Clinical Practice Guidelines Antenatal care - Module I

7.4 Proteinuria

Page last updated: 02 April 2013

Detection of proteinuria in the first trimester does not predict pre-eclampsia but may lead to identification and treatment of kidney disease or urinary tract infection.

7.4.1 Background

High amounts of protein in the urine (proteinuria) can be caused by a range of conditions. Proteinuria in the first trimester may suggest underlying kidney disease or the presence of urinary tract infection (see Section 8.5). After 20 weeks pregnancy, proteinuria is associated with pre-eclampsia.

Kidney disease in Australia

The first phase of the AusDiab study found that 16% of participants had at least one indicator of kidney damage (Chadban et al 2003; Atkins et al 2004) and the subsequent phase found that every year 1% of adults developed reduced kidney function and 1% had evidence of kidney damage (Barr et al 2006). Kidney disease is more prevalent among Aboriginal and Torres Strait Islander peoples than in the non-Indigenous population, with the overall age-standardised rate being 10 times the non- Indigenous rate (AIHW 2008). Between 2001 and 2004–05, there was a significant increase in the proportion of Aboriginal and Torres Strait Islander people reporting kidney problems (from 1% to 2%) (Barr et al 2006).

Risks associated with proteinuria in pregnancy

  • Maternal proteinuria has been strongly associated with preterm birth (Franceschini et al 2005).
  • Chronic kidney disease in pregnancy has been associated with pre-eclampsia, preterm labour, small for-gestational age babies and perinatal death (Bramham et al 2011).

7.4.2 Testing for proteinuria

Summary of the evidence

Testing for proteinuria in pregnancy in combination with blood pressure measurement at each antenatal visit is recommended in the United Kingdom (NICE 2008).

Accuracy of tests for detecting proteinuria

The 24-hour urine collection test is considered ‘the gold standard’ for testing for proteinuria in women during pregnancy, although it is often inconvenient for pregnant women to undertake a 24-hour urine collection. The test is frequently used as a reference point when evaluating the accuracy of other tests such as urine dipstick visual check, urine automated analyser, 2-hour and 12-hour tests, spot protein:creatinine ratio or microalbumin:creatinine ratio (Risberg et al 2004; Price et al 2005; Waugh et al 2005; Schubert et al 2006; Rizk et al 2007; Abebe et al 2008; Côté et al 2008a; Dwyer et al 2008; Kyle et al 2008; Gangaram et al 2009a; 2009b). One study has questioned the accuracy of the 24-hour urine test (Côté et al 2008b).

Studies evaluating other test types have found that:
  • dipstick testing — is inaccurate in predicting significant proteinuria (Waugh et al 2004; Gangaram et al 2005) and has a high incidence of false positives (Davey & MacGillivray 1988; Phelan et al 2004);
  • 2-hour and 12-hour collections — correlate with 24-hour collections in quantifying proteinuria, with the 12-hour collection having higher sensitivity (89% versus 86%), specificity (93% versus 82%) and positive predictive value (84% versus 77%) and lower false positive (12% versus 18%) and false negative (11% versus 14%) rates than 2-hour collection (Abebe et al 2008); and
  • protein:creatinine ratio — is a better screening test than automated dipstick urinalysis to detect significant proteinuria (Risberg et al 2004; Dwyer et al 2008), may be useful to rule out clinically significant proteinuria (Waugh et al 2004; Price et al 2005; Côté et al 2008a; Meads et al 2008; Gangaram et al 2009a) and has the advantage of results being available immediately (Kyle et al 2008).
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Automated analysis of dipsticks

Due to considerable observer errors involved in dipstick urinalysis, an RCOG Study Group recommended that automated dipstick readers be employed (Shennan & Waugh 2003). This can significantly improve false positive and false negative rates. An initial result of 1+ or greater of protein should be confirmed by a 24-hour urinary protein measurement or a protein:creatinine ratio (Rodriguez-Thompson & Lieberman 2001).

Consensus-based recommendation

iii. Routinely offer testing for proteinuria at the first antenatal visit, regardless of stage of pregnancy.

Recommendation Grade B

6. For point-of-care testing, use an automated analyser if available, as visual inspection of a urinary dipstick is the least accurate method to detect true proteinuria.

Repeat testing in the first trimester

Repeat testing for proteinuria in the first trimester is of little or no benefit in predicting pre-eclampsia and should be confined to women with other risk factors such as existing or newly diagnosed high blood pressure and new or pre-existing kidney disease (Beunis et al 2004; Alto 2005; Sirohiwal et al 2009).

