Nephrotic Syndrome Differential Diagnoses

Sections

DDx

Diagnostic Considerations

Heart failure may cause a presentation similar to that of nephrotic syndrome. In typical cases of heart failure, however, the patient will have a history of heart disease and/or features of poor heart function on exam, such as a third heart sound and even low blood pressure. In heart failure without kidney disease, the patient will have little or no proteinuria.

Nephrotic syndrome with renal impairment, such as may occur in IgA nephropathy, may cause secondary reduction in heart function, with cardiomegaly on exam. Such patients would typically be hypertensive and have substantial proteinuria on urinalysis.

Patients with cirrhosis may have substantial fluid retention, both as ascites and as peripheral edema. However, patients with cirrhosis will have little or no proteinuria unless they have associated kidney disease.

Differential Diagnoses

Workup

Tapia C, Bashir K. Nephrotic Syndrome. 2019 Jan. [Medline]. [Full Text].
Wu MY, Chen CS, Yiang GT, Cheng PW, Chen YL, Chiu HC, et al. The Emerging Role of Pathogenesis of IgA Nephropathy. J Clin Med. 2018 Aug 20. 7 (8):716-21. [Medline]. [Full Text].
Haraldsson B, Nyström J, Deen WM. Properties of the glomerular barrier and mechanisms of proteinuria. Physiol Rev. 2008 Apr. 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. 2002 May. 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. 2001 Nov. 60(5):1885-92. [Medline].
Hamm LL, Batuman V. Edema in the nephrotic syndrome: new aspect of an old enigma. J Am Soc Nephrol. 2003 Dec. 14(12):3288-9. [Medline].
Rostoker G, Behar A, Lagrue G. Vascular hyperpermeability in nephrotic edema. Nephron. 2000 Jul. 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. 1985 Jun 13. 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. 1977 Aug. 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. 1999 May. 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. 2003 Jun. 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. 2004 Aug 26. 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. 2008 Jan 15. 117(2):224-30. [Medline].
Rood IM, Deegens JKJ, Lugtenberg D, Bongers EMHF, Wetzels JFM. Nephrotic Syndrome With Mutations in NPHS2: The Role of R229Q and Implications for Genetic Counseling. Am J Kidney Dis. 2018 Sep 18. [Medline].
Glassock RJ. Antiphospholipase A2 receptor autoantibody guided diagnosis and treatment of membranous nephropathy: a new personalized medical approach. Clin J Amer Soc Nephrol. 2014. 9:1341-3. [Medline].
Hunley TE, Corzo D, Dudek M, Kishnani P, Amalfitano A, Chen YT, et al. Nephrotic syndrome complicating alpha-glucosidase replacement therapy for Pompe disease. Pediatrics. 2004. 114:e532-5. [Medline].
Lathara Z, Ambruzs JM, Cohen EP. Alloimmune Membranous Nephropathy in Fabry Disease. J Am Soc Nephrol Abstract Supplement. 2015. SA-PO004. [Full Text].
George BA, Zhou XJ, Toto R. Nephrotic syndrome after bevacizumab: case report and literature review. Am J Kidney Dis. 2007 Feb. 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. 2006 Oct. 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. 2007 May. 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. 2003 Jul. 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. 2004 Aug. 46(4):436-8. [Medline].
Kazi JI, Mubarak M. Pattern of glomerulonephritides in adult nephrotic patients--report from SIUT. J Pak Med Assoc. 2007 Nov. 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. 2006 Mar 9. 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. 2009 Jan. 24(1):117-22. [Medline].
Fine DM, Wasser WG, Estrella MM, Atta MG, Kuperman M, Shemer R, et al. APOL1 risk variants predict histopathology and progression to ESRD in HIV-related kidney disease. J Am Soc Nephrol. 2012. 23:343-50. [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. 1999 May. 55(5):1885-90. [Medline].
Arneil GC, Lam CN. Long-term assessment of steroid therapy in childhood nephrosis. Lancet. 1966 Oct 15. 2(7468):819-21. [Medline].
Gipson DS, Troost JP, Lafayette RA, et al. Complete Remission in the Nephrotic Syndrome Study Network. Clin J Am Soc Nephrol. 2016. 11:81-9. [Medline].
Beins NT, Dell KM. Long-Term Outcomes in Children with Steroid-Resistant Nephrotic Syndrome Treated with Calcineurin Inhibitors. Front Pediatr. 2015. 3:104. [Medline].
Harrison P. MENTOR: Rituximab Is a Winner in Membranous Nephropathy. Medscape Medical News. Available at https://www.medscape.com/viewarticle/915207. July 3, 2019; Accessed: July 9, 2019.
Donadio JV Jr, Torres VE, Velosa JA, Wagoner RD, Holley KE, Okamura M. Idiopathic membranous nephropathy: the natural history of untreated patients. Kidney Int. 1988 Mar. 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. 2008 May. 23(5):1595-9. [Medline].
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. 2009 Jul 2. 361(1):11-21. [Medline]. [Full Text].
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. 2011 Jun. 6(6):1286-91. [Medline]. [Full Text].
[Guideline] Kidney Disease Improving Global Outcomes. KDIGO Clinical Practice Guideline for Glomerulonephritis. Kidney International. Available at http://www.kdigo.org/clinical_practice_guidelines/pdf/KDIGO-GN-Guideline.pdf. June 2012; Accessed: December 14, 2018.
