Diagnose This (March 15, 2021)

What is your diagnosis in a patient (non-smoker) with worsening proteinuria and a negative immunofluorescence panel?

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Answer: The light microscopic image of a PAS-stain demonstrates severe, nodular glomerulosclerosis compatible with nodular diabetic glomerulopathy, RPS class III. Clinically, the patient carried a diagnosis of type II diabetes for >10 years with a recent hemoglobin A1c of 12%. Of note, in the absence of diabetes, nodular glomerulosclerosis can also be seen in what is known as idiopathic nodular glomerulosclerosis, thought to be secondary to hypertension and/or smoking (see references). While light chain deposition disease can also lead to a nodular sclerosis pattern of injury, the immunofluorescence panel was negative in this case and no deposits were present by electron microscopy.

References: 
Markowitz GS, Lin J, et al.  Idiopathic Nodular Glomerulosclerosis is a Distinct Clinical Pathologic Entity Linked to Hypertension and Smoking.  Human Pathology 2002 August; 33 (a): 826-35.

Nasr S, D’Agati V.  Nodular Glomerulosclerosis in the Non-diabetic Smoker.  J Am Soc Nephrol 2007; 18: 2032-2036.