eMedicine Specialties > Nephrology > Glomerular Diseases

Proteinuria: Differential Diagnoses & Workup

Author: Edgar V Lerma, MD, Clinical Associate Professor of Medicine, Section of Nephrology, Department of Medicine, University of Illinois at Chicago College of Medicine; Consulting Staff, Associates in Nephrology, SC
Coauthor(s): Kevin McLaughlin, MB, ChB, MSc, PhD, Associate Professor, Department of Medicine, University of Calgary Faculty of Medicine, Calgary Health Region
Contributor Information and Disclosures

Updated: Aug 19, 2009

Differential Diagnoses

Other Problems to Be Considered

Nonglomerular proteinuria (ie, nonalbumin proteinuria)

Tubular proteinuria: This is associated with the presence of proteins with a low molecular weight, such as b2-microglobulin, immunoglobulin light chains, amino acids, and retinol-binding protein. These normally are filtered by the glomerulus and almost completely reabsorbed in the proximal tubule. Diseases that interfere with proximal tubular function, such as tubulointerstitial nephritis, reduce reabsorption of these proteins and lead to tubular proteinuria.

Overflow proteinuria: This occurs when proteins of low molecular weight are filtered normally by the glomerulus and reabsorbed at the proximal tubule but are produced in an amount greater than the reabsorptive capacity of the proximal tubule. Overflow proteinuria almost always is caused by excess production of immunoglobulin light chains such as is associated with multiple myeloma or monoclonal gammopathy of uncertain significance (MGUS).

If urine dipsticks are specific for albumin, this screening test cannot be used to detect tubular and overflow proteinuria.

Workup

Laboratory Studies

  • To determine whether patients have transient proteinuria, perform the following:
    • Urinalysis and microscopic examination on at least 3 separate occasions
    • Albumin-to-creatinine or protein-to-creatinine ratio in random urine sample
    • Urinalysis on early morning sample, before patients are involved in physical activity
  • To determine whether patients have orthostatic proteinuria, perform the following:
    • Urine microscopy
    • Split urine collection, daytime (7 am to 11 pm) and overnight (11 pm to 7 am)
  • To determine whether proteinuria may be glomerular in origin, perform the following:
    • Urine microscopy
    • Urine collection (24 h) for quantification of albumin (or protein) excretion and creatinine clearance
    • Serum creatinine, albumin, cholesterol, and blood glucose determinations
    • If indicated, autoantibodies determinations, including antinuclear (ANA), anti-DNA, complement levels, and cryoglobulins
    • If indicated, hepatitis B, hepatitis C, and HIV serologies
    • If indicated, urine and plasma protein electrophoresis

Imaging Studies

  • Renal ultrasound scan, if glomerular disease is being considered
  • Chest x-ray, if indicated

Other Tests

  • Renal biopsy should be considered in adult patients with persistent proteinuria because the diagnostic and prognostic information yielded is likely to guide the choice of specific therapy (see Medical Care).
    • In children, most cases of nephrotic syndrome are due to steroid-sensitive minimal-change disease. In such cases, this is a reasonable assumption, and a trial of therapy should be given, reserving biopsy for unresponsive cases.
    • In adult patients who have isolated proteinuria of less than 1 g/d with no other indicators of renal disease, the renal prognosis is good and the need for specific treatment is unlikely. Most nephrologists would treat these patients with the nonspecific measures detailed in Medical Care and only proceed to biopsy if the degree of proteinuria increased or if the patient developed progressive renal decline.

More on Proteinuria

Overview: Proteinuria
Differential Diagnoses & Workup: Proteinuria
Treatment & Medication: Proteinuria
Follow-up: Proteinuria
References
Further Reading
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References

  1. Wu Y, Chen Y, Chen D, et al. Presence of foam cells in kidney interstitium is associated with progression of renal injury in patients with glomerular diseases. Nephron Clin Pract. Aug 12 2009;113(3):c155-c161. [Medline].

  2. Jackson CE, Solomon SD, Gerstein HC, et al. Albuminuria in chronic heart failure: prevalence and prognostic importance. Lancet. Aug 15 2009;374(9689):543-50. [Medline].

  3. Hladunewich MA, Troyanov S, Calafati J, et al. The natural history of the non-nephrotic membranous nephropathy patient. Clin J Am Soc Nephrol. Aug 6 2009;[Medline].

  4. Hebert LA, Birmingham DJ, Shidham G, et al. Random spot urine protein/creatinine ratio is unreliable for estimating 24-Hour proteinuria in individual systemic lupus erythematosus nephritis patients. Nephron Clin Pract. Aug 12 2009;113(3):c177-c182. [Medline].

  5. Nakamura T, Sato E, Fujiwara N, et al. Co-administration of ezetimibe enhances proteinuria-lowering effects of pitavastatin in chronic kidney disease patients partly via a cholesterol-independent manner. Pharmacol Res. Aug 7 2009;[Medline].

