Differential Diagnosis of Nodular Glomerulosclerosis

I recently had to look up the differential diagnosis of nodular glomerulosclerosis: we had recently sent a clinic patient to undergo a renal biopsy based on a history of nephrotic-range proteinuria (urine protein to creatinine ratio of about 4) and a gradually rising serum creatinine last measured at 1.7 mg/dL. The pathologist was eager to ascribe a diagnosis of diabetic nephropathy upon describing nodular glomerulosclerosis in the biopsy specimen; however, there was one big problem with this diagnosis: the patient did not have diabetes!

So: what else causes nodular glomerulosclerosis besides diabetic nephropathy? Chronic MPGN is part of the differential diagnosis, as are dysproteinemias such as amyloidosis or monoclonal Ig deposition disease. Organized glomerular deposition diseases such as immunotactoid GN, fibrillary GN, or fibronectin glomerulopathy can also result in nodular glomerulosclerosis. Chronic hypoxic or ischemic conditions--as might be found in individuals with congenital cyanotic heart disease or cystic fibrosis, for instance--can also result in nodular glomerulosclerosis. The diagnosis we are entertaining in our patient is an entity termed "idiopathic nodular glomerulosclerosis" (ING), which appears to be associated with a long-standing history of smoking and hypertension. There are several case series of ING which describe biopsy findings as would be expected in diabetic nephropathy in non-diabetic patients, including this review by members of the Pathology Dept of Columbia University.