Nephrotic Syndrome Medication
- Author: Eric P Cohen, MD; Chief Editor: Vecihi Batuman, MD, FACP, FASN more...
Medication Summary
Corticosteroids (prednisone), cyclophosphamide, and cyclosporine are used to induce remission in nephrotic syndrome. Diuretics are used to reduce edema. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers are administered to reduce proteinuria.
Treatment should be dictated by the type of renal pathology causing nephrotic syndrome.
Minimal-change disease has an excellent response to corticosteroids, while in focal glomerulosclerosis, only 20 % patients respond well to corticosteroids. Renal biopsy is very helpful to differentiate minimal-change disease and its variants such as IgM nephropathy and C1q nephropathy. Very few randomized trials are available to guide treatment for minimal-change disease in adults. Prednisone in short courses from 12-20 weeks’ duration remains the mainstay of treatment for patients with minimal-change disease.
Immunosuppressive medications other than steroids are usually reserved for steroid-resistant patients with persistent edema, or for steroid-dependent patients with significant steroid-related adverse effects.
Cyclophosphamide may benefit patients who have frequently relapsing steroid-sensitive nephrotic syndrome. Associated complications include bone marrow suppression, hair loss, azoospermia, hemorrhagic cystitis, malignancy, mutations, and infertility.
Cyclosporine is indicated when relapses occur after cyclophosphamide treatment. Cyclosporine may be preferable in a pubertal male who is at risk of developing cyclophosphamide-induced azoospermia. Cyclosporine is a highly effective maintenance therapy for patients with steroid-sensitive nephrotic syndrome who are able to stop steroids or take lower doses; however, some evidence suggests that although remission is maintained as long as cyclosporine is administered, relapses are frequent when treatment is discontinued.
Cyclosporine can be nephrotoxic and can cause hirsutism, hypertension, and gingival hypertrophy.
For focal glomerulosclerosis, predisone, cyclosporine, and cyclophosphamide have all been used in treatment. Corticosteroids should be the first-line agent, with cyclophosphamide or cyclosporine as backup for steroid-resistant cases. Mycophenolate and rituximab have also been used in treating focal glomerulosclerosis. However, data on the use of these latter 2 agents are not convincing.
For idiopathic membranous nephropathy, prednisone along with chlorambucil or cyclophosphamide remains important for treatment. Other agents that have been used for the treatment are cyclosporine, synthetic corticotropin, and rituximab.
Rituximab has been effective in some cases of nephrotic syndrome that relapse after prednisone treatment or in cases resistant to prednisone treatment.[36] This drug is a chimeric murine/human antibody against the CD20 antigen of B cells. It presumably exerts its benefit by suppressing antibody production. Its adverse effect to cause immunosuppression cannot be ignored.
Corticosteroids
Class Summary
Corticosteroids have anti-inflammatory properties and modify the body's immune response to diverse stimuli.
Prednisone
Prednisone is an immunosuppressant used in treatment of autoimmune disorders. This agent may decrease inflammation by reversing increased capillary permeability and suppressing polymorphonuclear neutrophil (PMN) activity. It may be administered as a single dose in the morning or as divided doses; studies show that a single dose is equally effective and greatly improves compliance.
Immunomodulators
Class Summary
These agents regulate key steps of the immune system.
Cyclophosphamide
Cyclosporine (Sandimmune, Neoral, Gengraf)
Cyclosporine is a cyclic polypeptide that suppresses cell-mediated immune reactions.
For children and adults, base dosing on ideal body weight
Rituximab (Rituxan)
Rituximab is a chimeric humanized murine monoclonal antibody against CD20 antigen found on the surface of lymphocytes.
Immunosuppressants
Class Summary
These agents inhibit key steps that mediate immune reactions.[37, 38]
Mycophenolate (CellCept, Myfortic)
Mycophenolate inhibits inosine monophosphate dehydrogenase and suppresses de novo purine synthesis by lymphocytes, thereby inhibiting their proliferation. It inhibits antibody production.
Diuretics
Class Summary
These agents are used for symptomatic treatment of edema.
Furosemide (Lasix)
Furosemide increases urine output by inhibiting sodium transport in the ascending loop of Henle and the distal renal tubule. The dose must be individualized to the patient. Depending on response, administer at increments of 20-40 mg, no sooner than 6-8 h after the previous dose, until desired diuresis occurs.
Spironolactone (Aldactone)
Spironolactone is used for management of edema resulting from excessive aldosterone excretion. It competes with aldosterone for receptor sites in distal renal tubules, thus enhancing sodium excretion.
Angiotensin-converting Enzyme (ACE) Inhibitors
Class Summary
ACE inhibitors block conversion of angiotensin I to angiotensin II and prevent secretion of aldosterone from the adrenal cortex. These agents are indicated in metabolic alkalosis due to hyperaldosteronism.
Captopril
Captopril prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in lower aldosterone secretion.
