Micrograph of glomerulus in membranoproliferative glomerulonephritis with increased mesangial matrix and increased mesangial cellularity. Kidney biopsy. PAS stain.
Membranoproliferative glomerulonephritis (MPGN) is a type of glomerulonephritis caused by deposits in the kidney glomerular mesangium and basement membrane (GBM) thickening,[2] activating the complement system and damaging the glomeruli.
MPGN accounts for approximately 4% of primary renal causes of nephrotic syndrome in children and 7% in adults.[3]
It should not be confused with membranous glomerulonephritis, a condition in which the basement membrane is thickened, but the mesangium is not.
Type
There are three types of MPGN, but this classification is becoming obsolete as the causes of this pattern are becoming understood.[citation needed]
Type I
Type I, the most common by far, is caused by immune complexes depositing in the kidney. It is characterised by subendothelial and mesangial immune deposits.[citation needed]
Type II is today more commonly known as dense deposit disease (DDD).[5] Most cases of dense deposit disease do not show a membranoproliferative pattern.[6] It forms a continuum with C3 glomerulonephritis; together they make up the two major subgroups of C3 glomerulopathy.[7]
DDD is associated with deposition of complement C3 within the glomeruli with little or no staining for immunoglobulin. The presence of C3 without significant immunoglobulin suggested to early investigators that DDD was due to abnormal activation of the complement alternative pathway (AP). There is now strong evidence that DDD is caused by uncontrolled AP activation.[10]
Spontaneous remissions of MPGN II are rare; approximately half of those affected with MPGN II will progress to end stage renal disease within ten years.[11]
Type III is very rare, it is characterized by a mixture of subepithelial and subendothelial immune and/or complement deposits. These deposits elicit an immune response, causing damage to cells and structures within their vicinity. Has similar pathological findings of Type I disease.[13]
The GBM is rebuilt on top of the deposits, causing a "tram tracking" appearance under the microscope.[17] Mesangial cellularity is increased.[18]
Treatment
Primary MPGN is treated with steroids, plasma exchange and other immunosuppressive drugs.
Secondary MPGN is treated by treating the associated infection, autoimmune disease or neoplasms. Pegylated interferon and ribavirin are useful in reducing viral load. [19]
^West CD, McAdams AJ (March 1998). "Glomerular paramesangial deposits: association with hypocomplementemia in membranoproliferative glomerulonephritis types I and III". Am. J. Kidney Dis. 31 (3): 427–34. doi:10.1053/ajkd.1998.v31.pm9506679. PMID9506679.
^(reviewed in Appel et al., 2005; Smith et al., 2007). Smith, R. J. ., Harris, C. L., & Pickering, M. C. (2011). Dense Deposit Disease. Molecular Immunology, 48(14), 1604–1610. http://doi.org/10.1016/j.molimm.2011.04.005/
^Swainson CP, Robson JS, Thomson D, MacDonald MK (1983). "Mesangiocapillary glomerulonephritis: a long-term study of 40 cases". J. Pathol. 141 (4): 449–68. doi:10.1002/path.1711410404. PMID6363655. S2CID25434508.
^Colville D, Guymer R, Sinclair RA, Savige J (2003). "Visual impairment caused by retinal abnormalities in mesangiocapillary (membranoproliferative) glomerulonephritis type II ("dense deposit disease")". Am. J. Kidney Dis. 42 (2): E2–5. doi:10.1016/S0272-6386(03)00665-6. PMID12900843.
^Pickering, M. C., D’Agati, V. D., Nester, C. M., Smith, R. J., Haas, M., Appel, G. B., … Cook, H. T. (2013). C3 glomerulopathy: consensus report. Kidney International, 84(6), 1079–1089. http://doi.org/10.1038/ki.2013.377
^Neary J, Dorman A, Campbell E, Keogan M, Conlon P (July 2002). "Familial membranoproliferative glomerulonephritis type III". Am. J. Kidney Dis. 40 (1): e1.1–e1.6. doi:10.1053/ajkd.2002.33932. PMID12087587.
