Urinary Protein Excretion Estimation
Avoid using overnight or first morning void as urine sample.
- Patients in whom renal disease is suspected (to rule out).
- Patients with known renal disease (to assess progression).
- Patients with low-grade proteinuria and otherwise intact renal function (to monitor).
- The Urinary Protein Excretion Estimation (sometimes referred to as “spot urine protein/creatinine ratio” or “protein/creatinine ratio”) calculates the protein/creatinine ratio from a random urine sample to estimate 24-hour protein excretion.
- Based on the physiologic principle that urinary creatinine excretion is constant if glomerular filtration rate (GFR) is constant and therefore protein/creatinine ratio from a single urine sample should reflect protein excretion, cancelling out the time factor.
- Confirmed for correlation with 24-hour protein excretion in multiple studies (see Evidence Appraisal/EBM).
- Correlation is lowest for urine samples voided overnight and upon arising.
- Can be used only in presence of stable renal function (GFR).
- If albumin is the predominant component, persistent proteinuria suggests renal disease, even in the absence of decreased glomerular filtration rate, hypertension, or other abnormal findings on urinalysis.
- 24-hour urine collection is time consuming, inconvenient for patients, and subject to collection error. The Urinary Protein Excretion Estimation avoids these problems without sacrificing accuracy, by using a single urine sample.
- Proteinuria is an independent risk factor for cardiovascular and renal disease, and predicts end organ damage. Detecting an increase in protein excretion has both diagnostic and prognostic value in initial detection and confirmation of renal disease.
- Quantifying proteinuria can also help assess effectiveness of therapy and progression of disease.
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- UPEE >3.5 g per day in adults is associated with nephrotic syndrome.
- Decrease in protein excretion to less than 2 g per day, either in response to therapy or spontaneously, is associated with improved long-term prognosis.
- Patients with persistent low-grade proteinuria unrelated to decreased kidney function or a systemic disease typically have no long-term complications, even if untreated.
- Many nephrologists use an antihypertensive drug, such as an angiotensin-converting enzyme (ACE) inhibitor, to reduce or eliminate proteinuria.
- Patients with low-grade proteinuria should be evaluated yearly to make sure it is not getting worse and that kidney function is stable.
24-hour Urinary Protein Excretion Estimation = Urine Protein / Urine Creatinine
Urine protein/creatinine ratio in mg per g approximates protein excretion in mg per 24 hours.
Facts & Figures
UPEE <0.2 g/day
Within normal limits
UPEE 0.2–3.5 g/day
UPEE >3.5 g/day
The use of UPEE as a correlate for 24-hour urinary protein excretion was first investigated by Ginsberg et al and published in the New England Journal of Medicine in 1983. They hypothesized that because urinary creatinine excretion is constant if glomerular filtration rate (GFR) is constant, a calculated protein/creatinine ratio from a single urine sample should reflect protein excretion and, being a ratio, also cancel out the time factor.
They tested their hypothesis in 46 patients with renal disease, measuring both (1) total protein from 24-hour urine collection and (2) protein/creatinine ratio from a random urine sample for each. They also collected random urine samples from 30 healthy controls with no history or evidence of renal disease and calculated protein/creatinine ratio from each. Comparing the 24-hour protein and random protein/creatinine ratio showed correlation coefficients ranging between 0.82-0.97.
They also found that the relationship between proteinuria in random urine and 24-hour collection varied by as much as 30%, but that during “normal daylight activity” (i.e., when most random samples are likely to be collected) the variation was minimal.
Numerous subsequent studies have validated this correlation, including by Schwab et al (1987) in inpatients and outpatients with renal disease, Houser (1984) in pediatric patients, Neithardt et al (2002) in pregnant patients, and others.
A systematic review by Price et al (2005) evaluated 16 studies investigating proteinuria and used likelihood ratios to measure ability of random protein/creatinine ratio to predict presence or absence of proteinuria. Patient groups were primarily those with preeclampsia or renal disease. Summary estimates of the LR(+) and the LR(−) across the 10 preeclampsia studies were 4.2 (95% CI, 2.6–6.9) and 0.14 (0.09–0.24), respectively.
Sensitivities and specificities for the tests ranged between 69-96% and 41%- 97%, respectively, whereas the positive and negative predictive values ranged between 46%-95% and 45%-98%, respectively. The positive likelihood ratios ranged between 1.8-16.5, and the negative likelihood ratios between 0.06-0.35.
Original/Primary ReferenceGinsberg JM, Chang BS, Matarese RA, Garella S. Use of single voided urine samples to estimate quantitative proteinuria. N Engl J Med. 1983 Dec 22;309(25):1543-6.
ValidationPrice CP, Newall RG, Boyd JC. Use of Protein:Creatinine Ratio Measurements on Random Urine Samples for Prediction of Significant Proteinuria: A Systematic Review. Clinical Chemistry 2005; v. 51, p.1577-1586. Published July 14, 2005.
Other ReferencesSiwach SB, Kalra OP, Sharma R, Singh V, Chopra JS. Estimation of 24 hour protein excretion from single random urine specimen. Indian J Med Res. 1990 Apr;92:105-8.Schwab SJ, Christensen RL, Dougherty K, Klahr S. Quantitation of proteinuria by the use of protein-to-creatinine ratios in single urine samples. Arch Intern Med. 1987 May;147(5):943-4.Houser M. Assessment of proteinuria using random urine samples. J Pediatr. 1984 Jun;104(6):845-8.Neithardt AB, Dooley SL, Borensztajn J. Prediction of 24-hour protein excretion in pregnancy with a single voided urine protein-to-creatinine ratio. Am J Obstet Gynecol. 2002;186(5):883-6.
About the Creator
Jay M. Ginsberg, MD is a practicing nephrologist in Connecticut. Dr. Ginsberg graduated from Jefferson Medical College of Thomas Jefferson University in 1977 and has been in practice for 40 years. He completed a residency at Rhode Island Hospital and also specializes in internal medicine.
To view Dr. Jay M. Ginsberg's publications, visit PubMed
- George Neiderman, MD