Testing in rural and remote areas
Considerations in urine testing in rural and remote areas include (Bookallil et al 2005):
  • the availability of appropriate storage facilities for dipstick tests and for urine collections for women with abnormal dipstick results (see below); and
  • if a woman has an abnormal dipstick result, whether specimens can be provided to pathology services within the timeframe in which they can still be cultured (ideally within 24 hours).

7.4.3 Responding to test results

A finding of 300 mg/24 hours or more or a protein:creatinine ratio of 30 mg/mmol of creatinine is customarily regarded as significant (Ferrazzani et al 1990; Waugh et al 2003). However, a proteinuria threshold of 500 mg/24 hours has been suggested to be more predictive in relation to the likelihood of adverse outcome (Shennan & Waugh 2003).
  • Women with abnormal dipstick urine test results (including the presence of leukocytes, nitrites or blood) should have a midstream urine sample sent for microscopic examination, culture and sensitivity testing. If the result is asymptomatic bacteriuria, this should be treated appropriately (Murray et al 2002).
  • Women found to have true proteinuria and/or haematuria at their first antenatal visit may have underlying kidney disease, which should be investigated (Murray et al 2002).

7.4.4 Practice summary — testing for proteinuria

When — At first antenatal visit
Who — Midwife; GP; obstetrician; Aboriginal and Torres Strait Islander health worker; multicultural health worker
  • Explain the risks associated with proteinuria in pregnancy — Discuss the importance of identifying kidney disease or urinary tract infection early in pregnancy.
  • Arrange treatment or referral if required — For women with proteinuria, further testing may be required to exclude urinary tract infection or kidney disease and monitoring for pre-eclampsia may be needed.

7.4.5 Resources

Lowe SA, Brown MA, Dekker G et al (2008) Guidelines for the management of hypertensive disorders of pregnancy 2008. Society of Obstetric Medicine of Australia and New Zealand. Aust NZ J Obstet Gynaecol 49(3): 242–46.

NICE (2010) Hypertension in Pregnancy: the Management of Hypertensive Disorders during Pregnancy. National Collaborating Centre for Women’s and Children’s Health. Commissioned by the National Institute for Health and Clinical Excellence. London: RCOG Press.

SOGC (2008) Diagnosis, Evaluation, and Management of the Hypertensive Disorders of Pregnancy. Clinical Practice Guideline No. 206. Toronto: Society of Obstetricians and Gynaecologists of Canada.
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7.4.6 References

Abebe J, Eigbefoh J, Isabu P et al (2008) Accuracy of urine dipsticks, 2-h and 12-h urine collections for protein measurement as compared with the 24-h collection. J Obstet Gynaecol 28(5): 496–500.

AIHW (2008) The Health and Welfare of Australia’s Aboriginal and Torres Strait Islander Peoples. ABS Cat No 4704.0, AIHW Cat No IHW 21. Commonwealth of Australia.

Alto WA (2005) No need for glycosuria/proteinuria screen in pregnant women. J Fam Pract 54(11): 978–83.

Atkins RC, Polkinghorne KR, Briganti EM et al (2004) Prevalence of albuminuria in Australia: the AusDiab Kidney Study. Kidney Int 66: S22–4.

Barr ELM, Magliano DJ, Zimmet PJ et al (2006) AusDiab 2005 The Australian Diabetes, Obesity and Lifestyle Study. Tracking the Accelerating Epidemic: Its Causes and Outcomes. Melbourne: International Diabetes Institute.

Beunis MH, Schweitzer KJ, Van Hooff MHA et al (2004) Midtrimester screening for microalbuminuria in healthy pregnant women. J Obstetrics Gynaecol 24(8): 863–65.

Bookallil M, Chalmers E, Bell A (2005) Challenges in preventing pyelonephritis in pregnant women in Indigenous communities. Rural Remote Health 5: 395 (online).

Bramham K, Briley AL, Seed PT et al (2011) Pregnancy outcome in women with chronic kidney disease: a prospective cohort study. Reprod Sci online 1 Feb 2011 rsx.sagepub.com/content/early/2011/01/27/1933719110395403.

Chadban SJ, Briganti EM, Kerr PG et al (2003) Prevalence of kidney damage in Australian adults: The AusDiab kidney study. J Am Soc Nephrol 14(7 Suppl 2): S131–8.

Côté AM, Brown MA, Lam E et al (2008a) Diagnostic accuracy of urinary spot protein:creatinine ratio for proteinuria in hypertensive pregnant women: systematic review. Brit Med J 336: 1003.

Côté A-M, Lam EM, von Dadelszen P et al (2008b) The 24-hour urine collection: gold standard or historical practice? Am J Obstet Gynecol 199(6): 625.e1–625.e6.

