Q J Med 1999; 92: 631-635
© 1999 Association of Physicians
Pregnancy does not adversely affect renal transplant function
From the Renal Unit and Renal Transplant Unit, Royal Liverpool University Hospital and The Liverpool Womens' Hospital, Liverpool, UK
Received 19 March 1999 and in revised form 24 August 1999
Dr A.V. Crowe, 6C Link, Royal Liverpool University Hospital, Prescot Street, Liverpool L7 8XP. e-mail: avcrowe{at}aol.com.uk
 |
Summary |
|---|
 Top Summary IntroductionMethodsResultsDiscussionReferences |
|---|
Women with functioning transplanted kidneys often become fertile again. Indeed, renal function, endocrine status and libido rapidly improve after renal transplantation, and 1:50 women of childbearing age become pregnant. However, there is concern regarding the haemodynamic changes of pregnancy, which could lead to a decline in graft function (temporary or permanent). We examined obstetric data and renal parameters in 29 patients and 33 pregnancies. Mean serum creatinine and creatinine clearance remained stable throughout pregnancy and 1 year postpartum. However, there was a significant increase in proteinuria from a mean of 0.45 g/24 h around the time of conception to 1.11 g/24 h at delivery (p<0.05). The proteinuria resolved to baseline levels at 3 months postpartum. We highlight certain parameters to be considered before conception to allow a good obstetric outcome and prolong stable renal function: serum creatinine <150 µmol/l, proteinuria <1 g/day, absence of histological evidence of chronic allograft rejection, controlled blood pressure (140/90) and stability of maintenance immunosuppression.
|
Introduction |
|---|
|
TopSummaryIntroductionMethodsResultsDiscussionReferences |
|---|
Normal endocrine and menstrual function is restored within 1 to 20 months following successful renal transplantation.1,2 The incidence of pregnancy in women of childbearing age with kidney transplants is estimated at 2%.3 Over 2000 pregnancies have been reported in recipients world-wide. However, important changes in glomerular haemodynamics are known to occur in pregnancy (hyperfiltration) which may adversely affect long-term graft prognosis.4,5 We thus reviewed our data over 26 years to examine the effects of pregnancy (and postpartum) on renal allograft function.
|
Methods |
|---|
|
TopSummaryIntroductionMethodsResultsDiscussionReferences |
|---|
Between 1972 and 1998, a total of 1509 renal transplants were performed at our centre, including 274 females of reproductive age (16–45 years). The number of patient-years of women of childbearing age with a functioning graft was 1931.
Of those females, 33 pregnancies were observed in 29 recipients. Nine patients had received a kidney transplant from a live-related donor and 20 from cadaveric donors. Three patients had pancreatico-renal transplants. The mean age of the women at conception was 29 years (range 19–39 years). The causes of end-stage renal failure were: glomerulonephritis (19), reflux nephropathy (3), diabetic nephropathy (3), polycystic kidney disease (1), dysplastic kidneys (2) and renal cortical necrosis (1).
Data collection included information with respect to: drug-treated hypertension before pregnancy, hypertension during pregnancy, pre-eclampsia, diabetes, rejection episodes, pregnancy outcome (miscarriage, stillborn, therapeutic abortion, live birth) and gestational age.
Serum creatinine and 24-h urine collections for creatinine clearance and urinary protein were measured within 1 month before estimated conception, within 1 month before birth, 3 months postpartum and 1 year postpartum. Renal allograft survival was assessed at 2 years.
Statistics
Results are expressed as means±SEM unless otherwise stated. Statistical significance was evaluated by the student's t test.
|
Results |
|---|
|
TopSummaryIntroductionMethodsResultsDiscussionReferences |
|---|
Graft data
At the time of pregnancy, maintenance immunosuppression was as follows: azathioprine (1–2 mg/kg) and prednisolone (5–10 mg/day) (14), cyclosporin (3–4 mg/kg) and prednisolone (5–10 mg/day) (10), cyclosporin (3 mg/kg), azathioprine (1 mg/kg) and prednisolone (5–10 mg/day) (7) and cyclosporin (4 mg/kg) only (2).
