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Nephrotic Syndrome

Nephrotic Syndrome
Author: Eric P Cohen, MD; Chief Editor: Vecihi Batuman, MD, FACP , FASN more...
Updated: Dec 9, 2014

Background
Nephrotic syndrome is kidney disease with proteinuria, hypoalbuminemia, and edema. Nephrotic-range proteinuria
is 3 grams per day or more. On a single spot urine collection, it is 2 g of protein per gram of urine creatinine.
There are many specific causes of nephrotic syndrome . These include kidney diseases such as minimal-change
nephropathy, focal glomerulosclerosis, and membranous nephropathy. Nephrotic syndrome can also result from
systemic diseases that affect other organs in addition to the kidneys, such as diabetes, amyloidosis, and lupus
erythematosus.
Nephrotic syndrome may affect adults and children, of both sexes and of any race. It may occur in typical form, or in
association with nephritic syndrome. The latter connotes glomerular inflammation, with hematuria and impaired
kidney function.

Classification
Nephrotic syndrome can be primary, being a disease specific to the kidneys, or it can be secondary, being a renal
manifestation of a systemic general illness. In all cases, injury to glomeruli is an essential feature.
Primary causes of nephrotic syndrome include the following, in approximate order of frequency:
Minimal-change nephropathy
Focal glomerulosclerosis
Membranous nephropathy
Hereditary nephropathies
Secondary causes include the following, again in order of approximate frequency:
Diabetes mellitus
Lupus erythematosus
Amyloidosis and paraproteinemias
Viral infections (eg, hepatitis B, hepatitis C, human immunodeficiency virus [HIV] )
Preeclampsia
Nephrotic-range proteinuria may occur in other kidney diseases, such as IgA nephropathy. In that common
glomerular disease , one third of patients may have nephrotic-range proteinuria . [1]
Nephrotic syndrome may occur in persons with sickle cell disease and evolve to renal failure. Membranous
nephropathy may complicate bone marrow transplantation, in association with graft versus host disease.
Kidney diseases that affect tubules and interstitium, such as interstitial nephritis, will not cause nephrotic syndrome.
The above causes of nephrotic syndrome are largely those for adults, and this article will concentrate primarily on
adult nephrotic syndrome. However, nephrotic syndrome in infancy and childhood is an important entity. For
discussion of this topic, see the Medscape Reference article Pediatric Nephrotic Syndrome.
From a therapeutic perspective, nephrotic syndrome may be classified as steroid sensitive, steroid resistant, steroid
dependent, or frequently relapsing.
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. (See Treatment and Medication.)

Contributor Information and Disclosures


Author
Eric P Cohen, MD Professor, Department of Medicine, Division of Nephrology, Medical College of Wisconsin;
Nephrology Section Chief, Zablocki Veterans Affairs Hospital
Eric P Cohen, MD is a member of the following medical societies: American Society of Nephrology, Central
Society for Clinical Research, International Society of Nephrology, and Radiation Research Society
Disclosure: Nothing to disclose.
Coauthor(s)
Ramapriya Sinnakirouchenan, MD Fellow, Division of Nephrology, Medical College of Wisconsin
Ramapriya Sinnakirouchenan, MD is a member of the following medical societies: American Society of
Nephrology and Indian Medical Association
Disclosure: Nothing to disclose.
Specialty Editor Board
Laura Lyngby Mulloy, DO, FACP Professor of Medicine, Chief, Section of Nephrology, Hypertension, and
Transplantation Medicine, Glover/Mealing Eminent Scholar Chair in Immunology, Medical College of Georgia
Disclosure: Nothing to disclose.
Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center
College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Medscape Salary Employment
Eleanor Lederer, MD Professor of Medicine, Chief, Nephrology Division, Director, Nephrology Training
Program, Director, Metabolic Stone Clinic, Kidney Disease Program, University of Louisville School of Medicine;
Consulting Staff, Louisville Veterans Affairs Hospital
Eleanor Lederer, MD is a member of the following medical societies: American Association for the Advancement
of Science, American Federation for Medical Research, American Society for Biochemistry and Molecular
Biology, American Society for Bone and Mineral Research, American Society of Nephrology, American Society
of Transplantation, International Society of Nephrology, Kentucky Medical Association, National Kidney
Foundation, and Phi Beta Kappa
Disclosure: Dept of Veterans Affairs Grant/research funds Research; American Society of Nephrology Salary

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Nephrotic Syndrome

ASN Council Position; University of Louisville Salary Employment


Chief Editor
Vecihi Batuman, MD, FACP, FASN Huberwald Professor of Medicine, Section of Nephrology-Hypertension,
Tulane University School of Medicine; Chief, Renal Section, Southeast Louisiana Veterans Health Care System
Vecihi Batuman, MD, FACP, FASN, is a member of the following medical societies: American College of
Physicians, American Society of Hypertension, American Society of Nephrology, and International Society of
Nephrology
Disclosure: Nothing to disclose.

