Martin Zeier*,
Bernd Döhler,
Gerhard Opelz and
Eberhard Ritz*
Departments of *Internal Medicine/Nephrology and Immunology, University of Heidelberg, Heidelberg, Germany.
Correspondence to Dr. Martin Zeier, Department of Internal Medicine/Nephrology, University of Heidelberg, Bergheimer Str. 56 a, 69115 Heidelberg, Germany. Phone: 49-6221-91120; Fax: 49-6221-162476;
ABSTRACT. Differences in actuarial graft survival accordingto donor gender have been reported for renal allografts andfor cardiac and hepatic allografts, but for the latter in smallseries with limited biostatistical power. Using the large databaseof the Collaborative Transplant Study (CTS), this study is anevaluation of graft survival according to donor and recipientgender for renal (n = 124,911), cardiac (n = 25,432), and hepatic(n = 16,410) transplants. Confounders, such as calendar year,geographical area, race, donor and recipient age, HLA mismatch,cold ischemia time, and others, as well as interaction termswere taken into consideration. Death-censored actuarial renalallograft survival from female compared with male donors wasless in female recipients and even more so in male recipients.The donor gender-associated risk ratio for graft loss was 1.15in female recipients and 1.22 in male recipients. The age-genderinteraction term was statistically significant, the gender effectbeing more pronounced for younger (16 to 45 yr) compared witholder (>45 yr) donors. Serum creatinine concentrations 1yr after transplantation were also higher for recipients withkidney grafts coming from female donors irrespective of recipientgender. For first cardiac transplants, graft survival was inferiorwhen the donor was female and the recipient male, but no statisticaldifference according to donor gender was demonstrable in femalerecipients. For first hepatic transplants overall, no significantdifferences according to donor gender were noted. The proportionof recipients who had treatment for rejection crisis duringthe first year was higher for male recipients of kidneys fromfemale donors compared with male donors. No difference accordingto donor gender was demonstrable in female recipients. For cardiacand hepatic grafts, no significant effect of donor gender onthe proportion of patients treated for rejection episodes wasnoted. The data show that adverse effects of female donor genderfor different organs is much less uniform than reported in thepast. An important confounder is donor age. A gender effecton graft survival is also observed for cardiac allografts. Therefore,in addition to potential "nephron underdosing," further pathomechanismsmust play a role, possibly differences in immunogenicity accordingto donor gender. E-mail: martin_zeier@med.uni-heidelberg.de
It has been noted for a considerable time that kidney transplantsfare better in female than in male recipients (1,2). More recentstudies also documented inferior short-term and long-term graftsurvival when female kidneys were transplanted into male patients(3–5). This phenomenon was also seen in combined kidneyand pancreas transplantation (6). The findings have not beenentirely consistent, however, presumably because of the smallnumber of individuals assessed and the failure to account forconfounding factors.
The observation of worse functional prognosis of female graftsis of interest in view of the fact that the renal prognosisin primary chronic renal disease is considerably better in femalepatients, as documented by experimental (7–10) and clinicalobservations (11–15). This has been ascribed to a protectiveeffect of estrogens.
An intriguing hypothesis has been offered to account for theeffect of donor gender on renal allograft outcome, i.e., thepostulate that female kidneys contain fewer nephrons (nephronunderdosing) (16), thereby increasing the workload of the individualnephrons (16,17). The general concept that the total numberof nephrons transplanted is a determinant of long-term graftoutcome has been well illustrated by experimental studies, where,all other things being equal, graft outcome was better whentwo kidneys were transplanted (18,19). Preliminary evidencein humans also appears to point in the same direction (20,21).
We evaluated the problem of whether the above gender effectis specific for kidney grafts or whether it is more generallyseen with other solid organ grafts as well. In the first case,gender-dependent differences in renal function and/or structurewould be the most plausible explanation. In the latter case,organ-unrelated effects of donor gender on immune-recognitionand/or immune effector mechanisms would be more logical candidates.
To address this issue, we compared long-term graft outcome forkidney as well as other solid organ grafts on the basis of thevery large and complete database of the Collaborative TransplantStudy (CTS).
