Membranous glomerulonephritis is an inflammatory disease of the renal corpuscles characterized by the deposition of immune complexes. Patients primarily suffer from nephrotic syndrome. Treatment can range from medication to reduce symptomatic proteinuria to immunosuppressive therapy.
What is membranous glomerulonephritis?
Glomeruli corpusculi renalis refers to a tissue portion of the renal corpuscles. This morphologically and functionally essential component is predominantly responsible for the ultrafiltration of primary urine. The renal corpuscles including the glomuri can be affected by various diseases. One of these renal diseases is 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 is responsible for about five percent of the development of nephrotic syndromes. In adulthood, the disease is even the most frequent cause of nephrotic syndrome. Membranous glomerulonephritis affects the male and female sexes with approximately equal frequency. All ethnic groups are affected by the disease. In about two-thirds of all cases, no cause can be determined for the disease of membranous glomerulonephritis. For one-third, there is talk of secondary glomerulonephritis secondary to primary disease.
Causes
In children, the primary diseases most commonly associated with membranous glomerulonephritis include infectious diseases such as hepatitis. Apart from these, the disease may be a consequence of HIV, malaria, autoimmune diseases, or syphilis. Among autoimmune diseases, systemic lupus erythematosus is a common cause. In addition to these triggers, primary tumor diseases may be a cause. The cases documented so far also suggest that membranous glomerulonephritis is sometimes caused by drug use, for example in association with substances such as gold and penicillamine. Immune complexes are deposited on the basement membrane of the glomeruli in the disease. This deposition is preceded by sensitization by what is probably an endogenous antigen. In secondary forms, the sensitizing antigens can be traced to the underlying primary disease. Multivalent antibodies bind antigens in this form of the disease and give rise to immune complexes at the glomerular basement membrane. After activation of the complement system, complement factors C5b to C9 are deposited and trigger inflammatory reactions.
Symptoms, complaints, and signs
Patients with membranous glomerulonephritis suffer from nephrotic syndrome in about 80 percent of all cases. Characteristic symptoms of this phenomenon include proteinuria or hypoproteinemia. Proteinuria is associated with protein loss, which promotes infections, 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, edema is progressively increased. Weight gain may occur. Beyond the manifestations of a nephrotic syndrome, patients of membranous glomerulonephritis in many cases suffer from microhematuria and hypertension. Accordingly, they often excrete blood with the urine. In most cases, however, this blood is not visible to the naked eye. Hypertension, meanwhile, causes an increase in pressure or tissue tension that exceeds the physiological norm. Hypercholesterolemia may also develop in the course of the disease. The severity of individual symptoms varies from case to case. Mild pain may occur due to inflammation.
Diagnosis and course of the disease
The initial suspicion of membranous glomerulonephritis is raised by evidence of proteinuria, microhematuria, elevated creatinine, hypalbuminemia, or hypercholesterolemia. A renal biopsy is obtained to confirm the suspected diagnosis of glomerulonephritis. Light microscopy reveals a thickened basement membrane of the renal corpuscles.Electron microscopy reveals immune complex depots, basement membrane spikes and fusions of podocyte foot processes. Patients with the disease have a relatively favorable course even without treatment. Within five years, total loss of renal function occurs in only about 14 percent of affected individuals. For one third of patients, the situation normalizes within one year without treatment. For another third, the symptoms at least recede. Asians have the best prognosis. Patients with drug-induced glomerulonephritis also have excellent prospects for recovery.
Treatment and therapy
General therapy for membranous nephropathy controls water retention with diuretics, ensures nutritional intake, reduces proteinuria and hypertension with ACE inhibitors or AT1 antagonists, and corrects dyslipidemia with statin administration. Thromboembolic complications are prevented by the administration of anticoagulants. In addition to these conservative drug measures, immunosuppressive therapy is recommended for patients with a particularly severe course of the disease. Because of the sometimes severe consequences of immunosuppressive treatment, immunosuppressive therapy is only given in cases with an extremely unfavorable prognosis. In some cases, alkylating substances such as cyclophosphamide or chlorambucil are administered in combination with agents such as prednisone. In addition, the selectively anti-B cell and monoclonal antibody rituximab can reduce proteinuria. If all conventional steps fail, one year of mycophenolate mofetil treatment may be given. Instead of cyclosporine, tacrolimus can be given in case of intolerance. In addition, pentoxifylline sometimes improved proteinuria in patients in the past. The same effects have been observed for nonsteroidal anti-inflammatory drugs, which, however, can be harmful to the kidneys. All treatment measures should be understood as symptomatic therapeutic steps. Causal treatment does not yet exist for patients with mammary glomerulonephritis because the causes remain unknown in many cases. Causal or symptomatic treatment of primary disease should be sought in the case of secondary glomerulonephritis.
Outlook and prognosis
Membranous glomerulonephritis is characterized by a nephrotic syndrome in approximately 80 percent of affected individuals. The remainder of affected individuals remain largely asymptomatic. One-third of patients can expect spontaneous remission. Another third experience partial remission. Only one third of those affected experience chronic kidney failure. This requires a kidney transplant. The best prognosis is for patients who experience spontaneous remission of membranous glomerulonephritis within one year. A worse prognosis is partial remission. In this, protein excretion decreases to levels below 2 grams per day. Nevertheless, some patients experience a complete loss of kidney function after five or ten years. The course can be somewhat improved by means of renin-angiotensin-aldosterone system inhibition with medication. Only patients with an unfavorable prognosis receive immunosuppressive therapy. Here, the expected early loss of renal function is at the top of the list of risks. Oddly enough, in people from Asia, the prognosis is better for severe disease. Even for children, adolescents and women with non-nephrotic proteinuria, the prognosis can be positive after three years. The prerequisite is normal renal function. The same applies to people suffering from drug-induced membranous nephritis. Here, however, there is an initial deterioration. Improvement may be three years away.
Prevention
Comprehensive preventive measures for membranous glomerulonephritis do not yet exist. Preventive steps are therefore only possible in moderation because the primary cause of the disease remains unexplained in many cases.
Follow-up
The severity of symptoms differs according to the degree of disease. In 80 percent of all cases with membranous glomerulonephritis, affected individuals have nephrotic syndrome. Symptoms of this syndrome include proteinuria or hypoproteinemia. Proteinuria is accompanied by protein loss, which promotes, for example, infections, thrombosis, edema and ascites. Therefore, regular visits to the treating physician are indispensable, which makes follow-up care in the true sense unnecessary.Since the treatment of membranous glomerulonephritis is relatively complex and lengthy, follow-up care nevertheless focuses on managing the disease well and with confidence. Sufferers should try to focus on a positive healing process despite the adversity. To build the appropriate mindset, 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, adjunctive therapy can help to better absorb the treatment process and adopt a more positive attitude.
