Internal Medicine · Vol. 4, No. 1 · 2020 · pp. 3–9 · e-ISSN 2572-9233

Proteinuria: A Guide to Diagnosis and Assessment

Sasha-Kay D’Aguilar, Amith Skandhan

DOI: https://doi.org/10.17140/imoj-4-112 · Published 2020-06-26 · Licence: https://creativecommons.org/licenses/by/4.0 · © 2020 The Author(s)

Also available as PDF (figures and tables appear in the PDF).

Abstract

Proteinuria is a common incidental finding that physicians face in the inpatient and outpatient setting. Proteinuria may represent a benign pathology in asymptomatic patients, or it can be a sign of significant renal or systemic disease. The latter is usually associated with persistent proteinuria or other clinical findings such as renal failure. This article will focus on the mechanisms, causes and diagnostic approach of proteinuria. Proteinuria is a common incidental finding that physicians face in the inpatient and outpatient setting. Proteinuria may represent a benign pathology in asymptomatic patients, or it can be a sign of significant renal or systemic disease. The latter is usually associated with persistent proteinuria or other clinical findings such as renal failure This article will focus on the mechanisms, causes and diagnostic approach of proteinuria.

Keywords: Proteinuria; Glomerular; Tubular; Nephritic; Nephrotic

Conclusion

Proteinuria is a common finding that physicians will encounter. Although commonly transient and benign, proteinuria may also indicate significant renal disease, such as a glomerulopathy, tubu lointerstitial nephritis or vasculitis. Glomerular diseases are the 6 Short Communication | Volume 4 | Number 1|

Figure 2. Algorithm for the Approach to Persistent Proteinuria that is not Due to Orthostatic Proteinuria

Figure 3. Algorithm for the Approach to Non-isolated Proteinuria 7Short Communication | Volume 4 | Number 1|

Figure 1. Algorithm for the Approach to Proteinuria

8 Short Communication | Volume 4 | Number 1| third leading cause of end-stage kidney disease (ESKD) in the United States, accounting for approximately 10,000 incident cases of ESKD per year, third to diabetes mellitus and hypertension.39 In addition, albuminuria is frequently used as an index for kidney function to detect early stages of chronic kidney disease (CKD), which can progress to ESKD.3 Unfortunately, proteinuria can be commonly missed. One of the factors that may contribute to late diagnosis is the sensitivity and preferentiality of the urine dipstick test, i.e. it primarily detects albumin at severely increased levels. Consequently, when proteinuria is found incidentally, it should not be ignored but rather, at the very least, causes of false-positive results should be ruled out.2,5 If these causes are absent, then there should be a systematic approach to managing these patients. In order to provide an appropriate assessment of patients with proteinuria, physicians must understand the physiological aspects of protein handling by the kidney and recognize the clinical and lab findings that suggest renal pathology. Proteinuria due to clinically significant renal disease is persistent and should be evaluated further. When proteinuria is due to glomerular/renal disease, early diagnosis is critical to prevent further renal damage.5 CONFLICT OF INTEREST The authors declare that they have no conflicts of interest.