Renal, cardiac, and hepatic transplants at centers participatingin the CTS were analyzed: 464 renal transplant centers in 49countries, 165 cardiac transplant centers in 29 countries, and103 hepatic transplant centers in 25 countries. We assessedfirst renal transplants performed from 1985 to 2000, first orthotopiccardiac transplants from 1985 to 2000, and first hepatic transplantsfrom 1988 to 2000. Transplants were included only when recipientand donor age were at least 16 yr at the time of transplantation.The age characteristics of the patients are summarized in Table 1.In addition to first cadaveric kidney grafts, 5716 kidneygrafts between HLA-identical siblings were evaluated. Clinicalfollow-up information was obtained at 3, 6, and 12 mo aftertransplantation and yearly thereafter.
Table 1. Age characteristics (yr) of the patients (first cadaveric kidney, heart, and liver grafts)a
Multivariate Cox regression analysis (22) was used to explainthe effects of the donor gender on graft survival time. Apartfrom donor gender, relevant explanatory variables with correspondingscaling were included in the Cox proportional hazards analysis:calendar year of transplantation, geographical area, recipientrace, recipient age, recipient gender, donor age, HLA mismatch,cold ischemia time, original disease, body mass index, systolicBP (outpatient clinic), pretransplant cytotoxic antibodies,pretransplant blood transfusions, immunosuppressive therapy,and interaction terms. Graft and patient survival graphs werecomputed according to Kaplan Meier (23). Patients who died withfunctioning grafts were counted as graft failures. In the analysisof serum creatinine concentration, significance of the differencebetween groups was estimated with the classic 2 test of fourfoldtables (24).
Actuarial Graft Survival of Renal Transplants According to Donor and Recipient Gender
Actuarial survival of first cadaver renal transplants was consistentlylower when the donor was female irrespective of whether therecipient was female or male. The univariate Kaplan-Meier estimatesof graft or patient survival are given in the respective figurelegends (Figures 1 and 2).
Figure 1. First cadaveric kidney transplants (1985 to 2000); actuarial graft survival. In female recipients, the 10-yr Kaplan-Meier estimate was 48.4 ± 0.4 yr for male donors and 46.9 ± 0.6 yr for female donors (P = 0.0020). In male recipients, it was 46.5 ± 0.3 yr for male donors and 42.1 ± 0.5 yr for female donors (P < 0.0001).
Figure 2. First cadaveric kidney transplants (1985 to 2000); actuarial patient survival. In female recipients, the 10-yr Kaplan-Meier estimate was 71.3 ± 0.4 yr for male donors and 69.7 ± 0.6 yr for female donors (P = 0.0191). In male recipients, it was 68.0 ± 0.3 yr for male donors and 65.2 ± 0.5 yr for female donors (P < 0.0001).
By multivariate Cox regression analysis, the donor gender-relatedrisk ratio (female donors versus male donors) was 1.15 (95%CI [confidence interval], 1.07 to 1.23; P < 0.0001) whenthe recipient was female and even higher at 1.22 (95% CI, 1.16to 1.29; P < 0.0001) when the recipient was male. The effectof donor gender is thus greater in male recipients than femalerecipients.
With respect to patient survival, the actuarial survival ofthe recipients of renal transplants was also slightly but significantlyless if the donor of the renal graft was female, and this wastrue irrespective of whether the recipient was male or female(Figure 2). The magnitude of the effect was not sufficient toexplain the difference of allograft survival according to donorgender. The so-called functional allograft survival was evennumerically more adverse than the uncorrected actuarial graftsurvival. The donor gender-related risk ratio (female donorsversus male donors) was 1.17 (95% CI, 1.08 to 1.27; P = 0.0002)when the recipient was female and 1.30 (95% CI, 1.22 to 1.39;P < 0.0001) when the recipient was male.
Influence of Donor Age on Actuarial Renal Graft Survival According to Donor Gender
The interaction term of donor gender/donor age was significant.Table 2 illustrates that the inferior actuarial graft survivalin female recipients of kidneys from female donors was demonstrableonly for younger female donors, i.e., 45 yr. In addition, therisk ratio was higher when kidneys of younger female donors(16 to 45 yr) compared with kidneys from older female donors(>45 yr) were transplanted in male recipients.