Patients receiving prednisolone and azathioprine had significantly lower serum creatinine around the time of conception compared with other groups (p<0.05) (Table 1
). Also, these patients had significantly lower proteinuria at the time of labour compared with the others (p<0.05).
|
The mean interval between transplantation and conception was 43±6.9 months (range 5–121 months). Eight pregnancies (24%) occurred <2 years post-transplant, and remained with stable graft function 1 year postpartum. Six pregnancies (18%) were conceived 5 years post transplant with stable graft function 1 year postpartum.
Two-thirds of all patients who conceived had good renal function (serum creatinine <150 µmol/l, Table 2). By contrast, all patients with serum creatinine >200 µmol/l required renal replacement therapy within 2 years of delivery. Three of these patients had confirmed histological evidence of chronic allograft rejection and required renal replacement therapy within 6 months.
|
The results of subsequent renal allograft function are summarized in Table 3
. There was no significant difference in the mean serum creatinine and creatinine clearance throughout pregnancy and 1 year postpartum. Proteinuria, however, did rise maximally at delivery, but promptly fell thereafter to conception levels and did not increase further subsequently. Graft survival was 90% (26/29) at 2 years postpartum.
|
One patient only had biopsy-proven acute-on-chronic rejection at 3 months postpartum and subsequently lost the allograft. A successful live birth was still delivered at 29 weeks gestation. Two other patients with creatinine clearances of 10 ml/min and histological evidence of chronic allograft rejection lost their grafts within 6 months.
The renal function of one patient deteriorated prior to labour. This was because of an obstructed ureter which required a nephrostomy. Following successful delivery of the baby and contraction of the uterus, the obstruction resolved and renal function returned to normal.
One patient who was delivered for presumed pre-eclampsia developed septicaemia from a urinary tract infection and concurrent deterioration in renal function 1 day postpartum. Subsequently a renal biopsy showed acute tubular necrosis. She required haemodialysis for 6 weeks before her graft function returned to normal.
There were three patients who had two deliveries each without adversely affecting renal function.
Obstetric data
Results of maternal co-morbid factors and outcomes are shown in Table 4. All patients were normotensive (blood pressure 140/90) at the time of conception, even in those who needed antihypertensive treatment. Normotension remained so throughout pregnancy apart from the four pre-eclamptic patients.
|
In total there were 28 healthy live births. Of these, 21 (75%) were delivered prematurely (<37 weeks), with a mean gestational age of 34.2±0.63 weeks. No congenital abnormalities were recorded. One of the pancreatico-renal transplant patients delivered twins succesfully.
There were four miscarriages, one stillbirth, and one neonatal death of unknown cause. All four miscarriages occurred at 6 weeks gestation. There were no therapeutic abortions or ectopic pregnancies.
|
Discussion |
|---|
|
TopSummaryIntroductionMethodsResultsDiscussionReferences |
|---|
Pregnancy in renal transplantation has been previously associated with a successful outcome if pre-conception graft function is good, especially if hypertension is absent, and if the time interval from grafting is at least 2–3 years.6–8 Our results agree with these previous reports. Most of the pregnancies and successful outcomes were in patients with good renal function (serum creatinine <150 µmol/l).9 By contrast, patients with serum creatinine >200 µmol/l had progression of renal impairment, and all required renal replacement therapy within 2 years after delivery.
A significant increase in glomerular filtration rate occurs in pregnancy in renal transplant recipients in the first 2 trimesters, with a transient decrease of renal function in the last 12 weeks.4,10 We are unable to show this in our series.
