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enal Allograft Function and Cardiovascular Risk in Recipients ofidney Transplantation After Successful Pregnancy

.J. Gutiérrez, P. González, I. Delgado, E. Gutiérrez, E. González, R.C. Siqueira, A. Andrés, and.M. Morales

ABSTRACT

Successful pregnancy is one of the better indicators of quality of life for women whoare of child-bearing age with restored fertility after kidney transplantation. Ourobjective was to evaluate whether pregnancy represented a risk factor for worsening ofrenal function or for cardiovascular disease among renal transplant recipients. From1976 to 2007, we followed 30 successful pregnancies in 27 renal recipients in ourhospital; three women had two twin gestations. We compared this population with 27women with renal transplants who were not pregnant. They were of similar ages attransplantation (pregnant 31.1 � 5.4 years vs not pregnant 31.3 � 5.4 years, P � NS)and similar evolution time between kidney transplantation and pregnancy (51.5 � 36months vs 47.2 � 41 months respective; P � NS). There were no acute rejectionepisodes or graft losses. Renal function measured by serum creatinine and MDRD4 atthe end of pregnancy was lower among the pregnant compared with the control group:mainly, 1.1 � 0.2 mg/dL versus 0.9 � 0.2 mg/dL (P � .05), and 66 � 20 mL/min/1.73m2 versus 80 � 26 mL/min/1.73 m2 (P � .03). At 1 and 10 years, renal function wassimilar among the groups. Ten pregnant women developed preeclampsia (37%) andthree, gestational diabetes mellitus (11%). There was one major cardiovascular event(4%; acute myocardial infarction) among the pregnant group, whereas there were twoin the control group (7.4%; stroke and severe hypertensive retinopathy). One deathoccurred in each group secondary to cardiovascular complications. Our results showedthat successful pregnancy after renal transplantation did not represent a long-term riskfactor to worsen renal function and or produce severe cardiovascular complications.Therefore, pregnancy should be promoted. for young women with renal transplants

that show excellent function.

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UCCESSFUL PREGNANCY is one of the betterindicators of quality of life for women who are of

hild-bearing age with restored fertility after kidney trans-lantation. Therefore, women with good renal function maye selected to become pregnant. There are several articlesnd registries showing excellent results. Gestational diabe-es and preeclampsia are well-known complications in theseregnancies. However, there is little information concern-

ng the long-term cardiovascular risk among this young,elected population.

The aim of this study was to evaluate whether pregnancyepresented a risk factor for kidney allograft deteriorationr cardiovascular disease among renal transplant recipients.

o conduct this study, we analyzed the long-term renal 2

2009 Published by Elsevier Inc.60 Park Avenue South, New York, NY 10010-1710

ransplantation Proceedings, 41, 2399–2402 (2009)

llograft function, the cardiovascular risk, the presence ofardiovascular events, and the survival of renal transplantecipients after a successful pregnancy compared with aopulation nonpregnant renal transplant recipients of similar-ge.

Pregnancy was advised according to the criteria of theuropean Best Practice Guidelines: at least 2 years afteridney transplantation, stable renal function with a serum

From the Nephrology Department, Hospital 12 de Octubre,adrid, Spain.Address reprint requests to Jose M. Morales, Nephrology

epartment, Hospital 12 de Octubre, Avda de Cordoba s/n,

8041 Madrid, Spain. E-mail: jmorales@h12o.es

0041-1345/09/$–see front matterdoi:10.1016/j.transproceed.2009.06.042

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reatinine low 2 mg/dL, absence of recent acute rejectionpisodes, absence of hypertension or an only mild disor-er controlled with one antihypertensive drug, protein-ria �0.5 g/d, and no pyelocalyceal dilatation on ultra-onography.1