Table 2. Risk ratio of female donor versus male donor according to age of donora
Actuarial Graft Survival of HLA-Identical Sibling Renal Transplants According to Donor and Recipient Gender
As expected, early graft function was remarkably good for renalgrafts from HLA-identical siblings. After several years, thetendency for lower actuarial graft survival of grafts from femaledonors became apparent. By Cox regression analysis, the riskratio for the graft of a female donor relative to that of amale donor was 1.11 (95% CI, 0.98 to 1.26; P = 0.0876). Therisk ratio of a graft transplanted into a female recipient relativeto a male recipient was 0.82 (95% CI, 0.72 to 0.94; P = 0.0030)(Figure 3).
Figure 3. Kidney transplants (1985 to 2000); actuarial graft survival in HLA-identical siblings. In female recipients, the 10-yr Kaplan-Meier estimate was 70.1 ± 2.5 yr for male donors and 70.1 ± 2.1 yr for female donors (P = 0.4684). In male recipients, it was 68.1 ± 1.7 yr for male donors and 65.2 ± 1.8 yr for female donors (P = 0.1191).
Actuarial Cardiac Graft Survival According to Donor and Recipient Gender
As shown in Figure 4, cardiac transplants from female donorshad significantly inferior actuarial survival in male recipients,whereas no difference according to donor gender was demonstrablein female recipients. By Cox regression analysis, the risk ratiofor the graft of female donors was 1.13 (95% CI, 1.08 to 1.19;P < 0.0001) in male recipient, but it was not significantlydifferent from 1.0 for grafts of female donors transplantedinto female recipients compared with grafts from male donors.
Figure 4. First orthotopic heart transplants (1985 to 2000); actuarial graft survival. In female recipients, the 10-yr Kaplan-Meier estimate was 49.9 ± 1.7 yr for male donors and 51.8 ± 1.7 yr for female donors (P = 0.9581). In male recipients, it was 48.0 ± 0.6 yr for male donors and 46.2 ± 1.0 yr for female donors (P < 0.0001).
Actuarial Hepatic Graft Survival According to Donor and Recipient Gender
Overall there were no significant differences of actuarial graftsurvival according to donor gender (Figure 5). By Cox regressionanalysis, the risk ratio related to donor gender (female donorsversus male donors) was 0.94 (95% CI, 0.87 to 1.03; P = 0.1782)when the recipient was female and 1.07 (95% CI, 0.99 to 1.15;P = 0.0731) when the recipient was male.
Figure 5. First liver transplants (1988 to 2000); actuarial graft survival. In female recipients, the 5-yr Kaplan-Meier estimate was 63.4 ± 0.9 yr for male donors and 63.4 ± 1.0 yr for female donors (P = 0.4331). In male recipients, it was 61.5 ± 0.7 yr for male donors and 59.3 ± 1.0 yr for female donors (P = 0.0258).
Separate analysis according to geographical area showed thatworse actuarial survival rates were found in North Americancenters when livers of female donors were transplanted to malerecipients (risk ratio, 1.22; 95% CI, 1.04 to 1.44; P = 0.0149),whereas no such difference was seen in Western Europe.
Proportion of Renal Graft Recipients with Serum Creatinine Concentrations <130 µmol/L
As shown in Table 3, the proportion of patients who had low(< 130 µmol/L) serum creatinine concentrations waslower for recipients of grafts from female donors. Men haveon average higher serum creatinine concentrations than women;separate analyses according to recipient gender were thereforeperformed. In either recipient gender, there was a highly significantdifference between recipients of grafts from female comparedwith male donors. The relative difference (%) was highest after1 yr and decreased thereafter, possibly because of progressivedropout of individuals with the highest serum creatinine values.
Table 3. Proportion of renal allograft recipients with serum creatinine < 130 µmol/L according to donor and recipient gender
Proportion of Recipients of Different Organ Grafts Requiring Treatment for Acute Rejection According to Donor and Recipient Gender
The salient feature of Table 4 is the finding that the proportionof male recipients of renal allografts who received organs fromfemale donors and who required antirejection therapy was greaterthan the proportion of male recipients who had received an organfrom a male donor.
Table 4. Proportion of recipients of different organ grafts for whom treatment of acute rejection during the first year after transplantation has been reported
A difference according to donor gender was not found in recipientsof heart or liver grafts. In contrast among recipients of heartgrafts, a significantly higher frequency was found in femalesirrespective of donor gender, and a similar trend, althoughnot statistically significant, was noted in recipients of livergrafts.
