Idiopathic Nodular Glomerulosclerosis and Occult Colorectal Malignancy: A Canary in the Coal Mine

Abstract

Idiopathic nodular glomerulosclerosis (ING) is a rare glomerulopathy typically associated with heavy smoking, obesity, and longstanding uncontrolled hypertension in older adults. Paraneoplastic glomerulopathies, most commonly membranous nephropathy, are well-recognized complications of solid malignancies, but ING has not been reported as a paraneoplastic manifestation. This case describes a 50-year-old nonsmoking, nonobese man with resistant hypertension who presented with severe hyponatremia secondary to gastrointestinal losses and was found to have biopsy-proven ING. Subsequent workup revealed advanced-stage colorectal adenocarcinoma (pT4a N2b). The temporal relationship between progressive renal dysfunction (creatinine elevation from 1.4–1.5 mg/dL since 2022 to 1.7 mg/dL at presentation) and chronic gastrointestinal symptoms, the absence of typical ING risk factors (no smoking history, normal body mass index, and age 50 years), persistent inflammatory markers prompting malignancy screening, and the atypically rapid progression to advanced ING with 40%–45% tubulointerstitial fibrosis suggest a possible paraneoplastic association. This case highlights the clinical significance of investigating for occult malignancy in patients with ING who lack classic risk factors, and proposes ING as a potential novel paraneoplastic glomerulopathy associated with colorectal cancer. Further studies are needed to establish causality and elucidate potential pathogenic mechanisms.