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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The changes in glomerular permeability that occur during development were assessed in 1- and 6-wk-old canines by analyzing dextran-sieving curves obtained in six animals at each age. The fractional clearance of the smallest dextran molecules (18 A) was 0.97 +/- 0.02 (+/- SE) in both 1- and 6-wk-old animals, and it became progressively less at larger molecular sizes. The sieving curves were consistent with an isosporous model of a glomerular capillary. When axial changes in protein concentration were included in the mathematical model, the apparent pore radius was 62.7 +/- 1.7 and 61.7 +/- 1.69 A in 1- and 6-wk-old puppies, respectively (P greater than 0.7). The effects of developmental changes in hydrostatic pressure and renal blood flow were balanced by the increases in serum protein concentration and filtration fraction leaving the fractional clearances of macromolecules unchanged. In contrast, the total cross-sectional pore area per unit path length (Aw/delta x) increased during this 6-wk period by approximately 7.5-fold (from 1.39 +/- 0.2 to 10.55 +/- 3.0 10(-5) cm, P less than 0.0001), and the ultrafiltration coefficient rose from 0.012 +/- 0.002 to 0.093 +/- 0.012 ml X s-1 X mmHg-1 (P less than 0.0001). The findings reveal constancy of pore size and an increase in total pore area as a function of age. Analysis by classical pore theory yielded similar findings. We conclude that the predominant factor determining the rise in glomerular filtration rate during development is the large increment in Aw/delta x, which in turn is due to increases in the surface area and pore density of the glomerular capillaries.