ATIENTS AND METHODS

rom 1976 to 2007, 30 successful pregnancies were achieved in 27enal recipients followed in our hospital; three women had two setsf twin gestations. We compared this population with a similar-ged group of 27 nonpregnant renal transplant recipients of similarge and similar follow-up time after transplantation: pregnant �1.1 � 5.4 years versus not pregnant � 31.3 � 5.4 years (P � ns)nd 51.5 � 36 months versus 47.2 � 41 months respectively (P �S). This retrospective observational study compared the twoopulations of renal transplant recipients.When pregnancy was diagnosed, mycophenolate mofetil and/or

apamycin as well as angiotensin-converting enzyme inhibitornd/or angiotensin receptor antagonists were stopped. Immuno-uppressive therapy was based on calcineurin inhibitors, preferen-ially tacrolimus, with or without steroids. After delivery, steroidoses were increased. Appointments were performed monthly inhe obstetrics and the renal transplant outpatient clinics during theestation period, measuring renal allograft function, blood pres-ure, and fetal echography.

We calculated the cardiovascular risk using the World Healthrganization (WHO) and ISH 2003 Risk Stratification, for a

erious cardiovascular event (stroke or acute myocardial infarc-ion) in 10 years, considering also the presence of arterial hyper-ension, diabetes mellitus, kidney disease, periphercal arteriopathy,arget organ injury, such as proteinuria, and hypertensive retinop-thy, and a number of risk factors, such as age, gender, totalholesterol �240 mg/dL or low-density lipoprotein cholesterol160 mg/dL or high-density lipoprotein cholesterol �40 mg/dL,

Table 1. Cardiovascular Risk by WHO and ISH 2003Risk Stratification

Blood Pressure (mm Hg)

140–159/90–99 160–179/100–109 ?180/110

ithout risk factors Low risk Middle risk High risk–2 risk factors Middle risk Middle risk High risk2 risk factors(target organlesion,associatedclinical condition)

High risk High risk Very high risk

Low risk, �15%; middle risk, 15%–20%; high risk, �20%; very high risk,30%.WHO, World Health Organization; ISH, .

Table 2. Renal

1 mo Postparturition

PregnantGroup

Not PregnantGroup P

erum creatinine (mg/dL) 1.1 � 0.2 0.9 � 0.2 .05DRD4 (mL/min/m2) 66 � 20 80 � 26 .03

roteinuria (g/d) 0.8 � 1.4 0.1 � 0.1 .02 0.4 �

besity, smoking, and familiar history of cardiovascular diseaseTable 1).

ESULTSidney Allograft Function

s expected, before pregnancy, both groups displayed goodenal function (MDRD4 � 70.7 � 21 mL/min/m2 vs 79 � 21L/min/m2, P � NS), without proteinuria (0.13 � 0.1 g/d vs

.14 � 0.1 g/d, P � NS). There were no acute rejectionpisodes or graft losses during pregnancy and puerperium.enal function as measured by serum creatinine andDRD4 glomerulas filtration at the end of pregnancy was

ower among the pregnant group: 1.1 � 0.2 mg/dL versus.9 � 0.2 mg/dL (P � .05), and 66 � 20 mL/min/1.73 m2

ersus 80 � 26 mL/min/1.73 m2 (P � .03). However, at 1nd 10 years after delivery, renal function was similarmong the groups (Table 2). Proteinuria at the end ofregnancy was greatest among the pregnant group: 0.8 �.4 g/d versus 0.1 � 0.1 g/d, (P � .02), a difference thatersisted at 1 year postdelivery (0.4 � 0.6 g/d vs 0.1 � 0.1/d, P � .03), but disappeared at 10 years (0.3 � 0.2 g/d vs.4 � 0.6 g/d, P � NS). Four pregnant patients and oneatient in the control group developed graft loss due tohronic allograft nephropathy.

ardiovascular Risk

efore pregnancy both groups showed similar cardiovascu-ar risk factors according WHO and ISH 2003 Risk Strati-cation: 33.3% versus 37.03%, (P � NS; Table 3). Allatients showed good control of blood pressure (BP): 123 �0/80.6 � 9.5 mm Hg in the pregnant group versus 126 �4/73.5 � 16.5 mm Hg in the control group (P � NS) on aimilar number of antihypertensive drugs (0.68 � 0.7 vs.67 � 0.7 drugs/d, P � NS). Ten women developedreeclampsia (37%) during pregnancy and three, gesta-ional diabetes mellitus (11%). At 1 month after delivery,ean BP was similar among both groups (Table 3), but the

regnant women received more antihypertensive drugs0.9 � 0.9 vs 0.6 � 0.7 drugs/d; P � .05). At 1 and 10 years,hese differences did not exist.

