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Gestational Proteinuria

Contributor: Sharon Keiser, MD 
Last Update: 05/17/18 

New ICD codes (2017)
012.14 – Gestational proteinuria, complicating childbirth
012.15 – Gestational proteinuria, complicating the puerperium
012.24 – Gestational edema with proteinuria, complicating childbirth
012.25 – Gestational edema with proteinuria, complicating the puerperium

Definition:  Gestational proteinuria is a retrospective diagnosis, based on the appearance of significant proteinuria in the absence of hypertension after 20 weeks gestation.  This proteinuria resolves by 12 weeks postpartum.  Proteinuria that develops prior to 20 weeks gestation is suggestive of preexisting renal disease.  The exact incidence of gestational proteinuria is unknown.

Pathogenesis of gestational proteinuria is uncertain, however, it is thought to be similar to preeclampsia, in that anti-angiogenic factors (soluble fms-like tyrosine 1 and endoglin) are increased in these patients, although not as severely as in patients with overt preeclampsia.  Additionally, endothelial growth factors are decreased in these patients as they are in preeclampsia, although again to a lesser degree.

Proteinuria increases with increasing gestation; significant proteinuria is defined as at least 300mg per day in a 24-hour urine collection. The 24-hour urine collection is considered to be the gold standard in quantification of urine protein excretion; however, a 12 hour collection is also feasible.  Protein-to-creatinine ratio (P:C) is an alternative; a result of >0.19 has an acceptable sensitivity/specificity/positive predictive value to be predictive of significant proteinuria.

Since urinary protein concentration can be affected by blood, infection, posture, hydration and exercise, a positive dipstick (>1+) must be quantified for verification of significant proteinuria.

Close observation of patients with gestational proteinuria is warranted, as at least 20% of cases will progress to overt preeclampsia. The presence of isolated proteinuria in itself does not appear to subject the pregnancy to maternal risks, although higher levels of proteinuria are associated with a greater likelihood of progression to preeclampsia.  Isolated proteinuria does not correlate with overall fetal/neonatal outcomes, therefore should not be utilized to make determinations about delivery mode or timing, however lower Apgar scores at 5 minutes and a higher likelihood of IUGR have been observed, therefore close observation for IUGR is warranted.

Evaluation and Management

  1. Rule out urinary tract infection
  2. Review history for renal disease or diabetes and outcome(s) of prior pregnancies.
  3. If presumptive diagnosis is made by dipstick, confirm with quantitative urine protein with either 12- or 24-hour urine total protein/CrCl (>300mg/24 hour urine collection, at least 1 L vol/at least 1G creatinine) or spot P:C >0.3.
  4. If spot P:C is >0.19 <0.3, need 12- or 24-hour urine collection.
  5. Evaluate patient for preeclampsia
  6. Evaluate fetal growth, serially if diagnosis is made prior to term.
  7. BP check and review of systems focused on symptoms related to preeclampsia performed at least every other week.
  8. If preeclampsia does not develop, deliver at or during week 40 (or based on other obstetric indications).
  9.  Postpartum follow-up must include a 12- or 24 hour urine protein/CrCl or a P:C, with referral to nephrology if proteinuria has not resolved.

References

  1.  Diagnosis Coding in Obstetrics and Gynecology ICD-10-CM Changes for 2017.  
  2. Ekiz A, Kaya B, Polat I, et al.  The outcome of pregnancy with new onset proteinuria without hypertension: retrospective observational study.  J Matern Fetal Neonatal Med. 2016;29(11):1765-9.
  3. Morikawa M, Yamada T, Minakami H. Outcome of pregnancy in patients with isolated proteinuria Current Opinion in Obstetrics and Gynecology 2009, 21:491–495. 
  4. T. Yamada et al.  Isolated proteinuria as an initial sign of severe preeclampsia. Open Journal of Obstetrics and Gynecology 1 (2011) 13-16.  
  5. National Kidney Foundation clinical practice guidelines for chronic kidney disease: Evaluation, classification and stratification – Guideline #9 (Approach to chronic kidney disease), 2002
  6. Masuyama H, Suwaki N, Nakatsukasa H, et al.   Circulating angiogenic factors in preeclampsia, gestational proteinuria and preeclampsia superimposed on chronic glomerulonephritis.  Am J. Obstet Gynecol 2006; 194(2):551-556.
  7. National Kidney Foundation Clinical Practice Guidelines for Chronic Kidney Disease:  Evaluation, classification and stratification – Guideline #5 (Assessment of proteinuria), 2002.
  8. Akaishi R, Yamada T, Morikawa M, et al. Clinical features of isolated gestational proteinuria progressing to pre-eclampsia: retrospective observational study.  BMJ Open 2014;4:e004870. doi:10.1136/bmjopen-2014-004870.
  9. Takahiro Yamada, Mana Obata-Yasuoka, Hiromi Hamada
et al.  Isolated gestational proteinuria preceding the diagnosis of preeclampsia – an observational study.  Acta Obstetricia et Gynecologica Scandinavica 95 (2016) 1048–1054.
  10. S Shinar, J Asher-Landsberg, A Schwartz, M Ram-Weiner, MJ Kupferminc and A Many.

         Isolated proteinuria is a risk factor for pre-eclampsia: a retrospective analysis of the maternal and neonatal outcomes in women presenting with isolated gestational proteinuria. Journal of Perinatology (2016) 36, 25–29
© 2016 Nature America, Inc.

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