Dense deposit disease is not a membranoproliferative glomerulonephritis

Walker, Patrick D.; Ferrario, Franco; Joh, Kensuke; Bonsib, Stephen M.

doi:10.1038/modpathol.3800773

Cited by 105 publications

(87 citation statements)

References 21 publications

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“…In our patient population there was a female predominance (1.9:1), similar to the reports by Cameron et al, Bennett et al, and Little et al (6,13,15). In other studies, the female/male ratio ap- proached unity (2,8). The gender and racial composition were not significantly different between children and adults.…”

Section: Discussionsupporting

confidence: 79%

“…For many years, DDD was also called membranoproliferative GN (MPGN) type II. Because recent studies have indicated that the light microscopic pattern in most patients is not membranoproliferative, the modern trend is to consider DDD a distinct entity, rather than a variant of MPGN (2,3). The rarity of DDD, which afflicts only two to three individuals per million population (4), has impeded studies into its clinical course and optimal treatment.…”

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confidence: 99%

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Dense Deposit Disease

Nasr

Valeri

Appel

et al. 2009

Clinical Journal of the American Society of Nephrology

156

157

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Background and objectives: Dense deposit disease (DDD) is a rare disorder that most commonly affects children. This study reports the largest North American series addressing clinicopathologic and outcome differences in children and adults.Design, setting, participants, & measurements: Thirty-two patients with DDD were analyzed from the archives of Columbia University between 1977 and 2007. Characteristic intramembranous electron-dense deposits defined all diagnoses.Results: The cohort included 14 children (<16 yr) and 18 adults, with 39% of adults >60 yr. The female/male ratio was 1.9. At presentation, the mean 24-h urine protein was 4.6 g, nephrotic syndrome was present in 33%, renal insufficiency in 59%, and hematuria in 87% of patients. Compared with adults, children had lower incidence of renal insufficiency and were more likely to have reduced C3. Histologic pattern included membranoproliferative, mesangial, endocapillary, and crescentic glomerulonephritis. Treatment included immunosuppression (IS) alone in seven, renin angiotensin system (RAS) blockade alone in six, and combined IS/RAS blockade in 11. On follow-up (mean 63 mo) available in 27 patients, 26% had complete response, 48% had persistent renal dysfunction, and 26% had ESRD. Correlates of ESRD were older age and higher creatinine at biopsy, the absence of combined IS/RAS blockade therapy and the presence of subepithelial humps, but not histologic pattern. On multivariate analysis, age and creatinine emerged as the only independent predictors of ESRD.Conclusions: DDD is clinically and pathologically heterogeneous. Adults have worse outcome than children, despite similar treatment. Combined IS/RAS blockade appears superior to either agent alone.

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Section: Discussionsupporting

confidence: 79%

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confidence: 99%

Dense Deposit Disease

Nasr

Valeri

Appel

et al. 2009

Clinical Journal of the American Society of Nephrology

156

157

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“…Numbers indicate the position of the last represented amino acid in splitting (double contour or "tram track" appearance) of the glomerular basement membrane, thereby causing injury of podocytes, glomerular capillaries, and mesangial cells. 2 Familial occurrence has been described for both primary/idiopathic forms of MPGN [3][4][5][6] and for rare forms of thrombotic microangiopathy, [7][8][9][10] but little is known about the underlying genetic etiology. We performed homozygosity mapping and whole exome sequencing in a large index family from Turkey with four siblings affected with autosomal recessive disease with histologic signs of MPGN accompanied by prominent endothelial distress to identify genetic variants causative of this admixed phenotype.…”

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confidence: 99%

DGKE Variants Cause a Glomerular Microangiopathy That Mimics Membranoproliferative GN

Özaltın

Li²,

Rauhauser³

et al. 2013

Journal of the American Society of Nephrology

132

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Renal microangiopathies and membranoproliferative GN (MPGN) can manifest similar clinical presentations and histology, suggesting the possibility of a common underlying mechanism in some cases. Here, we performed homozygosity mapping and whole exome sequencing in a Turkish consanguineous family and identified DGKE gene variants as the cause of a membranoproliferative-like glomerular microangiopathy. Furthermore, we identified two additional DGKE variants in a cohort of 142 unrelated patients diagnosed with membranoproliferative GN. This gene encodes the diacylglycerol kinase DGK«, which is an intracellular lipid kinase that phosphorylates diacylglycerol to phosphatidic acid. Immunofluorescence confocal microscopy demonstrated that mouse and rat Dgk« colocalizes with the podocyte marker WT1 but not with the endothelial marker CD31. Patch-clamp experiments in human embryonic kidney (HEK293) cells showed that DGK« variants affect the intracellular concentration of diacylglycerol. Taken together, these results not only identify a genetic cause of a glomerular microangiopathy but also suggest that the phosphatidylinositol cycle, which requires DGKE, is critical to the normal function of podocytes.

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“…Walker et al 2 identified four distinct histologic patterns of DDD, including mesangial proliferative (45%), membranoproliferative (25%), acute proliferative/ exudative (12%) mimicking a postinfectious GN, and crescentic overlying a mesangioproliferative, membranoproliferative, focal, or diffuse endocapillary proliferative GN (18%). Two cases were deemed unclassified with intermediately electron dense transformation of the GBMs and mesangial region.…”

Section: Discussionmentioning

confidence: 99%

“…1 The membranoproliferative GN pattern is a constellation composed of thickened capillary walls with double contours, glomerular hypercellularity, and increased mesangial matrix. Light microscopy (LM) findings in DDD often deviate from this classic description, 2 and the entity is now grouped under the umbrella term C3 glomerulopathy. 3 We recently saw a patient with DDD presenting as a focal and segmental necrotizing GN with crescents, reminiscent of a small vessel vasculitis with an unusual clinical course.…”

mentioning

confidence: 99%

Dense Deposit Disease Mimicking a Renal Small Vessel Vasculitis

Singh¹,

Singh²,

Bhardwaj

et al. 2016

Journal of the American Society of Nephrology

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Dense deposit disease is caused by fluid-phase dysregulation of the alternative complement pathway and frequently deviates from the classic membranoproliferative pattern of injury on light microscopy. Other patterns of injury described for dense deposit disease include mesangioproliferative, acute proliferative/exudative, and crescentic GN. Regardless of the histologic pattern, C3 glomerulopathy, which includes dense deposit disease and C3 GN, is defined by immunofluorescence intensity of C3c two or more orders of magnitude greater than any other immune reactant (on a 0-3 scale). Ultrastructural appearances distinguish dense deposit disease and C3 GN. Focal and segmental necrotizing glomerular lesions with crescents, mimicking a small vessel vasculitis such as ANCA-associated GN, are a very rare manifestation of dense deposit disease. We describe our experience with this unusual histologic presentation and distinct clinical course of dense deposit disease, discuss the pitfalls in diagnosis, examine differential diagnoses, and review the relevant literature.

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Dense deposit disease is not a membranoproliferative glomerulonephritis

Cited by 105 publications

References 21 publications

Dense Deposit Disease

Dense Deposit Disease

DGKE Variants Cause a Glomerular Microangiopathy That Mimics Membranoproliferative GN

Dense Deposit Disease Mimicking a Renal Small Vessel Vasculitis

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