Membranoproliferative glomerulonephritis type II
| Classification according to ICD-10 | |
|---|---|
| N03 | Chronic nephritic syndrome |
| N03.6 | Dense deposit disease, membranoproliferative glomerulonephritis, type II |
| ICD-10 online (WHO version 2019) | |
The membranoproliferative glomerulonephritis type II (Dense Deposit Disease, MPGN II) is a rare kidney disease that occurs mainly in children aged between 5 and 15 years. The disease is equally common in both sexes. Within 10 years, around 50% of those affected reach the end stage of the disease requiring dialysis . In contrast to the other forms of membranoproliferative glomerulonephritis , type II does not have any deposits of immune complexes in the kidney corpuscles (glomeruli) .
Symptoms
The condition has one of the following five symptoms:
- Detection of red blood cells in the urine (hematuria)
- Detection of protein in the urine (proteinuria)
- simultaneous occurrence of hematuria and proteinuria
- acute nephritic syndrome : hematuria, water retention (edema) and high blood pressure (hypertension) ( Volhard -Trias)
- Nephrotic syndrome : proteinuria with a protein loss of more than 1 g / m² / body surface area per day, hypoproteinemia , peripheral edema due to hypoalbuminemia of <2.5 g / dl in the serum and hyperlipoproteinemia
diagnosis
The diagnosis requires a kidney biopsy . The electron microscopic examination shows dense deposits in the glomerular basement membrane that can be stained with osmium salts (osmiophile) . In the immunohistochemical examination, the complement component C3 can be detected in the deposits , but not IgG . In addition, there can be disturbances in the distribution of adipose tissue (partial lipodystrophy ) and characteristic deposits in the retina of the eye, so-called drusen , which lead to impaired vision in around 10% of patients. The fundus of patients with membranoproliferative glomerulonephritis Tap II shows similarities to the fundus of people who suffer from age- related macular degeneration .
Pathogenesis
The cause of membranoproliferative glomerulonephritis type II appears to be an uncontrolled activation of the alternative pathway of the complement cascade . Over 80% of those affected have an autoantibody against the C3 convertase of the alternative C3bBb pathway , which means that factor H can no longer deactivate it. The C3 convertase splits C3 into C3a and C3b and is then disinhibited. This autoantibody is also known as C3 Nephritic Factor (C3NeF) . C3NeF is also detectable in about half of the cases of membranoproliferative glomerulonephritis type I and III , but the detection of dense deposits in the basement membrane is characteristic of type II . Also mutations in factor H and factor H autoantibodies can lead II for membranoproliferative glomerulonephritis type.
By mass spectrometry , in addition to C3, precursors of the components of the membrane attack complex C5, C8α and C9, as well as complement factor H-related protein 1 (FHR1) , vitronectin and apolipoprotein E (ApoE) could be detected in glomeruli of patients with dense depostid disease . The uncontrolled activation of the alternative route thus possibly leads to an excessive production of the membrane attack complex and this ultimately to damage to the kidney corpuscles.
therapy
Non-specific therapy
The aim of the non-specific therapy is to inhibit the progression ( progression ) of the kidney damage. Treatment requires aggressive control of blood pressure and a reduction in the amount of protein in the urine (proteinuria). The antihypertensive substances of first choice are ACE inhibitors and AT1 antagonists .
The lowering of elevated blood lipids with the help of statins may also have a positive influence on the course of the disease.
Steroids are unlikely to be effective.
By mycophenolate mofetil may proliferation can T cells and B cells and thus the production of C3 nephritis factor are inhibited. The antibody-producing B cells can be destroyed by the monoclonal antibody rituximab . So far, however, there are no studies on these treatment options.
Specific therapy
If mutations in the gene for factor H are detected, treatment should be carried out with fresh frozen plasma or plasmapheresis with plasma exchange.
Eculizumab , a monoclonal antibody against complement factor C5, can reduce the damage caused by C5a to the kidney corpuscle.
Sulodexide , a mixture of the glycosaminoglycans heparin and dermatan sulfate , inhibits heparanase in the kidney corpuscle . Heparanase is experimenting with increased glomerular diseases and damages the glomerular basement membrane by degradation of proteoglycans .
Therapy Register
Due to the rarity of the disease, it is not possible to conduct randomized, controlled studies . For this reason, all disease courses should be recorded in a central register (see web links).
Web links
- Dense Deposit Disease Pathology - Pathopic image database of the University of Basel ( PathoPic - Instructions ; PDF; 2.2 MB)
- Agnes Fogo: Dense Deposit Disease . In: Am J Kidney Dis . No. 31 , 1998, pp. E1 ( article ).
Individual evidence
- ↑ Gerald B. Appel et al .: Membranoproliferative Glomerulonephritis Type II (Dense Deposit Disease) An Update . In: J Am Soc Nephrol . No. 16 , 2005, pp. 1392-1403 ( Article ).
- ^ Sanjeev Sethi, et al .: Glomeruli of Dense Deposit Disease contain components of the alternative and terminal complement pathway . In: Kidney International . 75, No. 9, May 2009, ISSN 1523-1755 , pp. 952-960. doi : 10.1038 / ki.2008.657 . PMID 19177158 .
- ↑ John R Sedor: tissue proteomics: a new investigative tool for renal biopsy analysis . In: Kidney International . 75, No. 9, May 2009, ISSN 1523-1755 , pp. 876-879. doi : 10.1038 / ki.2009.54 . PMID 19367311 .
- ^ Richard JH Smith et al., Dense Deposit Disease Focus Group: New Approaches to the Treatment of Dense Deposit Disease . In: J Am Soc Nephrol . No. 18 , 2007, p. 2447-2456 ( Article ).
