Differentiating Acute Rejection From Preeclampsia After Kidney Transplantation

Abstract

OBJECTIVE: To evaluate the clinical and laboratory characteristics in pregnancy that differentiate preeclampsia from acute renal allograft rejection and to investigate the maternal, neonatal, and graft sequelae of these diagnoses. METHODS: We conducted a retrospective case-controlled registry study of data abstracted from Transplant Pregnancy Registry International deliveries between 1968 and 2019. All adult kidney transplant recipients with singleton pregnancies of at least 20 weeks of gestation were included. Acute rejection was biopsy proven and preeclampsia was diagnosed based on contemporary criteria. Variables were compared using χ2, Fisher exact, and Wilcoxon rank sum tests as appropriate. Multivariable linear regression was used to analyze preterm birth. Kaplan-Meier curves with log-rank test and Cox proportional hazards model were used to compare graft loss over time. RESULTS: There were 26 pregnant women with biopsy-confirmed acute rejection who were matched by the year they conceived to 78 pregnant women with preeclampsia. Recipients with acute rejection had elevated peripartum serum creatinine levels (73% vs 14%, P<.001), with median intrapartum creatinine of 3.90 compared with 1.15 mg/dL (P<.001). Conversely, only patients with preeclampsia had a significant increase in proteinuria from baseline. Although there were no significant differences in maternal outcomes, graft loss within 2 years postpartum (42% vs 10%) and long-term graft loss (73% vs 35%) were significantly increased in recipients who experienced acute rejection (P<.001 for both). The frequency of delivery before 32 weeks of gestation was 53% with acute rejection and 20% with preeclampsia. After controlling for hypertension and immunosuppressant use, acute rejection was associated with higher frequency of delivery at less than 32 weeks of gestation (adjusted odds ratio 4.04, 95% CI 1.10–15.2). CONCLUSION: In pregnancy, acute rejection is associated with higher creatinine levels, and preeclampsia is associated with increased proteinuria. Acute rejection in pregnancy carries a risk of prematurity and graft loss beyond that of preeclampsia for kidney transplant recipients. FUNDING SOURCE: The Transplant Pregnancy Registry International is supported in part by an educational grant from Veloxis Pharmaceuticals.

Pregnancy after transplant in the older adolescent: Anticipatory guidance for the pediatric provider

“…It is clinically important to distinguish between the two conditions as kidney rejection requires treatment and preeclampsia may require delivery. 49 Transplant biopsy is the standard for diagnosis of acute rejection. 43 In kidney transplant recipients, planned pregnancies confer better outcomes than unplanned pregnancies.…”

Parenthood With Kidney Failure: Answering Questions Patients Ask About Pregnancy

“…55,68 Pregnancy-related hypertension and pre-eclampsia will precipitate early delivery but can be difficult to differentiate from declining kidney from other causes, including rejection. 97 Calcineurin inhibitor toxicity maybe confused with pre-eclampsia as both cause graft dysfunction, thrombotic microangiopathy, and hypertension. 79,98 Tacrolimus levels are difficult to interpret in pregnancy because of the change in the free versus bound tacrolimus ratio.…”

“…Acute rejection during pregnancy has been reported in 1% to 10% of pregnancies. 55,97 The impact of transplant-to-pregnancy interval on long-term graft outcomes is uncertain with conflicting data from various studies. 53,[69][70][71]78,95 Overall, the potential impact of pregnancy must be individualized to each patient and graft.…”

Pregnancy care in solid organ transplant recipients

“…This condition can present asymptomatically with elevated serum creatinine and proteinuria or symptomatically with pain at graft site, fever, and oliguria. It can be difficult to clinically distinguish from pre‐eclampsia but typically presents with median creatinine level of 3.90 mg/dL compared with 1.15 mg/dl for pre‐eclampsia, lower rates of proteinuria, and higher rates of preterm birth and graft loss 34 . Ultrasound‐guided kidney biopsy can be used to confirm the diagnosis on a case‐by‐case basis.…”

“…It can be difficult to clinically distinguish from pre-eclampsia but typically presents with median creatinine level of 3.90 mg/dL compared with 1.15 mg/dl for preeclampsia, lower rates of proteinuria, and higher rates of preterm birth and graft loss. 34 Ultrasound-guided kidney biopsy can be used to confirm the diagnosis on a case-by-case basis. Frequent surveillance of renal function by monitoring serum creatinine and urine protein is therefore required throughout pregnancy, with a 24-h measurement collected at baseline and repeated if there are concerns for worsened proteinuria; a urine protein to creatinine ratio can also be used for a spot measurement of proteinuria.…”