Finding of pathological thrombomodulin gene variant in a patient with idiopathic nodular glomerulosclerosis and chronic thrombotic microangiopathy-like changes

Ramy Hanna; Jonathan E Zuckerman; Antoney Ferrey; Everado Arias Torres; Sam Tonthat; Marina Barsoum; Lena Ghobry; Olivia Wassef; Kamyar Kalantarzadeh

doi:10.1177/2050313X20940510

Finding of pathological thrombomodulin gene variant in a patient with idiopathic nodular glomerulosclerosis and chronic thrombotic microangiopathy-like changes

SAGE Open Med Case Rep. 2020 Jul 10:8:2050313X20940510. doi: 10.1177/2050313X20940510. eCollection 2020.

Authors

Ramy Hanna¹, Jonathan E Zuckerman², Antoney Ferrey¹, Everado Arias Torres³, Sam Tonthat¹, Marina Barsoum⁴, Lena Ghobry⁵, Olivia Wassef⁶, Kamyar Kalantarzadeh¹

Affiliations

¹ Division of Nephrology, Hypertension and Kidney Transplantation, University of California Irvine, Irvine, CA, USA.
² Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
³ Department of Medicine, University of California Irvine, Irvine, CA, USA.
⁴ School of Pharmaceutical Sciences, Chapman University, Orange, CA, USA.
⁵ University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, USA.
⁶ Division of Nephrology, Department of Medicine, University of California Los Angeles, Los Angeles, CA, USA.

Abstract

Idiopathic nodular glomerulosclerosis is an unusual histopathological finding that has commonly been observed in male smokers with hypertension. It has remained an enigmatic condition and is best described as a diabetic pattern of glomerular injury seen in non-diabetic patients. It is also one of the few nicotine (smoking)-associated/smoking-associated patterns of renal injury. We present an even more unusual manifestation of this pathological finding in a 59-year-old Hispanic female who presented with chronic kidney disease approaching need for renal replacement therapy. The patient had idiopathic nodular glomerulosclerosis on kidney biopsy, despite no prior history of diabetes, nor smoking history, including no secondhand smoking exposure. The patient did have hypertension. The renal biopsy also showed evidence of chronic thrombotic-microangiopathic changes within arteries and arterioles. Genetic testing of the alternative pathway revealed an unusual and likely pathological variant of thrombomodulin supporting complement dysfunction as having a role in the presentation.

Keywords: Idiopathic nodular sclerosis; alternative pathway activation; hypertension; thrombomodulin mutation; thrombotic microangiopathy.

Publication types

Case Reports