renal transplantation outcome through matching donors and recipients. Ann Transplant. 2009;14(4):20–25. [PubMed] [Google Scholar]

[B21] 21.Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. 10.7326/0003-4819-151-4-200908180-00136Ann Intern Med. 2009;151(4):W-65–W-94. doi: 10.7326/0003-4819-151-4-200908180-00136. [DOI] [PubMed] [Google Scholar]

[B22] 22.Meier-Kriesche HU, Ojo AO, Leavy SF, Hanson JA, Leichtman AB, Magee JC, et al. Gender differences in the risk for chronic renal allograft failure. 10.1097/00007890-200102150-00016Transplantation. 2001;71(3):429–432. doi: 10.1097/00007890-200102150-00016. [DOI] [PubMed] [Google Scholar]

[B23] 23.Moosa MR. Impact of age, gender and race on patient and graft survival following renal transplantation: developing country experience. S Afr Med J. 2003;93(9):689–695. [PubMed] [Google Scholar]

[B24] 24.Muller V, Szabó A, Viklicky O, Gaul I, Portl S, Philipp T, et al. Sex hormones and gender related-differences: their influence on chronic renal allograft rejection. Kid Intern. 1999;55(5):2011–2020. doi: 10.1046/j.1523-1755.1999.00441.x. [DOI] [PubMed] [Google Scholar]

[B25] 25.Neugarten J, Srinivas T, Tellis V, Silbiger S, Greenstein S. The effect of donor gender on renal allograft survival. J Am Soc Nephrol. 1996;7(2):318–324. doi: 10.1681/ASN.V72318. [DOI] [PubMed] [Google Scholar]

[B26] 26.Nicholson ML, Windmill DC, Horsburgh T, Harris KP. Influence of allograft size to recipient body-weight ratio on the long-term outcome of renal transplantation. 10.1046/j.1365-2168.2000.01390.xBr J Surg. 2000;87(3):314–319. doi: 10.1046/j.1365-2168.2000.01390.x. [DOI] [PubMed] [Google Scholar]

[B27] 27.Nyberg G, Blohmé I, Nordén G. Gender differences in a kidney transplant population. 10.1093/ndt/12.3.559Nephrol Dial Transplant. 1997;12(3):559–563. doi: 10.1093/ndt/12.3.559. [DOI] [PubMed] [Google Scholar]

[B28] 28.Oertelt-Prigione S. Sex and gender in medical literature. In: Oertelt-Prigione S, Regitz-Zagrosek V, editors. Sex and gender aspects in clinical medicine. London: Springer; 2012. pp. 9–15. [Google Scholar]

[B29] 29.Oien CM, Reisaeter AV, Leivestad T, Dekker FW, Line PD, OS I. Living donor kidney transplantation: the effects of donor age and gender on short-and long-term outcomes. 10.1097/01.tp.0000255583.34329.ddTransplantation. 2007;83(5):600–606. doi: 10.1097/01.tp.0000255583.34329.dd. [DOI] [PubMed] [Google Scholar]

[B30] 30.Paavonen T. Hormonal regulation of immune responses. 10.3109/07853899409147900Ann Med. 1994;26(4):255–258. doi: 10.3109/07853899409147900. [DOI] [PubMed] [Google Scholar]

[B31] 31.Panajotopoulos N, Ianhez LE, Neumann J, Sabbaga E, Kalil J. Immunological tolerance in human transplantation. The possible existence of a maternal effect. 10.1097/00007890-199009000-00016Transplantation. 1990;50(3):443–445. doi: 10.1097/00007890-199009000-00016. [DOI] [PubMed] [Google Scholar]

[B32] 32.Perovic S, Jankovic S. Renal transplantation vs hemodialysis: cost-effectiveness analysis. 10.2298/VSP0908639PVojnosanit Pregl. 2009;66(8):639–644. doi: 10.2298/vsp0908639p. [DOI] [PubMed] [Google Scholar]

[B33] 33.Poggio ED, Hila S, Stephany B, Fatica R, Krishnamurthi V, Del Bosque C, et al. Donor kidney volume and outcomes following live donor kidney transplantation. 10.1111/j.1600-6143.2005.01225.xAm J Transplant. 2006;6(3):616–624. doi: 10.1111/j.1600-6143.2005.01225.x. [DOI] [PubMed] [Google Scholar]

[B34] 34.Pugliese O, Quintieri F, Mattucci DA, Venettoni S, Taioli E, Costa AN. Kidney graft survival in Italy and factors influencing it. 10.7182/prtr.15.4.lt8514u040417g86Prog Transplant. 2005;15(4):385–391. doi: 10.1177/152692480501500411. [DOI] [PubMed] [Google Scholar]

[B35] 35.Sánchez Garcia F, Torres A, Magariño M, Wichmann I, Nuñez Roldán A. Influence of cyclosporine on sex-related differences observed in the outcome of cadaveric human-kidney allografts. Inmunologia. 1989;8(3):107–109. [Google Scholar]

[B36] 36.Sanfey H. Gender-specific issues in liver and kidney failure and transplantation: a review. 10.1089/jwh.2005.14.617J Womens Health. 2005;14(7):617–626. doi: 10.1089/jwh.2005.14.617. [DOI] [PubMed] [Google Scholar]

[B37] 37.Segev DL, Kucirka LM, Oberai PC, Parekh RS, Boulware LE, Powe NR, et al. Age and comorbidities are effect modifiers of gender disparities in renal transplantation. 10.1681/ASN.2008060591J Am Soc Nephrol. 2009;20(3):621–628. doi: 10.1681/ASN.2008060591. [DOI] [PMC free article] [PubMed] [Google Scholar]