Palmer SC, Nand K, Strippoli GF. Interventions for minimal change disease in adults with nephrotic syndrome. Cochrane Database Syst Rev. 2008 Jan 23. CD001537. [Medline].
Vaziri ND. Disorders of lipid metabolism in nephrotic syndrome: mechanisms and consequences. Kidney Int. 2016 Jul. 90 (1):41-52. [Medline].
Agrawal S, Zaritsky JJ, Fornoni A, Smoyer WE. Dyslipidaemia in nephrotic syndrome: mechanisms and treatment. Nat Rev Nephrol. 2018 Jan. 14 (1):57-70. [Medline].
Kallash M, Smoyer WE, Mahan JD. Rituximab Use in the Management of Childhood Nephrotic Syndrome. Front Pediatr. 2019. 7:178. [Medline]. [Full Text].
Mühlig AK, Lee JY, Kemper MJ, Kronbichler A, Yang JW, Lee JM, et al. Levamisole in Children with Idiopathic Nephrotic Syndrome: Clinical Efficacy and Pathophysiological Aspects. J Clin Med. 2019 Jun 16. 8 (6):[Medline]. [Full Text].
Sinha A, Puraswani M, Kalaivani M, Goyal P, Hari P, Bagga A. Efficacy and safety of mycophenolate mofetil versus levamisole in frequently relapsing nephrotic syndrome: an open-label randomized controlled trial. Kidney Int. 2019 Jan. 95 (1):210-218. [Medline].
Ravani P, Bonanni A, Rossi R, Caridi G, Ghiggeri GM. Anti-CD20 Antibodies for Idiopathic Nephrotic Syndrome in Children. Clin J Am Soc Nephrol. 2015 Nov 19. 160 (5 Pt 1):1062-7. [Medline].
Ruggenenti P, et al; Rituximab in Nephrotic Syndrome of Steroid-Dependent or Frequently Relapsing Minimal Change Disease Or Focal Segmental Glomerulosclerosis (NEMO) Study Group. Rituximab in steroid-dependent or frequently relapsing idiopathic nephrotic syndrome. J Am Soc Nephrol. 2014 Apr. 25 (4):850-63. [Medline].
Maxted AP, Dalrymple RA, Chisholm D, McColl J, Tse Y, Christian MT, et al. Low-dose rituximab is no less effective for nephrotic syndrome measured by 12-month outcome. Pediatr Nephrol. 2019 May. 34 (5):855-863. [Medline]. [Full Text].
Bonanni A, Rossi R, Murtas C, Ghiggeri GM. Low-dose ofatumumab for rituximab-resistant nephrotic syndrome. BMJ Case Rep. 2015 Sep 16. 2015:[Medline].
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. 2014 Sep 15. [Medline].
Hahn D, Hodson EM, Willis NS, Craig JC. Corticosteroid therapy for nephrotic syndrome in children. Cochrane Database Syst Rev. 2015 Mar 18. CD001533. [Medline].
Yadav M, Sinha A, Khandelwal P, Hari P, Bagga A. Efficacy of low-dose daily versus alternate-day prednisolone in frequently relapsing nephrotic syndrome: an open-label randomized controlled trial. Pediatr Nephrol. 2018 Sep 7. 6 (1):63-9. [Medline].
Dufek S, Holtta T, Trautmann A, et al. Management of children with congenital nephrotic syndrome: challenging treatment paradigms. Nephrol Dial Transplant. 2018 Jun 21. [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. 2007 May. 2(3):445-53. [Medline].
du Buf-Vereijken PW, Branten AJ, Wetzels JF. Idiopathic membranous nephropathy: outline and rationale of a treatment strategy. Am J Kidney Dis. 2005 Dec. 46(6):1012-29. [Medline].
Fervenza FC, et al; MENTOR Investigators. Rituximab or Cyclosporine in the Treatment of Membranous Nephropathy. N Engl J Med. 2019 Jul 4. 381 (1):36-46. [Medline].
National Center for Immunization and Respiratory Diseases. General recommendations on immunization --- recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2011 Jan 28. 60 (2):1-64. [Medline]. [Full Text].
Centers for Disease Control and Prevention (CDC). Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine for adults with immunocompromising conditions: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 2012 Oct 12. 61 (40):816-9. [Medline]. [Full Text].
Grohskopf LA, Sokolow LZ, Broder KR, Olsen SJ, Karron RA, Jernigan DB, et al. Prevention and Control of Seasonal Influenza with Vaccines. MMWR Recomm Rep. 2016 Aug 26. 65 (5):1-54. [Medline].
Cohen JI. Strategies for herpes zoster vaccination of immunocompromised patients. J Infect Dis. 2008 Mar 1. 197 Suppl 2:S237-41. [Medline].
Liu D, Ahmet A, Ward L, Krishnamoorthy P, Mandelcorn ED, Leigh R, et al. A practical guide to the monitoring and management of the complications of systemic corticosteroid therapy. Allergy Asthma Clin Immunol. 2013 Aug 15. 9 (1):30. [Medline]. [Full Text].
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. 2014 Oct 16. 10:CD004293. [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. 2010 Dec. 5(12):2207-12. [Medline]. [Full Text].
Bomback AS, Tumlin JA, Baranski J, et al. Treatment of nephrotic syndrome with adrenocorticotropic hormone (ACTH) gel. Drug Des Devel Ther. 2011 Mar 14. 5:147-53. [Medline]. [Full Text].
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].
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. 2010 Mar. 339(3):233-8. [Medline].
Roberti I, Vyas S. Long-term outcome of children with steroid-resistant nephrotic syndrome treated with tacrolimus. Pediatr Nephrol. 2010 Mar 9. [Medline].
Rood IM, Deegens JKJ, Lugtenberg D, Bongers EMHF, Wetzels JFM. Nephrotic Syndrome With Mutations in NPHS2: The Role of R229Q and Implications for Genetic Counseling. Am J Kidney Dis. 2018 Sep 18. [Medline].

