Pregnancy and Long-Term Kidney Function in Chronic Kidney Disease: A Systematic Review and Meta-Analysis

Introduction: Pregnancy may accelerate kidney function decline in women with CKD, particularly in advanced stages. Some clinicians may therefore advise against pregnancy. Exact impact of pregnancy and subgroup risks (e.g., for patients with proteinuria or hypertension) are still uncertain. For CKD patients who wish to conceive, establishing the impact of pregnancy and identifying those at risk for progression is crucial. Methods: We conducted a systematic review and meta-analysis in human and animal studies separately, synthesizing all available evidence on long-term kidney function after pregnancy in women with pre-existing CKD. Primary outcome was standardized mean difference (SMD) in kidney function before versus after pregnancy. For clinical implications, we calculated mean glomerular filtration rate (GFR) differences. Secondary outcomes were incidences of kidney failure (KF)/kidney replacement therapy (KRT) after delivery and kidney function deterioration. Subanalyses stratified studies as mild versus advanced CKD if studies had ≤25% vs. >25% of participants CKD stage 3-5, (unless cohorts defined otherwise) and chronic hypertension as <25% vs. >25% of participants having chronic hypertension. Results: We analyzed 36 human studies including 2945 patients, 4623 pregnancies and 12 animal studies. Pregnancy had no effect on long-term kidney function in mild CKD cohorts (SMD -0.22[-0.56,0.13]) over a mean follow-up of 4.4 (SD 0.7) years. However, kidney function was significantly lower after pregnancy in advanced CKD cohorts (SMD -0.55[-0.80, -0.30]), pooled eGFR decline -8.96 ml/min [-17.4,-0.48], mean follow-up 2.6 years. Chronic hypertension affected overall SMD (β=-0.01 [-0.02, -0.001], P =0.03). Pooled KF/KRT incidence was 9%, mean follow-up 6.5 years. Pregnancy did not affect kidney function after delivery in animal nephropathy models. Conclusion: Results for mild CKD patients are reassuring as pregnancy does not impact long-term kidney function. Animal studies support clinical findings in mild CKD and offer insights in the potential underlying mechanisms. Advanced CKD patients should be informed on risking kidney function decline in pregnancy. Studies including eGFR-slopes pre-and post-pregnancy are scarce, limiting understanding of pregnancy’s impact next to natural disease progression in advanced CKD. This highlights the need for future research including multiple eGFR measurements over time.