# Pregnancy-Related Kidney Disease

## 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

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

## References

1.  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](https://pubmed.ncbi.nlm.nih.gov/29355168/)
2.  Dines V, Suvakov S, Kattah A, et al. Preeclampsia and the Kidney: Pathophysiology and Clinical Implications. *Compr Physiol*. 2023;13(1):4231-4267. [DOI](https://doi.org/10.1002/cphy.c210051) \| [PubMed](https://pubmed.ncbi.nlm.nih.gov/36715282/)
3.  Fakhouri F, Roumenina L, Provot F, et al. Pregnancy-associated hemolytic uremic syndrome revisited in the era of complement gene mutations. *J Am Soc Nephrol* 2010. [PubMed 20203157](https://pubmed.ncbi.nlm.nih.gov/20203157/).
4.  Zheng XL, Vesely SK, Cataland SR, et al. ISTH guidelines for the diagnosis of thrombotic thrombocytopenic purpura. *J Thromb Haemost* 2020. [PubMed 32914582](https://pubmed.ncbi.nlm.nih.gov/32914582/).
5.  Piccoli GB, Conijn A, Consiglio V, et al. Pregnancy in dialysis patients: is the evidence strong enough to lead us to change our counseling policy? *Clin J Am Soc Nephrol* 2010. [PubMed 19965547](https://pubmed.ncbi.nlm.nih.gov/19965547/).
6.  Jim B, Garovic VD. Acute Kidney Injury in Pregnancy. *Semin Nephrol* 2017. [PubMed 28711077](https://pubmed.ncbi.nlm.nih.gov/28711077/).
7.  Kuklina EV, Ayala C, Callaghan WM. Hypertensive disorders and severe obstetric morbidity in the United States. *Obstet Gynecol*. 2009;113(6):1299-1306. [PubMed](https://pubmed.ncbi.nlm.nih.gov/19461426/)
8.  Wiles KS, Furniss G, Amos A, et al. Clinical practice guideline on pregnancy and renal disease. *BMC Nephrol*. 2019;20:401. [PubMed](https://pubmed.ncbi.nlm.nih.gov/31672135/)


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