However, we did show an increase in 24-h urinary protein excretion in the third trimester which seemed to regress by 3 months postpartum. This concurs with previous findings.4,9
The incidence of acute rejection was very low in our series at 3%: up to 14.5% has been reported.2,11,12 However, all three patients with histological features of chronic allograft rejection had a poor prognosis and required renal replacement therapy within 6 months postpartum. It is difficult to say for sure whether pregnancy hastened the deterioration in renal function of these patients with chronic rejection, because our numbers are small and the pre-conception renal function was poor. However, the hyperfiltration of pregnancy is certainly a risk factor.
There was no need to alter immunosuppression significantly at conception or thereafter in our patients because of stable renal function. Recent data concurs with stability of renal function in recipients who wait 2 years or more after transplantation before becoming pregnant.2,11,13 By contrast, an interval of >5 years may have a deleterious effect on pregnancy outcome,14,15 either because of an ageing recipient or because of further deterioration in renal function with time.
Graft survival was similar in all immunosuppression groups in our study. Patients receiving prednisolone and azathioprine, in particular, had significantly better renal function before and during pregnancy. Our findings agree with others,16 in that repeated pregnancies did not seem to adversely affect graft function.
Cyclosporin is known to have variable bioavailability with potential nephrotoxicity.17 It is therefore surprising that despite the known physiological changes of pregnancy,18 dosage was not altered. Hypertension has been exacerbated in women transplant recipients treated with cyclosporin in some studies,19 but not in ours.
Prognosis is considerably better when women have received a pancreas as well as a kidney allograft,20 as in three of our patients, and should be the treatment of choice for women with diabetic nephropathy.21
The incidence of pre-eclampsia in our series (12%) is lower than in previous reports.11 This is probably because blood pressure control was strictly implemented.
Miscarriage occurs in <16% of transplant patients, which is the same percentage as in the normal population.6,8 This does not appear to be influenced by the type of immunosuppression or the interval following transplantation.22 The incidence of miscarriage in our study (12%) was lower.
Prematurity is common in all series, ranging between 20% and 59%.23 A decline in renal function at this time is considered to be important.11 Exogenous steroids have been reported to be associated with premature rupture of the membranes.24 The majority of our group (75%) were intentionally delivered premature. The kidney transplant does not actually constitute an obstacle to vaginal delivery.11 However, caesarian sections rates in these circumstances appear to be frequent, at 25%–80%22 (79% in our series).
The outcome of pregnancy in renal transplantation is usually favourable. Serum creatinine <150 µmol/l, proteinuria less than 1g/day, absence of histological evidence of chronic allograft rejection and controlled blood pressure (140/90) and stability of maintenance immunosuppression have been identified as good indicators for a successful outcome for mother and child. However, the physiological haemodynamic changes associated with pregnancy may exacerbate any of the above parameters if they are abnormal. Frequent medical and obstetric review of the renal transplant recipient and the fetus is paramount and we strongly recommend it.
|
References |
|---|
|
TopSummaryIntroductionMethodsResultsDiscussionReferences |
|---|
1. Murray JE, Reid DE, Harrison JH, Merrill JP. Successful pregnancies after human renal transplantation. N Engl J Med 1963; 269:341.
2. Rudolph JE, Schweitzer RT, Bartus SA. Pregnancy in renal transplant patient. Transplantation 1979; 27:26.[Web of Science][Medline]
3. Lau J, Scott JR. Pregnancy following renal transplantation. Clin Obstet Gynecol 1983; 28:339–50.
4. Davison JM. The effect of pregnancy on kidney function in renal allograft recipients. Kidney Int 1985; 27:74.[Web of Science][Medline]
5. First MR, Pollak VE. Pregnancy and renal disease. In: Schrier RW, Gottschalk, eds. Diseases of the kidney. Boston, Little Brown, 1993:2287.
