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Kidney Week

Abstract: TH-PO193

The Search for Liquid Biopsies: Serum Biomarkers and Kidney Structure in Early Diabetic Kidney Disease

Session Information

Category: Diabetic Kidney Disease

  • 702 Diabetic Kidney Disease: Clinical

Authors

  • Looker, Helen C., National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, Arizona, United States
  • Md Dom, Zaipul, Joslin Diabetes and Endocrinology Research Center, Boston, Massachusetts, United States
  • Nelson, Robert G., National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, Arizona, United States
  • Krolewski, Andrzej S., Joslin Diabetes and Endocrinology Research Center, Boston, Massachusetts, United States
Background

The Joslin Kidney Panel (JKP) of 21 circulating proteins biomarkers linked to inflammation, axon guidance, fibrosis, and tubular damage is associated with kidney failure in Caucasians with type 1 diabetes from the Joslin Kidney Study and in American Indians with type 2 diabetes. We examined the association of these proteins with early kidney structural lesions in a subset of the American Indians who also underwent a research kidney biopsy.

Methods

GFR was measured by the urinary clearance of iothalamate and serum samples collected at these visits were measured on an OLINK platform using a proximity extension assay. Research kidney biopsies were obtained a median of 1.3 years from the clearance study. Kidney structure was assessed using standard morphometric techniques. Regression models with Lasso selection and k-fold cross-validation were used to assess best biomarkers for each measure.

Results

Mean age of the 107 participants (78 women) was 45.5 (SD 9.6) years, blood pressure 123 (13) / 77 (9) mmHg, HbA1c 9.2 (2.3)%, GFR 150 (47) ml/min, and median diabetes duration was 12.8 (IQR 11.0-19.4) years. All participants had GFR >60 ml/min; 40 (37%) had moderate albuminuria and 21 (20%) had severe albuminuria. Biomarker concentrations correlated positively with global glomerular sclerosis, glomerular basement membrane width, mesangial fractional volume, cortical interstitial fractional volume, and podocyte foot process width and negatively with glomerular filtration surface density, total filtration surface density, podocyte density, and percentage of endothelial fenestrations (Figure). KIM1 was the leading biomarker for most morphometric parameters based on regression models (Figure).

Conclusion

The JKP of biomarkers that includes proteins linked to multiple diabetic kidney disease (DKD) pathways demonstrated associations with a broad range of early structural lesions associated with DKD progression.

Funding

  • NIDDK Support