What are the causes of albuminuria in a pregnant female?

Causes of Albuminuria in Pregnancy

Albuminuria in pregnancy is primarily caused by preeclampsia/gestational hypertension, pre-existing chronic kidney disease, pre-existing hypertension with superimposed gestational hypertension, gestational proteinuria (an isolated entity), and less commonly by diabetic nephropathy or iatrogenic causes such as NSAIDs. 1

Primary Pregnancy-Related Causes

Preeclampsia and Gestational Hypertension

• Preeclampsia is the most important cause of new-onset albuminuria after 20 weeks gestation, defined as gestational hypertension with proteinuria (≥300 mg/24h or protein/creatinine ratio ≥30 mg/mmol) or other organ dysfunction. 1
• Proteinuria is present in approximately 75% of preeclampsia cases, though notably proteinuria is no longer required for the diagnosis of preeclampsia if other features of organ dysfunction are present. 1, 2
• The shift from normal to high albumin excretion in severe preeclampsia occurs rapidly, usually preceded by rising uric acid and decreasing platelet count. 3

Gestational Proteinuria (Isolated)

• Gestational proteinuria is a distinct entity characterized by new-onset proteinuria without hypertension or other preeclampsia features. 1
• Women with gestational proteinuria have placental growth factor levels intermediate between normal pregnancies and preeclampsia, suggesting they may have an early form of preeclampsia. 1
• Three possible outcomes exist: (1) proteinuria resolves postpartum with no preeclampsia development, (2) proteinuria becomes the first feature of preeclampsia when BP subsequently rises, or (3) proteinuria persists postpartum indicating underlying renal disease. 1

Pre-Existing Medical Conditions

Chronic Kidney Disease

• Pre-existing renal disease is a major cause of albuminuria throughout pregnancy, and proteinuria that persists beyond 6-12 weeks postpartum confirms primary renal disease requiring long-term nephrology follow-up. 1, 2
• Women with baseline proteinuria >190 mg/24h before conception or in early pregnancy have increased risk of pregnancy-induced hypertension. 1

Pre-Existing Hypertension

• Chronic hypertension can cause albuminuria independently and increases risk when superimposed gestational hypertension develops. 1
• Pre-existing hypertension usually persists >6 weeks postpartum, distinguishing it from gestational causes. 1

Diabetic Nephropathy

• Women with type 1 diabetes frequently develop hypertension associated with diabetic nephropathy manifested by gross proteinuria. 1
• Baseline assessment of proteinuria should be undertaken before conception in diabetic women, as proteinuria >190 mg/24h is associated with increased pregnancy risks. 1

Iatrogenic and Other Causes

Medication-Induced

• NSAIDs used for postpartum analgesia can cause albuminuria, as can ergot derivatives for postpartum hemorrhage or ephedrine used to correct hypervolemia after regional anesthesia. 1

Physiologic Changes

• Normal pregnancy shows a small but significant rise in albumin excretion in the third trimester, sustained pre-delivery and in the first postnatal week, but this remains within normal limits. 3

Critical Diagnostic Considerations

A common pitfall is assuming all proteinuria in pregnancy represents preeclampsia. The key is timing and persistence:

• Proteinuria appearing before 20 weeks gestation suggests pre-existing renal disease rather than preeclampsia. 1
• Proteinuria persisting beyond 6-12 weeks postpartum confirms underlying renal disease requiring nephrology referral. 1, 2
• Evaluation at 3 months postpartum is essential to determine if proteinuria persists and represents primary renal disease. 2

Prognostic Implications

• Massive proteinuria (>5 g/24h) is associated with more severe neonatal outcomes and earlier delivery. 1
• Microalbuminuria detected antepartum predicts adverse pregnancy outcomes in a dose-dependent manner: as urine albumin/creatinine ratio increases from normal to microalbuminuria to macroalbuminuria, adverse outcomes increase stepwise (13.8% to 24.1% to 62.1%). 4
• Women with hypertensive pregnancies have 37% increased risk of future microalbuminuria compared to those with normotensive pregnancies, even years after delivery. 5