Congenital Anomalies of the Kidney and Urinary Tract (CAKUT): An Emerging Relationship With Pregestational Diabetes Mellitus Among First Nations and Non-First Nations People in Saskatchewan-Results From the DIP: ORRIIGENSS Project

Objectives: Because congenital anomalies of the kidneys and urinary tract (CAKUT) represent a frequent cause of end stage renal disease (ESRD) in the young, we explored the epidemiology of CAKUT and the role of diabetes in pregnancy.

Methods: This was a retrospective cohort study of CAKUT, by maternal diabetes status, from among all 1980‒2009 births in Saskatchewan First Nations (FN) and non-First Nations (non-FN) people. We determined frequencies, predictors and complications of CAKUT, as well as cumulative survival (to 2014) of affected persons until ESRD and death.

Results: Of the 411,055 babies (204,167 mothers) in the Saskatchewan maternal-infant database, 2,540 had CAKUT (391 FN and 2,149 non-FN). Overall annual CAKUT incidence was 0.63% for non-FN and 0.57% for FN (p=0.082), but 5-year CAKUT incidence only increased among FN (0.40% in 1980‒1984 and 0.76% in 2005‒2009, p<0.0001) and was highest among offspring of FN mothers with pregestational diabetes (pre-G/DM) (0% before 1995, 2.51% in 2000‒2004 and 1.66% in 2005-2009). Pre-G/DM, but not gestational diabetes mellitus (GDM), was an independent predictor of CAKUT in non-FN (odds ratio, 1.79; 95% confidence interval, 1.20 to 2.69), and in FN interacting with maternal history of stillbirth (odds ratio, 7.90; 95% confidence interval, 1.14 to 54.6). ESRD was >100-fold more likely among offspring with CAKUT compared with all other offspring and was responsible for 40% of ESRD cases in young FN and non-FN people.

Conclusions: In Saskatchewan, pre-G/DM is an emerging cause of CAKUT, accounting for 40% of ESRD cases in FN/non-FN children and young adults. Because pre-G/DM‒related CAKUT is potentially preventable with optimal glycemic management, increased recognition of this serious complication is required.