Idiopathic nodular glomerulosclerosis

doi:10.1016/S0272-6386(99)70086-7

American Journal of Kidney Diseases

Volume 34, Issue 3, September 1999, Pages 560-564

https://doi.org/10.1016/S0272-6386(99)70086-7 Get rights and content

Abstract

Idiopathic nodular glomerulosclerosis is an unusual entity with light microscopic and ultrastructural features similar to those of nodular diabetic glomerulosclerosis but without evidence of abnormal glucose metabolism. We report 2 patients whose renal biopsies showed nodular glomerulosclerosis with afferent and efferent arteriolosclerosis, glomerular basement membrane thickening, focal mesangiolysis and capillary microaneurysm formation, and who had no evidence of abnormal glucose metabolism or other features of diabetes mellitus. Review of the literature shows that, of the 27 reported cases of idiopathic nodular glomerulosclerosis (not including the 2 cases reported herein), 11 showed evidence of abnormal glucose metabolism or were frankly diabetic. Of the remaining 16 cases with normal serum blood glucose measurements, 3 had diabetic retinopathy and 1 had a delayed insulin response curve. The cause and pathogenesis of the glomerular nodules are discussed, and it is suggested that arteriolar stenosis and glomerular ischemia may be involved in the development these lesions.

Section snippets

Materials and methods

Between 1993 and 1998 there were 6 patients without overt diabetes mellitus whose renal biopsies showed idiopathic nodular glomerulosclerosis. Four cases were rejected because they showed evidence of abnormal glucose metabolism.

The 2 cases that we report had renal biopsies processed for light microscopy, direct immunofluorescence, and electron microscopy. Tissue for histology was fixed in 3% paraformaldehyde and embedded in polyglycol methacrylate. One-micrometer sections were stained with

Patient 1

This 70-year-old white man presented with peripheral edema and renal insufficiency. He had a history of hypertension for 10 years and coronary artery disease. There was no personal or family history of diabetes mellitus or renal disease. The patient weighed 102 kg, and body mass index was 33.3 kg/m². Medications included diltiazem and nitroglycerine. Funduscopy was normal. Abdominal and renal ultrasound was normal. Laboratory results were as follows: serum creatinine was 5.0 mg/dL; blood urea

Discussion

We report 2 cases of nodular glomerulosclerosis in patients with no clinical evidence of diabetes mellitus or any suggestion of abnormal glucose metabolism. The histological findings are identical to those seen in typical diabetic nephropathy. It is possible that these patients are subclinically diabetic and that their serum glucose fluctuates into the diabetic range during periods when they are not tested. However, we have no evidence to support this.

There have been 27 previously reported

References (31)

J-L Preud'homme et al.
Monoclonal immunoglobulin deposition disease (Randall type): Relationship with structural abnormalities of immunoglobulin chains
Kidney Int
(1994)
DA Nash et al.
Diabetic glomerulosclerosis without glucose intolerance
Am J Med
(1975)
J Winaver et al.
Diabetic nephropathy as the mode of presentation of diabetes mellitus
Metabolism
(1979)
J Macrae et al.
Diabetic nephropathy without hyperglycemia
J Diab Complications
(1990)
YS Kanwar et al.
Occurrence of intercapillary nodular glomerulosclerosis in the absence of glucose intolerance
Am J Kidney Dis
(1990)
S Herf et al.
An evaluation of diabetic and pseudodiabetic glomerulosclerosis
Am J Med
(1979)
JMB Bloodworth
A re-evaluation of diabetic glomerulosclerosis 50 years after the discovery of insulin
Hum Pathol
(1978)
Y Saito et al.
Mesangiolysis in diabetic glomeruli: Its role in the formation of nodular lesions
Kidney Int
(1988)
T Morita et al.
Mesangiolysis
Kidney Int
(1983)
P Kimmelstiel et al.
Intercapillary lesions in the glomeruli of the kidney
Am J Pathol
(1936)

M-A Gall et al.

Risk factors for development of incipient and overt diabetic nephropathy in patients with non–insulin dependent diabetes mellitus: prospective, observational study

BMJ

(1997)

N Mandalenakis et al.

Lobular glomerulonephritis and membranoproliferative glomerulonephritis

Medicine

(1971)

DB Jones

Mebranoproliferative glomerulonephritis: One or many diseases?

Arch Pathol Lab Med

(1977)

M Yoshimura et al.

Peculiar glomerular lesions in Takayasu's arteritis

Clin Nephrol

(1985)

PW Sanders et al.