6. Davison JM. Renal transplantation and pregnancy. Am J Kidney Dis 1987; 9:374.[Web of Science][Medline]
7. Hou S. Pregnancy in women with chronic renal disease. N Engl J Med 1985; 312:836.[Medline]
8. Bumgardner GL, Matas AJ. Transplantation and pregnancy. Transplantation Rev 1992; 6:139.
9. Nojima M, Ichikawa Y, Fujimoto T, Arima M, Hosokawa S, Shimamda K, Ito K, Tamori N, Koyama K, Nagano S, Ikoma F. Influence of pregnancy on graft function after renal transplantation. Transplant Proc 1996; 28:1582–5.[Medline]
10. First RM, Combs CA, Weiskittel P, Miodovnik M. Lack of effect of pregnancy on renal allograft survival or function. Transplantation 1995; 59:472–6.[Medline]
11. Davison JM. Dialysis, transplantation, and pregnancy. Am J Kidney Dis 1991; 17:127–32.[Web of Science][Medline]
12. Armenti VT, Ahlswede BA, Jarrell BE, Moritz MJ, Burke JF. National Transplantation Pregnancy Registry—outcome of 154 pregnancies in cyclosporine-treated female kidney transplant recipients. Transplantation 1994; 57:502.[Web of Science][Medline]
13. Armenti VT, Ahlswede MJ, Moritz MJ, Jarrell BE. National transplantation pregnancy registry: analysis of pregnancy outcomes of female kidney recipients with relation to time interval from transplant to conception. Trans Proc 1993; 25:1036–7.
14. Bung P, Molitor D. Pregnancy and postpartum after kidney transplantation and cyclosporine therapy-Review of the literature adding a new case. J Perinat Med 1991; 19:397–401.
15. Panagiotopoulos A, Goeschen K. Schwangerschaftysverlauf nach Nierentransplantation. Die Hebamme 1988; 1:25–7.
16. Ehrich JHH, Loirat C, Davison JM, Rizzoni G, Wittkop B, Selwood NH, Mallick NP. Repeated successful pregnancies after kidney transplantation in 102 women (report by the EDTA Registry) Nephrol Dial Transplant 1996; 1:1314–17.
17. Myers BD, Ross J, Newton L, Luetscher J, Perlroth M. Cyclosporine-associated chronic nephropathy. N Engl J Med 1984; 311:699–705.[Abstract]
18. Armenti VT, Jarrell JS, Radomski JS, McGroy CH, Gaughan WJ, Moritz MJ. National transplantation pregnancy registry(NTPR): cyclosporin dosing and pregnancy outcome in female renal transplant recipients. Trans Proc 1996; 28:2111–12.
19. Rieu P, Neyrat N, Hiesse C, Charpentier B. Thirty-three pregnancies in population of 1725 renal transplant patients. Trans Proc 1997; 29:2459–60.
20. Calne RY, Brons EGM, Williams PF, Evans EB, Robinson RE, Dossa M. Successful pregnancy after paratopic segmental pancreas and kidney transplantation. Br Med J 1988; 296:1709.
21. Remuzzi G, Ruggenenti P, Mauer SM. Pancreas and kidney/pancreas transplants:experimental medicine or real improvement? Lancet 1994; 343:27.[Web of Science][Medline]
22. Gaughan WJ, Moritz MJ, Radomski JS, Burke JF, Armenti VT. National transplantation pregnancy registry: report on outcomes in cyclosporine-treated female kidney transplant recipients with an interval from transplant to pregnancy of greater than five years. Am J Kid Dis 1996; 28:266–9.[Web of Science][Medline]
23. Touraine JL, Audra N, Lefrancois N, Garnier JL, Dargent D, Martin X, Guerard A. Pregnancy in renal transplant patients: 45 case reports. Trans Proc 1997; 29:2472–4.
24. Muirhead N, Sabharwal AR, Rieder M, Lazarovitis AI, Hollomby DJ. The outcome of pregnancy following renal transplantation—The experience of a single center. Transplantation 1992; 54:429–32.[Medline]
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||