Display options
Cite
Eadon MT, Lampe S, Baig MM, et al. Clinical, histopathologic and molecular features of idiopathic and diabetic nodular mesangial sclerosis in humans. Nephrol Dial Transplant. 2021;doi: 10.1093/ndt/gfaa331.
Eadon, M. T., Lampe, S., Baig, M. M., Collins, K. S., Melo Ferreira, R., Mang, H., Cheng, Y. H., Barwinska, D., El-Achkar, T. M., Schwantes-An, T. H., Winfree, S., Temm, C. J., Ferkowicz, M. J., Dunn, K. W., Kelly, K. J., Sutton, T. A., Moe, S. M., Moorthi, R. N., Phillips, C. L., Dagher, P. C. (2021). Clinical, histopathologic and molecular features of idiopathic and diabetic nodular mesangial sclerosis in humans. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, . https://doi.org/10.1093/ndt/gfaa331
Eadon, Michael T, et al. "Clinical, histopathologic and molecular features of idiopathic and diabetic nodular mesangial sclerosis in humans." Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association vol. (2021). doi: https://doi.org/10.1093/ndt/gfaa331
Eadon MT, Lampe S, Baig MM, Collins KS, Melo Ferreira R, Mang H, Cheng YH, Barwinska D, El-Achkar TM, Schwantes-An TH, Winfree S, Temm CJ, Ferkowicz MJ, Dunn KW, Kelly KJ, Sutton TA, Moe SM, Moorthi RN, Phillips CL, Dagher PC. Clinical, histopathologic and molecular features of idiopathic and diabetic nodular mesangial sclerosis in humans. Nephrol Dial Transplant. 2021 Feb 04; doi: 10.1093/ndt/gfaa331. Epub 2021 Feb 04. PMID: 33537765.
Copy Download .nbib Format: NLM
Share it on

Nephrol Dial Transplant. 2021 Feb 04; doi: 10.1093/ndt/gfaa331. Epub 2021 Feb 04.

Clinical, histopathologic and molecular features of idiopathic and diabetic nodular mesangial sclerosis in humans.

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association

Michael T Eadon, Sam Lampe, Mirza M Baig, Kimberly S Collins, Ricardo Melo Ferreira, Henry Mang, Ying-Hua Cheng, Daria Barwinska, Tarek M El-Achkar, Tae-Hwi Schwantes-An, Seth Winfree, Constance J Temm, Michael J Ferkowicz, Kenneth W Dunn, Katherine J Kelly, Timothy A Sutton, Sharon M Moe, Ranjani N Moorthi, Carrie L Phillips, Pierre C Dagher,

Affiliations

  1. Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
  2. Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
  3. Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN, USA.
  4. Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.

PMID: 33537765 DOI: 10.1093/ndt/gfaa331

Abstract

BACKGROUND: Idiopathic nodular mesangial sclerosis, also called idiopathic nodular glomerulosclerosis (ING), is a rare clinical entity with an unclear pathogenesis. The hallmark of this disease is the presence of nodular mesangial sclerosis on histology without clinical evidence of diabetes mellitus or other predisposing diagnoses. To achieve insights into its pathogenesis, we queried the clinical, histopathologic and transcriptomic features of ING and nodular diabetic nephropathy (DN).

METHODS: All renal biopsy reports accessioned at Indiana University Health from 2001 to 2016 were reviewed to identify 48 ING cases. Clinical and histopathologic features were compared between individuals with ING and DN (n = 751). Glomeruli of ING (n = 5), DN (n = 18) and reference (REF) nephrectomy (n = 9) samples were isolated by laser microdissection and RNA was sequenced. Immunohistochemistry of proline-rich 36 (PRR36) protein was performed.

RESULTS: ING subjects were frequently hypertensive (95.8%) with a smoking history (66.7%). ING subjects were older, had lower proteinuria and had less hyaline arteriolosclerosis than DN subjects. Butanoate metabolism was an enriched pathway in ING samples compared with either REF or DN samples. The top differentially expressed gene, PRR36, had increased expression in glomeruli 248-fold [false discovery rate (FDR) P = 5.93 × 10-6] compared with the REF and increased 109-fold (FDR P = 1.85 × 10-6) compared with DN samples. Immunohistochemistry revealed a reduced proportion of cells with perinuclear reaction in ING samples as compared to DN.

CONCLUSIONS: Despite similar clinical and histopathologic characteristics in ING and DN, the uncovered transcriptomic signature suggests that ING has distinct molecular features from nodular DN. Further study is warranted to understand these relationships.

© The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Keywords: PRR36; diabetic nephropathy; laser microdissection; nodule; transcriptomics

Publication Types

Grant support