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Interstitial fibrosis scored on whole-slide digital imaging of kidney biopsies is a predictor of outcome in proteinuric glomerulopathies.

Publication ,  Journal Article
Mariani, LH; Martini, S; Barisoni, L; Canetta, PA; Troost, JP; Hodgin, JB; Palmer, M; Rosenberg, AZ; Lemley, KV; Chien, H-P; Zee, J; Smith, A ...
Published in: Nephrol Dial Transplant
February 1, 2018

BACKGROUND: Interstitial fibrosis (IF), tubular atrophy (TA) and interstitial inflammation (II) are known determinants of progression of renal disease. Standardized quantification of these features could add value to current classification of glomerulopathies. METHODS: We studied 315 participants in the Nephrotic Syndrome Study Network (NEPTUNE) study, including biopsy-proven minimal change disease (MCD = 98), focal segmental glomerulosclerosis (FSGS = 121), membranous nephropathy (MN = 59) and IgA nephropathy (IgAN = 37). Cortical IF, TA and II were quantified (%) on digitized whole-slide biopsy images, by five pathologists with high inter-reader agreement (intra-class correlation coefficient >0.8). Tubulointerstitial messenger RNA expression was measured in a subset of patients. Multivariable Cox proportional hazards models were fit to assess association of IF with the composite of 40% decline in estimated glomerular filtration rate (eGFR) and end-stage renal disease (ESRD) and separately as well, and with complete remission (CR) of proteinuria. RESULTS: IF was highly correlated with TA (P < 0.001) and II (P < 0.001). Median IF varied by diagnosis: FSGS 17, IgAN 21, MN 7, MCD 1 (P < 0.001). IF was strongly correlated with baseline eGFR (P < 0.001) and proteinuria (P = 0.002). After adjusting for clinical pathologic diagnosis, age, race, global glomerulosclerosis, baseline proteinuria, eGFR and medications, each 10% increase in IF was associated with a hazard ratio of 1.29 (P < 0.03) for ESRD/40% eGFR decline, but was not significantly associated with CR. A total of 981 genes were significantly correlated with IF (|r| > 0.4, false discovery rate (FDR) < 0.01), including upstream regulators such as tumor necrosis factor, interferon gamma (IFN-gamma), and transforming growth factor beta 1 (TGF-B1), and signaling pathways for antigen presentation and hepatic fibrosis. CONCLUSIONS: The degree of IF is associated with risk of eGFR decline across different types of proteinuric glomerulopathy, correlates with inflammatory and fibrotic gene expression, and may have predictive value in assessing risk of progression.

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Published In

Nephrol Dial Transplant

DOI

EISSN

1460-2385

Publication Date

February 1, 2018

Volume

33

Issue

2

Start / End Page

310 / 318

Location

England

Related Subject Headings

  • Young Adult
  • Urology & Nephrology
  • Survival Rate
  • Proteinuria
  • Prognosis
  • Pathology, Clinical
  • Nephritis, Interstitial
  • Male
  • Humans
  • Glomerulonephritis
 

Citation

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Mariani, L. H., Martini, S., Barisoni, L., Canetta, P. A., Troost, J. P., Hodgin, J. B., … Bagnasco, S. M. (2018). Interstitial fibrosis scored on whole-slide digital imaging of kidney biopsies is a predictor of outcome in proteinuric glomerulopathies. Nephrol Dial Transplant, 33(2), 310–318. https://doi.org/10.1093/ndt/gfw443
Mariani, Laura H., Sebastian Martini, Laura Barisoni, Pietro A. Canetta, Jonathan P. Troost, Jeffrey B. Hodgin, Matthew Palmer, et al. “Interstitial fibrosis scored on whole-slide digital imaging of kidney biopsies is a predictor of outcome in proteinuric glomerulopathies.Nephrol Dial Transplant 33, no. 2 (February 1, 2018): 310–18. https://doi.org/10.1093/ndt/gfw443.
Mariani LH, Martini S, Barisoni L, Canetta PA, Troost JP, Hodgin JB, et al. Interstitial fibrosis scored on whole-slide digital imaging of kidney biopsies is a predictor of outcome in proteinuric glomerulopathies. Nephrol Dial Transplant. 2018 Feb 1;33(2):310–8.
Mariani, Laura H., et al. “Interstitial fibrosis scored on whole-slide digital imaging of kidney biopsies is a predictor of outcome in proteinuric glomerulopathies.Nephrol Dial Transplant, vol. 33, no. 2, Feb. 2018, pp. 310–18. Pubmed, doi:10.1093/ndt/gfw443.
Mariani LH, Martini S, Barisoni L, Canetta PA, Troost JP, Hodgin JB, Palmer M, Rosenberg AZ, Lemley KV, Chien H-P, Zee J, Smith A, Appel GB, Trachtman H, Hewitt SM, Kretzler M, Bagnasco SM. Interstitial fibrosis scored on whole-slide digital imaging of kidney biopsies is a predictor of outcome in proteinuric glomerulopathies. Nephrol Dial Transplant. 2018 Feb 1;33(2):310–318.
Journal cover image

Published In

Nephrol Dial Transplant

DOI

EISSN

1460-2385

Publication Date

February 1, 2018

Volume

33

Issue

2

Start / End Page

310 / 318

Location

England

Related Subject Headings

  • Young Adult
  • Urology & Nephrology
  • Survival Rate
  • Proteinuria
  • Prognosis
  • Pathology, Clinical
  • Nephritis, Interstitial
  • Male
  • Humans
  • Glomerulonephritis