From single-center studies (4,5), it had been known that short-termand long-term graft survival was worse when kidneys from femaledonors were transplanted to male recipients. On the basis ofresults in small series it has also been claimed that graftoutcome was worse for heart and liver allografts coming fromfemale donors (33–38).
Our analysis concerned the large CTS registry comprising morethan 100,000 kidney transplantations from 1985 to 2000. Inferiorgraft outcome was documented when kidneys of female donors weretransplanted into male recipients compared with kidneys frommale donors transplanted into female or male recipients (Figure 1).A similar difference according to donor gender was foundfor patient survival: survival was consistently better for femalerecipients of kidneys of male donors compared with male recipientsof kidneys of female donors (Figure 2). The same dependencyof graft survival on donor gender was even observed in HLA-identicalsiblings (Figure 3). It was also seen in cadavaric graft recipientson immunosuppression with calcineurin inhibitors or without(data not given). Such an effect of donor gender was obviousnot only when graft survival but also when graft function wasconsidered. After 1, 3, and 10 yr after transplantation, theproportion of recipients with a serum creatinine concentrationbelow 130 µmol/L was higher in patients who received theirrenal allografts from a male donor irrespective of recipientgender (Table 3).
A proposal to explain earlier observations (4,5,40,41) of aworse outcome of kidney grafts coming from female donors wasthe idea of nephron underdosing (18–20). Experimental(17,18) and clinical studies (19–21) underline an adverseeffect of nephron underdosing. In one study (25), long-termgraft function was better when two kidney grafts were transplantedas compared with one. In allogeneic or syngeneic transplantation,a reduction of nephron mass had an adverse effect on graft functionand morphology (26). There is also some clinical evidence thatlong-term graft function is better when two kidneys are transplantedinto one recipient (20,21). The evidence is not perfectly consistent,however; Vianello (27), found that an imbalance of the donorand recipient kidney/body weight ratio had no major effect onkidney graft function and survival after 4 yr.
What is the evidence for fewer nephrons in kidneys of females?Anatomic studies have documented larger kidney weight in men(28), but the results were inconsistent when the kidney sizewas corrected for body surface area (16,28). In animals, kidneysize and weight is greater in males (7,29), even when correctedfor body weight (29,30). Information on the number of glomeruliin the two genders is also conflicting: Nyengard (31) and MacLachlan(32) found similar numbers of glomeruli in males and females,but larger glomerular volumes. In the renal ablation model,larger glomerular volumes were found in male animals in some(7,32) but not all studies (7,8).
Although we cannot discount an effect of nephron underdosing,the observation that a similar dependence of graft outcome ondonor gender is found for nonrenal allografts as well, i.e.,heart grafts, strongly suggests that other mechanisms must alsoplay a role.
Our observations are in line with smaller series, which showedearlier onset of allograft rejection (33,34) in recipients ofhearts from female donors and more pronounced vascular intimalhyperplasia by intravascular ultrasound (35).
For liver transplants, the reported results were even more striking.Kahn (36) reported that no less than 60% of livers from femaledonors failed in male recipients, corresponding to a 3.7-foldhigher risk of graft failure. Data from the UNOS registry (37)and several other series confirmed inferior graft and patientsurvival in males receiving the liver from a female donor (38).Our data confirm this effect in North American centers, butfor unknown reasons, no such effect was seen in Western Europe.
In the search for alternative mechanisms involved in the donorgender effect, we considered immunologic factors. The importanceof immune factors may be indirectly assessed by the number ofepisodes necessitating antirejection therapy.
Indeed, a significantly higher proportion of patients had requiredantirejection treatment by 1 yr after transplantation when kidneysfrom female donors had been transplanted into male recipients,compared with kidneys from male donors transplanted into malerecipients (Table 4). Our observation is in line with the recentsingle-center experience of Vereerstraten (5), who saw a higherincidence of acute rejection episodes (but also more technicalproblems) in male recipients of kidney grafts from female donors.This finding contrasts with some small earlier studies.
