Nephrology Hypertension

Pre-eclampsia

Does this patient have pre-eclampsia?

How do you diagnose pre-eclampsia?

Pre-eclampsia is defined as the new onset of hypertension (BP > 140/90) and proteinuria (≥ 300 mg protein in a 24 hr urine collection) after 20 weeks of gestational age. Hypertension plus other signs such as thrombocytopenia, elevated serum transaminase levels, or systemic organ failure may be sufficient for the diagnosis in the absence of proteinuria. It affects 5-7% of all pregnancies and is responsible for approximately 60,000 maternal deaths every year, mainly in third world countries.

Eclampsia is a life-threatening complication and is characterized by grand mal seizures. A severe variant of preeclampsia features hemolysis elevated liver function tests, and low platelets (HELLP syndrome).

Proteinuria is one of the essential criteria for the clinical diagnosis of pre-eclampsia. Proteinuria occurs due to glomerular endotheliosis, a manifestation of extensive endothelial damage in preeclampsia.

Severe pre-eclampsia is defined as: Systolic blood pressure at least 160 mmHg or diastolic pressure of 110 mmHg, proteinuria of at least 5 g/24 h, platelet count below 100,000 /�L, elevated serum transaminases, oliguria, pulmonary edema, epigastric pain, or cerebral or visual disturbances

What tests to perform?

Blood pressure measurement, urine dipstick testing, Protein/creatinine ratio in random sample of urine, full blood count, liver function tests, renal function tests, clotting studies.

How should patients with pre-eclampsia be managed?

The only known cure for pre-eclampsia is delivery. If a patient is diagnosed with pre-eclampsia and is near term, induction of labor is the most accepted practice. If the patient is preterm, admission to the hospital is considered and the pregnancy is closely monitored. In some instances glucocorticoids are given to promote fetal lung maturity.

The pregnancy is permitted to continue as long as blood pressure remains well controlled and there are no significant laboratory abnormalities; ie, low platelets, abnormal liver function tests, worsening kidney function ie, worsening creatinine, oliguria or the presence of severe growth retardation which would favor delivery. There are multiple antihypertensives used in current clinical practice, which have proven to be of benefit in the treatment of hypertension in pregnant women, the most common ones used in practice are, labetalol, nifedipine, hydralazine and methyldopa.

Delivery is considered at any stage of pregnancy if hypertension is severe and remains uncontrolled for 24-48 hours. Other indications for delivery include the presence of liver abnormalities, decreasing GFR, headache, epigastric discomfort, seizures or the presence of severe growth retardation or abnormal fetal testing.

The NHBPEP recommends that diastolic BP levels of 105 mmHg be treated.

Management of convulsions in eclampsia has been accomplished with IVmagnesium sulphate. This approach is superior to diazepam or phenytoin for both prevention and treatment.

It appears that maternal and fetal clinical condition, gestational age, biochemical and hematological parameters remain the primary determinants for timing delivery in women with preeclampsia

Common indications for delivery before 34-35 week’s gestation are:

  • - Uncontrollable blood pressure

  • - Deteriorating renal function and oliguria

  • - Pulmonary edema

  • - Persistent HELLP syndrome

  • - Deteriorating liver function

  • - Eclampsia

Magnesium sulfate is the drug of choice for prevention of eclampsia and further seizure.

What happens to patients with pre-eclampsia?

Most women with pre-eclampsia become normotensive within 2 weeks of delivery. This may be the result of a slower rate of recovery of damaged endothelial cells, which is a hallmark of pre-eclampsia. The pathogenesis of pre-eclampsia is discussed elsewhere.

The kidney is the organ most likely to be affected by endothelial injury in pre-eclampsia. Kidney injury is rare but can be seen in severe disease. Oliguria (urine output < 500cc/day) indicates a much more severe clinical picture. Sudden onset or worsening of edema is a cause of concern in pre-eclamptic patients. Thrombocytopenia and liver damage are other clinical manifestations.

Central nervous system (CNS) effects include headache and blurred vision with hyperreflexia. Seizures indicate a progression to eclampsia and require immediate delivery of the fetus. This may include pathological correlates of hemorrhage, ischemic brain damage, petechiae. Pulmonary edema can also be seen in progressive disease. Patients with pre-eclampsia are at higher risk for future cardiovascular and cerebrovascular disease, as well as end-stage renal disease, although the absolute risk is low.

Patients with severe pre-eclampsia or eclampsia should be hospitalized immediately, considered for prompt delivery, given intravenous magnesium sulfate for seizure treatment or prophylaxis, and treated with intravenous therapies to control blood pressure. This includes consideration for intravenous labetolol or hydralazine, oral nicardipine or sustained action oral nifedipine.

Are there clinical practice guidelines to inform decision making?

  • The management of severe pre-eclampsia and eclampsia, London (UK): Royal College of Obstetricians and Gynaecologists

  • ACOG practice bulletin on diagnosing and managing preeclampsia and eclampsia

Other considerations

Recent findings in clinical trials have shown elevated soluble endoglin levels, an endogenous antiangiogenic protein of placental origin, in women with preeclampsia before of the onset of symptomatology. Similar elevated levels of sFlt1 (circulating soluble fms-like tyrosine kinase 1) have been seen in patients with pre-eclampsia, and by the time pre-eclamptic manifestations are pronounced, these levels have been found to be two to four times the levels found in normal pregnancy.

Meta-analysis that included more than 32,000 women suggested a small but significant reduction of the relative risk for pre-eclampsia with the use of aspirin (RR 0.81-0.90)

Indications to quantify proteinuria in pregnant individuals:

  1. Monitoring proteinuria in the setting of proteinuric CKD

  2. Diagnosis of pre-eclampsia

Twenty-four hour urine collection remains the gold standard for protein quantification. Protein/creatinine ratios in random urine samples to assess proteinuria remains controversial, but it has become an accepted clinical practice. When a result is suspected to be equivocal a 24 hr urine collection should be pursued.

What is the evidence?

Abalos, E, Duley, L, Steyn, DW, Henderson-Smart, DJ. "Antihypertensive drug therapy for mild to moderate hypertension during pregnancy". Cochrane Database Syst Rev Jan. vol. 24. 2007. pp. CD002252.

Lindheimer, MD, Taler, SJ, Cunningham, FG. "Hypertension in pregnancy". J Am Soc Hypertens Mar-Apr. vol. 4. 2010. pp. 68-78.

Podymow, T, August, P. "Postpartum course of gestational hypertension and pre-eclampsia". Hypertension in Pregnancy. vol. 25. 2006. pp. 210.

Visintin, C, Mugglestone, MA, Almerie, MQ. "management of hyeprtensive disorders during pregnancy: summary of NICE guidance". BMJ. vol. 341. 2010. pp. c2007.

Tuffnell, DJ, Shennan, AH, Waugh, JJ. "The management of severe pre-eclampsia/eclampsia". Royal College of Obstetricians and Gynaecologists. 2006.

Thangaratinam, S, Coomarasamy, A, O’Mahoney, F. "Estimation of proteinuria as a predictor of complications for pre-eclampsia: a systematic review". BMC Medicine. vol. 7. 2009. pp. 1-9.

Davison, JM. "Renal disorders in pregnancy". Curr Opin Obstet Gynecol. vol. 3. 2001. pp. 109-114.

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