  6. Burton C, Harris KP. The role of proteinuria in the progression of chronic renal failure. Am J Kidney Dis. Jun 1996;27(6):765-75. [Medline].

  7. Giatras I, Lau J, Levey AS. Effect of angiotensin-converting enzyme inhibitors on the progression of nondiabetic renal disease: a meta-analysis of randomized trials. Angiotensin-Converting-Enzyme Inhibition and Progressive Renal Disease Study Group. ALYSIS. Sep 1 1997;127(5):337-45. [Medline].

  8. Klahr S, Levey AS, Beck GJ. The effects of dietary protein restriction and blood-pressure control on the progression of chronic renal disease. Modification of Diet in Renal Disease Study Group. N Engl J Med. Mar 31 1994;330(13):877-84. [Medline].

  9. Lewis EJ, Hunsicker LG, Bain RP. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group [published erratum appears in N Engl J Med 1993 Jan 13;330(2):152]. N Engl J Med. Nov 11 1993;329(20):1456-62. [Medline].

  10. Robinson RR. Isolated proteinuria in asymptomatic patients. Kidney Int. Sep 1980;18(3):395-406. [Medline].

  11. Ruggenenti P, Perna A, Mosconi L. Proteinuria predicts end-stage renal failure in non-diabetic chronic nephropathies. The "Gruppo Italiano di Studi Epidemiologici in Nefrologia" (GISEN). Kidney Int Suppl. Dec 1997;63:S54-7. [Medline].

  12. Springberg PD, Garrett LE Jr, Thompson AL Jr. Fixed and reproducible orthostatic proteinuria: results of a 20-year follow-up study. Ann Intern Med. Oct 1982;97(4):516-9. [Medline].

  13. Waugh NR, Robertson AM. Protein restriction in diabetic renal disease. In: The Cochrane Database of Systematic Reviews [serial CD-ROM]. Issue 4. 1999.

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Keywords

proteinuria, microalbuminuria, microalbumin, albuminuria, glomerulonephritis, nephrotic syndrome, diabetic nephropathy, albumin creatinine ratio, glomerulosclerosis, membranous glomerulonephritis, minimal-change disease, focal segmental glomerulosclerosis, glomerular proteinuria

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Contributor Information and Disclosures

Author

Edgar V Lerma, MD, Clinical Associate Professor of Medicine, Section of Nephrology, Department of Medicine, University of Illinois at Chicago College of Medicine; Consulting Staff, Associates in Nephrology, SC
Edgar V Lerma, MD is a member of the following medical societies: American Heart Association, American Medical Association, American Society of Hypertension, American Society of Nephrology, Chicago Medical Society, Illinois State Medical Society, National Kidney Foundation, and Society of General Internal Medicine
Disclosure: Nothing to disclose.

Coauthor(s)

Kevin McLaughlin, MB, ChB, MSc, PhD, Associate Professor, Department of Medicine, University of Calgary Faculty of Medicine, Calgary Health Region
Kevin McLaughlin, MB, ChB, MSc, PhD is a member of the following medical societies: American Society of Nephrology, American Society of Transplantation, and College of Physicians and Surgeons of Alberta
Disclosure: Nothing to disclose.

Medical Editor

Frank C Brosius III, MD, Nephrology Program Director, Professor of Internal Medicine and Physiology, Department of Internal Medicine, Division of Nephrology, University of Michigan School of Medicine
Frank C Brosius III, MD is a member of the following medical societies: Alpha Omega Alpha, American Diabetes Association, American Society of Nephrology, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

George R Aronoff, MD, Director, Professor, Departments of Internal Medicine and Pharmacology, Section of Nephrology, Kidney Disease Program, University of Louisville School of Medicine
George R Aronoff, MD is a member of the following medical societies: American Federation for Medical Research, American Society of Nephrology, Kentucky Medical Association, and National Kidney Foundation
Disclosure: Nothing to disclose.

CME Editor

Rebecca J Schmidt, DO, FACP, FASN, Professor of Medicine, Section Chief, Department of Medicine, Section of Nephrology, West Virginia University School of Medicine
Rebecca J Schmidt, DO, FACP, FASN is a member of the following medical societies: American College of Osteopathic Internists, American College of Physicians, American Medical Association, American Society of Nephrology, International Society of Nephrology, National Kidney Foundation, Renal Physicians Association, and West Virginia State Medical Association
Disclosure: Abbott Grant/research funds Speaking and teaching; Genzyme Honoraria Consulting; Amgen Honoraria Speaking and teaching; Ortho Biotech Honoraria Speaking and teaching

Chief Editor

Vecihi Batuman, MD, FACP, FASN, Professor of Medicine, Section of Nephrology-Hypertension, Tulane University School of Medicine; Chief, Medicine Service, 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.

 
 
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