Dense deposit disease: clinicopathologic study of 32 pediatric and adult patients

Abstract

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.

Figure 1.

Light microscopic patterns of dense deposit disease (DDD). (A) In this patient with membranoproliferative pattern, there are large nonargyrophilic deposits expanding the mesangium and thickening the glomerular capillary walls, with segmental duplications. (Jones methenamine silver, ×400). (B) An example of mesangial pattern illustrates the mild increase in mesangial cell number and matrix, with preservation of luminal patency. (periodic acid–Schiff, ×600). (C) The endocapillary proliferative and exudative pattern features global occlusion of glomerular capillaries by endocapillary cells, including infiltrating neutrophils and monocytes, with lobular accentuation. Many of the glomerular basement membranes display ribbon-like thickening. (hematoxylin and eosin, ×400). (D) An example of crescentic proliferation with membranoproliferative features in the underlying tuft. There is prominent ribbon-like thickening of the glomerular basement membranes and nodular mesangial expansion. (periodic acid–Schiff, ×400).

Figure 2.

Immunofluorescence features of DDD. (A) Staining for C3 highlights the glomerular capillary walls globally in a semilinear pattern. In some capillaries, there appears to be a double layer of linear staining (arrows). A few ring forms are seen in the mesangium. Semilinear deposits are also present in Bowman's capsule and adjacent tubular basement membranes. (×400). (B) In this example, the mesangium contains numerous characteristic ring forms staining for C3, with weaker linear staining of the glomerular capillary walls (×400).

Figure 3.

Electron microscopic features of DDD. (A) Highly electron-dense intramembranous deposits thicken the glomerular basement membranes. In areas, the deposits are interrupted, producing sausage shapes. There is circumferential mesangial interposition (×4000). (B) Intramembranous interrupted electron-dense deposits are present within a tubular basement membrane (×3000). (C) The ring forms seen by immunofluorescence correspond to rounded electron densities within the mesangium, shown here. A few small intramembranous deposits are also present in the glomerular basement membranes (×2000). (D) Some of the glomerular capillary wall deposits “drop off” the lamina densa, forming inframembranous densities (×4000).

Figure 4.

Kaplan–Meier survival analysis in childhood and adulthood DDD.