Pregnancy-Related Kidney Disease - Urine Nephrology Now

Andrew Bland, MD, MBA, MS

Physiologic Renal Changes in Normal Pregnancy

Hemodynamic Changes

Parameter	Change	Clinical Implication
GFR	Increases 40–50%; peaks 2nd trimester	SCr <0.8 mg/dL normal; 1.0+ may indicate compromise
Renal plasma flow	Increases 50–80%	Decreased filtration fraction
Blood pressure	Decreases 10–15 mmHg (2nd/3rd trimester)	Returns to baseline postpartum
Kidney size	Increases 1–1.5 cm length	Reversible postpartum
Collecting system	Physiologic hydronephrosis (R > L); 80–90% by 3rd trimester	Do NOT interpret as obstruction; resolves 4–6 wks postpartum

Metabolic Changes

Acid-base: Chronic respiratory alkalosis (hyperventilation); serum HCO3 decreases 4–5 mEq/L (to 19–21)
Osmolality: Decreases ~10 mOsm/kg (set point reset); sodium decreases 3–5 mEq/L (physiologic hyponatremia)
Glucose: Glucosuria common (decreased reabsorptive threshold + increased filtered load)
Protein: Proteinuria increases to ~250 mg/day (normal <150); UPCR often <0.2

Clinical Pearl

Serum creatinine >0.8 mg/dL in pregnancy may indicate renal compromise (vs non-pregnant baseline). Physiologic hydronephrosis is common and resolves postpartum—do not pursue imaging unless there are clinical signs of obstruction.

Preeclampsia & Eclampsia

Pathophysiology

Definition: New-onset hypertension (≥140/90 mmHg) + proteinuria (≥0.3 g/24h) after 20 weeks gestation
Incidence: 3–5% of pregnancies
Mechanism: Shallow placental trophoblast invasion → placental ischemia → release of sEng, sFlt-1 → systemic endothelial dysfunction

Renal Pathology

Glomerular endotheliosis: Swollen endothelial cells narrowing capillary lumens
No immune complex deposits (light microscopy normal)
Foot process effacement (may resemble MCD)
Tubular necrosis in severe cases; cortical necrosis (rare; most severe)

Clinical Features

Maternal: New-onset HTN (often ≥160/110 in severe form), proteinuria (often nephrotic-range), headache, vision changes, epigastric/RUQ pain, edema
Severe features: BP ≥160/110, creatinine elevation, pulmonary edema, seizure (eclampsia)
Fetal: IUGR, preterm delivery, neonatal complications

HELLP Syndrome

Definition: Hemolysis, Elevated Liver enzymes, Low Platelets (variant of severe preeclampsia)
Usually 3rd trimester or early postpartum
Microangiopathic hemolytic anemia (schistocytes), elevated LDH/bilirubin, platelets <100,000
Often lacks significant proteinuria/HTN—can be misdiagnosed as TTP
AKI common (50% of HELLP); TMA pattern; cortical necrosis possible

Management

Condition	Treatment	BP Target	Key Points
Preeclampsia	Delivery (only curative); labetalol/nifedipine; MgSO4 for seizure prophylaxis	140–150/90–100 (not <130/80)	After 37 wks: deliver. Before 37 wks: individualize. Avoid ACE-I/ARB (teratogenic)
HELLP	Urgent delivery (<24h if >34 wks); platelet transfusion if <50K + bleeding; ICU	Same as preeclampsia	<34 wks: individualize timing
Eclampsia	MgSO4 (4–6 g IV load, 1–2 g/hr maintenance); emergent delivery	Stabilize before delivery	Continue MgSO4 12–24h postpartum

Prognosis

80–90% resolve completely postpartum; renal function usually recovers within days to weeks
Persistent HTN in 10–15% at 1 year postpartum; 15–25% recurrence risk in future pregnancies
Long-term: Increased cardiovascular disease risk (HTN, stroke, MI) and increased CKD risk

Thrombotic Microangiopathy (TMA) in Pregnancy

Critical Distinction: Three Overlapping TMAs

HELLP can masquerade as TTP. Always check ADAMTS13 activity. Normal in HELLP, <10% in TTP. This distinction is lifesaving—TTP requires emergent plasma exchange.

Condition	Peak Timing	Mechanism	ADAMTS13	Plasma Exchange
Preeclampsia/HELLP	3rd trimester/postpartum	Endothelial dysfunction, ischemic	Normal (often >60%)	Limited role
TTP	Any trimester; postpartum	ADAMTS13 deficiency	<10% (diagnostic)	ESSENTIAL; lifesaving
aHUS	Any trimester; postpartum	Complement dysregulation	Normal (>10%)	Variable; eculizumab emerging

TTP Management in Pregnancy

Plasma exchange (ESSENTIAL): Daily until ADAMTS13 normalizes, platelet count rises, schistocytes clear
Caplacizumab: Anti-VWF nanobody; emerging benefit
Avoid platelet transfusion (except life-threatening bleeding)
Delivery: TTP usually requires immediate treatment regardless of trimester

aHUS Management

Plasma exchange: May help; less clearly essential than TTP
Eculizumab (C5 inhibitor): Can induce remission; emerging standard of care
Delivery may improve outcome (removes pregnancy stimulus to TMA)

