Proteinuria in pregnancy: What does it mean?

The spot urine protein:creatinine ratio

This method of quantifying proteinuria is easier then a 24-hour collection, can be run off a spot urine sample, and nephrologists have substituted this for a 24-hour Urine collection in just about all proteinuric conditions. A spot urine sample should be taken and sent for protein and creatinine. The ratio of the two approximates a 24-hour collection by accounting for protein concentration.

If the ratio of protein:creatinine is 125 mg/g , this estimates 125 g of protein on a 24-hour collection. The test has been well-validated in nonpregnant women and in men with a correlation coefficient of 0.97, and it has real advantages over the 24-hour Urine collection both because it minimizes collection and laboratory errors and results are usually available in several hours.7 As you can imagine, patients also prefer it.

Most of the studies that have examined its accuracy in pregnancy have included fewer than 200 patients and have included hospitalized patients, outpatients, those at high risk for preeclampsia, and patients who have full-blown nephrotic syndrome.8-11 Despite these limitations, all the studies have found a strong correlation between spot analysis and 24-hour collection, save one; but this one has some methodologic problems.

THE PUBLISHED DIAGNOSTIC CRITERIA for preeclampsia include a 24-hour Urine collection with >300 mg of protein. Studies have shown that using a cut-off of a spot protein:creatinine ratio of >190 mg/g had a sensitivity of 97%, specificity of 70%, positive predictive value of 75%, and a negative predictive value of 87%.9 For this reason, some had advocated using a cut-off of >140 mg/g to be used as a threshold to justify a confirmatory 24-hour urine. Once the diagnosis is made, spot urine tests could be measured throughout pregnancy.

For patients with more overt proteinuria, or once the diagnosis of preeclampsia is made, management rarely changes if protein measurements change subtly. Some of these subtle differences may be missed by a spot urine test, although one could argue that that is also true with inadequate collections on a 24-hour urine sample. Given the increased expeditiousness and ease of a spot urine test over a 24-hour collection, clinicians should become comfortable using this test. It can be used to monitor progress during pregnancy in patients who were previously proteinuric or to quantify new proteinuria.

Doing a lab workup once proteinuria is detected

Many patients will be first diagnosed with proteinuria during pregnancy. As mentioned previously, if it is detected early in pregnancy, it’s likely from some underlying renal disease. If proteinuria appears later, preeclampsia rises to the top of the differential diagnosis list. Workup depends on when the proteinuria is detected, and all patients should be screened with a urine dipstick during their first trimester.

Early proteinuria (<20 weeks)

Figure 2: Evaluation for proteinuria early in pregnancy (<20 weeks)

Figure 2: Evaluation for proteinuria early in pregnancyIf proteinuria is detected early in pregnancy, women should be sent to a nephrologist for full evaluation (Figure 2). If the patient has diabetes, there may be no need to do further workup. If the patient is not diabetic, or if the course is unlikely to be related to diabetes, then a more exhaustive workup should be undertaken.

URINE MICROSCOPY done on freshly spun urine sediment can yield much information. Glomerular disease will usually present with dysmorphic red cells or red cell casts in the urine. White blood cell casts may indicate interstitial nephritis or pyelonephritis.

BLOOD TESTS should be done as appropriate to the patient’s history and physical exam (Table 4). Evaluating renal function with a serum creatinine concentration is critical. Serum creatinine concentration normally falls during pregnancy, with normal levels being < 0.6 mg/dL. Autoimmune diseases, such as systemic lupus erythematosis, often present with proteinuria and renal dysfunction before other systemic abnormalities are apparent and may flare during pregnancy. Infections such as human immunodeficiency virus (HIV) or hepatitis can also present first with proteinuria.

Table 4: Workup of proteinuriaULTRASOUND can also prove useful, as kidneys that have been affected by a disease process over time (as opposed to acutely) will have increased echogenicity and kidney size can be a clue to diagnosis. Obstruction can also be ruled out with U/S. Bear in mind, however, that size increases by approximately 1 cm during pregnancy, and kidneys (particularly the right) may appear mildly obstructed with dilated calices due to the “physiologic obstruction of pregnancy.”

This temporary appearance on U/S, which is likely due to progesterone’s effect on the collecting system, is totally benign and should resolve by 12 weeks postpartum. Bilateral obstruction can cause kidney failure and may present as mild proteinuria, although alone the obstruction will not cause nephrotic range proteinuria.

WE RESERVE RENAL BIOPSY for those patients in whom a diagnosis of proteinuria is unclear and in whom management decisions depend on actual pathology. With U/S guidance, and an experienced clinician’s hand, this is a very safe and well-tolerated procedure.

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