Kidney Week

Abstract: SA-PO315

Genetic Risk Factors for Kidney Disease in Type 1 Diabetes

Session Information

• Diabetic Kidney Disease: Clinical Pathology, Diagnostic and Treatment Advances
  October 26, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Diabetic Kidney Disease

• 702 Diabetic Kidney Disease: Clinical

Authors

• Limonte, Christine P., University of Washington, Seattle, Washington, United States

Christine P. Limonte, MD

• Gao, Xiaoyu, The George Washington University, Washington, District of Columbia, United States

Xiaoyu Gao, MS

• Bebu, Ionut, The George Washington University, Washington, District of Columbia, United States

Ionut Bebu, PhD

• Karger, Amy B., University of Minnesota Twin Cities, Minneapolis, Minnesota, United States

Amy B. Karger, MD, PhD

• Lorenzi, Gayle, University of California San Diego, La Jolla, California, United States

Gayle Lorenzi, RN

• Perkins, Bruce A., University of Toronto, Toronto, Ontario, Canada

Bruce A. Perkins, MD, MPH

• De Boer, Ian, University of Washington, Seattle, Washington, United States

Ian De Boer, MD, MS

• Paterson, Andrew, University of Toronto, Toronto, Ontario, Canada

Andrew Paterson

Background

The genetic risk factors underlying kidney disease in type 1 diabetes (T1D) remain poorly understood. We examined whether previously-established genetic risk scores (GRS) for eGFR and albuminuria from general population cohorts correlate with these measures in adults with T1D beyond established demographic and clinical risk factors in the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) study.

Methods

We applied eGFR and albuminuria GRS derived previously in general population cohorts to 1,304 DCCT/EDIC participants with available genome-wide genotyping. Associations of eGFR GRS with continuous eGFR and of albuminuria GRS with continuous albumin excretion rate (AER) were assessed using linear regression models. Associations of eGFR GRS with incident eGFR <60 ml/min/1.73m² and of albuminuria GRS with sustained AER > 30mg/24h and AER > 300 mg/24h were assessed using Cox proportional hazards models. Models were adjusted for age, sex, hemoglobin A1c, diabetes duration, systolic blood pressure, triglycerides, and beta-blocker use.

Results

Overall, participants had a mean age of 60 years and 53% were male. 49% of participants were randomized to intensive versus conventional glucose-lowering therapy in the DCCT. Participants were followed for a median (IQR) 35 (33, 37) years. eGFR GRS was significantly associated with continuous eGFR (2.7+0.3 ml/min/1.73m² higher eGFR per 1 SD higher GRS; p<0.0001) and incident eGFR <60 ml/min/1.73m² (HR=0.83 [95% CI 0.74, 0.93] per 1 SD higher GRS; p=0.001). Albuminuria GRS was significantly associated with incident AER >30mg/24h (HR=1.12 [95% CI 1.03, 1.23] per 1 SD higher GRS; p=0.01), but not incident AER >300mg/24h or continuous AER. Associations were similar in analyses stratified by the original DCCT treatment group assignment (intensive versus conventional insulin therapy).

Conclusion

Genetic factors that predict eGFR and albuminuria in the general population are similarly associated with these measures in adults with T1D after adjusting for demographic and diabetes-related clinical risk factors, including glycemic exposure as measured by hemoglobin A1c and by the original DCCT randomization to intensive versus conventional insulin therapy.

Funding

• NIDDK Support