Kidney Disease in Women With Previous Gestational Diabetes Mellitus: A Nationwide Register-Based Cohort Study

OBJECTIVE

This study investigated the association between gestational diabetes mellitus (GDM) and incident kidney disease, the mediating effects of diabetes and hypertension, and the impact of severity of metabolic dysfunction during pregnancy on the risk of incident kidney disease.

RESEARCH DESIGN AND METHODS

This Danish nationwide register-based cohort study included all women giving birth between 1997 and 2018. Outcomes included chronic kidney disease (CKD) and acute kidney disease based on diagnosis codes. Cox regression analyses explored the association between GDM and kidney disease. A proxy for severity of metabolic dysfunction during pregnancy was based on GDM diagnosis and insulin treatment during GDM-pregnancy and included in the models as interaction term. The mediating effects of subsequent diabetes and hypertension prior to kidney disease were quantified using mediation analyses.

RESULTS

We included 697,622 women. Median follow-up was 11.9 years. GDM associated with higher risk of CKD (adjusted hazard ratio [aHR] 1.92 [95% CI 1.67–2.21]) whereas acute kidney disease was unrelated to GDM. There were indirect effects of diabetes and hypertension on the association between GDM and CKD; 75.7% (95% CI 61.8–89.6) and 30.3% (95% CI 25.2–35.4), respectively, as assessed by mediation analyses. The CKD risk was significantly increased in women with insulin-treated GDM and no subsequent diabetes compared to women without GDM (aHR 2.35 [95% CI 1.39–3.97]).

CONCLUSIONS

The risk of CKD was significantly elevated after GDM irrespective of subsequent development of diabetes and hypertension. Furthermore, women with severe metabolic dysfunction during pregnancy had the highest CKD risk.