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Diagnosis: Dense deposits disease

Dense deposit disease (DDD)/membranoproliferative glomerulonephritis type II (MPGNII) is characterized by proteinuria, acute nephritic syndrome, or nephrotic syndrome. It most frequently affects children between ages five and 15 years. DDD/MPGNII can be associated with acquired partial lipodystrophy (APL). Drusen, whitish-yellow deposits within Bruch's membrane of the retina often develop in the second decade of life; they initially have little impact on vision, but cause vision problems from subretinal neovascular membranes, macular detachment, and central serous retinopathy in about 10% of affected individuals.

The definitive diagnosis of DDD requires renal biopsy. Many cases will require electron microscopy (EM) for a precise diagnoses, but cases with histologic and immunopathologic features typical of the disease, as the present case, can be diagnosed without EM. In our case was very useful for diagnosis presence of deposits along tubular basement membranes (Figures 9 and 11), the strong PAS positivity of ribbon like capillary walls in glomeruli (Figure 8), and negativity of this ribbon like deposits for metenamine-silver stain (Figures 6, 7 and 9). On immunofluorescence, the presence of C3 alone, without Igs was also very useful.

Prognosis in DDD es not the best. Spontaneous remissions are uncommon and about 50% of affected individuals develop end-stage renal disease (ESRD) within ten years of diagnosis. DDD recurs in most transplanted kiedneys, but many patients will not have graft loss due to de disease.

There are now many reports of the successful use of a monoclonal anti-C5 antibody therapy (eculizumab) in C3 glomerulopathies (as DDD) and clinical trials are in progress.

See the chapter Membranoproliferative glomerulonephritis and dense deposit disease of our tutorial.

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References

• Herlitz LC, Bomback AS, Markowitz GS, Stokes MB, Smith RN, Colvin RB, Appel GB, D'Agati VD. Pathology after Eculizumab in Dense Deposit Disease and C3 GN. J Am Soc Nephrol. 2012;23(7):1229-37. [PubMed link]
• Servais A, Noël LH, Roumenina LT, Le Quintrec M, Ngo S, Dragon-Durey MA, Macher MA, Zuber J, Karras A, Provot F, Moulin B, Grünfeld JP, Niaudet P, Lesavre P, Frémeaux-Bacchi V. Acquired and genetic complement abnormalities play a critical role in dense deposit disease and other C3 glomerulopathies. Kidney Int. 2012 Mar 28. doi: 10.1038/ki.2012.63. [Epub ahead of print] [PubMed link]
• Pickering M, Cook HT. Complement and glomerular disease: new insights. Curr Opin Nephrol Hypertens. 2011;20(3):271-7. [PubMed link]
• Smith RJ, Harris CL, Pickering MC. Dense deposit disease. Mol Immunol. 2011;48(14):1604-10. [PubMed link]
• Corchado JC, Smith RJ. Dense Deposit Disease/Membranoproliferative Glomerulonephritis Type II. In : GeneReviews, May 19, 2011.. www.ncbi.nlm.nih.gov/books/NBK1425/
• Martínez-Barricarte R, Heurich M, Valdes-Cañedo F, Vazquez-Martul E, Torreira E, Montes T, Tortajada A, Pinto S, Lopez-Trascasa M, Morgan BP, Llorca O, Harris CL, Rodríguez de Córdoba S. Human C3 mutation reveals a mechanism of dense deposit disease pathogenesis and provides insights into complement activation and regulation. J Clin Invest. 2010;120(10):3702-12. [PubMed link]
• Nasr SH, Valeri AM, Appel GB, Sherwinter J, Stokes MB, Said SM, Markowitz GS, D'Agati VD. Dense deposit disease: clinicopathologic study of 32 pediatric and adult patients. Clin J Am Soc Nephrol. 2009 Jan;4(1):22-32. [PubMed link]
• Walker PD. Dense deposit disease: new insights. Curr Opin Nephrol Hypertens. 2007;16(3):204-12. [PubMed link]

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