Late-onset proteinuria

When proteinuria develops later in pregnancy, it can be from intrinsic renal disease or preeclampsia. Most patients with preeclampsia will develop de novo hypertension and proteinuria with the increase in severity of both occurring over days, not weeks. This is why it is so important to do early screening for proteinuria in pregnancy. Also remember that patients with underlying renal disease are at increased risk for preeclampsia, and at times it can be difficult to determine whether the worsening proteinuria is from progressing renal disease or new-onset preeclampsia. In these cases, it is prudent to assume it is preeclampsia and treat the patient accordingly, as the risks are greater with this diagnosis. Once the patient has delivered, “stand alone” preeclampsia will usually resolve whereas primary renal disease may improve, but not completely resolve. Preeclampsia, unlike other causes of proteinuria, is often an indication for preterm delivery.

How do you manage the patient?

Patients with proteinuria levels <3.0 g/d are usually asymptomatic. However, those who have >3.0 g/d (and a serum albumin <3.0 g/dL) develop edema because of excess sodium and water retention. This edema may worsen hypertension, particularly near term, and can complicate delivery if there is severe vulvar edema. When possible, the underlying cause of nephrotic syndrome should be treated. Standard antiproteinuric therapy, such as ace-inhibitors and angiotensin receptor blockers, must be avoided in pregnancy because of their teratogenic effects.

Management in these cases is largely symptomatic and patients should be put on a low sodium diet (<1.5 g/d), and placed on bed rest if edema is significant. In general, diuretic therapy should be avoided because it may reduce extracellular fluid volume and decrease placental perfusion. There are, however, rare occasions when therapy is needed, and in those cases, diuretics should be used every other day and with a goal of slow diuresis of 1 to 2 lb per day. Diuretics should never be used in preeclampsia (unless patients are postpartum), as this state is characterized by a low circulating plasma volume.

What’s the prognosis?

Isolated proteinuria does not seem to be harmful to the developing fetus, although it does predispose to maternal complications such as worsening edema and hypertension.13 If women have proteinuria without hypertension, the outcome of pregnancies is excellent with no increase in fetal death rates. Preeclampsia is a different situation, as that disease clearly carries risks of preterm delivery as well as maternal and fetal complications. However in preeclampsia, the degree of proteinuria (once >300 mg) seems to have little overall effect and should not be used as an argument for preterm delivery if all other markers of maternal and fetal health are acceptable.

Proteinuria in pregnancy results from preexisting underlying renal disease, or from preeclampsia. These two disease states carry very different prognostic implications for both mother and developing baby. Proteinuria detected early in pregnancy should be investigated for underlying causes. You can screen for proteinuria with urinary dipstick, but be mindful of false-positive and false-negative results. The 24-hour Urine collection remains the gold standard test for quantification, but evidence is rapidly mounting for the use of a spot urine protein:creatinine ratio that gives faster results with greater ease for patients.

DR. BREWSTER is Assistant Professor of Medicine, Section of Nephrology, Yale University School of Medicine, New Haven, CT.
By: Ursula C. Brewster, MD

REFERENCES
_{1. Karumanchi SA, Maynard SE, Stillman IE, et al. Preeclampsia: a renal perspective. Kidney Int. 2005;67:2101-2113.}

2. Jeyabalan A, Conrad KP. Renal function during normal pregnancy and preeclampsia. Front Biosci. 2007;12:2425-2437.

3. Tryggvason K, Patrakka J, Wartiovaara J. Hereditary proteinuria syndromes and mechanisms of proteinuria. N Engl J Med. 2006;354:1387-1401.

4. Sumpio BE, Hayslett JP. Renal handling of proteins in normal and disease states. Q J Med. 1985;57:611-635.

5. Higby K, Suiter CR, Phelps JY, et al. Normal values of urinary albumin and total protein excretion during pregnancy. Am J Obstet Gynecol. 1994;171:984-989.

6. Price CP, Newall RG, Boyd JC. Use of protein:creatinine ratio measurements on random urine samples for prediction of significant proteinuria: a systematic review. Clin Chem. 2005;51:1577-1586.

7. Ginsberg JM, Chang BS, Matarese RA, et al. Use of single voided urine samples to estimate quantitative proteinuria. N Engl J Med. 1983;309:1543-1546.

8. Magali R, Farshad S, Liston RM, et al. Random protein-creatinine ratio for the quantitation of proteinuria in pregnancy. Obstet Gynecol. 1997;90:893-895.

9. Rodriguez-Thompson D, Lieberman ES. Use of a random urinary protein-to-creatinine ratio for the diagnosis of significant proteinuria during pregnancy. Am J Obstet Gynecol. 2001;185:808-811.

10. Neithardt AB, Dooley SL, Borensztajn J. Prediction of a 24-hour protein excretion in pregnancy with a single voided urine protein-to-creatinine ratio. Am J Obstet Gynecol. 2002;186:883-886.

11. Yamasmit W, Chaithongwongwatthana S, Charoenvidhya D, et al. Random urinary protein-to-creatinine ratio for prediction of significant proteinuria in women with preeclampsia. J Matern Fetal Neonatal Med. 2004;16:275-279.

12. Durnwald C, Mercer B. A prospective comparison of total protein/creatinine ratio versus 24-hour urine protein in women with suspected preeclampsia. Am J Obstet Gynecol. 2003;189:848-852.

13. Airoldi J, Weinstein L. Clinical significance of proteinuria in pregnancy. Obstet Gynecol Surv. 2007;67:117-124.