Media Gallery

Schematic drawing of the glomerular barrier. Podo = podocytes; GBM = glomerular basement membrane; Endo = fenestrated endothelial cells; ESL = endothelial cell surface layer (often referred to as the glycocalyx). Primary urine is formed through the filtration of plasma fluid across the glomerular barrier (arrows); in humans, the glomerular filtration rate (GFR) is 125 mL/min. The plasma flow rate (Qp) is close to 700 mL/min, with the filtration fraction being 20%. The concentration of albumin in serum is 40 g/L, while the estimated concentration of albumin in primary urine is 4 mg/L, or 0.1% of its concentration in plasma. Courtesy of the American Physiological Society (www.the-aps.org) and reproduced from Haraldsson B, Nystrom J, Deen WM. Properties of the glomerular barrier and mechanisms of proteinuria. Physiol Rev. 2008 Apr;88(2):451-87.
Incidence of important causes of nephrotic syndrome, in number per million population. The left panel shows systemic causes, and the right panel lists primary renal diseases that can cause nephrotic syndrome. fgs = focal glomerulosclerosis, MN = membranous nephropathy, min change = minimal-change nephropathy. Data are in part from Swaminathan et al and Bergesio et al.
A schema of the average patient age at presentation in various common forms of nephrotic syndrome. (Timeline not to scale.)
Forces determining capillary filtration

of 4

Author

Eric P Cohen, MD Professor, Department of Medicine, Division of Nephrology, University of Maryland School of Medicine; Nephrology Section Chief, Baltimore Veterans Affairs Hospital

Eric P Cohen, MD is a member of the following medical societies: American Society of Nephrology, International Society of Nephrology, Radiation Research Society, Société Francophone de Dialyse

Disclosure: Nothing to disclose.

Coauthor(s)

Cassiopia Lippold, MD Resident Physician, Department of Internal Medicine, Pinnacle Health Hospitals

Cassiopia Lippold, MD is a member of the following medical societies: American College of Physicians, American Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Eleanor Lederer, MD, FASN 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, FASN 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, Phi Beta Kappa

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: American Society of Nephrology<br/>Received income in an amount equal to or greater than $250 from: Healthcare Quality Strategies, Inc<br/>Received grant/research funds from Dept of Veterans Affairs for research; Received salary from American Society of Nephrology for asn council position; Received salary from University of Louisville for employment; Received salary from University of Louisville Physicians for employment; Received contract payment from American Physician Institute for Advanced Professional Studies, LLC for independent contractor; Received contract payment from Healthcare Quality Strategies, Inc for independent cont.

Chief Editor

Vecihi Batuman, MD, 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, FASN is a member of the following medical societies: American College of Physicians, American Society of Hypertension, American Society of Nephrology, International Society of Nephrology, Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

Additional Contributors

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, Georgia Regents University

Disclosure: Nothing to disclose.

Ramapriya Sinnakirouchenan, MD, MBBS Assistant Professor, Department of Medicine, Division of Nephrology, Medical College of Wisconsin; Medical Director of Dialysis Unit, Fresenius Kidney Care

Ramapriya Sinnakirouchenan, MD, MBBS is a member of the following medical societies: American Society of Nephrology

Disclosure: Nothing to disclose.

Nephrotic Syndrome Differential Diagnoses

Diagnostic Considerations

Differential Diagnoses

About

Membership

Apps

WebMD Network

Editions

What to Read Next on Medscape

Nephrotic Syndrome Differential Diagnoses

Diagnostic Considerations

Differential Diagnoses

References

Tables

Contributor Information and Disclosures

What would you like to print?

Find Us On

About

Membership

Apps

WebMD Network

Editions

What to Read Next on Medscape

Related Conditions and Diseases

Medscape Consult

News & Perspective

Tools

Slideshow

Most Popular Articles

Recommended