||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,
||Pierre Dagher on 5/5/2021
||Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
|Volume : Pages
||Not Specified : Not Specified
||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)., 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., 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., 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.