The effect of preeclampsia on long-term kidney function among pregnant women with chronic kidney disease

Background The association between superimposed preeclampsia and an elevated risk of long-term kidney function decline or end-stage renal disease (ESRD) in patients with chronic kidney disease (CKD) remains uncertain. This study aimed to analyze the association between preeclampsia and kidney function deterioration in CKD patients. Methods This is a retrospective cohort study, included the clinical information of 103 pregnant CKD patients with preeclampsia and 103 matched CKD patients without preeclampsia who were followed-up for a minimum of 1 year after their first pregnancy from January 1, 2009, to May 31, 2022. Cox proportional hazards regression analysis was conducted to evaluate the effects of preeclampsia on long-term kidney function decline or ESRD among CKD patients. Kaplan–Meier curves were used to compare renal survival within different subgroups and compared by the log-rank test. Results During the follow-up period, 44 (42.72%) CKD patients with preeclampsia and 20 (19.42%) without preeclampsia had an estimated glomerular filtration rate (eGFR) decline >30% or developed ESRD. Compared with CKD patients without preeclampsia, the eGFR declined more significantly in patients with preeclampsia [98.43 (79.48, 116.47) to 81.32 (41.20, 102.97) mL/min/1.73 m2 vs. 100.00 (74.86, 120.04) to 89.45 (63.69, 105.60) mL/min/1.73 m2; P =0.041]. Multivariable analysis showed that early-onset preeclampsia (HR=2.82, 95% CI: 1.48–5.39, P <0.01) and late-onset preeclampsia (HR=2.51, 95% CI: 1.28–4.93, P <0.05) were both risk factors for an eGFR decline >30% or ESRD. Conclusions Preeclampsia was associated with a higher risk of long-term kidney function decline or ESRD among CKD patients, especially in patients with early-onset preeclampsia. Evidence before this study Chronic kidney disease (CKD) is proposed as a high-risk factor for preeclampsia, which is an idiopathic disease during pregnancy with multisystemic involvement, including the kidney. It is believed that pregnancy accelerates renal function decline in patients with stage 3-4 CKD. Yet, little is known about whether superimposed PE is associated with an increased risk of renal function decline in patients with CKD. Peking University First Hospital has been paying special attention to the perinatal care of patients with CKD since 2009. Given the high risk of both adverse maternal and neonatal outcomes among women with CKD, multidisciplinary care that includes nephrologists and maternal-fetal medicine specialists was set up in 2018, leading to the referral of more patients with CKD in Beijing and its surrounding areas to our hospital for perinatal care and delivery. Our analysis of the follow-up data of pregnant CKD patients with and without preeclampsia in our hospital over the past 14 years will help us better understand the relationship between preeclampsia and reduction in renal function in patients with CKD. Added value of this study This longitudinal cohort study including 103 pregnant CKD patients with preeclampsia and 103 matched CKD patients without preeclampsia with minimum follow-up of 1 year, the association between preeclampsia and long-term kidney function decline or ESRD among CKD patients were analyzed. Compared with CKD patients without preeclampsia, the eGFR declined more significantly in patients with preeclampsia [98.43 (79.48, 116.47) to 81.32 (41.20, 102.97) mL/min/1.73 m2 vs. 100.00 (74.86, 120.04) to 89.45 (63.69, 105.60) mL/min/1.73 m2; P=0.041]. Multivariable analysis showed that increased Scr levels (HR=3.02, 95% CI: 1.53–5.94, P=0.001), higher CKD stage (HR=2.76, 95% CI: 1.46–5.22, P=0.002), proteinuria ≥1.00 g/24h (HR=2.70, 95% CI: 1.39–5.25, P=0.003), early-onset preeclampsia (HR=2.82, 95% CI: 1.48–5.39, P<0.01) and late-onset preeclampsia (HR=2.51, 95% CI: 1.28–4.93, P<0.05) were risk factors for an eGFR decline >30% or ESRD. Implications of all the available evidence This study indicates that preeclampsia was associated with increased risk of eGFR decline<30% or ESRD, especially early-onset preeclampsia. Therefore, for patients with CKD, seeking good prophylactic treatment to prevent the onset of preeclampsia during pregnancy, especially early-onset preeclampsia, is of great significance not only for improving pregnancy outcomes but also for improving long-term prognosis of renal function. The use of LDA to prevent early-onset preeclampsia has a new clinical significance. In addition to improving pregnancy outcomes, LDA may be beneficial for reducing kidney function decline in pregnant CKD patients. This study provided critical evidence to support further prospective studies investigating the association between LDA and long-term kidney function prognosis. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by National High Level Hospital Clinical Research Funding (Interdepartmental Clinical Research Project of Peking University First Hospital) (No. 2022CR20). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Not Applicable The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was undertaken in accordance with the Declaration of Helsinki and approved by the Ethics Committee of Peking University First Hospital [No. 2022 (233)]. The data were anonymous, and the requirement for informed consent was therefore waived. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Not Applicable I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Not Applicable I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Not Applicable The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.