TY - JOUR
T1 - The Role of Glomerular Epithelial Injury in Kidney Function Decline in Patients With Diabetic Kidney Disease in the TRIDENT Cohort
AU - Palmer, Matthew B.
AU - Abedini, Amin
AU - Jackson, Casey
AU - Blady, Shira
AU - Chatterjee, Shatakshee
AU - Sullivan, Katie Marie
AU - Townsend, Raymond R.
AU - Brodbeck, Jens
AU - Almaani, Salem
AU - Srivastava, Anand
AU - Avasare, Rupali
AU - Ross, Michael J.
AU - Mottl, Amy K.
AU - Argyropoulos, Christos
AU - Hogan, Jonathan
AU - Susztak, Katalin
N1 - Funding Information:
The TRIDENT study is funded by Gilead , GSK , Regeneron , and Boehringer Ingelheim . The funders have no influence on the design and analysis. We thank the University of Pennsylvania Diabetes Research Center for the use of the Core (P30-DK19525). The abstract of the paper was presented in ASN kidney week 2020 as a poster and published in the abstract book.
Funding Information:
The TRIDENT study is funded by Gilead, GSK, Regeneron, and Boehringer Ingelheim. The funders have no influence on the design and analysis. We thank the University of Pennsylvania Diabetes Research Center for the use of the Core (P30-DK19525). The abstract of the paper was presented in ASN kidney week 2020 as a poster and published in the abstract book.
Publisher Copyright:
© 2021 International Society of Nephrology
PY - 2021/4
Y1 - 2021/4
N2 - Introduction: Although 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 microscopic (EM) structural changes with clinical parameters and prognosis in DKD is incompletely understood. Methods: This is an interim analysis of 62 patients diagnosed with biopsy-confirmed DKD from the multicenter TRIDENT (Transformative Research in Diabetic Nephropathy) study. Twelve LM and 8 EM descriptors, representing changes in glomeruli, tubulointerstitium, and vasculature were analyzed for their relationship with clinical measures of renal function. Patients were followed every 6 months. Results: Multivariable linear regression analysis revealed that estimated glomerular filtration rate (eGFR) upon enrollment correlated the best with interstitial fibrosis. On the other hand, the rate of kidney function decline (eGFR slope) correlated the most with glomerular lesions including global glomerulosclerosis and mesangiolysis. Unbiased clustering analysis based on histopathologic data identified 3 subgroups. The first cluster, encompassing subjects with the mildest histologic lesions, had the most preserved kidney function. The second and third clusters had similar degrees of kidney dysfunction and structural damage, but differed in the degree of glomerular epithelial cell and podocyte injury (podocytopathy DKD subtype). Cox proportional hazard analysis showed that subjects in cluster 2 had the highest risk to reach ESKD (hazard ratio: 17.89; 95% confidence interval: 2.13–149.79). Glomerular epithelial hyperplasia and interstitial fibrosis were significant predictors of ESKD in the multivariate model. Conclusion: The study highlights the association between fibrosis and kidney function and identifies the role of glomerular epithelial changes and kidney function decline.
AB - Introduction: Although 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 microscopic (EM) structural changes with clinical parameters and prognosis in DKD is incompletely understood. Methods: This is an interim analysis of 62 patients diagnosed with biopsy-confirmed DKD from the multicenter TRIDENT (Transformative Research in Diabetic Nephropathy) study. Twelve LM and 8 EM descriptors, representing changes in glomeruli, tubulointerstitium, and vasculature were analyzed for their relationship with clinical measures of renal function. Patients were followed every 6 months. Results: Multivariable linear regression analysis revealed that estimated glomerular filtration rate (eGFR) upon enrollment correlated the best with interstitial fibrosis. On the other hand, the rate of kidney function decline (eGFR slope) correlated the most with glomerular lesions including global glomerulosclerosis and mesangiolysis. Unbiased clustering analysis based on histopathologic data identified 3 subgroups. The first cluster, encompassing subjects with the mildest histologic lesions, had the most preserved kidney function. The second and third clusters had similar degrees of kidney dysfunction and structural damage, but differed in the degree of glomerular epithelial cell and podocyte injury (podocytopathy DKD subtype). Cox proportional hazard analysis showed that subjects in cluster 2 had the highest risk to reach ESKD (hazard ratio: 17.89; 95% confidence interval: 2.13–149.79). Glomerular epithelial hyperplasia and interstitial fibrosis were significant predictors of ESKD in the multivariate model. Conclusion: The study highlights the association between fibrosis and kidney function and identifies the role of glomerular epithelial changes and kidney function decline.
KW - diabetic kidney disease
KW - end-stage kidney disease
KW - glomerular epithelial injury
KW - kidney function
KW - pathological descriptors
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U2 - 10.1016/j.ekir.2021.01.025
DO - 10.1016/j.ekir.2021.01.025
M3 - Article
AN - SCOPUS:85103318360
SN - 2468-0249
VL - 6
SP - 1066
EP - 1080
JO - Kidney International Reports
JF - Kidney International Reports
IS - 4
ER -