Idiopathic Nodular Glomerulosclerosis Research Articles

Non-neoplastic Kidney Diseases in Adult Tumor Nephrectomy and Nephroureterectomy Specimens in a Southeast Asian Tertiary Medical Center

OBJECTIVE: Non-neoplastic kidney diseases are concurrently present in up to 15% of patients with renal and ureteral tumors, which have been most studied in the United States. This study was conducted to determine the prevalence and spectrum of renal parenchymal diseases in similar patients from a Southeast Asian academic institution.METHODS: We searched the database of the Department of Anatomical Pathology, Faculty of Medicine Vajira Hospital, Navamindradhiraj University (2012–2022) and found 194 adult nephrectomy and nephroureterectomy specimens with renal, renal pelvis, and ureteral tumors. Additional stains included periodic acid-Schiff, methenamine silver, and Masson trichrome. Direct immunofluorescence microscopy was performed on the paraffin tissue sections for immunoglobulin (Ig) G, IgA, IgM, and kappa and lambda light chains. Clinical information, including age, gender, and co-morbidities, was obtained from the electronic medical records.RESULTS: Analysis of the 194 cases demonstrated the average age was 61 years (range: 17-89 years), with 126 males (65%) and 68 females (35%). After re-examination of the non-neoplastic renal parenchyma, 14 cases (7%) had diffused and/or nodular mesangial sclerosis. Diabetic nephropathy (12 cases) and idiopathic nodular glomerulosclerosis (2 cases) were diagnosed and associated with either stage 1 or 2 genitourinary cancers. Another case was diagnosed with atheroembolic renal disease. In all cases, the concurrent renal diseases were not identified during the initial evaluation.CONCLUSION: Examination of the non-neoplastic renal parenchyma is important to identify non-neoplastic kidney diseases, such as diabetic nephropathy, so early treatment may result in improved clinical outcomes for kidney and urothelial cancer patients.

A Rare Case of Sporadic Medullary Cystic Kidney Disease with Rapidly Progressive Renal Dysfunction and Renal Enlargement Complicated by Idiopathic Nodular Glomerulosclerosis.

An 81-year-old man with hypertension and a history of smoking presented with renal enlargement and progressive renal dysfunction despite no family history of kidney disease. A renal biopsy revealed diffuse tubular, dilated, and atrophic distal tubules with cystic formation and thin irregularities in the tubular basement membrane. Although no known genetic abnormalities were detected, the patient was diagnosed with medullary cystic kidney disease (MCKD). In addition, idiopathic nodular glomerulosclerosis, which is characterized by significant mesangial expansion and accentuated glomerular nodularity and is associated with hypertension and cigarette smoking, was identified as a complication of MCKD. We herein report a rare case of sporadic MCKD with idiopathic nodular glomerulosclerosis.

A Study of Nodular Glomerulopathy – A Single-center Experience and Review

ABSTRACT Background: Mesangial expansion is a histopathological manifestation characterized by abnormal proliferation of mesangial cells and accumulation of matrix proteins within the central region of the glomerulus. While diabetes is a well-known cause of mesangial expansion, several rare diseases can also present with this pathology. This study aimed to estimate the prevalence of lesions exhibiting mesangial expansion in a tertiary care center in Tirunelveli, India, and elucidate the spectrum of disorders contributing to mesangial expansion lesions in renal biopsies. Methodology: A retrospective analysis of renal biopsies conducted at Tirunelveli Medical College and Hospital from 2016 to 2022 was performed. Kidney tissue samples were subjected to light microscopy and immunofluorescence studies using appropriate stains. Patients with isolated mesangial expansion were identified. Demographic details, clinical indications for biopsy, and pathological findings were recorded and analyzed. Results: Out of 616 kidney biopsies, mesangial expansion was present in 39 patients (6.33%). Notably, nodular mesangial expansion was observed in 33 patients (5.3%), with diabetes being the most prevalent associated condition (74.19%). Amyloidosis, heavy chain deposition disease, fibrillary glomerulonephritis, collagen fibrotic glomerulopathy, and idiopathic nodular glomerulosclerosis were identified as other contributors to mesangial expansion. Glomerular filtration rate and interstitial fibrosis and tubular atrophy were worse in the diabetic population. Conclusions: This study sheds light on the varied etiologies contributing to mesangial expansion beyond diabetes, emphasizing the importance of specialized staining methods for precise diagnosis.

