Membranous glomerulonephritis is an inflammatory disease of the renal corpuscles characterized by the deposition of immune complexes. Patients mainly suffer from nephrotic syndrome. Treatment can range from medication to reduce symptomatic proteinuria to immunosuppressive therapy.
What is membranous glomerulonephritis?
A part of the tissue of the renal corpuscles is called glomeruli corpusculi renalis. The morphologically and functionally essential component is mainly responsible for the ultrafiltration of the primary urine. The renal corpuscles including the glomuri can be affected by various diseases. One of these renal disorders is membranous glomerulonephritis. See AbbreviationFinder for abbreviations related to Membranous Glomerulonephritis.
This inflammatory disease is also known as membranous glomerulopathy, epimembranous glomerulonephritis or membranous nephropathy and is one of the chronic kidney diseases. Deposits of individual immune complexes on the outer basement membrane of the glomeruri characterize the clinical picture. In childhood, membranous glomerulonephritis accounts for around five percent of the development of nephrotic syndromes.
In adulthood, the disease is even the most common cause of nephrotic syndrome. Membranous glomerulonephritis affects males and females with about the same frequency. All ethnic groups are affected by the disease. In around two-thirds of all cases, no cause can be determined for membranous glomerulonephritis. A third reported secondary glomerulonephritis as a result of a primary disease.
In children, the primary diseases most commonly associated with membranous glomerulonephritis are infectious diseases such as hepatitis. That being said, the disease can be a result of HIV, malaria, autoimmune diseases, or syphilis. Systemic lupus erythematosus is a common cause of autoimmune diseases.
In addition to these triggers, primary tumor diseases are possible causes. The cases of illness documented to date also indicate that membranous glomerulonephritis is sometimes caused by the intake of medication, for example in association with substances such as gold and penicillamine. In the disease, immune complexes are deposited on the basement membrane of the glomeruli.
This deposition is preceded by sensitization by a presumably endogenous antigen. In the secondary forms, the sensitizing antigens can be traced back to the underlying primary disease. In this form of the disease, multivalent antibodies bind to antigens and form immune complexes on the glomerular basement membrane. After activation of the complement system, complement factors C5b to C9 are deposited and trigger inflammatory reactions.
Symptoms, Ailments and Signs
About 80 percent of patients with membranous glomerulonephritis suffer from nephrotic syndrome. Characteristic symptoms of this phenomenon include proteinuria or hypoproteinemia. Proteinuria is associated with a loss of protein that promotes infection, ascites, edema, and thrombosis.
As large amounts of albumin are lost, osmolarity within the vascular bed decreases and fluid reaches the interstitium. For this reason, the edema is progressively increased. Weight gain may occur. In addition to the manifestations of nephrotic syndrome, patients with membranous glomerulonephritis often suffer from microscopic hematuria and hypertension. They therefore often excrete blood with the urine.
In most cases, however, this blood is not visible to the naked eye. Meanwhile, hypertension causes an increase in pressure or an increase in tissue tension that exceeds the physiological norm in the tissue. Hypercholesterolemia can also develop as the disease progresses. The severity of each symptom differs from case to case. Mild pain can occur due to inflammation.
Diagnosis and course of the disease
The first suspicion of membranous glomerulonephritis is the detection of proteinuria, microscopic hematuria, increased creatinine, hypoalbuminemia, or hypercholesterolemia. A kidney biopsy is performed to confirm the presumptive diagnosis. A thickened Basel membrane of the renal corpuscles is visible under the light microscope.
Immune complex depots, basement membrane spikes and fusions of the podocyte foot processes are impressive with the electron microscope. Patients with the disease have a relatively benign outcome even without treatment. Within five years, only about 14 percent of those affected experience a total loss of kidney function.
For a third of the patients, the situation returns to normal within a year if left untreated. For another third, the symptoms at least go away. Asians have the best prognosis. Patients with drug-induced glomerulonephritis also have excellent prospects of recovery.
Treatment and therapy
General therapy for membranous nephropathy controls water retention with diuretics, secures food intake, reduces proteinuria and hypertension with ACE inhibitors or AT1 antagonists, and corrects dyslipidemia with statins. Thromboembolic complications are prevented by administering anticoagulants.
In addition to these conservative drug measures, immunosuppressive therapy is recommended for patients with a particularly severe course . Due to the sometimes severe consequences of immunosuppressive treatment, immunosuppressive therapy only takes place if the prognosis is extremely unfavorable. In some cases, alkylating substances such as cyclophosphamide or chlorambucil are administered in combination with agents such as prednisone.
In addition, the anti-B cell monoclonal antibody rituximab can reduce proteinuria. If all conventional steps fail, one year of mycophenolate mofetil treatment can be given. Tacrolimus can be given instead of cyclosporine in case of intolerance. In addition, pentoxifylline has improved some of the patients’ proteinuria in the past.
The same effects were observed for non-steroidal anti -inflammatory drugs, which, however, can have a kidney-damaging effect. All treatment measures are to be understood as symptomatic therapy steps. A causal treatment does not yet exist for patients with membraneous glomerulonephritis, as the causes remain unknown in many cases. A causal or symptomatic treatment of primary diseases should be aimed for in the case of secondary glomerulonephritis.
Outlook & Forecast
Membranous glomerulonephritis is characterized by a nephrotic syndrome in about 80 percent of those affected. The rest of those affected remain largely symptom-free. One-third of patients can expect spontaneous remission. Another third experienced a partial remission. Only a third of those affected have chronic kidney failure. This requires a kidney transplant.
Patients in whom membranous glomerulonephritis heals spontaneously within a year have the best prognosis. A worse prognosis is partial remission. This reduces protein excretion to values below 2 grams per day. Nevertheless, some of those affected experience a complete loss of kidney function after five or ten years. The course of the disease can be somewhat improved by means of medicinal renin-angiotensin-aldosterone system inhibition.
Only patients with an unfavorable disease prognosis receive immunosuppressive therapy. Here the expected early loss of renal function is at the top of the list of risks. Oddly enough, people from Asia have a better prognosis when the disease is severe.
The prognosis after three years can also be positive for children, adolescents and women with non-nephrotic proteinuria. Normal kidney function is required. The same applies to people who suffer from drug-induced membranous nephritis. Here, however, there is a deterioration. The improvement can take three years to come.
Comprehensive preventive measures for membranous glomerulonephritis do not yet exist. Preventive steps are only possible to a limited extent because the primary cause of the disease remains unclear in many cases.
The severity of the symptoms differs according to the degree of the disease. Nephrotic syndrome accounts for 80 percent of all cases of membranous glomerulonephritis. Symptoms of this syndrome include proteinuria or hypoproteinemia. Proteinuria is accompanied by a loss of protein, which promotes infections, thrombosis, edema and ascites, for example. Regular visits to the treating doctor are therefore essential, which means that follow-up care is not actually necessary. Since the treatment of membranous glomerulonephritis is relatively complex and lengthy, follow-up care nevertheless focuses on dealing with the disease in a good and confident manner. Those affected should try to focus on a positive healing process despite the adversity. To establish the right attitude, relaxation exercises and meditation can help calm and focus the mind. If psychological upsets are present and persist, this should be clarified with a psychologist. Sometimes an accompanying therapy can help to better absorb the treatment process and adopt a more positive attitude.