Membranous nephropathy (MN, also membranous glomerulonephritis) is a chronic inflammatory kidney disease. As has been known for many years, deposits in the kidney form over the course of the disease. These affect the kidney function and lead to inflammation. Despite intensive research, the exact causes remained unknown for a long time. It was only in 2009 and 2014 that two antibodies were found that cause these damaging deposits in the more frequent form of the disease, primary membranous nephropathy (pMN), and consequently hinder the filtering of the blood. They are autoantibodies: antibodies which are directed against the body's own structures.
Typical symptoms of pMN are:
The disease can vary in severity, ranging from spontaneous improvement to persistent proteinuria or complete kidney failure.
In 2009, researchers identified the first autoantibody involved in the development of pMN in the blood of MN patients. It is directed against the protein PLA2R (phospolipase A2 receptor), which occurs in cells of the blood-urine filter of the kidney. Antibodies against PLA2R accumulate there in greater numbers and form the damaging deposits that destroy these cells and thereby reduce the filter function of the kidney. The discovery of anti-PLA2R autoantibodies is considered a milestone in nephrological research. They can be found in the blood of 70% to 80% of patients.
Through further research, a second autoantibody was found in 2014 that is directed against a protein present in the kidney (THSD7A, thrombospondin type-1 domain-containing 7A). It is found in the blood of up to 15% of those pMN patients who do not have antibodies against PLA2R.
Besides pMN, there is also the secondary form of MN. It is due to another underlying disease, e.g. an infection, another autoimmune disease, a tumour disease or drug intoxication. This secondary membranous nephropathy (sMN) is present in up to 20 to 30% of MN patients. No respective autoantibodies were found in these patients.
Diagnostic differentiation of primary and secondary MN is very important for the treatment. While therapy in sMN mainly focuses on the underlying disease, pMN can in most cases be treated successfully with immunosuppressives.
In some persons, no causative autoantibodies can be detected, nor does the MN have other identifiable causes. These forms of MN are referred to as idiopathic.