Animal experiments suggest that kidneys of females express moreHLA antigens and are more antigenic (39,40). This hypothesisis supported by the finding that survival of kidney grafts comingfrom female compared with male donors is particularly poor inhighly sensitized recipients (41). HLA matching does not completelyabrogate the donor gender effect in first cadaver renal transplantsand living related donor transplants (42,43). But a gender effectwas demonstrable in our study, even in HLA-identical siblings,possibly pointing to an additional role of non-HLA factors.
A further possibility to consider would be an influence of chromosomalsex or sex hormones on vascular endothelial cells, one potentialinterface relevant for allograft recognition (44). Indeed, sexhormones influence some endothelial cell indices, e.g., androgenexposure increases mononuclear cell adhesion to vascular endothelialcells (45), and both androgens and estrogens affect endothelialcell proliferation (46).
In contrast to previous reports (4,5,41) that female genderand older donor age are associated with an increased risk ofgraft failure, the analysis of the CTS database showed an increasedrisk for kidneys from younger (16 to 45 yr) female donors (Table 2).One hypothesis to explain our results might be a gender-relateddifference of the density of dendritic cells in the kidney.
Our results contrast with the findings of Meier-Kriesche (47),who examined a large database (n = 73,477) and found a higherrisk of acute rejections for female recipients but a higherrisk of chronic rejection in males. This may be explained bymore intense stimulation of the immune system in a high-estrogenenvironment, as suggested by some experimental and clinicalstudies (48). Apart from the recipient’s hormonal status,the hormonal status of donor may also be important.
A further consideration would be gender differences in the susceptibilityto ischemia reperfusion injury with delayed resumption of graftfunction or technical problems. Whether kidneys of female donorsare more susceptible to ischemia/reperfusion injury is controversial.According to our study, at any given duration of cold ischemia,kidney and heart transplants coming from female donors had consistentlyworse graft survival compared with male donors. Consequently,differences in the duration of ischemia do not explain the worseoutcome for kidneys grafted from female donors, but this observationdoes not exclude that there are differences in susceptibilityof grafts to ischemia/reperfusion injury according to donorgender.
Footnotes
Dr. William Harmon served as guest editor and supervised thereview and final disposition of this manuscript.
Richie RE, Niblack GD, Johnson HK, Green WF, MacDonell RC, Turner BI, Tallent M B: Factors influencing the outcome of kidney transplants. Ann Surg 197: 672–677, 1983[Medline]
Reed E, Cohen CJ, Barr ML, Ho E, Reemtsma K, Rose EA, Hardy M, Suciu-Foca N: Effect of recipient gender and race on heart and kidney allograft survival. Transplant Proc 24: 2670–2671, 1992[Medline]
Neugarten J, Silbiger S R: The impact of gender on renal transplantation. Transplantation 15: 1145–1152, 1994
Neugarten J, Srinivas T, Tellis V, Silbiger S, Greenstein S: The effect of donor gender on renal allograft survival. J Am Soc Nephrol 7: 318–324, 1996[Abstract]
Vereerstraeten P, Wissing M, De Pauww L, Abramowicz D, Kinnaert: Male recipients of kidneys from female donors are at increased risk of graft loss from both rejection and technical failure. Clin Transplant 13: 181–186, 1999[CrossRef][Medline]
Douzdjian V, Rice JC, Carson RW, Gugliuzza KG, Fish J C: Renal allograft failure after simultaneous pancreas-kidney transplantation: univariate and multivariate analyses of donor and recipient risk factors. Clin Transplant 10: 271–277, 1996[Medline]
Remuzzi A, Puntorieri S, Mazzoleni A, Remuzzi G: Sex related differences in glomerular ultrafiltration and proteinuria in Munich-Wistar rats. Kidney Int 34: 481–486, 1988[Medline]