References

  1. MadariagaHMLermaEV. Approach to the Patient with Renal Disease. In: Lerma EV, Rosner MH, Perazella MA, eds. CUR-RENT Diagnosis & Treatment: Nephrology & Hypertension. 2 nd ed. New York, NY: McGraw-Hill; 2019
  2. RovinBH. Assessment of urinary protein excretion and evaluation of isolated non-nephrotic proteinuria in adults. uptodate. com. Web site. https://www.uptodate.com/contents/assessmentof-urinary-protein-excretion-and-evaluation-of-isolated-nonnephrotic-proteinuria-in-adults. Retrieved December 4, 2019.Ac cessed December 11, 2019
  3. VartPGramsME. Measuring and assessing kidney function. Seminars in Nephrology. 2016; 36(4): 262–272. doi: 10.1016/j.sem nephrol.2016.05.00310.1016/j.sem https://doi.org/10.1016/j.sem
  4. LewisJBNeilsonEG. Glomerular Diseases. In: Jameson J, Fauci AS, Kasper DL, Hauser SL, Longo DL, Loscalzo J, eds. Harrison's Principles of Internal Medicine. 2nd ed. New York, NY: McGraw-Hill;. Web site. http://accessmedicine.mhmedical.com.ezproxy.acomedu.org/content.aspx?bookid=2129&sectionid=192281295. Accessed December 4, 2019
  5. KashifWSiddiqiNDincerAPDincerHEHirschS. Proteinuria: how to evaluate an important finding. Cleveland Clinic Journal of Medicine. 2003; 70(6): 535-543. doi: 10.3949/ccjm.70.6.53510.3949/ccjm.70.6.535 https://doi.org/10.3949/ccjm.70.6.535
  6. CarterCEGansevoortRTSchevenLHeerspinkHJLShlipakMGde JongPE. Influence of urine creatinine on the relationship between the albumin-to-creatinine ratio and cardiovascular events. Clin J Am Soc Nephrol. 2012; 7: 595-603. doi: 10.2215/ CJN.09300911
  7. CKD Work Group. Kidney Disease: Improving Global Out comes (KDIGO) KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Inter Suppl. 2013; 3: 1-150
  8. National Kidney Foundation. K/DOQI clinical practice guide lines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis. 2002; 39: S1-S266
  9. D'AmicoGBazziC. Pathophysiology of proteinuria. Kidney International. 2003; 63(3): 809-814. doi: 10.1046/j.1523- 1755.2003.00840.x10.1046/j.1523-1755.2003.00840.x https://doi.org/10.1046/j.1523-1755.2003.00840.x
  10. MountDB. Azotemia and Urinary Abnormalities. In: Jameson J, Fauci AS, Kasper DL, Hauser SL, Longo DL, Loscalzo J. eds. Harrison's Principles of Internal Medicine, 20th ed. New York, NY: McGraw-Hill. http://accessmedicine.mhmedical.com.ezproxy. acomedu.org/content.aspx?bookid=2129&sectionid=192013131. Accessed December 4, 2019
  11. VehaskariVMRapolaJ. Isolated proteinuria: analysis of a school-age population. J Pediatr. 1982; 101: 661-668. doi: 10.1016/ s0022-3476(82)80287-4
  12. TophamPSJethwaAWatkinsMReesYFeehallyJ. The value of urine screening in a young adult population. Fam Pract. 2004; 21: 18(1): 18-21. doi: 10.1093/fampra/cmh10510.1093/fampra/cmh105 https://doi.org/10.1093/fampra/cmh105
  13. RobinsonRR. Isolated proteinuria in asymptomatic patients. Kidney Int. 1980; 18: 395-406
  14. PoortmansJR. Postexercise proteinuria in humans. Facts and mechanisms. JAMA.1985; 253: 236-240
  15. Springberg PD, Garrett LE, Thompson AL, Collins NF, Lor don RE, Robinson RR. Fixed and reproducible orthostatic pro teinuria: results of a 20-year follow-up study. Ann Intern Med. 1982; 97: 516. doi: 10.7326/0003-4819-97-4-516 https://doi.org/10.7326/0003-4819-97-4-516
  16. RytandDASpreiterS. Prognosis in postural (orthostatic) proteinuria: forty to fifty-year follow-up of six patients after diagnosis by Thomas Addis. N Engl J Med. 1981; 305: 618-621. doi: 10.1056/ NEJM198109103051105
  17. SebestyenJFAlonUS. The teenager with asymptomatic pro teinuria: think orthostatic first. Clin Pediatr (Phila). 2011; 50: 179- 182. doi: 10.1177/000992281038090410.1177/0009922810380904 https://doi.org/10.1177/0009922810380904
  18. DylewskiJKooiengaLTeitelbaumI. Nephrotic Syndrome Submit your article to this journal | https://openventio.org/submit-manuscript/ 9Short Communication | Volume 4 | Number 1| versus Nephritic Syndrome. In: Lerma EV, Rosner MH, Perazella MA. eds. Current Diagnosis & Treatment: Nephrology & Hypertension. New York, NY: McGraw-Hill; Web site. http://accessmedicine. mhmedical.com.ezproxy.acomedu.org/content.aspx?bookid=228 7&sectionid=177428454. Accessed December 11, 2019
  19. KelepourisE. Overview of heavy proteinuria and the nephrotic syndrome.Uptodate.com. Web site. https://www.uptodate.com/ contents/overview-of-heavy-proteinuria-and-the-nephrotic-syndrome#!. Retrieved December 4, 2019, Accessed December 11, 2019
