When you detect proteinuria in a pregnant woman, a number of conditions should come to mind. It can mean a lupus flair or suggest the presence of preeclampsia. But in many women, it may signal the existence of a previously undiagnosed renal condition. While proteinuria after 20 weeks’ gestation may indicate preeclampsia, its existence earlier suggests underlying renal disease, most commonly diabetic nephropathy.

But other important causes exist in young women (Table 1). To explore all these options, we will first review the normal changes in the kidney during pregnancy, briefly touch on mechanisms of proteinuria, and then focus mostly on evaluation and management. All women with proteinuria should be evaluated by a nephrologist, particularly during their pregnancies, as renal conditions can decline rapidly in this setting.

Kidney physiology in normal pregnancy

Normal pregnancy causes dramatic changes in systemic and renal hemodynamics. Cardiac output increases, plasma volume expands, and there is a decrease in systemic vascular resistance and blood pressure starting early in the first trimester. This retention of 6 to 8 L of water and increased plasma volume is accompanied by significant sodium (Na) retention, averaging approximately 1,000 mEq.

Despite total body volume expansion, the kidney senses a relative “under-filling” and the plasma renin-angiotensin-aldosterone system (RAAS) is activated. This provides a checks and balances system to the massive systemic vasodilation of pregnancy.₁ In the end, systemic blood pressure falls, despite the increasing cardiac output, with a nadir at about 16 to 20 weeks’ gestation.

Throughout gestation, the glomerular filtration rate (GFR) increases by 50% and renal plasma flow by 50% to 85%.₂ The increased GFR is caused by renal vasodilatation, mediated in large part by the ovarian hormone relaxin. GFR rises by 25% by the fourth gestational week, peaking by week 9. Because of this increase, serum blood urea nitrogen (BUN) and creatinine concentrations fall.

The change in GFR has important implications for patients with either preexisting or de novo proteinuria. As GFR increases, proteinuria increases. Clinicians should expect this as pregnancy progresses and not be alarmed. However, it is concerning if the level of proteinuria starts to change rapidly.

What’s the mechanism behind proteinuria?

With an increase in renal blood flow during pregnancy, approximately 6,000 g of albumin travel through the renal circulation each day. Albumin plays a critical role in maintaining serum oncotic pressure, and its concentration must be conserved.

Three mechanisms exist to prevent albumin/protein loss by filtration in the normal kidney.

  * First, the pore size of the fenestrated capillary endothelium in the glomerular capillary loops are too small for the bulkier albumin to routinely pass through.
  * Second, the glomerular basement membrane is made up of negatively charged proteins that repel the negatively charged albumin proteins acting as a “charge” barrier to their filtration.
  * Lastly, the structure of the epithelial slit diaphragms act as a barrier to albumin passing.