Membranous Glomerulonephritis Medication

Corticosteroids alone are ineffective in the treatment of membranous nephropathy. Additionally, cyclophosphamide and chlorambucil should be reserved for patients who exhibit clinical features, such as severe or prolonged nephrosis, renal insufficiency, or hypertension.

Alternating monthly treatment with a combination of chlorambucil and steroids for 6 months has also been tried, with some success, especially in patients with a creatinine level of less than 1.7 mg/dL. A 20-year follow-up of these patients showed complete remission in 9 out of 15 patients and partial remission in 4 out of 15 patients; 2 out of 15 patients did not respond. The 10-year survival rate of the treated patients was 100%, whereas that of the untreated patients was 40%.^[7] Cyclophosphamide can be used as an alternative, and cyclosporine is indicated in those patients in whom the above cannot be used or in patients with a high risk of progression.

One review failed to show any long-term effects of immunosuppressive treatment on patient and/or renal survival. An increased number of discontinuations were because of adverse events in the immunosuppressive treatment groups. Within the class of alkylating agents, weak evidence supports the efficacy of cyclophosphamide as compared to chlorambucil. On the other hand, cyclophosphamide had fewer adverse effects leading to patient withdrawal than chlorambucil.

Recently, mycophenolate mofetil has been used with some success. A comparison of mycophenolate mofetil with cyclophosphamide showed decreased proteinuria and improved renal function in most patients, but mycophenolate mofetil did not appear as effective as or better tolerated than cyclophosphamide.^[8]

Tacrolimus has also been used with some success. Monoclonal antibodies against the B cell surface antigen CD20 have been used to explore whether specific inhibition of B cells may help improve the outcome of idiopathic membranous nephropathy and may avoid the adverse effects of steroids and immunosuppressants. Promising results have recently been obtained with rituximab, a monoclonal antibody against the CD20 antigen of B lymphocytes that is able to deplete these cells.^[9]

Titrating rituximab to circulating CD20 B cells may improve safety by avoiding hypersensitivity; it also may limit the costs of treatment while achieving similar results.^[10] However, it has not been possible to precisely predict which patients will respond to rituximab.^[11]

In secondary membranous nephropathy associated with hepatitis B, in addition to interferon, lamivudine monotherapy may induce and maintain complete remission.^[12]

Histology findings in idiopathic membranous nephropathy have been associated with the risk of renal failure, but whether they are independent of the clinical variables at the time of biopsy, predict rate of progression, or should guide therapy is uncertain. Although these histologic features were associated with a reduced renal survival rate, they did not predict this outcome independently of the baseline clinical variables nor did they correlate with the rate of decline in function.^[13]

Class Summary

Used to control volume overload.

Furosemide (Lasix)

Has a potent diuretic effect because it blocks sodium reabsorption in the thick ascending loop of Henle.

Class Summary

Decrease the increased cholesterol associated with nephrotic syndrome.

Simvastatin (Zocor)

Decreases intracellular cholesterol pools and increases LDL receptors, which causes a decrease in LDL-C.

Atorvastatin (Lipitor)

Inhibits 3-hydroxy-3-methylglutaryl coenzyme A, which, in turn, inhibits cholesterol synthesis and increases cholesterol metabolism.

Class Summary

Induce remission of proteinuria.

Prednisone (Deltasone, Meticorten, Orasone, Sterapred)

Exerts an anti-inflammatory effect via the inhibition of inflammatory mediator gene transcription.

Methylprednisolone (Adlone, Medrol, Solu-Medrol)

Exerts an anti-inflammatory effect via inhibition of inflammatory mediator gene transcription.

Cyclophosphamide (Cytoxan, Neosar)

Used for remission of nephrotic syndrome. Interferes with normal function of DNA by alkylation and cross-linking the strands of DNA and by possible protein modification.

Chlorambucil (Leukeran)

For remission of proteinuria; given with prednisone (0.5 mg/kg/d) every other month. Steroids are given as 1 g methylprednisolone IV for 3 d. Interferes with DNA replication and RNA transcription by alkylation and cross-linking the strands of DNA

Class Summary

For remission of nephrotic syndrome.

Cyclosporine A (Sandimmune)

Inhibits production and release of IL-2, leading to inhibition of IL-2–mediated activation of T lymphocytes.

Class Summary

Control blood pressure and proteinuria.

Lisinopril (Zestril, Prinivil)

Inhibition of ACE leads to decreased plasma angiotensin II, which, in turn, leads to decreased vasopressor activity and decreased aldosterone secretion. ACE inhibitors minimize secondary intraglomerular hypertension and hypertrophy, leading to decreased proteinuria in idiopathic membranous nephropathy.

Enalapril (Vasotec)

Competitive inhibitor of ACE. Reduces angiotensin II levels, decreasing aldosterone secretion.

Class Summary

Used to decrease proteinuria.

Ibuprofen (Motrin, Ibuprin)

Exerts its effects by inhibiting both constitutive and inducible isoforms of cyclooxygenase, which produces a mild-to-moderate anti-inflammatory and analgesic effect. NSAIDs decrease intraglomerular pressure and decrease proteinuria.

Naproxen (Anaprox, Naprelan, Naprosyn)

For relief of mild to moderate pain; inhibits inflammatory reactions and pain by decreasing activity of cyclooxygenase, which is responsible for prostaglandin synthesis.

Ketoprofen (Actron, Orudis, Oruvail)

For relief of mild to moderate pain and inflammation.

Small doses are initially indicated in small and elderly patients and in those with renal or liver disease. Doses >75 mg do not increase therapeutic effects. Administer high doses with caution and closely observe patient for response.