Acute Kidney Injury in Pregnancy

Pregnancy-Specific Causes

Timing	Cause	Mechanism
1st trimester	Hyperemesis gravidarum	Volume depletion
Any	Preeclampsia/HELLP	Endothelial dysfunction
Any	Placental abruption	DIC → AKI
Postpartum	Amniotic fluid embolism	Intravascular coagulation
Postpartum	Massive hemorrhage	Volume depletion, DIC
Postpartum	Infection/sepsis	Septic shock

Management Principles

Volume status assessment critical: Many pregnancy-related AKI are volume-responsive
Careful fluid balance; avoid excessive diuretics
Dialysis if: fluid overload, hyperkalemia, severe acidosis, uremia
Maintain renal perfusion (avoid aggressive diuresis); close fetal monitoring

CKD in Pregnancy

Outcomes by GFR Category

GFR Category	Pregnancy Outcome	Fetal Outcome	Maternal Risk
>60 (CKD 1–2)	Good; mild GFR decline common	Excellent	Low
30–60 (CKD 3)	Careful monitoring; variable	Good if well-managed	Moderate
<30 (CKD 4)	Reduced fertility; high complication risk	Acceptable with intensive management	High
On dialysis (CKD 5)	Very rare successful pregnancies; high miscarriage	Poor unless intensified dialysis	Very high

Management Strategies

Pre-Conception

Baseline renal function, proteinuria assessment
BP control (target <130/80)
Stop ACE-I/ARB if conception planned (teratogenic)
Assess for complications (anemia, bone disease)

During Pregnancy

Monthly monitoring (vs routine 2–4 weeks)
Target BP: 120–140/80–90 mmHg; labetalol, nifedipine preferred
Monitor proteinuria; nephrotic-level may develop/worsen
Dialysis adjustments: If dialysis-dependent, may need intensification (more frequent/longer sessions)

Medication Safety in Pregnancy

Critical: ACE-I/ARB Contraindicated in Pregnancy

ACE-I and ARBs cause fetal AKI, oligohydramnios, and fetal loss. Must be stopped if conception is planned or confirmed. Safe alternatives: labetalol, nifedipine, hydralazine, methyldopa.

Drugs to Avoid

Drug Class	Why Avoid	Safe Alternatives
ACE-I/ARB	Fetal AKI, oligohydramnios, fetal loss	Labetalol, nifedipine
Thiazide diuretics	Electrolyte derangement, reduced placental perfusion	Hydralazine (IV), labetalol
NSAIDs	Especially 3rd trimester; ductus arteriosus closure, AKI	Acetaminophen
Spironolactone	Potential fetal side effects	Other agents

Safe Agents

Labetalol: Combined alpha-beta blocker; safe throughout pregnancy
Nifedipine (extended-release): Safe; used extensively
Hydralazine: Safe; typically used IV for severe HTN
Methyldopa: Safe; older agent, less commonly used now

Lactation

Most antihypertensives safe in breastfeeding
ACE-I/ARB: Safe postpartum (can resume)
Diuretics: Can reduce milk supply; use cautiously

Clinical Pearls

Serum creatinine >0.8 mg/dL in pregnancy may indicate renal compromise (vs non-pregnant baseline)
Physiologic hydronephrosis common; resolves postpartum—do not pursue imaging unless signs of obstruction
Preeclampsia does not equal eclampsia: Eclampsia requires seizure; treat preeclampsia before it progresses
HELLP can masquerade as TTP: Check ADAMTS13 (normal in HELLP, low in TTP)
TTP in pregnancy is an OBSTETRIC EMERGENCY—plasma exchange is lifesaving
aHUS can be triggered by pregnancy/postpartum: Consider complement mutation testing
Proteinuria <0.3 g/day normal in pregnancy; 0.3–1 g/day needs investigation; >1 g/day pathologic
ACE-I/ARB must be stopped if conception planned—risk of fetal AKI, oligohydramnios, neonatal death
Dialysis-dependent pregnancy possible but rare; requires intensified dialysis schedule
Postpartum follow-up essential: Monitor BP, renal function; assess long-term CVD/CKD risk

References

Wiles KS, Chappell LC, Clark DJ, et al. Reproductive health and pregnancy in women with chronic kidney disease. Nat Rev Nephrol. 2018;14(3):165-184. PubMed
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Fakhouri F, Noël LH, Zuber J, et al. Short-term response to plasma exchange in atypical hemolytic uremic syndrome. Clin J Am Soc Nephrol. 2009;4(10):1664-1672. PubMed
Cataland SR, Peyvandi F, Lämmle B. TTP without ADAMTS13 deficiency. J Thromb Haemost. 2012;10(6):1143-1145. PubMed
Piccoli GB, Attini R, Vasile A, et al. Pregnancy and dialysis: still challenging. Nephrol Dial Transplant. 2014;29(8):1454-1461. PubMed
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Kuklina EV, Ayala C, Callaghan WM. Hypertensive disorders and severe obstetric morbidity in the United States. Obstet Gynecol. 2009;113(6):1299-1306. PubMed
Wiles KS, Furniss G, Amos A, et al. Clinical practice guideline on pregnancy and renal disease. BMC Nephrol. 2019;20:401. PubMed