International variation in ESRD, non-ESRD deaths in type 1 diabetes highlighted
medwireNews: The risk for end-stage renal disease (ESRD) is high among patients with type 1 diabetes and advanced nephropathy but varies by country, shows an analysis of cohorts from Finland, France, Denmark, and the USA.
Furthermore, the pattern of countries with the highest versus lowest ESRD risk was reversed when the researchers measured mortality unrelated to ESRD, which was mainly due to cardiovascular causes.
Writing in Diabetes Care, Jan Skupien (Jagiellonian University Medical College, Krakow, Poland) and colleagues note that the “striking international differences in ESRD risk and mortality unrelated to ESRD could not be explained by so-called ‘competing risks’.”
The study included 1518 White patients with type 1 diabetes and persistent macroalbuminuria in chronic kidney disease (CKD) stages 1–3 who were recruited to one of four international cohorts between 1993 and 2002 and followed up for 3–18 years.
Despite approximately 75–95% of patients receiving renoprotective treatment, there were 505 cases of ESRD (32.2 per 1000 patient–years) during follow-up, with incidence increasing with increasing CKD stage.
Cumulative incidence at 10 years was highest among the 432 patients in the Joslin (USA) cohort, at 31.1%, followed by 25.0% in the FinnDiane cohort (Finland, n=486), 17.8% in the INSERM cohort (France, n=232), and 16.5% in the Steno cohort (Denmark, n=368).
Compared with patients in the FinnDiane cohort, those in the Joslin cohort were a significant 44% more likely to develop ESRD, while those in the Steno and INSERM cohorts were 46% and 33% less likely, respectively.
There were 228 deaths unrelated to ESRD (14.5 per 1000 patient–years) during follow-up, which were not associated with CKD stage.
In contrast to ESRD rates, patients in the Steno cohort had the highest 10-year cumulative incidence of non-ESRD deaths, at 15.4%, followed by those in INSERM, FinnDiane, and Joslin, at 13.7%, 9.1%, and 7.1%, respectively.
Furthermore, patients in the Joslin cohort had a significant 33% lower risk for non-ESRD death than those in the other three cohorts.
Adjusted analyses showed that the risk for ESRD was significantly associated with higher glycated hemoglobin and systolic blood pressure, and with younger age and lower baseline estimated glomerular filtration rate (eGFR). Men and smokers also had a higher risk for ESRD than women and nonsmokers, respectively.
Conversely, the risk for non-ESRD mortality was significantly associated with older age, higher baseline eGFR, and smoking.
Since the risk factors for each outcome only partially overlap, the researchers say they consider progression to ESRD and mortality unrelated to ESRD “as independent disease processes.”
“Therefore, the international differences in both outcomes could be due to unknown genetic or environmental factors that vary among populations, different health attitudes, or alternatively, they might be attributed to gene-environment interactions,” Skupien et al conclude.
They add that the genetic causes are currently being investigated in the JDRF Diabetic Nephropathy Collaborative Research Initiative study.
By Laura Cowen
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