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

Citation
Eadon, M. 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, pp. 72-84.
Center Indiana University
Author 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, Kidney Precision Medicine Project
Keywords PRR36, diabetic nephropathy, laser microdissection, nodule, transcriptomics
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.

Year of Publication
2021
Journal
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
Volume
37
Issue
1
Number of Pages
72-84
Date Published
12/2021
ISSN Number
1460-2385
DOI
10.1093/ndt/gfaa331
Alternate Journal
Nephrol Dial Transplant
PMID
33537765
PMCID
PMC8826640
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