Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate®

Differential diagnosis and evaluation of glomerular disease

Lee A Hebert, MD
Samir V Parikh, MD
Section Editor
Richard J Glassock, MD, MACP
Deputy Editor
Albert Q Lam, MD


The presence of some form of glomerular disease, as opposed to primary tubulointerstitial or vascular disease, is usually suspected from the history (including a family history of glomerular disease), physical examination (eg, edema), and from one or more of the following urinary findings: hematuria (particularly if the red cells have a dysmorphic appearance), red cell casts, lipiduria (since glomerular permeability must be increased to allow the filtration of large lipoproteins), and proteinuria, which may be in the nephrotic range (greater than 3.5 g/day). (See "Etiology and evaluation of hematuria in adults", section on 'Glomerular versus nonglomerular bleeding' and "Urinalysis in the diagnosis of kidney disease", section on 'The assessment of lipiduria' and "Assessment of urinary protein excretion and evaluation of isolated non-nephrotic proteinuria in adults" and "Evaluation of proteinuria in children".)

Despite these clues, the ability to distinguish glomerular disease from chronic tubulointerstitial disease may be difficult. Although tubulointerstitial disease does not directly increase protein excretion, nephron loss can induce secondary glomerulosclerosis leading to proteinuria that may reach the nephrotic range. Such patients may be erroneously considered to have a primary glomerular disease (see "Epidemiology, classification, and pathogenesis of focal segmental glomerulosclerosis", section on 'Pathogenesis of secondary FSGS'). Severe vascular diseases, such as malignant hypertension or a thrombotic microangiopathy, are other disorders that can be associated with hematuria and proteinuria and thus resemble primary glomerular disease.

Establishing the correct diagnosis usually requires renal biopsy. This topic will review how the clinical features at presentation can allow the clinician to narrow the differential diagnosis prior to biopsy. The mechanisms of glomerular injury are discussed separately. (See "Mechanisms of immune injury of the glomerulus" and "Mechanisms of glomerular crescent formation".)


Although there are many causes of glomerular disease, most patients present with one of two patterns, nephrotic or nephritic, that are based upon the urine sediment and the degree of proteinuria (table 1).

Nephrotic pattern — The nephrotic pattern is characterized by proteinuria that is usually above 3.5 g/day and lipiduria, but few cells or casts other than fatty casts (picture 1A-B). Patients who also have edema and hyperlipidemia (the full-blown nephrotic syndrome) tend to have a more marked glomerular leak than those with proteinuria alone. Some patients also have microscopic hematuria. Red cell casts are usually not seen and, when present, may result from a concurrent glomerulonephritis as has been described in diabetic nephropathy. (See 'Limitations of this classification' below and "Overview of diabetic nephropathy", section on 'Hematuria'.)


