Nephrotic syndrome medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mehrian Jafarizade, M.D [2] ,Yazan Daaboul, Serge Korjian


There are currently no guidelines for the management of edema associated with nephrotic syndrome. The slow reversal of edema is important at a rate of 0.5-1 kg daily to prevent electrolyte disturbances, hypotension, ischemic acute tubular necrosis, and hemoconcentration associated with aggressive diuretic therapy. Since proteinuria is one of the most significant factors for progression of a disease and is associated with outcome, treatment of proteinuria in nephrotic syndrome must always be considered a priority. Angiotensin-converting enzyme inhibitors (ACE-I), with or without angiotensin-II receptor blockers (ARB) have been extensively studied and are well-known to decrease proteinuria and the risk of progression of renal disease in patients with nephrotic syndrome. Pneumococcal vaccines are recommended for all patients with nephrotic syndrome.

Medical Therapy

Treatment of Edema



Treatment of Proteinuria

  • Treatment with combined agents has been shown to effectively reduce proteinuria more than treatment with single agents.[5][6][7][10]
  • Follow-up with measurements of serum electrolytes is recommended periodically.

Treatment of Hyperlipidemia

  • There are currently no reliable randomized clinical trials to recommend the use of lipid-lowering therapy in patients with nephrotic syndrome.[1]
  • It is however well-established that treatment of nephrotic syndrome itself often resolves the associated hyperlipidemia.
  • One meta-analysis and post hoc subgroup analysis showed that statin might be effective in reducing cardiovascular disease in patients with nephrotic syndrome. As such, nephrotic syndrome should not change the indication for lipid-lowering treatment.[13][14][15][16][17]

Dietary Recommendations


Other recommendations, such as vaccinations and use of other prophylactic medications are listed below:[13]

  • Pneumococcal vaccines are recommended for all patients with nephrotic syndrome.
  • Prophylactic antibiotics are not recommended for patients with nephrotic syndrome.
  • Prophylactic anticoagulation is not recommended. Anticoagulation may be initiated in thrombotic events, with special consideration to the decreased efficiency of heparin in patients with nephrotic syndrome due to the decreased serum antithrombin III levels needed for heparin anticoagulation.

Contraindicated Medications

Nephrosis or the nephrotic phase of nephritis is considered an absolute contraindication to the use of the following medications:


  1. 1.0 1.1 1.2 1.3 1.4 1.5 Hull RP, Goldsmith DJ (2008). "Nephrotic syndrome in adults". BMJ. 336 (7654): 1185–9. doi:10.1136/bmj.39576.709711.80. PMC 2394708. PMID 18497417.
  2. 2.0 2.1 Brater DC (1998). "Diuretic therapy". N Engl J Med. 339 (6): 387–95. doi:10.1056/NEJM199808063390607. PMID 9691107.
  3. Ruggenenti P, Perna A, Mosconi L, Pisoni R, Remuzzi G (1998). "Urinary protein excretion rate is the best independent predictor of ESRF in non-diabetic proteinuric chronic nephropathies. "Gruppo Italiano di Studi Epidemiologici in Nefrologia" (GISEN)". Kidney Int. 53 (5): 1209–16. doi:10.1046/j.1523-1755.1998.00874.x. PMID 9573535.
  4. Locatelli F, Marcelli D, Comelli M, Alberti D, Graziani G, Buccianti G; et al. (1996). "Proteinuria and blood pressure as causal components of progression to end-stage renal failure. Northern Italian Cooperative Study Group". Nephrol Dial Transplant. 11 (3): 461–7. PMID 8710157.
  5. 5.0 5.1 Gansevoort RT, Sluiter WJ, Hemmelder MH, de Zeeuw D, de Jong PE (1995). "Antiproteinuric effect of blood-pressure-lowering agents: a meta-analysis of comparative trials". Nephrol Dial Transplant. 10 (11): 1963–74. PMID 8643149.
  6. 6.0 6.1 "Randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, non-diabetic nephropathy. The GISEN Group (Gruppo Italiano di Studi Epidemiologici in Nefrologia)". Lancet. 349 (9069): 1857–63. 1997. PMID 9217756.
  7. 7.0 7.1 Nakao N, Yoshimura A, Morita H, Takada M, Kayano T, Ideura T (2003). "Combination treatment of angiotensin-II receptor blocker and angiotensin-converting-enzyme inhibitor in non-diabetic renal disease (COOPERATE): a randomised controlled trial". Lancet. 361 (9352): 117–24. doi:10.1016/S0140-6736(03)12229-5. PMID 12531578. Review in: ACP J Club. 2003 Sep-Oct;139(2):40
  8. Ruggenenti P, Mosconi L, Vendramin G, Moriggi M, Remuzzi A, Sangalli F; et al. (2000). "ACE inhibition improves glomerular size selectivity in patients with idiopathic membranous nephropathy and persistent nephrotic syndrome". Am J Kidney Dis. 35 (3): 381–91. PMID 10692263.
  9. Korbet SM (2003). "Angiotensin antagonists and steroids in the treatment of focal segmental glomerulosclerosis". Semin Nephrol. 23 (2): 219–28. doi:10.1053/snep.2003.50020. PMID 12704582.
  10. Tsouli SG, Liberopoulos EN, Kiortsis DN, Mikhailidis DP, Elisaf MS (2006). "Combined treatment with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers: a review of the current evidence". J Cardiovasc Pharmacol Ther. 11 (1): 1–15. PMID 16703216.
  11. Crook ED, Habeeb D, Gowdy O, Nimmagadda S, Salem M (2005). "Effects of steroids in focal segmental glomerulosclerosis in a predominantly African-American population". Am J Med Sci. 330 (1): 19–24. PMID 16020995.
  12. Schieppati A, Perna A, Zamora J, Giuliano GA, Braun N, Remuzzi G (2004). "Immunosuppressive treatment for idiopathic membranous nephropathy in adults with nephrotic syndrome". Cochrane Database Syst Rev (4): CD004293. doi:10.1002/14651858.CD004293.pub2. PMID 15495098.
  13. 13.0 13.1 Kodner C (2009). "Nephrotic syndrome in adults: diagnosis and management". Am Fam Physician. 80 (10): 1129–34. PMID 19904897.
  14. Ordoñez JD, Hiatt RA, Killebrew EJ, Fireman BH (1993). "The increased risk of coronary heart disease associated with nephrotic syndrome". Kidney Int. 44 (3): 638–42. PMID 8231039.
  15. Crew RJ, Radhakrishnan J, Appel G (2004). "Complications of the nephrotic syndrome and their treatment". Clin Nephrol. 62 (4): 245–59. PMID 15524054.
  16. Fried LF, Orchard TJ, Kasiske BL (2001). "Effect of lipid reduction on the progression of renal disease: a meta-analysis". Kidney Int. 59 (1): 260–9. doi:10.1046/j.1523-1755.2001.00487.x. PMID 11135079.
  17. Tonelli M, Moyé L, Sacks FM, Cole T, Curhan GC, Cholesterol and Recurrent Events Trial Investigators (2003). "Effect of pravastatin on loss of renal function in people with moderate chronic renal insufficiency and cardiovascular disease". J Am Soc Nephrol. 14 (6): 1605–13. PMID 12761262.
  18. Guarnieri GF, Toigo G, Situlin R, Carraro M, Tamaro G, Lucchesli A; et al. (1989). "Nutritional state in patients on long-term low-protein diet or with nephrotic syndrome". Kidney Int Suppl. 27: S195–200. PMID 2636656.