References
1. Neelakantappa K, Gallo GR, Baldwin DS. Proteinuria in IgA nephropathy. Kidney Int. Mar 1988;33(3):71621. [Medline].
2. Haraldsson B, Nystrm J, Deen WM. Properties of the glomerular barrier and mechanisms of proteinuria.
Physiol Rev. Apr 2008;88(2):451-87. [Medline].
3. 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].
4. 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].
5. 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].
6. Rostoker G, Behar A, Lagrue G. Vascular hyperpermeability in nephrotic edema. Nephron. Jul
2000;85(3):194-200. [Medline].
7. 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].
8. 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].
9. 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].
10. 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].
11. 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].
12. 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].
13. 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].
14. 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].
15. 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].
16. 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].
17. 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].
18. Ozkaya N, Cakar N, Ekim M, Kara N, Akkk N, Yalinkaya F. Primary nephrotic syndrome during childhood
in Turkey. Pediatr Int. Aug 2004;46(4):436-8. [Medline].
19. Kazi JI, Mubarak M. Pattern of glomerulonephritides in adult nephrotic patients--report from SIUT. J Pak
Med Assoc. Nov 2007;57(11):574. [Medline].
20. Barsoum R. The changing face of schistosomal glomerulopathy. Kidney Int. 2004;66:2472-2484.
21. 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.
22. 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].
23. 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].
24. Kopp JB, Winkler C. HIV-associated nephropathy in African Americans. Kidney Int Suppl. Feb 2003;S43-9.
[Medline].
25. 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].
26. Arneil GC, Lam CN. Long-term assessment of steroid therapy in childhood nephrosis. Lancet. Oct 15
1966;2(7468):819-21. [Medline].
27. 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].
28. 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].
29. 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].
30. Cohen EP, Lemann J. The role of the laboratory in evaluation of kidney function. Clin Chem. 1991;37:785796.

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Nephrotic Syndrome
31. 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].
32. Beck LH Jr, Bonegio RG, Lambeau G, et al. M-type phospholipase A2 receptor as target antigen in
idiopathic membranous nephropathy. N Engl J Med. Jul 2 2009;361(1):11-21. [Medline]. [Full Text].
33. Hofstra JM, Beck LH Jr, Beck DM, Wetzels JF, Salant DJ. Anti-phospholipase A2 receptor antibodies
correlate with clinical status in idiopathic membranous nephropathy. Clin J Am Soc Nephrol. Jun
2011;6(6):1286-91. [Medline]. [Full Text].
34. 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].
35. 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].
36. 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].
37. Hibino S, Uemura O, Nagai T, Yamakawa S, Iwata N, Ito H, et al. Three year outcome of childhood
idiopathic nephrotic syndrome under a unified immunosuppressive protocol. Pediatr Int. Sep 15 2014;
[Medline].
38. 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].
39. Chen Y, Schieppati A, Chen X, Cai G, Zamora J, Giuliano GA, et al. Immunosuppressive treatment for
idiopathic membranous nephropathy in adults with nephrotic syndrome. Cochrane Database Syst Rev. Oct
16 2014;10:CD004293. [Medline].
40. 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].
41. Bomback AS, Tumlin JA, Baranski J, et al. Treatment of nephrotic syndrome with adrenocorticotropic
hormone (ACTH) gel. Drug Des Devel Ther. Mar 14 2011;5:147-53. [Medline]. [Full Text].
42. Bomback AS, Canetta PA, Beck LH Jr, Ayalon R, Radhakrishnan J, Appel GB. Treatment of resistant
glomerular diseases with adrenocorticotropic hormone gel: a prospective trial. Am J Nephrol.
2012;36(1):58-67. [Medline].
43. 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].
44. Roberti I, Vyas S. Long-term outcome of children with steroid-resistant nephrotic syndrome treated with
tacrolimus. Pediatr Nephrol. Mar 9 2010;[Medline].

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