Enalapril (Vasotec)
A competitive inhibitor of ACE, enalapril reduces angiotensin II levels, decreasing aldosterone secretion.
Lisinopril (Prinivil, Zestril)
This agent inhibits ACE, the enzyme that converts angiotensin I to angiotensin II.
Angiotensin II receptor antagonists
Class Summary
ARBs antagonize the action of angiotensin II at the type 1 receptor, reducing systemic arterial blood pressure and blunting the intrarenal effect of angiotensin II. If ACE inhibitors cause cough, ARBs may be substituted.
Valsartan (Diovan)
Valsartan is a prodrug that directly antagonizes angiotensin II receptors. It displaces angiotensin II from the AT1 receptor and may lower blood pressure by antagonizing AT1-induced vasoconstriction, aldosterone release, catecholamine release, arginine vasopressin release, water intake, and hypertrophic responses. Valsartan may induce more complete inhibition of the renin-angiotensin system than do ACE inhibitors. It does not affect bradykinin and is less likely to be associated with cough and angioedema. Valsartan is for use in patients who are unable to tolerate ACE inhibitors.
Losartan (Cozaar)
This ARB blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II. It may induce a more complete inhibition of the renin-angiotensin system than ACE inhibitors, does not affect the response to bradykinin, and is less likely to be associated with cough and angioedema. It is used in patients unable to tolerate ACE inhibitors.
Neelakantappa K, Gallo GR, Baldwin DS. Proteinuria in IgA nephropathy. Kidney Int. Mar 1988;33(3):716-21. [Medline].
Haraldsson B, Nyström J, Deen WM. Properties of the glomerular barrier and mechanisms of proteinuria. Physiol Rev. Apr 2008;88(2):451-87. [Medline].
Russo LM, Bakris GL, Comper WD. Renal handling of albumin: a critical review of basic concepts and perspective. Am J Kidney Dis. May 2002;39(5):899-919. [Medline].
Norden AG, Lapsley M, Lee PJ, Pusey CD, Scheinman SJ, Tam FW. Glomerular protein sieving and implications for renal failure in Fanconi syndrome. Kidney Int. Nov 2001;60(5):1885-92. [Medline].
Hamm LL, Batuman V. Edema in the nephrotic syndrome: new aspect of an old enigma. J Am Soc Nephrol. Dec 2003;14(12):3288-9. [Medline].
Rostoker G, Behar A, Lagrue G. Vascular hyperpermeability in nephrotic edema. Nephron. Jul 2000;85(3):194-200. [Medline].
Appel GB, Blum CB, Chien S, Kunis CL, Appel AS. The hyperlipidemia of the nephrotic syndrome. Relation to plasma albumin concentration, oncotic pressure, and viscosity. N Engl J Med. Jun 13 1985;312(24):1544-8. [Medline].
Curry RC Jr, Roberts WC. Status of the coronary arteries in the nephrotic syndrome. Analysis of 20 necropsy patients aged 15 to 35 years to determine if coronary atherosclerosis is accelerated. Am J Med. Aug 1977;63(2):183-92. [Medline].
Mittal SK, Dash SC, Tiwari SC, Agarwal SK, Saxena S, Fishbane S. Bone histology in patients with nephrotic syndrome and normal renal function. Kidney Int. May 1999;55(5):1912-9. [Medline].
Tessitore N, Bonucci E, D'Angelo A, Lund B, Corgnati A, Lund B, et al. Bone histology and calcium metabolism in patients with nephrotic syndrome and normal or reduced renal function. Nephron. 1984;37(3):153-9. [Medline].
Gulati S, Godbole M, Singh U, Gulati K, Srivastava A. Are children with idiopathic nephrotic syndrome at risk for metabolic bone disease?. Am J Kidney Dis. Jun 2003;41(6):1163-9. [Medline].
Leonard MB, Feldman HI, Shults J, Zemel BS, Foster BJ, Stallings VA. Long-term, high-dose glucocorticoids and bone mineral content in childhood glucocorticoid-sensitive nephrotic syndrome. N Engl J Med. Aug 26 2004;351(9):868-75. [Medline].
Mahmoodi BK, ten Kate MK, Waanders F, Veeger NJ, Brouwer JL, Vogt L. High absolute risks and predictors of venous and arterial thromboembolic events in patients with nephrotic syndrome: results from a large retrospective cohort study. Circulation. Jan 15 2008;117(2):224-30. [Medline].
George BA, Zhou XJ, Toto R. Nephrotic syndrome after bevacizumab: case report and literature review. Am J Kidney Dis. Feb 2007;49(2):e23-9. [Medline].
Lefaucheur C, Stengel B, Nochy D, et al. Membranous nephropathy and cancer: Epidemiologic evidence and determinants of high-risk cancer association. Kidney Int. Oct 2006;70(8):1510-7. [Medline].