An atypical anti-GBM disease complicated by idiopathic nodular glomerulosclerosis: Case report.

Both atypical anti-glomerular basement membrane (anti-GBM) disease and idiopathic nodular glomerulosclerosis are rare diseases. We report a case of a 53-year-old non-diabetic male who presented with leg edema, nephritic range proteinuria, microscopic hematuria, and decreased renal function. The renal biopsy demonstrated membranoproliferative glomerulonephritis (MPGN) pattern of glomerular injury with focal crescent and segmental nodular glomerulosclerosis. The immunofluorescence studies showed intense linear IgG (IgG1 and IgG4) deposits along the GBM but negative serology. Electron microscopy demonstrated GBM thickening and fibrillar deposition. The presence of MPGN with crescents and the linear IgG along the GBM were consistent with a diagnosis of atypical ant-GBM disease. Superimposed nodular glomerulosclerosis was considered to be idiopathic by excluding other glomerular diseases characterized by fibrillar deposition and nodular glomerulosclerosis. Both diseases were found to have a strong causative association with patient's history of long-term heavy smoking. This unusual case with combination of atypical anti-GBM disease and idiopathic nodular glomerulosclerosis, has brought great challenge for the diagnosis and also made the clinical course highly complicated. This nodular glomerulosclerosis with anti-GBM-like glomerulonephritis may represent a distinct pattern of kidney injury observed in heavy smokers.

A case of idiopathic nodular glomerulosclerosis successfully treated by intensive blockade of the renin-angiotensin-aldosterone system.

Idiopathic nodular glomerulosclerosis has a poor renal prognosis and is characterized by diffuse nodular glomerulosclerotic lesions in the absence of diabetic mellitus. Here, we report the case of a 69-year-old woman with no smoking history who developed renal dysfunction and proteinuria in the absence of overt diabetes or obesity. A biopsy specimen showed nodular mesangial sclerosis with arteriolar hyalinosis and severe large-vessel arteriosclerosis, leading to a diagnosis of idiopathic nodular glomerulosclerosis. Addition of esaxerenone to her existing renin-angiotensin-aldosterone inhibitor therapy led to a rapid decrease in the proteinuria levels and the maintenance of renal function without any complications for more than a year. The results suggest that intensive renin-angiotensin-aldosterone blockade might be an effective treatment for idiopathic nodular glomerulosclerosis.

Nodular-like glomerular lesion after long-standing chronic renal infection in a patient with medullary sponge kidney and mild hyperglycemia

A 63-year-old Japanese woman was admitted to our institute for the evaluation of proteinuria. The patient was diagnosed with medullary sponge kidney, distal type renal tubular acidosis, and renal infection at the age of 37. Thereafter, the patient had repeated renal infections. Urinary proteinuria appeared at around the age of 61 and gradually increased up to 1.0 g daily. In the same period, glycated hemoglobin (HbA1c) increased to 7.0%. On kidney biopsy, light microscopy showed a nodular glomerular lesion and capsular drop. Linear staining for immunoglobulin G along the glomerular basement membrane was observed by immunofluorescence. Electron microscopy showed thickening of the glomerular basement membrane to a width of 800–900 nm. A class III glomerular lesion was diagnosed according to the Tervaert classification. This case indicates that mild but prolonged hyperglycemia for more than 10 years may also contribute to the formation of nodular lesions, although long-standing repeated chronic renal infection and chronic acidosis may have been a precipitating factor in the formation of diabetic nephropathy, including nodular glomerular lesions. This hypothesis is of interest because nodular lesions specific to diabetes are currently considered to be associated with long-term severe hyperglycemia. Learning points Nodular glomerular lesions in diabetes mellitus are thought to be associated with long-term severe hyperglycemia. This case shows that although mild, long-term hyperglycemia for more than 10 years may also contribute to the formation of nodular lesions and that repeated chronic kidney infections over the years and chronic acidosis may be facilitating factors in the formation of diabetic nephropathy, including nodular glomerular lesions. This case appears to be idiopathic nodular glomerulosclerosis of the medullary sponge kidney associated with chronic urinary tract infection.

MO229: Is Nodular Glomerulosclerosis Always Associated with Diabetic Nephropathy?

