The Role of Glomerular Epithelial Injury in Kidney Function Decline in Patients With Diabetic Kidney Disease in the TRIDENT Cohort.
diabetic kidney disease
end-stage kidney disease
glomerular epithelial injury
kidney function
pathological descriptors
Journal
Kidney international reports
ISSN: 2468-0249
Titre abrégé: Kidney Int Rep
Pays: United States
ID NLM: 101684752
Informations de publication
Date de publication:
Apr 2021
Apr 2021
Historique:
received:
01
11
2020
revised:
11
01
2021
accepted:
18
01
2021
entrez:
29
4
2021
pubmed:
30
4
2021
medline:
30
4
2021
Statut:
epublish
Résumé
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. 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. 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. The study highlights the association between fibrosis and kidney function and identifies the role of glomerular epithelial changes and kidney function decline.
Identifiants
pubmed: 33912757
doi: 10.1016/j.ekir.2021.01.025
pii: S2468-0249(21)00028-0
pmc: PMC8071659
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1066-1080Subventions
Organisme : NIDDK NIH HHS
ID : K23 DK120811
Pays : United States
Informations de copyright
© 2021 International Society of Nephrology. Published by Elsevier Inc.
Références
Diabetes. 2015 Dec;64(12):4099-111
pubmed: 26293507
J Am Soc Nephrol. 2019 Oct;30(10):2000-2016
pubmed: 31537649
J Am Soc Nephrol. 2009 Aug;20(8):1813-21
pubmed: 19443635
JAMA. 2011 Apr 20;305(15):1553-9
pubmed: 21482743
Clin J Am Soc Nephrol. 2016 Feb 5;11(2):254-61
pubmed: 26792530
Adv Chronic Kidney Dis. 2014 May;21(3):256-9
pubmed: 24780452
Diabetes. 2002 May;51(5):1580-7
pubmed: 11978659
Biometrics. 2017 Sep;73(3):811-821
pubmed: 28099990
Nat Rev Nephrol. 2016 Aug;12(8):453-71
pubmed: 27263398
Cardiovasc Endocrinol. 2017 Feb 15;6(1):8-16
pubmed: 31646113
J Clin Med. 2015 Sep 07;4(9):1761-73
pubmed: 26371050
Kidney Int Suppl. 2005 Dec;(99):S82-6
pubmed: 16336583
J Am Soc Nephrol. 2000 Sep;11(9):1667-73
pubmed: 10966491
J Am Soc Nephrol. 2017 Oct;28(10):2838-2844
pubmed: 28790143
Nat Rev Drug Discov. 2016 Aug;15(8):568-88
pubmed: 27230798
Am J Nephrol. 2011;33(5):381-9
pubmed: 21454968
Hum Pathol. 1994 Nov;25(11):1213-27
pubmed: 7959667
Kidney Int. 2020 Jan;97(1):10-13
pubmed: 31901339
Ecol Evol. 2019 Nov 19;9(23):13231-13243
pubmed: 31871641
Kidney Int. 2017 Aug;92(2):388-396
pubmed: 28577854
JCI Insight. 2019 Sep 19;4(18):
pubmed: 31534053
Kidney Int. 1995 Dec;48(6):1929-35
pubmed: 8587254
Curr Diab Rep. 2017 May;17(5):30
pubmed: 28364354
J Am Soc Nephrol. 2016 Aug;27(8):2393-406
pubmed: 26701981
Kidney Int. 2008 Jul;74(1):22-36
pubmed: 18418356
Clin J Am Soc Nephrol. 2017 Jan 6;12(1):69-78
pubmed: 28062677
Am J Nephrol. 2016;44(4):289-299
pubmed: 27626625
Nephrol Dial Transplant. 2018 Feb 1;33(2):310-318
pubmed: 28339906
J Clin Invest. 1997 Jan 15;99(2):342-8
pubmed: 9006003
J Am Soc Nephrol. 2020 Apr;31(4):841-854
pubmed: 32086276
Nephrol Dial Transplant. 2019 Aug 1;34(8):1280-1285
pubmed: 30698804
Am J Kidney Dis. 2020 Jan;75(1):84-104
pubmed: 31473020
Arch Pathol Lab Med. 2018 May;142(5):613-625
pubmed: 29457738
Am J Physiol Renal Physiol. 2009 Apr;296(4):F819-29
pubmed: 19211686
J Am Soc Nephrol. 2018 Aug;29(8):2213-2224
pubmed: 29866798
Diabetes. 1983 May;32 Suppl 2:64-78
pubmed: 6400670
Am J Kidney Dis. 2018 Jan;71(1):91-101
pubmed: 29153995
Sci Rep. 2019 Aug 14;9(1):11862
pubmed: 31413285
J Clin Invest. 1984 Oct;74(4):1143-55
pubmed: 6480821
J Am Soc Nephrol. 2019 Jun;30(6):1049-1059
pubmed: 31152118
N Engl J Med. 2009 Jul 2;361(1):40-51
pubmed: 19571282
J Am Soc Nephrol. 2018 Feb;29(2):694-703
pubmed: 29180393
J Am Soc Nephrol. 2009 Dec;20(12):2503-12
pubmed: 19729434
Arch Pathol Lab Med. 2009 Feb;133(2):224-32
pubmed: 19195966
Nephrol Dial Transplant. 2015 Jun;30(6):918-23
pubmed: 25183630
Ann Intern Med. 2009 May 5;150(9):604-12
pubmed: 19414839
Curr Diab Rep. 2016 May;16(5):45
pubmed: 27053072
Kidney Int. 2004 Nov;66(5):1901-6
pubmed: 15496161
JAMA. 2016 Aug 9;316(6):602-10
pubmed: 27532915
Diabetes Metab. 2012 Oct;38(4):291-7
pubmed: 22622176
Mod Pathol. 2016 Jul;29(7):671-84
pubmed: 27102348
Am J Kidney Dis. 2018 Nov;72(5):653-661
pubmed: 29784612
Kidney Int. 2017 Jun;91(6):1300-1311
pubmed: 28366227
J Am Soc Nephrol. 2000 Nov;11(11):2095-105
pubmed: 11053486
Mol Metab. 2019 Dec;30:250-263
pubmed: 31767176
J Am Soc Nephrol. 2010 Apr;21(4):556-63
pubmed: 20167701
Nephrol Dial Transplant. 2015 Feb;30(2):257-66
pubmed: 25063425