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Jul 2017. | This topic last updated: Jun 18, 2014.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Praga M, Borstein B, Andres A, et al. Nephrotic proteinuria without hypoalbuminemia: clinical characteristics and response to angiotensin-converting enzyme inhibition. Am J Kidney Dis 1991; 17:330.
  2. Fries JW, Mendrick DL, Rennke HG. Determinants of immune complex-mediated glomerulonephritis. Kidney Int 1988; 34:333.
  3. O'Neill WM Jr, Wallin JD, Walker PD. Hematuria and red cell casts in typical diabetic nephropathy. Am J Med 1983; 74:389.
  4. Goorno W, Ashworth CT, Carter NW. Acute glomerulonephritis with absence of abnormal urinary findings. Diagnosis by light and electron microscopy. Ann Intern Med 1967; 66:345.
  5. Yata N, Ikeda M, Ishikura K, et al. Typical MPGN with few urinary abnormalities. Am J Kidney Dis 2004; 43:918.
  6. Bruns FJ, Adler S, Fraley DS, Segel DP. Long-term follow-up of aggressively treated idiopathic rapidly progressive glomerulonephritis. Am J Med 1989; 86:400.
  7. Nasr SH, Said SM, Valeri AM, et al. Membranous glomerulonephritis with ANCA-associated necrotizing and crescentic glomerulonephritis. Clin J Am Soc Nephrol 2009; 4:299.
  8. Marshall S, Dressler R, D'Agati V. Membranous lupus nephritis with antineutrophil cytoplasmic antibody-associated segmental necrotizing and crescentic glomerulonephritis. Am J Kidney Dis 1997; 29:119.
  9. Rodriguez, EF, Nasr, SH, Sethi, S, et al. Membranous glomerulonephritis with crescents (abstract). Lab Invest 2011; 91 (suppl 1):350A.
  10. Furuta T, Seino J, Saito T, et al. Insulin deposits in membranous nephropathy associated with diabetes mellitus. Clin Nephrol 1992; 37:65.
  11. Rivera F, López-Gómez JM, Pérez-García R, Spanish Registry of Glomerulonephritis. Clinicopathologic correlations of renal pathology in Spain. Kidney Int 2004; 66:898.
  12. Iseki K, Miyasato F, Uehara H, et al. Outcome study of renal biopsy patients in Okinawa, Japan. Kidney Int 2004; 66:914.
  13. Gesualdo L, Di Palma AM, Morrone LF, et al. The Italian experience of the national registry of renal biopsies. Kidney Int 2004; 66:890.
  14. Heaf J. The Danish Renal Biopsy Register. Kidney Int 2004; 66:895.
  15. Simon P, Ramee MP, Boulahrouz R, et al. Epidemiologic data of primary glomerular diseases in western France. Kidney Int 2004; 66:905.
  16. Nair R, Bell JM, Walker PD. Renal biopsy in patients aged 80 years and older. Am J Kidney Dis 2004; 44:618.
  17. Bahiense-Oliveira M, Saldanha LB, Mota EL, et al. Primary glomerular diseases in Brazil (1979-1999): is the frequency of focal and segmental glomerulosclerosis increasing? Clin Nephrol 2004; 61:90.
  18. Lewis EJ, Carpenter CB, Schur PH. Serum complement component levels in human glomerulonephritis. Ann Intern Med 1971; 75:555.
  19. Rose BD. Pathophysiology of Renal Disease, 2nd ed, McGraw-Hill, New York 1987. p.166.
  20. Korbet SM, Genchi RM, Borok RZ, Schwartz MM. The racial prevalence of glomerular lesions in nephrotic adults. Am J Kidney Dis 1996; 27:647.
  21. Griffin KA, Schwartz MM, Korbet SM. Pulmonary-renal syndrome of bacterial endocarditis mimicking Goodpasture's syndrome. Am J Kidney Dis 1989; 14:329.
  22. Wu HC, Wen YK, Chen ML, Fan CS. Pulmonary-renal syndrome in a patient with bacterial endocarditis. J Formos Med Assoc 2005; 104:588.
  23. Niles JL, Böttinger EP, Saurina GR, et al. The syndrome of lung hemorrhage and nephritis is usually an ANCA-associated condition. Arch Intern Med 1996; 156:440.
  24. Boyce NW, Holdsworth SR. Pulmonary manifestations of the clinical syndrome of acute glomerulonephritis and lung hemorrhage. Am J Kidney Dis 1986; 8:31.
  25. Gallagher H, Kwan JT, Jayne DR. Pulmonary renal syndrome: a 4-year, single-center experience. Am J Kidney Dis 2002; 39:42.
  26. Yoshizawa N, Yamakami K, Fujino M, et al. Nephritis-associated plasmin receptor and acute poststreptococcal glomerulonephritis: characterization of the antigen and associated immune response. J Am Soc Nephrol 2004; 15:1785.
  27. Lewy JE, Salinas-Madrigal L, Herdson PB, et al. Clinico-pathologic correlations in acute poststreptococcal glomerulonephritis. A correlation between renal functions, morphologic damage and clinical course of 46 children with acute poststreptococcal glomerulonephritis. Medicine (Baltimore) 1971; 50:453.
  28. Gubler M, Levy M, Broyer M, et al. Alport's syndrome. A report of 58 cases and a review of the literature. Am J Med 1981; 70:493.
  29. Kashtan CE. Alport syndrome and thin glomerular basement membrane disease. J Am Soc Nephrol 1998; 9:1736.
  30. Aarons I, Smith PS, Davies RA, et al. Thin membrane nephropathy: a clinico-pathological study. Clin Nephrol 1989; 32:151.
  31. Smith MC, Cooke JH, Zimmerman DM, et al. Asymptomatic glomerulonephritis after nonstreptococcal upper respiratory infections. Ann Intern Med 1979; 91:697.
  32. Sagel I, Treser G, Ty A, et al. Occurrence and nature of glomerular lesions after group A streptococci infections in children. Ann Intern Med 1973; 79:492.
  33. Howard AD, Moore J Jr, Gouge SF, et al. Routine serologic tests in the differential diagnosis of the adult nephrotic syndrome. Am J Kidney Dis 1990; 15:24.
  34. Haas M, Meehan SM, Karrison TG, Spargo BH. Changing etiologies of unexplained adult nephrotic syndrome: a comparison of renal biopsy findings from 1976-1979 and 1995-1997. Am J Kidney Dis 1997; 30:621.
  35. Johnson RJ, Couser WG. Hepatitis B infection and renal disease: clinical, immunopathogenetic and therapeutic considerations. Kidney Int 1990; 37:663.
  36. O'Regan S, Fong JS, de Chadarévian JP, et al. Treponemal antigens in congenital and acquired syphilitic nephritis: demonstration by immunofluorescence studies. Ann Intern Med 1976; 85:325.
  37. D'Amico G, Colasanti G, Ferrario F, Sinico RA. Renal involvement in essential mixed cryoglobulinemia. Kidney Int 1989; 35:1004.
  38. Hebert LA, Cosio FG, Neff JC. Diagnostic significance of hypocomplementemia. Kidney Int 1991; 39:811.
  39. Hepburn NJ, Ruseva MM, Harris CL, Morgan BP. Complement, roles in renal disease and modulation for therapy. Clin Nephrol 2008; 70:357.
  40. Quigg RJ. Complement and the kidney. J Immunol 2003; 171:3319.
  41. Yoshikawa N, Ito H, Yamada Y, et al. Membranous glomerulonephritis associated with hepatitis B antigen in children: a comparison with idiopathic membranous glomerulonephritis. Clin Nephrol 1985; 23:28.
  42. Motoyama O, Iitaka K. Henoch-Schonlein purpura with hypocomplementemia in children. Pediatr Int 2005; 47:39.
  43. Kikuchi Y, Yoshizawa N, Oda T, et al. Streptococcal origin of a case of Henoch-Schoenlein purpura nephritis. Clin Nephrol 2006; 65:124.
  44. Soma J, Sato K, Sakuma T, et al. Immunoglobulin gamma3-heavy-chain deposition disease: report of a case and relationship with hypocomplementemia. Am J Kidney Dis 2004; 43:E10.
  45. Kambham N, Markowitz GS, Appel GB, et al. Heavy chain deposition disease: the disease spectrum. Am J Kidney Dis 1999; 33:954.