Obesity measured by body mass index at 1 month andyear postdelivery was highest among pregnant women

ersus nonpregnant women: 25.2 � 4.2 kg/m2 versus 21.8 �.1 kg/m2 (P � .01) and 25.1 � 4 kg/m2 versus 22.2 � 3.2g/m2 (P � .03). This difference persisted at 10 yearsostdelivery: 25.2 � 3.7 kg/m2 versus 22.5 � 2.8 kg/m2

P � .03).

raft Function

12 mo Postparturition 10 y Postparturition

nantup

Not PregnantGroup P

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RENAL FUNCTION AFTER PREGNANCY 2401

Cholesterol at 1 month postdelivery was higher amongregnant women compared with nonpregnant women:35 � 47 mg/dL versus 201 � 40 mg/dL (P � .01). At 1nd 10 years postdelivery, these differences disappearedTable 2).

There was one main cardiovascular event (4%) amongregnant women, an acute myocardial infarction, while twoccurred among the control group (7.4%)—one stroke andne severe hypertensive retinopathy. There was one death

n each group secondary to cardiovascular complications.

ISCUSSION

hese results emphasized that, in selected renal transplantecipients, pregnancy is good option with excellent results.herefore, we should encourage young women with excel-

ent renal function to get pregnant. Our experience isimilar to data from single centers or registries but untilow there has been little information concerning the long-erm cardiovascular risks in women with successful preg-ancies.Before pregnancy, both populations were similar. After a

uccessful pregnancy, despite an initial decline in renalunction after delivery (possibly secondary to preeclamp-ia), the MDRD improved, becoming similar to the controlroup even 10 years there after. Therefore, our resultstrongly suggested that pregnancy did not have a deleteri-us effect upon renal allograft function as other authorsave reported.2 In fact, the prevalence of chronic allograftephropathy was also similar between groups and notifferent from the general transplant population.Concerning cardiovascular risk, pregnancy only pro-otes an increased vascular score at the puerperium,

ortunately without clinical expression.3– 6 However, afterhe puerperium and in the long-term at 10 years, the riskecame similar in both populations. In fact, cardiovascu-

ar events and cardiovascular mortality were similar.herefore, our results suggested that pregnancy did not

epresent a new cardiovascular risk factor for young renalransplant recipients.

This study had several limitations, mainly being retro-pective with a small number of patients. Neverthless, wehink that this information has important clinical value.

In summary, our results showed that a successful preg-ancy after renal transplantation did not represent a riskactor for worsening of renal function or severe long-termardiovascular complications. Therefore, pregnancy shoulde promoted for young transplant recipients with excellentenal function.

EFERENCES

1. EBPG Expert Group on Renal Transplantation: Europeanest practice guidelines for renal transplantation. Section IV:ong-term management of the transplant recipient. IV.10. Preg-ancy in renal transplant recipients. Nephrol Dial Transplant7:50, 20022. Armenti VT, Radomski JS, Moritz MJ, et al: Report from the

National Transplantation Pregnancy Registry (NTPR): outcomesof pregnancy after transplantation. Clin Transplant 103, 2004B

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2402 GUTIÉRREZ, GONZÁLEZ, DELGADO ET AL

3. Sturgiss SN, Davison JM: Effect of pregnancy on the long-erm function of renal allografts: an update. Am J Kidney Dis6:54, 19954. Kashanizadeh N, Nemati E, Sharifi-Bonab M, et al: Impact of

regnancy on the outcome of kidney transplantation. Transplant

roc 39:1136, 2007 n

5. Fischer T, Neumayer HH, Fischer R, et al: Effect of preg-ancy on long-term kidney function in renal transplant recipientsreated with cyclosporine and with azathioprine. Am J transp:2732, 20056. Gutierrez MJ, Acebedo-Ribó M, Garcia-Donaire JA, et al: Preg-

ancy in renal transplant recipients. Transplant Proc 37:3721, 2005