Lombet JR, Adler SG, Anderson PS, Nast CC, Olsen DR, Glassock R J: Sex vulnerability in the subtotal nephrectomy model of glomerulosclerosis in the rat: J Lab Clin Med 114: 66–74, 1989[Medline]
Gafter U, Ben-Bassat M, Levi J: Castration inhibits glomerular hypertrophy and proteinuria in uninephrectomized male rats. Eur J Clin Invest 20: 360–365, 1990[Medline]
Zeier M, Schönherr R, Amann K, Ritz E: Effects of testosterone on glomerular growth after uninephrectomy. Nephrol Dial Transplant 1998: 13, 2234–2240
Silbiger S, Neugarten J: The impact of gender on the progression of chronic renal disease. Am J Kidney Dis 25: 515–533, 1995[Medline]
Coggins CH, Lewis JB, Caggiula AW, Castaldo LS, Klahr S, Wang S R: Differences between women and men with chronic renal disease. Nephrol Dial Transplant 13: 1430–1437, 1998[Abstract/Free Full Text]
Jungers P, Hannedouche T, Itakura Y, Albouze G, Descamps-Latscha B, Man N K: Progression rate to endstage renal failure in non-diabetic kidney diseases: A multivariate analysis of determinant factors. Nephrol Dial Transplant 10: 1353–1360, 1995[Abstract/Free Full Text]
Ruggenenti P, Gaspari F, Perna A, Remuzzi G: Cross-sectional longitudinal study of spot morning urine protein: creatinine ration, 24 hour urine protein excretion rate, glomerulular filtration rate, and endstage renal failure in chronic renal disease in patients without diabetes. Br Med J 316: 504–509, 1998[Abstract/Free Full Text]
Neugarten J, Acharya A, Silbiger S R: Effect of gender on the progression of nondiabetic renal disease: a meta-analysis. J Am Soc Nephrol 11: 319–329, 2000[Abstract/Free Full Text]
Kasiske BL, Umen J A: The influence of age, sex, race and body habitus on kidney weight in humans. Arch Pathol Lab Med 110: 55–60, 1986[Medline]
Brenner BM, Cohen RA, Milford E L: In renal transplantation, one size may not fit all. J Am Soc Nephrol 3: 162–169, 1992[Medline]
MacKenzie HS, Azuma H, Rennke HG, Tilney NL, Brenner B M: Renal mass as a determinant of late allograft outcome: Insights from experimental studies in rats. Kidney Int 52: S 38–S42, 1995
Taal MW, Tilney NL, Brenner BM, MacKenzie H S: Renal mass: An important determinant of late allograft outcome. Transplant Rev 12: 74–84, 1998
Remuzzi G, Grinyo J, Ruggenenti P, Beatini M, Cole EH, Milford EL, Brenner B M: Early experience with dual kidney transplantation in adults using expanded donor criteria. J Am Soc Nephrol 10: 2591–2598, 1999[Abstract/Free Full Text]
Gridelli B, Remuzzi G: Strategies for making more organs available for transplantation: N Engl J Med 343: 404–410, 2000[Free Full Text]
Cox DR: Regression models and life tables. J Royal Statistical Society. Series B 1972: 187–220
Kaplan EL, Meier P: Nonparametric estimation from incomplete observations. J Am Stat Assoc 53: 457–481, 1958[CrossRef]
Dunn OJ, Clark V A: Applied statistics: analysis of variance and regression. New York: John Wiley; 1974: 236
Heemann UW, Azuma H, Tullis SG, MacKenzie HS, Schmid C, Brenner BM, Tilney N L: Influence of renal mass on chronic kidney allograft rejection in rats. Transplant Proc 27: 549, 1995[Medline]
Azuma H, Nadeau K, Mackenzie HS, Brenner BM, Tilney T L: Nephron mass modulates the hemodynamic, cellular, and molecular response of the rat renal allograft. Transplantation 63: 519–528, 1997[CrossRef][Medline]
Vianello A, Calconi G, Amici G, Chiara G, Pignata G, Maresca M C: Importance of donor/recipient body weight ratio as a cause of kidney graft loss in the short to medium term. Nephron 72: 205–211, 1996[Medline]
Latimer J K: The action of testosterone propionate upon the kidneys of rats, dogs and men. J Urol 48: 778–794, 1942
Oudar O, Elger M, Bankir L, Ganten D, Ganten U, Kriz W: Differences in renal kidney morphology between males, females and testosterone treated females. Renal Physiol Biochem 14: 92–102, 1991[Medline]