Abstract BACKGROUND AND AIMS Nodular glomerulosclerosis (NGS) is a histological diagnosis that can be found in several etiologies. It corresponds to a particular form of expansion of the extracellular matrix within the mesangium. Glomerulosclerosis is not very specific, its nodular form is on the other hand more interesting from an etiological point of view since only a few pathologies can take this aspect, the most frequent are diabetes (mainly), membranoproliferative glomerulonephritis (MPGN) and renal expression of gammopathies monoclonal. In the absence of an identified etiology, NGS is said to be idiopathic. This entity, described 30 years ago, is very rare and therefore largely unrecognized. Some pathophysiological hypotheses have emerged in recent years, particularly involving smoking, high blood pressure or insulin resistance. The aims of our study were as follows: METHOD Monocentric retrospective study of patients with NGS in renal biopsy, collected between January 2016 and December 2021 at Mohammed VI University hospital of Marrakech. The epidemiological, clinical and etiological characteristics were studied. RESULTS We have collected 108 NGS. Of our patients, 47.22% presented with NGS of diabetic origin and 52.95% with non-diabetic NGS. For patients with NGS of diabetic origin, the indication for PBR was glomerular syndrome (19 patients), nephrotic syndrome (7 patients), rapidly progressive renal failure or severe renal failure (11 patients), recent diabetes (7 patients), absence of diabetic retinopathy (3 patients), presence of extra-renal signs (2 patients) and monoclonal peak (2 patients). The diagnosis of idiopathic NGS was made after eliminating all the etiologies of NGS (normal complement dosage, no diabetes, no monoclonal peak, negative IFD, history of smoking and hypertension and dyslipidemia) and immunohistochemistry. Two patients were tested for deposits of the kappa and lambda chains, thus eliminating the myeloma. Among the risk factors for idiopathic SNB detected in our work, we cite: CONCLUSION The most common etiology of NGS remains diabetes, but this lesion can be seen in other conditions such as MPGN, Randall disease, amyloidosis, monotypic immunoglobulin deposition, non-immunoglobulin and idiopathic glomerulopathies. Idiopathic nodular glomerulosclerosis is a rare entity, frequent in most series in humans, which contrasts with the data of our study. On the other hand, a causal link between this histological entity and smoking, hypertension and Metabolic syndrome has been well established in several studies, which is consistent with the data from our work.

IgA Nephropathy Is the Most Common Underlying Disease in Patients With Anticoagulant-Related Nephropathy

IntroductionAnticoagulant-related nephropathy (ARN) is a relatively novel recognized entity characterized by hematuria-associated acute kidney injury (AKI) in the context of overanticoagulation. Preexisting or underlying kidney disease seems to be a predisposing factor; however, few studies have described histologic findings in patients with ARN. We aimed to evaluate underlying kidney pathology in patients on oral anticoagulation who presented an episode of AKI with hematuria in whom a kidney biopsy was performed.MethodsRetrospective observational multicenter case study in patients treated with oral anticoagulants who developed macroscopic or intense hematuria followed by AKI. Only patients with available kidney biopsy specimens were included. Histologic findings and clinical data throughout follow-up were analyzed.ResultsA total of 26 patients were included with a median age of 75 years (62–80) and a follow-up period of 10.1 months. Of the patients, 80% were male, and most cases (92%) were on anticoagulation with vitamin K antagonists (VKAs). At admission, median serum creatinine (SCr) level was 4.2 mg/dl (2.8–8.2), median international normalized ratio (INR) 2.4 (1.5–3.4), and 11 patients (42%) required acute dialysis during hospitalization. Kidney biopsy results revealed that all patients except 1 had an underlying nephropathy: IgA nephropathy (IgAN) in 19, probable IgAN in 1, diabetic nephropathy in 3, nephrosclerosis in 1, and idiopathic nodular glomerulosclerosis in 1. At 12 weeks after discharge, only 6 subjects (24%) attained complete kidney recovery whereas 7 (28%) remained on chronic dialysis.ConclusionIgAN was the most common underlying kidney disease in our biopsy-proven series of ARN, in which a significant percentage of patients did not achieve kidney function recovery.

Idiopathic nodular glomerulosclerosis and dilated cardiomyopathy – A rare association or a coincidence?

Idiopathic nodular glomerulosclerosis and dilated cardiomyopathy – A rare association or a coincidence?