  20. PragaMBorsteinBAndresAArenasJOlietAMontoyoC. Nephrotic proteinuria without hypoalbuminemia: clinical char acteristics and response to angiotensin-converting enzyme inhibition. Am J Kidney Dis. 1991; 17: 330-338. doi: 10.1016/s0272- 6386(12)80483-510.1016/s0272-6386(12)80483-5 https://doi.org/10.1016/s0272-6386(12)80483-5
  21. CollierVU. Board Basics: An Enhancement to Mksap 18. Philadelphia, PA, USA: American College of Physicians; 2018
  22. ConstantinerMSehgalARHumbertLConstantinerDArceLSedorJR. A dipstick protein and specific gravity algorithm accurately predicts pathological proteinuria. Am J Kidney Dis. 2005; 45: 833-841. doi: 10.1053/j.ajkd.2005.02.01210.1053/j.ajkd.2005.02.012 https://doi.org/10.1053/j.ajkd.2005.02.012
  23. CarrollMFTemteJL. Proteinuria in adults: A diagnostic approach. Am Fam Physician. 2000; 62: 1333-1340
  24. SimervilleJAMaxtedWCPahiraJJ. Urinalysis: A comprehensive review. Am Fam Physician. 2005; 71: 1153-1162
  25. TappDCCopleyJB. Effect of red blood cell lysis on protein quantitation in hematuric states. Am J Nephrol. 1988; 8: 190-193. doi: 10.1159/00016758110.1159/000167581 https://doi.org/10.1159/000167581
  26. RudenskyB. False-positive test for protein using dipsticks: contamination with chlorhexidine antiseptic. JAMA. 1981; 246: 1089. doi: 10.1001/jama.1981.0332010002501610.1001/jama.1981.03320100025016 https://doi.org/10.1001/jama.1981.03320100025016
  27. RoseBD. Pathophysiology of Renal Disease. 2 nd ed. New York, USA: McGraw-Hill; 1987: 11
  28. MorcosSKel-NahasAMBrownPHaylorJ. Effect of iodinated water soluble contrast media on urinary protein assays. BMJ. 1992; 305: 29. doi: 10.1136/bmj.305.6844.29-a10.1136/bmj.305.6844.29-a https://doi.org/10.1136/bmj.305.6844.29-a
  29. StevensLACoreshJGreeneTLeveyAS. Assessing kidney function--measured and estimated glomerular filtration rate. N Engl J Med. 2006; 354: 2473-2483. doi: 10.1056/NEJMra05441510.1056/nejmra054415 https://doi.org/10.1056/nejmra054415
  30. ShemeshOGolbetzHKrissJPMyersBD. Limitations of creatinine as a filtration marker in glomerulopathic patients. Kidney Int. 1985; 28: 830-838. doi: 10.1038/ki.1985.20510.1038/ki.1985.205 https://doi.org/10.1038/ki.1985.205
  31. GinsbergJMChangBSMatareseRAGarellaS. Use of single voided urine samples to estimate quantitative proteinuria. N Engl J Med. 1983; 309: 1543-1546. doi: 10.1056/NEJM19831222309250310.1056/nejm198312223092503 https://doi.org/10.1056/nejm198312223092503
  32. SchwabSJChristensenRLDoughertyKKlahrS. Quantitation of proteinuria by the use of protein-to-creatinine ratios in single urine samples. Arch Intern Med. 1987; 147: 943-944. doi: 10.1001/archinte.1987.0037005013502210.1001/archinte.1987.00370050135022 https://doi.org/10.1001/archinte.1987.00370050135022
  33. AbitbolCZillerueloGFreundlichMStraussJ. Quantitation of proteinuria with urinary protein/creatinine ratios and random testing with dipsticks in nephrotic children. J Pediatr. 1990; 116: 243-247. doi: 10.1016/s0022-3476(05)82881-110.1016/s0022-3476(05)82881-1 https://doi.org/10.1016/s0022-3476(05)82881-1
  34. ShidhamGHebertLA. Timed urine collections are not needed to measure urine protein excretion in clinical practice. Am J Kidney Dis. 2006; 47: 8-14. doi: 10.1053/j.ajkd.2005.10.01310.1053/j.ajkd.2005.10.013 https://doi.org/10.1053/j.ajkd.2005.10.013
  35. NareshCNHayenACraigJCChadbanSJ. Day-to-day vari ability in spot urine protein-creatinine ratio measurements. Am J Kidney Dis. 2012; 60: 561-566. doi: 10.1053/j.ajkd.2012.04.01010.1053/j.ajkd.2012.04.010 https://doi.org/10.1053/j.ajkd.2012.04.010
  36. MattixHJHsuCYShaykevichSCurhanG. Use of the albumin/creatinine ratio to detect microalbuminuria: Implications of sex and race. J Am Soc Nephrol. 2002; 13: 1034-1039
  37. BoulwareLEJaarBGTarver-CarrMEBrancatiFLPoweNR. Screening for proteinuria in US adults: A cost-effectiveness analysis. JAMA. 2003; 290: 3101-3114. doi: 10.1001/jama.290.23.310110.1001/jama.290.23.3101 https://doi.org/10.1001/jama.290.23.3101
  38. FuianoGMazzaGComiNCagliotiADe NicolaLIodiceC. Current indications for renal biopsy: A questionnairebased survey. Am J Kidney Dis. 2000; 35: 448-457. doi: 10.1016/ s0272-6386(00)70197-1
  39. AlguirePC. Mksap 18: Medical Knowledge Self-assessment Program. Philadelphia, PA, USA: American College of Physicians; 2018