[B38] 38.Shaheen FAM, Al Sulaiman M, Mousa D, El Din ABS, Hawas F, Fallatah A, et al. Impact of donor/recipient gender, age, HLA matching, and weight on short-term graft survival following living related renal transplantation. 10.1016/S0041-1345(98)01179-8Transplant Proc. 1998;30(7):3655–3658. doi: 10.1016/s0041-1345(98)01179-8. [DOI] [PubMed] [Google Scholar]

[B39] 39.Shaheen MF, Shaheen FAM, Attar B, Elamin K, Al Hayyan H, Al Sayyari A. Impact of recipient and donor nonimmunologic factors on the outcome of deceased donor kidney transplantation. 10.1016/j.transproceed.2009.12.052Transplant Proc. 2010;42(1):273–276. doi: 10.1016/j.transproceed.2009.12.052. [DOI] [PubMed] [Google Scholar]

[B40] 40.Tan JC, Kim JP, Chertow GM, Grumet FC, Desai M. Donor-recipient sex mismatch in kidney transplantation. 10.1016/j.genm.2012.07.004Gend Med. 2012;9(5):335–347. doi: 10.1016/j.genm.2012.07.004. [DOI] [PMC free article] [PubMed] [Google Scholar]

[B41] 41.Valdes F, Pita S, Alonso A, Rivera CF, Cao M, Fontan MP, et al. The effect of donor gender on renal allograft survival and influence of donor age on posttransplant graft outcome and patient survival. 10.1016/S0041-1345(97)01026-9Transplant Proc. 1997;29(8):3371–3372. doi: 10.1016/s0041-1345(97)01026-9. [DOI] [PubMed] [Google Scholar]

[B42] 42.Vereerstraeten P, Wissing M, Pauw L, Abramowicz D, Kinnaert P. Male recipients of kidneys from female donors are at increased risk of graft loss from both rejection and technical failure. 10.1034/j.1399-0012.1999.130205.xClin Transplant. 1999;13(2):181–186. doi: 10.1034/j.1399-0012.1999.130205.x. [DOI] [PubMed] [Google Scholar]

[B43] 43.Zeier M, Dohler B, Opelz G, Ritz E. The effect of donor gender on graft survival. 10.1097/01.ASN.0000030078.74889.69J Am Soc Nephrol. 2002;13(10):2570–2576. doi: 10.1097/01.asn.0000030078.74889.69. [DOI] [PubMed] [Google Scholar]

[B44] 44.Zhou JY, Cheng J, Huang HF, Shen Y, Jiang Y, Chen JH. The effect of donor recipient gender mismatch on short- and- long term graft survival in kidney transplantation: a systematic review and meta analysis. 10.1111/ctr.12191Clin Transplant. 2013;27(5):764–771. doi: 10.1111/ctr.12191. [DOI] [PubMed] [Google Scholar]

[B45] 45.Zukowski M, Kotfis K, Biernawska J, Zegan-Barańska M, Kaczmarczyk M, Ciechanowicz A, et al. Donor- recipient gender mismatch affects early graft loss after kidney transplantation. 10.1016/j.transproceed.2011.08.068Transplant Proc. 2011;43(8):2914–2916. doi: 10.1016/j.transproceed.2011.08.068. [DOI] [PubMed] [Google Scholar]

PERMALINK

Gender in the allocation of organs in kidney transplants: meta-analysis

Erika Vieira Almeida e Santiago

Micheline Rosa Silveira

Vânia Eloisa de Araújo

Katia de Paula Farah

Francisco de Assis Acurcio

Maria das Graças Braga Ceccato

Abstract

OBJECTIVE

METHODS

RESULTS

CONCLUSIONS

INTRODUCTION

METHODS

Table 1. Bibliographical search strategies for observational studies conducted in each database, on 12/12/2013.

RESULTS

Figure. Flowchart of study selection for systematic review.

Table 2. General characteristics of studies included in comparisons between genders.

Table 3. Summary of meta-analyses for survival of grafts according to donor genders (FD or MD) and recipient genders (FR or MR); and survival of patients according to kidney transplant recipient genders.

Table 4. Summary of meta-analyses for survival of grafts according to kidney transplant donor-recipient genders.

DISCUSSION

Funding Statement

Footnotes

REFERENCES

Gênero na alocação de órgãos no transplante renal: metanálise

Erika Vieira Almeida e Santiago

Micheline Rosa Silveira

Vânia Eloisa de Araújo

Katia de Paula Farah

Francisco de Assis Acurcio

Maria das Graças Braga Ceccato

Abstract

OBJETIVO

MÉTODOS

RESULTADOS

CONCLUSÕES

INTRODUÇÃO

MÉTODOS

Tabela 1. Estratégia de busca bibliográfica para estudos observacionais realizada em cada base eletrônica, em 12/12/2013.

RESULTADOS

Figura. Fluxograma da seleção de estudos para a revisão sistemática.

Tabela 2. Características gerais dos estudos incluídos nas comparações entre gênero.

Tabela 3. Resumo das metanálises para sobrevida do enxerto segundo o gênero do doador (DF ou DM) e do receptor (RF ou RM); e sobrevida do paciente segundo o gênero do receptor de transplante de renal.

Tabela 4. Resumo das metanálises para sobrevida do enxerto segundo o gênero do doador-receptor de transplante renal.

DISCUSSÃO

Footnotes

ACTIONS

PERMALINK

RESOURCES

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