MO378WHAT LIES BENEATH ANTICOAGULATION-RELATED ACUTE KIDNEY INJURY

Abstract Background and Aims Acute kidney injury (AKI) secondary to glomerular hemorrhage in the context of overanticoagulation, commonly known as anticoagulant-related nephropathy (ARN), is a relatively novel recognized entity. Preexisting or underlying kidney disease seems to be a predisposing factor; however, few studies have described histologic findings in patients with ARN. We aimed to examine underlying kidney pathology in patients on oral anticoagulation who presented an episode of AKI with hematuria in whom a kidney biopsy was performed. Method Spanish retrospective observational multicenter case study in patients treated with oral anticoagulants who developed macroscopic or intense hematuria followed by AKI. Only patients with available kidney biopsy specimens were included. Histologic findings and clinical data throughout follow-up were analyzed. The main outcome was to describe pathologic findings in kidney biopsy specimens of patients with clinical suspicion of ARN. The secondary outcome was to assess kidney outcomes during follow-up. Results Twenty-four patients were included with a median age of 76 years (interquartile range [IQR] 64-81) and a follow-up period of 10.1 (IQR 1.3-41.1) months. 79% were male, 22 (91%) had hypertension and 9 (37%) were diabetic. Most cases (91%) were on anticoagulation with vitamin K antagonists. At admission, 87% of cases presented gross hematuria with a median serum creatinine (SCr) of 4.2 mg/dl and a median INR of 2.3. During follow-up, median highest (peak) SCr was 6.3 mg/dl and 11 (45%) patients required acute dialysis. Kidney biopsy showed that all patients except one had an underlying nephropathy (confirmed IgA nephropathy in 16 [66.7%], probable IgA nephropathy in 2, diabetic nephropathy in 3, nephrosclerosis in 1, and idiopathic nodular glomerulosclerosis in 1). Tubules filled with red cells and red cell casts were observed in 66.7% of the cases and acute tubular necrosis in 70.8%. Management included anticoagulation withdrawal in 14 cases (58.3%) and immunosuppressive treatment with corticosteroids (n = 17 [70.8%]) and mycophenolic acid (n = 5 [20.8%]). At 12 weeks after discharge, 11 patients had >50% decrease in SCr (with respect to peak SCr), 6 had <50% decrease and 5 were on chronic dialysis. Conclusion IgA nephropathy was the most common underlying kidney disease in our biopsy-proven series of ARN, in which a significant percentage of patients did not achieve kidney function recovery.

Clinical, histopathologic and molecular features of idiopathic and diabetic nodular mesangial sclerosis in humans.

Idiopathic nodular mesangial sclerosis, also called idiopathic nodular glomerulosclerosis (ING), is a rare clinical entity with an unclear pathogenesis. The hallmark of this disease is the presence of nodular mesangial sclerosis on histology without clinical evidence of diabetes mellitus or other predisposing diagnoses. To achieve insights into its pathogenesis, we queried the clinical, histopathologic and transcriptomic features of ING and nodular diabetic nephropathy (DN). All renal biopsy reports accessioned at Indiana University Health from 2001 to 2016 were reviewed to identify 48 ING cases. Clinical and histopathologic features were compared between individuals with ING and DN (n = 751). Glomeruli of ING (n = 5), DN (n = 18) and reference (REF) nephrectomy (n = 9) samples were isolated by laser microdissection and RNA was sequenced. Immunohistochemistry of proline-rich 36 (PRR36) protein was performed. ING subjects were frequently hypertensive (95.8%) with a smoking history (66.7%). ING subjects were older, had lower proteinuria and had less hyaline arteriolosclerosis than DN subjects. Butanoate metabolism was an enriched pathway in ING samples compared with either REF or DN samples. The top differentially expressed gene, PRR36, had increased expression in glomeruli 248-fold [false discovery rate (FDR) P = 5.93 × 10-6] compared with the REF and increased 109-fold (FDR P = 1.85 × 10-6) compared with DN samples. Immunohistochemistry revealed a reduced proportion of cells with perinuclear reaction in ING samples as compared to DN. Despite similar clinical and histopathologic characteristics in ING and DN, the uncovered transcriptomic signature suggests that ING has distinct molecular features from nodular DN. Further study is warranted to understand these relationships.

