Elsevier

Human Pathology

Volume 33, Issue 8, August 2002, Pages 826-835
Human Pathology

Original Contributions
Idiopathic nodular glomerulosclerosis is a distinct clinicopathologic entity linked to hypertension and smoking*

https://doi.org/10.1053/hupa.2002.126189Get rights and content

Abstract

Idiopathic nodular glomerulosclerosis (ING) is an enigmatic condition that resembles nodular diabetic glomerulosclerosis but occurs in nondiabetic patients. We reviewed clinicopathologic features, immunohistochemical profiles, and outcomes in 23 patients with ING diagnosed from among 5,073 native renal biopsy samples (0.45%) at Columbia University from January 1996 to March 2001. This cohort, in which diabetes mellitus was excluded, consisted predominantly of older (mean age, 68.2 years) white (73.9%) men (78.3%). Clinical findings at presentation included renal insufficiency in 82.6% (mean serum creatinine = 2.4 mg/dL), proteinuria (> 3 g/d in 69.6%; mean 24-hour urine protein = 4.7 g/d), and—less frequently—full nephrotic syndrome (21.7%). There was a high prevalence of hypertension (95.7%; mean = 15.1 ± 3.4 years), smoking (91.3%; mean = 52.9 ± 6.9 pack-years), hypercholesterolemia (90%), and extrarenal vascular disease (43.5%). All 23 patients had prominent diffuse and nodular mesangial sclerosis, glomerular basement membrane thickening, arteriosclerosis, and arteriolosclerosis. Immunohistochemical staining for CD34, a marker of endothelial cells, showed an increased number of vascular channels within ING glomeruli compared with normal controls. Follow-up data were available for 17 patients, 6 of whom reached end-stage renal disease (ESRD) (35.3%). By Kaplan-Meier estimates, the median time after biopsy to ESRD was 26 months. Predictors of progression to ESRD included continuation of smoking (P =.0165), lack of angiotensin II blockade (P =.0007), degree of tubular atrophy and interstitial fibrosis (P =.0517), and degree of arteriosclerosis (P =.0096). In conclusion, ING is a progressive vasculopathic lesion linked to hypertension and cigarette smoking. HUM PATHOL 33:826-835. Copyright 2002, Elsevier Science (USA). All rights reserved.

Section snippets

Materials and methods

All native renal biopsy specimens (n = 5,073) accessioned in the Renal Pathology Laboratory at Columbia Presbyterian Medical Center from January 1996 to March 2001 were reviewed retrospectively for the presence of ING. ING was defined by (1) the absence of clinical evidence of DM; (2) the histological finding of nodular mesangial sclerosis; and (3) the exclusion by immunofluorescence and electron microscopy of chronic membranoproliferative glomerulonephritis, chronic thrombotic microangiopathy,

Results

The cohort of patients with ING had a mean age of 68.2 years (range, 47 to 80) and consisted of predominantly white (73.9%) and men (78.3%) (Table 1).Twenty-two of the 23 patients had a history of hypertension for a mean duration of 15.1 years. Twenty-one of the 23 patients (91.3%) had a history of smoking with a mean cumulative intake of 52.9 pack-years. This included 12 patients who were active smokers at the time of biopsy and 9 with a long-standing but remote history of tobacco use. A

Discussion

ING is a clinicopathologic entity that is by definition a diagnosis of exclusion. We report 23 cases of ING in which all previously defined entities that can produce nodular glomerulosclerosis were excluded. By analyzing the clinical and biopsy profile of this cohort, we identified common features that define ING as a distinct clinicopathologic entity. Patients with ING are typically older white men with a history of long-standing hypertension and smoking who present with renal insufficiency

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    *

    Address correspondence and reprint requests to Vivette D. D'Agati, MD, Columbia University, College of Physicians and Surgeons, Department of Pathology, Renal Pathology Laboratory, 630 W 168th St, VC 14-224, New York, NY 10032.

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