Walter F, Addis T: Organ work and organ weight. J Exp Med 69: 467–483, 1939[Abstract/Free Full Text]
Nyengaard JR, Bendtsen T F: Glomerular number and size in relation to age, kidney weight and body surface area in normal man. Anat Rec 232: 194–201, 1992[CrossRef][Medline]
McLachlan MSF, Guthrie JC, Anderson CK, Fulker M J: Vascular and glomerular changes in the aging kidney. J Pathol 121: 65–77, 1976
Kubo SH, Naftel DC, Mills R M Jr., O’Donnell J, Rodeheffer R J; Cintron GB, Kenzora JL, Bourge RC, Kirklin J K: Risk factors for late recurrent rejection after heart transplantation: a multiinstitutional study. The Transplant Cardiologists Research Database Group. J Heart Lung Transplant 14: 409–418, 1995[Medline]
Prendergast T W, Furukawa S, Beyer AJ, Browne BJ, Eisen HJ, Jeevanadam V: The role of gender in heart transplantation. Ann Thorac Surg 65: 88–94, 1998[Abstract/Free Full Text]
Mehra MR, Stapleton DD, Ventura HO, Escobar A, Cassidy CA, Smart FW, Collins TJ, Ramee SR, White C J: Influence of donor and recipient gender on cardiac allograft vasculopathy. An intravascular ultrasound study. Circulation 90: II 78–II82, 1994
Kahn D, Gavaler JS, Makowka L, van Thiel D H: Gender of donor influences outcome after orthotopic liver transplantation in adults. Dig Dis Sci 38: 1485–1488, 1993[CrossRef][Medline]
Marino IR, Doyle HR, Adrighetti L, Doria C, McMichael J, Gayowski T, Fung JJ, Tzakis AG, Strarzl T E: Effect of donor age and sex on the outcome of liver transplantation. Hepatology 22: 1754–1762, 1995[CrossRef][Medline]
Brooks BK, Levy MF, Jennings LW, Abbasoglu O, Vodapally M, Goldstein RM, Husberg BS, Gonwa TA, Klintmalm G B: Influence of donor and recipient gender on the outcome of liver transplantation. Transplantation 27: 1784–1787, 1996
Panatjotopoulos N, Ianhez LE, Neumann J, Sabbaga E, Kalil J: Immunological tolerance in human transplantation. The possible existence of an maternal effect. Transplantation 50: 443, 1990[Medline]
Shibue T, Kondo K, Iwaki Y, Terasaki P I: Effect of sex on kidney transplants.In: Terasaki P I ed. Clinical Transplants 1987. Los Angeles: UCLA Tissue Typing Laboratory, 1987: 351
Koka P, Cecka J M: Sex and age effects in renal transplantation.In: Terasaki PI, ed. Clinical Transplants 1990. Los Angeles: UCLA Tissue Typing Laboratory 1990: 437
Cecka J M: The roles of sex, race and ABO-groups.In: Terasaki P I ed. Clinical Transplants 1986. Los Angeles: UCLA Tissue Typing Laboratory, 1986: 199
Sanfilippo F, Vaughn WK, Spees EK, Lukas B A: The detrimental effects of delayed graft function in cadaver donor renal transplantation. Transplantation 38: 643, 1984[Medline]
Briscoe DM, Sayegh M H: A rendevouz before rejection: Where do T-cells meet transplant antigens? Nature Medicine 8: 220–221, 2002[CrossRef][Medline]
Somjen D, Kohen F, Jaffe A, Amir-Zaltsman Y, Knoll E, Stern N: Effects of gonodal steroids and their antagonists on DNA synthesis in human vascular cells. Hypertension 32: 39–45, 1998[Abstract/Free Full Text]
McCrohon JA, Jessup W, Handelsman DJ, Celermajer DS: Androgen exposure increases human monocyte adhesion to vascular endothelium and endothelial cell expression of vascular cell adhesion molecule-1. Circulation 99: 2317–2322, 1999[Abstract/Free Full Text]
Meier-Kriesche HU, Ojo AO, Leavey JA, Hanson AB, Leichtman JC, Magee D, Cibrik M, Kaplan B: Gender differences in the risk of chronic allograft failure. Transplantation 71: 429–432, 2001[CrossRef][Medline]
Paavonen T: Hormonal regulation of immune responses. Ann Int Med 26: 255–258, 1994
Received for publication November 15, 2001.
Accepted for publication June 14, 2002.
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Top
Abstract
Introduction
2 test of fourfold tables (24). 
45 yr. In addition, the risk ratio was higher when kidneys of younger female donors (16 to 45 yr) compared with kidneys from older female donors (>45 yr) were transplanted in male recipients. 
