Kidney Week

Abstract: PO0958

Comprehensive Ultrastructural Analysis Strongly Predicts Kidney Function Decline in the Multicenter TRIDENT Cohort

Session Information

• Diabetic Kidney Disease: Clinical - 1
  October 22, 2020 | Location: On-Demand
  Abstract Time: 10:00 AM - 12:00 PM

Category: Diabetic Kidney Disease

• 602 Diabetic Kidney Disease: Clinical

Authors

• Palmer, Matthew, University of Pennsylvania, Philadelphia, Pennsylvania, United States

Matthew Palmer,

• Abedini, Amin, University of Pennsylvania, Philadelphia, Pennsylvania, United States

Amin Abedini,

• Jackson, Casey, University of Pennsylvania, Philadelphia, Pennsylvania, United States

Casey Jackson,

• Blady, Shira, University of Pennsylvania, Philadelphia, Pennsylvania, United States

Shira Blady,

• Chatterjee, Shatakshee, University of Pennsylvania, Philadelphia, Pennsylvania, United States

Shatakshee Chatterjee,

• Sullivan, Katie, University of Pennsylvania, Philadelphia, Pennsylvania, United States

Katie Sullivan,

• Townsend, Raymond R., University of Pennsylvania, Philadelphia, Pennsylvania, United States

Raymond R. Townsend,

• Mottl, Amy K., University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States

Amy K. Mottl,

• Almaani, Salem, The Ohio State University Wexner Medical Center, Columbus, Ohio, United States

Salem Almaani,

• Srivastava, Anand, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States

Anand Srivastava,

• Avasare, Rupali S., Oregon Health & Science University, Portland, Oregon, United States

Rupali S. Avasare,

• Ross, Michael J., Albert Einstein College of Medicine/ Montefiore Medical Center, Bronx, New York, United States

Michael J. Ross,

• Brodbeck, Jens, Inflammation & Respiratory Therapeutics, Gilead Sciences Inc., Foster City, California, United States

Jens Brodbeck,

• Susztak, Katalin, University of Pennsylvania, Philadelphia, Pennsylvania, United States

Katalin Susztak,

Background

While diabetic kidney disease (DKD) is responsible for more than half of all chronic and end stage kidney disease (ESKD), the association of light (LM) and electron microscopical (EM) structural changes with clinical parameters and prognosis in late stage DKD is not completely determined.

Methods

TRIDENT (Transformative Research in Diabetic Nephropathy) is a multi-center observational cohort aimed to identify changes associated with kidney function decline in an unbiased manner. Sixty-two patients diagnosed with biopsy-confirmed DKD were enrolled. Digital scans of biopsy slides and EM were scored for twelve LM and eight EM parameters. Demographic and clinical features of the patients were recorded at enrollment and patients were followed-up every six months.

Results

The median estimated glomerular filtration rate (eGFR) was 28.91(20.87) ml/min/1.73m² and the urine protein to creatinine ratio (UPCR) at enrollment was 4.64(7.25) mg/mg. During a mean follow-up time of 10.6 months, the median change in eGFR was -25.8(58) % and median fold change in UPCR was 1.29(2.15) and 17 patients progressed to ESKD. Multiple linear regression analysis revealed that interstitial fibrosis independently associated with eGFR at enrollment. Glomerular lesions including global glomerulosclerosis and mesangiolysis were associated with eGFR decline. Foot process effacement significantly associated with UPCR at enrollment and mesangial hyalinosis predicted UPCR fold change. Unbiased clustering analysis identified three disease subgroups of which cluster 2(N=11) showed more pronounced damage by LM and EM parameters and had the fastest eGFR decline, while cluster 1(N=25) had the slowest eGFR decline and the least severe structural lesions. Cox regression analysis showed that the subjects in cluster 2 had the highest risk to reach ESKD (HR=14.8, 95%CI; 1.76-123.73, P=0.01).

Conclusion

This study confirms association of structural and clinical parameters even in late stage DKD. Furthermore, it highlights specific ultrastructural features that can strongly predict kidney function decline.