Recurrent Nodular Glomerulosclerosis in a Second Kidney Allograft

Kidney transplantation is considered the best choice for patients with end stage renal disease. However, recurrence of primary disease, especially glomerular disease represents a major problem. Nodular glomerulosclerosis with its wide differential diagnosis can recur post kidney transplantation and might results in graft failure. Here, we report a unique case of 35 years old male with idiopathic nodular glomerulosclerosis that recurred twice after two successful living donor kidney transplants.

Impaired glucose metabolism – A potential risk factor for idiopathic nodular glomerulosclerosis: A single center study

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.

AGEs-RAGE overexpression in a patient with smoking-related idiopathic nodular glomerulosclerosis.

We report a case of smoking-related idiopathic nodular glomerulosclerosis (ING) with overexpression of glomerular advanced glycation end products (AGEs) and their receptor (RAGE). A 59-year-old Japanese man with nephrotic syndrome, who had a smoking history of one pack of cigarettes per day for approximately 40 years, presented with a 3-year history of urinalysis abnormalities without clinical evidence of diabetic mellitus. The patient's leg edema progressively worsened over the previous 2 years, and he was admitted to our hospital. Renal biopsy showed mesangial expansion with diabetic Kimmelstiel-Wilson-like nodular lesions, glomerular basement thickening, and arteriosclerosis. No electron-dense deposits, fibrils, or microtubule deposits were seen in the glomeruli on electron microscopy. Skin AGE level measured using AGE reader was higher in this case than the average level in age-matched Caucasians. In addition, immunohistochemical analysis revealed that N-carboxymethyl lysine, one of the major AGEs, and RAGE were overexpressed and podocin expression was decreased in the peripheral area of the glomerular nodular lesions. These observations suggest that AGEs-RAGE system may be activated in smoking-related ING, possibly leading to the progression of renal dysfunction.

Idiopathic nodular glomerulosclerosis in a chronic marijuana user; a case report and review of the literature

Background: Nodular glomerulosclerosis is a characteristic histological finding of diabetic nephropathy (DN) with thickened glomerular basement membrane (GBM) and hyalinized arterioles. Idiopathic nodular glomerulosclerosis (ING), a rare distinct clinicopathologic entity, is the term used to denote classic DN confirmed by light microscopy, immunofluorescence, and electron microscopy in the absence of diabetes mellitus (DM). ING has been linked to heavy tobacco smoking, chronic hypertension, obesity and insulin resistance. Its association with marijuana use is unknown. Case Presentation: We report a case of biopsy-proved ING in the absence of pre-existing history of DM and heavy smoking. This report addresses the possible accentuation of tobacco use risk by marijuana. Conclusions: This report addresses the possible accentuation of tobacco use risk by marijuana.

Idiopathic nodular glomerulosclerosis- a rare case

Nodular glomerulosclerosis is considered a signature lesion of diabetes nephropathy, but when it occurs in the absence of diabetes, it is called Idiopathic Nodular Glomerulosclerosis (ING). Idiopathic nodular glomerulosclerosis is a very rare disease and has been associated with obesity, hypertension, and smoking. We report a case of ING presenting as end-stage renal failure requiring hemodialysis.

Vascular mesangial channels in human nodular diabetic glomerulopathy

The presence of vascular mesangial channels has been reported in idiopathic nodular glomerulosclerosis and diabetic glomerulopathy. However, only limited information on the morphology and immunohistochemical phenotype of these channels is available. This study aims to describe the light and electron microscopic features of these channels and delineate their immunohistochemical phenotype. Thirty-eight cases of human nodular diabetic glomerulopathy with mesangial channels identified by light microscopy were prospectively selected (2010-2012). The cases were stained with CD31/periodic acid-Schiff combined stain. Selected cases were immunostained for CD34, podoplanin, ERG, and Ki-67. Frequent, small and peripheral vascular mesangial channels were seen in all cases, whereas larger and more centrally located vascular channels were also observed. Communication between peripheral capillary loops and peripheral vascular mesangial channels was seen as was communication between peripheral and central vascular mesangial channels. The vascular mesangial channel lining cells showed a typical endothelial phenotype with strong expression of CD31, CD34, and ERG by immunohistochemistry. The lymphatic channel marker podoplanin was negative in all channels, and the proliferation marker Ki-67 showed no evidence of increased proliferation. By electron microscopy, mesangial channels show angulated, irregular borders with lining cells compatible with endothelium and surrounded by mesangial matrix. No basement membranes were identified surrounding the mesangial channels. These findings support the existence of vascular mesangial channels in nodular diabetic glomerulopathy and suggest neovascularization and altered blood flow within these glomeruli.