Wong W. Idiopathic nephrotic syndrome in New Zealand children, demographic, clinical features, initial management and outcome after twelve-month follow-up: results of a three-year national surveillance study. J Paediatr Child Health. May 2007;43(5):337-41. [Medline].
Kumar J, Gulati S, Sharma AP, Sharma RK, Gupta RK. Histopathological spectrum of childhood nephrotic syndrome in Indian children. Pediatr Nephrol. Jul 2003;18(7):657-60. [Medline].
Ozkaya N, Cakar N, Ekim M, Kara N, Akkök N, Yalçinkaya F. Primary nephrotic syndrome during childhood in Turkey. Pediatr Int. Aug 2004;46(4):436-8. [Medline].
Kazi JI, Mubarak M. Pattern of glomerulonephritides in adult nephrotic patients--report from SIUT. J Pak Med Assoc. Nov 2007;57(11):574. [Medline].
Barsoum R. The changing face of schistosomal glomerulopathy. Kidney Int. 2004;66:2472-2484.
Doe JY, Funk M, Mengel M, et al. Nephrotic syndrome in African children: lack of evidence for 'tropical nephrotic syndrome'?. Nephrol Dial Transplant. 2006;21:672-676.
Pakasa NM, Sumaili EK. The nephrotic syndrome in the Democratic Republic of Congo. N Engl J Med. Mar 9 2006;354(10):1085-6. [Medline].
Sumaili EK, Krzesinski JM, Zinga CV, Cohen EP, Delanaye P, Munyanga SM, et al. Prevalence of chronic kidney disease in Kinshasa: results of a pilot study from the Democratic Republic of Congo. Nephrol Dial Transplant. Jan 2009;24(1):117-22. [Medline].
Kopp JB, Winkler C. HIV-associated nephropathy in African Americans. Kidney Int Suppl. Feb 2003;S43-9. [Medline].
Bonilla-Felix M, Parra C, Dajani T, Ferris M, Swinford RD, Portman RJ. Changing patterns in the histopathology of idiopathic nephrotic syndrome in children. Kidney Int. May 1999;55(5):1885-90. [Medline].
Arneil GC, Lam CN. Long-term assessment of steroid therapy in childhood nephrosis. Lancet. Oct 15 1966;2(7468):819-21. [Medline].
Donadio JV Jr, Torres VE, Velosa JA, Wagoner RD, Holley KE, Okamura M. Idiopathic membranous nephropathy: the natural history of untreated patients. Kidney Int. Mar 1988;33(3):708-15. [Medline].
Jude EB, Anderson SG, Cruickshank JK, et al. Natural history and prognostic factors of diabetic nephropathy in type 2 diabetes. Quart J Med. 2002;95:371-7. [Medline].
Varghese SA, Powell TB, Budisavljevic MN, et al. Urine biomarkers predict the cause of glomerular disease. J Am Soc Nephrol. 2007;18:913-22. [Medline].
Cohen EP, Lemann J. The role of the laboratory in evaluation of kidney function. Clin Chem. 1991;37:785-796.
Gupta K, Iskandar SS, Daeihagh P, et al. Distribution of pathologic findings in individuals with nephrotic proteinuria according to serum albumin. Nephrol Dial Transplant. May 2008;23(5):1595-9. [Medline].
Palmer SC, Nand K, Strippoli GF. Interventions for minimal change disease in adults with nephrotic syndrome. Cochrane Database Syst Rev. Jan 23 2008;CD001537. [Medline].
Waldman M, Crew RJ, Valeri A, Busch J, Stokes B, Markowitz G, et al. Adult minimal-change disease: clinical characteristics, treatment, and outcomes. Clin J Am Soc Nephrol. May 2007;2(3):445-53. [Medline].
Fervenza FC, Abraham RS, Erickson SB, et al. Rituximab therapy in idiopathic membranous nephropathy: a two year study. Clin J Am Soc Nephrol. 2010;5:2188-2198. [Medline].
du Buf-Vereijken PW, Branten AJ, Wetzels JF. Idiopathic membranous nephropathy: outline and rationale of a treatment strategy. Am J Kidney Dis. Dec 2005;46(6):1012-29. [Medline].
Gulati A, Sinha A, Jordan SC, Hari P, Dinda AK, Sharma S, et al. Efficacy and safety of treatment with rituximab for difficult steroid-resistant and -dependent nephrotic syndrome: multicentric report. Clin J Am Soc Nephrol. Dec 2010;5(12):2207-12. [Medline]. [Full Text].
Chen M, Li H, Li XY, et al. Tacrolimus Combined With Corticosteroids in Treatment of Nephrotic Idiopathic Membranous Nephropathy: A Multicenter Randomized Controlled Trial. Am J Med Sci. Mar 2010;339(3):233-8. [Medline].
Roberti I, Vyas S. Long-term outcome of children with steroid-resistant nephrotic syndrome treated with tacrolimus. Pediatr Nephrol. Mar 9 2010;[Medline].
Print