Davey DA & MacGillivray I (1988) The classification and definition of the hypertensive disorders of pregnancy. Am J Obstet Gynecol 158(4): 892–98.

Dwyer BK, Druzin M, Gorman M et al (2008) Urinalysis vs urine protein – creatinine ratio to predict significant proteinuria in pregnancy. J Perinatol 28(7): 461–67.

Ferrazzani S, Caruso A, De Carolis S et al (1990) Proteinuria and outcome of 444 pregnancies complicated by hypertension. Am J Obstet Gynecol 162: 366–71.

Franceschini N, Savitz DA, Kaufman JS et al (2005) Maternal urine albumin excretion and pregnancy outcome. Am J Kidney Dis 45(6): 1010–18.

Gangaram R, Moodley J, Ojwang PJ et al (2005) The accuracy of urine dipsticks as a screening test for proteinuria in hypertensive disorders of pregnancy. Hypertens Preg 24(2): 117–23.

Gangaram R, Moodley J, Naicker M (2009a) Comparison of pregnancy outcomes in women with hypertensive disorders of pregnancy using 24-hour urinary protein and urinary microalbumin to creatinine ratio. Int J Gynecol Obstet 107(1): 19–22.

Gangaram R, Naicker M, Moodley J (2009b) Accuracy of the spot urinary microalbumin:creatinine ratio and visual dipsticks in hypertensive pregnant women. Eur J Obstet Gynecol Reprod Biol 144(2): 146–48.

Kyle PM, Fielder JN, Pullar B et al (2008) Comparison of methods to identify significant proteinuria in pregnancy in the outpatient setting. Brit J Obstet Gynaecol 115(4): 523–27.

Meads CA, Cnossen JS, Meher S et al (2008) Methods of prediction and prevention of pre-eclampsia: systematic reviews of accuracy and effectiveness literature with economic modelling. Health Technol Assess 12: 6.

Murray N, Homer CS, Davis GK et al (2002) The clinical utility of routine urinalysis in pregnancy: a prospective study. Med J Aust 177: 477–80.

NICE (2008) Antenatal Care. Routine Care for the Healthy Pregnant Woman. National Collaborating Centre for Women’s and Children’s Health. Commissioned by the National Institute for Health and Clinical Excellence. London: RCOG Press.
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Phelan LK, Brown MA, Davis GK et al (2004) A prospective study of the impact of automated dipstick urinalysis on the diagnosis of preeclampsia. Hypertens Preg 23(2): 135–42.

Price CP, Newall RG, Boyd JC (2005) Use of protein:creatinine ratio measurements on random urine samples for prediction of significant proteinuria: a systematic review. Clin Chem 51(9): 1577–86.

Risberg A, Risberg A, Sjöquist M et al (2004) Relationship between urinary albumin and albumin/creatinine ratio during normal pregnancy and pre-eclampsia. Scand J Clin Lab Invest 64(1): 17–23.

Rizk DEE, Agarwal M, Pathan J et al (2007) Predicting proteinuria in hypertensive pregnancies with urinary protein creatinine or calcium-creatinine ratio. J Perinatol 27(5): 272–77.

Rodriguez-Thompson D & Lieberman ES (2001) Use of a random urinary protein-to-creatinine ratio for the diagnosis of significant proteinuria during pregnancy. Am J Obstet Gynecol 185: 808–11.

Schubert FP, Abernathy MP, Schubert FP (2006) Alternate evaluations of proteinuria in the gravid hypertensive patient. J Reprod Med 51(9): 709–14.

Shennan AH & Waugh JJS (2003) The measurement of blood pressure and proteinuria. In: Critchley H, MacLean AB, Poston L et al (eds) Pre-eclampsia. London: RCOG Press, pp305–24.

Sirohiwal D, Dahiya K, Khaneja N (2009) Use of 24-hour urinary protein and calcium for prediction of preeclampsia. Taiwan J Obstet Gynecol 48(2): 113–15.

Waugh JJS, Clark TJ, Divakaran TG et al (2003) A systematic review and meta-analysis comparing protein/creatinine ratio measurements and dipstick urinalysis in predicting significant proteinuria in pregnancy. Presented at the British Maternal and Fetal Medicine Society,
University of York, 20–21 March 2003.

Waugh JJ, Clark TJ, Divakaran TG et al (2004) Accuracy of urinalysis dipstick techniques in predicting significant proteinuria in pregnancy. Obstet Gynecol 103(4): 769–77.

Waugh JJ, Bell SC, Kilby MD et al (2005) Optimal bedside urinalysis for the detection of proteinuria in hypertensive pregnancy: a study of diagnostic accuracy. Brit J Obstet Gynaecol 112(4): 412–17.