Pregnancy in renal transplant recipients: long-term effect on patient and graft survival. A single-center experience.

BACKGROUND: There are limited data on the effect of pregnancy on long-term renal allograft function. The aim of the study was to compare long-term graft and patient outcome between pregnant and nonpregnant women after renal transplantation. METHODS: The study group consisted of 39 women attending the Perinatal Division of the Rabin Medical Center who conceived after undergoing renal transplantation (total number of live births: 55). All had a functioning allograft at the time of conception. Each patient was matched with 3 controls for 12 factors known to affect graft survival. The controls were derived from a cohort of 250,000 transplant patients registered in the Collaborative Transplantation Study (CTS) database. The groups were compared for graft survival, long-term patient survival, and kidney function (CTS clinical grading scale). RESULTS: Graft (61.6%) and patient (84.8 %) survival from transplantation to the end of follow-up (15 years) in the women who conceived after transplantation did not differ from the rates observed in the 177 women in the matched control group (68.7% and 78.8 %, respectively). There were no between-group differences in long-term graft function. CONCLUSION: Pregnancy does not appear to have adverse effects on long-term graft or patient survival or kidney function in women after renal transplantation.

Renin-angiotensin system blockade prevents the increase in plasma transforming growth factor beta 1, and reduces proteinuria and kidney hypertrophy in the streptozotocin-diabetic rat.

INTRODUCTION: Combination therapy with angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) is used to improve renal outcome achieved by monotherapy in diabetic patients. In addition, interference with the renin-angiotensin system (RAS) reduced expression and excretion of transforming growth factor beta 1 (TGF-beta 1) in diabetic nephropathy. The aim of this study was to investigate the effects of interrupting the RAS by ACE inhibitor (ACE-I) or ARB monotherapy or by combination therapy on proteinuria, kidney hypertrophy and plasma TGF-beta 1 in diabetic rats. MATERIALS AND METHODS: Forty-one male Wistar rats were allocated to five groups: 1 = control rats, 2 = diabetic rats (streptozotocin [STZ] 55 mg/kg), 3 = diabetic rats as above receiving enalapril (20 mg/kg/day), 4 = diabetic rats receiving losartan (80 mg/kg/day), 5 = diabetic rats receiving both losartan and enalapril. The study lasted 60 days. RESULTS: Urinary protein excretion, kidney weight, serum ACE activity and plasma TGF-beta1 increased significantly in untreated diabetic rats compared with controls. Administration of losartan, enalapril, or both for 60 days prevented these changes. Furthermore, combined therapy for 30 days normalised urinary protein excretion, while monotherapy did not. Losartan inhibited serum ACE activity both in vivo and in vitro. Plasma TGF-beta 1 levels were positively correlated with blood glucose levels (r=0.4059) and with urinary protein excretion (r=0.3558). CONCLUSIONS: Combination therapy with losartan and enalapril was more effective than monotherapy with either drug in achieving an early antiproteinuric response. Long-term treatment with losartan was as effective as the combined treatment, possibly due to a dual inhibitory effect on the RAS. The antiproteinuric effect may be related, in part, to reduced TGF-beta 1.

Is immunosuppression therapy in renal allograft recipients teratogenic? A single-center experience.

The aim of the study was to determine whether immunosuppressive agents used in renal allograft recipients are teratogenic or otherwise associated with pregnancy outcome. The study population consisted of 38 renal allograft recipients treated with combinations of prednisone, azathioprine, cyclosporin A, and tacrolimus attending our Hypertension in Pregnancy Clinic. The 48 live offspring of 73 pregnancies in this group were evaluated for major congenital malformations and mild errors of morphogenesis. Findings were compared with those in 48 offspring of 41 women with primary renal disease not treated with immunosuppressive drugs. Pregnancy outcome parameters were also compared between the study and control groups in the perinatal period and on a long-term basis (2-7 years after birth). Two major anomalies (4.2%), subcoronal hypospadias and rudimentary thumb, and 10 mild errors of morphogenesis (20.8%) were detected in the study group. These rates did not differ significantly from those in the control group (4.2% and 16.6%, respectively). Pregnancy outcome was worse in the renal transplant patients than in the women with primary renal disease in terms of prematurity (60% vs. 21%, P = 0.001), growth restriction (52% vs. 17%, P = 0.001), and hospitalization in a neonatal intensive care unit (35% vs. 6%, P = 0.01). In conclusion, the similar prevalence of major anomalies and mild errors of morphogenesis in offspring of the renal transplant patients and the women with primary renal disease suggests that immunosuppressive therapy is not a teratogenic factor. It may, however, be associated with worse pregnancy outcome.