Diabetic Nephropathy without Diabetes.

Diabetic nephropathy without diabetes (DNND), previously known as idiopathic nodular glomerulosclerosis, is an uncommon entity and thus rarely suspected; diagnosis is histological once diabetes is discarded. In this study we describe two new cases of DNND and review the literature. We analyzed all the individualized data of previous publications except one series of attached data. DNND appears to be favored by recognized cardiovascular risk factors. However, in contrast with diabetes, apparently no factor alone has been demonstrated to be sufficient to develop DNND. Other factors not considered as genetic and environmental factors could play a role or interact. The most plausible hypothesis for the occurrence of DNND would be a special form of atherosclerotic or metabolic glomerulopathy than can occur with or without diabetes. The clinical spectrum of cardiovascular risk factors and histological findings support this theory, with hypertension as one of the characteristic clinical features.

A case of "hidden" diabetic nephropathy diagnosed by a combination of renal biopsy findings and continuous glucose monitoring system.

Although diabetic nephropathy is a microvascular complication of diabetes mellitus, some reports suggest that renal biopsy often shows this pathological change without a diagnosis of diabetes mellitus. Here, we report a case of a 65-year-old man who presented with proteinuria, hypoalbuminemia and hypertension without a diagnosis of diabetes mellitus. He drank alcohol regularly and was a heavy smoker. Renal biopsy revealed a diffuse increase in the mesangial area, mesangial nodules or well-developed hyalinosis, interstitial fibrosis, and arteriosclerosis consistent with the changes of diabetic nephropathy. Although we had initially diagnosed him with idiopathic nodular glomerulosclerosis, use of a continuous glucose monitoring system (CGMS) revealed that the changes in his daily blood glucose concentrations met with the diagnostic criteria of diabetes mellitus. Accordingly, we diagnosed him with diabetic nephropathy and initiated treatment for diabetes mellitus. This case suggests that some cases of diabetic nephropathy may be hidden among patients with impaired glucose tolerance, who are not diagnosed with diabetes mellitus. Use of a CGMS may be helpful in diagnosing this type of "hidden" diabetes mellitus. In addition to diet therapy, smoking control, treatment for hypertension, and strict control of hyperglycemia may be important for these patients.

Idiopathic nodular glomerulosclerosis in Chinese patients: a clinicopathologic study of 20 cases

The objective of this study is to investigate the frequency and clinicopathological features of idiopathic nodular glomerulosclerosis (ING) in Chinese patients, on which there has been no previously published information. Native kidney biopsies performed at a kidney histopathological center in Shanghai between January 1, 2009 and December 31, 2011 were retrospectively examined and relevant clinical data were reviewed. All kidney biopsy specimens (3,480) were examined. After excluding specimens from patients with diabetes, fasting hyperglycemia or hemoglobin A1c elevation and other known entities associated with nodular glomerulosclerosis, 20 ING cases (1 in 174 biopsies) were identified. Patients with ING had a median age of 55.5 years, 16 (80 %) were male, 19 (95 %) had a body mass index (BMI) ≥25 kg/m(2) [BMI ≥30 in 8 (40 %)], 18 (90 %) were hypertensive, 17 (85 %) had a history of cigarette smoking (mean pack-years 19.8 ± 2.4), and 10 (50 %) had hyperlipidemia. All 20 patients had >1 g/day proteinuria with a mean of 2.85 ± 0.33 g/day (seven had nephrotic-range proteinuria). Mean serum creatinine at the time of kidney biopsy was 4.23 ± 0.53 mg/dL (338.2 ± 44.7 μmol/L). Histopathologically, all specimens showed varying degrees of nodular glomerulosclerosis, glomerular basement membrane thickening, foot process effacement, interstitial fibrosis and arterial hyalinosis/sclerosis. Immunofluorescence was non-specific. At follow-up of 22.1 ± 1.15 days post-biopsy, six patients had developed end-stage renal failure and five had worsening serum creatinine concentrations not requiring dialysis. ING is rare and appears to be associated with overweight, hypertension and cigarette smoking in Chinese patients.