Spectrum of glomerular and tubulointerstitial renal lesions associated with montypical immunoglobulin light chain deposition

Lab Invest

(1991)

Cited by (51)

Impaired glucose metabolism – A potential risk factor for idiopathic nodular glomerulosclerosis: A single center study
2018, Medical Hypotheses
Citation Excerpt :
All these findings raise the possibility that IR and impaired glucose intolerance may play a central role in the pathogenesis of ING, otherwise deemed as “idiopathic”. Once considered a diagnosis of exclusion, ING is a distinct clinicopathologic entity [11]. It has been predominantly described in elderly Caucasian individuals and is linked to heavy smoking, hypertension, and obesity [12,13].
Nodular glomerulosclerosis is a characteristic histological finding of diabetic nephropathy (DN) with thickened glomerular basement membrane and hyalinized arterioles. Idiopathic nodular glomerulosclerosis (ING), a distinct clinicopathologic entity, is the term used to denote classic DN confirmed by light microscopy, immuno-fluorescence, and electron microscopy but in the absence of diabetes mellitus (DM). ING has been linked to heavy tobacco smoking, chronic hypertension, and obesity. We report the result of a retrospective study identifying seventeen subjects from Thomas Jefferson University (1999–2014) with biopsy-proven nodular glomerulosclerosis but no pre-existing history of DM. The main indications for percutaneous kidney biopsy (PKB) were either reduced renal function or the presence of proteinuria. The subjects’ mean (±SD) age was 60.2 (14.4) years, their highest documented random glucose level was 104.4 (23.5) mg/dL, serum creatinine measured 2.35 (1.03) mg/dL, and body mass index calculated 29.4 (6.2) kg/m². None of the patients fulfilled criteria for diabetes at the time of PKB. However, review of medical records revealed history of intermittently elevated blood glucose or borderline-high HgbA1c levels. The role of impaired glucose metabolism or insulin resistance, as a possible etiology for ING is potentially underestimated and needs additional studies.
“Diabetic nephropathy” in a non-diabetic patient
2016, Pathology Research and Practice
Kimmelstiel and Wilson originally described nodular glomerulosclerosis as the pathognomonic lesion of diabetic nephropathy. Nevertheless, nodular glomerulosclerosis pattern can rarely occur in non-diabetic patients. In such cases, the differential diagnosis includes membranoproliferative glomerulonephritis, light or heavy chain deposition disease, amyloidosis, fibrillary and immunotactoid glomerulonephritis and chronic hypoxic or ischemic conditions. In cases that the above entities cannot be proven, the term idiopathic nodular glomerulosclerosis is given.
Here, we report a case of a male patient with renal failure stage IV and non-nephrotic range proteinuria. He had a history of heavy smoking and hypertension. The kidney biopsy revealed diabetic-like lesions. However, there was no evidence of glucose impairment despite the thorough work-up at the biopsy time and thereafter. The laboratory data and the electron microscopy of the specimen could not prove any other cause of nodular glomerulosclerosis, and the final diagnosis was idiopathic nodular glomerulosclerosis. Moreover, we focus on the pathological differential diagnosis and work-up.
Diagnostic Pathology: Kidney Diseases: A volume in Diagnostic Pathology
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The Case Diabetic nephropathy in a nondiabetic smoker
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An unusual case of nephrotic syndrome and glucosuria
2012, American Journal of Kidney Diseases
Citation Excerpt :
They described 5 patients with nodular glomerulosclerosis without immune complex deposition and no systemic metabolic or inflammatory diseases. The term “idiopathic nodular glomerulosclerosis” was coined by Herzenberg et al2 when they reviewed 27 cases reported between 1971 and 1999. They found that 11 of these cases had glucose intolerance suggestive of underlying diabetes, and only 16 cases were consistent with true idiopathic nodular glomerulosclerosis.
A case of idiopathic nodular glomerulosclerosis successfully treated by intensive blockade of the renin–angiotensin–aldosterone system
2023, CEN Case Reports

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: Received November 25, 1998; accepted in revised form April 2, 1999.

: Address reprint requests to Alex B. Magil, MD, Department of Pathology and Laboratory Medicine, St Paul's Hospital, 1081 Burrard St, Vancouver, BC, Canada V6Z 1Y6. E-mail: [email protected]

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Case ReportIdiopathic nodular glomerulosclerosis

Abstract

Section snippets

Materials and methods

Patient 1

Discussion

Kidney Int

Am J Med

Metabolism

J Diab Complications

Am J Kidney Dis

Am J Med

Hum Pathol

Kidney Int

Kidney Int

Intercapillary lesions in the glomeruli of the kidney

Am J Pathol

Risk factors for development of incipient and overt diabetic nephropathy in patients with non–insulin dependent diabetes mellitus: prospective, observational study

BMJ

Lobular glomerulonephritis and membranoproliferative glomerulonephritis

Medicine

Mebranoproliferative glomerulonephritis: One or many diseases?

Arch Pathol Lab Med

Peculiar glomerular lesions in Takayasu's arteritis

Clin Nephrol

Spectrum of glomerular and tubulointerstitial renal lesions associated with montypical immunoglobulin light chain deposition

Lab Invest

Case Report
Idiopathic nodular glomerulosclerosis