Second and Third Trimester

7.5.2.1 Preeclampsia and Hemolysis, Elevated Liver Enzymes, and Low Platelets (HELLP) Syndrome

Preeclampsia is a pregnancy-specifi c condition generally defi ned as the new onset of persistent hypertension (diastolic blood pressure ≥90 mmHg) and proteinuria (≥300 mg in a 24-h urine collection) at or after 20 weeks’ gestation [ 17 ]. It is hypothesized that a disturbance in the placental function in early pregnancy causes preeclampsia, with a particular role for the impaired remodeling of the spiral artery [ 18 ]. Preeclampsia can be asymptomatic, especially in the early stages or with mild disease, but symptoms can include epigastric and right upper quadrant pain (40–

90 %), headache, visual changes, nausea, and vomiting [ 19 ]. Severe preeclampsia and the HELLP syndrome account for about 40 % of cases of AKI in pregnancy [ 20 ]. Although preeclampsia is one of the most important causes of pregnancy- related AKI, the majority of preeclamptic patients do not develop severe AKI. Otherwise, severe preeclampsia, characterized by multiple organ involve-ment (i.e., pulmonary edema, oliguria [<500 mL/24 h], and thrombocytopenia [platelet count <100,000 μL]) has a higher risk for AKI. The incidence of overt renal failure in severe preeclampsia is estimated at 1.5–2 % based on two case series [ 21 , 22 ].

Severe preeclampsia is a progressive condition requiring prompt attention of the clinician. Women at term diagnosed with preeclampsia are best managed by induc-tion of labor. After giving birth the symptoms usually resolve, but in some women the symptoms worsen during the fi rst 48 h postpartum. These women are particu-larly at risk for pulmonary edema, AKI, HELLP syndrome, and stroke [ 18 ].

The HELLP syndrome can occur in 4–14 % of cases of preeclampsia.

Characteristic laboratory abnormalities of HELLP syndrome include microangio-pathic hemolysis (anemia, decreased haptoglobin, increased lactate dehydrogenase [LDH], and a peripheral blood smear with signs of red cell destruction), elevated liver enzymes, and low platelet count. The platelet count is a marker of the severity of the disease and coincides with liver impairment [ 23 ].

7.5.2.2 Thrombotic Microangiopathies

Thrombotic microangiopathies (TMA) are defi ned by the occurrence of thrombi of fi brin and/or platelets in the microcirculation of multiple organs. TMA during preg-nancy are very uncommon cause for AKI. Pregpreg-nancy-related TMA used to be sub-typed as thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). Recently TMA has been reclassifi ed into four subtypes, and preg-nancy is considered only a precipitating factor [ 24 ].

Treatment of TMA should be aimed at treating the underlying pathogenic mech-anism in a multidisciplinary approach, which can be either fresh frozen plasma infusions with or without plasma exchange or inhibition of complement activation by eculizumab, as recently advocated by Fakhouri [ 24 ].

It can be a diagnostic challenge to differentiate TMA and preeclampsia/HELLP because thrombocytopenia and microangiopathic hemolytic anemia can present in both syndromes. Historical features such as the time of onset (after 20 weeks of gestation), earlier reported proteinuria, elevated liver enzymes, and/or hypertension support a diagnosis of preeclampsia/HELLP.

7.5.2.3 Acute Fatty Liver of Pregnancy

Acute fatty liver of pregnancy (AFLP) is a rare complication, with reported inci-dence of between 1 in 7,000 and 1 in 20,000 pregnancies [ 25 , 26 ]. AFLP is charac-terized by acute liver failure and coagulopathy with sudden onset during the third trimester. The severity of liver involvement is variable, ranging from moderate iso-lated hepatic transaminase elevations to fulminant liver failure with encephalopathy [ 25 ]. Other features include elevated bilirubin, prolonged partial thromboplastin time, thrombocytopenia, hypoglycemia, and anemia [ 27 ]. Acute (typically nonoli-guric) kidney dysfunction is common and seen in approximately 60 % of patients.

Renal recovery typically follows delivery and dialysis is rarely needed [ 25 , 27 ].

Early diagnosis, supportive measures, and prompt delivery are critical in the man-agement. Clinical clues help to distinguish AFLP and HELLP syndrome, although the distinction is academic since the appropriate treatment of both conditions is prompt delivery.

7.5.2.4 Renal Cortical Necrosis

Renal cortical necrosis (RCN) is a rare condition in the developed world. In the developing world reported RCN has become more infrequent over the last decades [ 28 ]. In a prospective cohort study of over 4,500 late pregnancy-related AKI, Prakash et al. found AKI occurred in 1 in 56 live births (85 cases), of which only two were attributed to RCN [ 3 ]. RCN presents characteristically on ultrasound or CT-scan with hypoechoic or hypodense areas in the renal cortex. Calcifi cations are a late fi nding, usually occurring after 1–2 months. Treatment is supportive, with a signifi cant chance for persistent loss of kidney function and need for renal replace-ment therapy.

7.5.2.5 Infectious Complications Contributing to AKI during Pregnancy

Pregnant patients are at risk for four specifi c infectious complications: urinary tract infections, chorioamnionitis (including septic abortion), endometritis (often post Caesarean section), and pneumonia. Progression to sepsis and septic shock is extraordinary, but poses signifi cant mortality for mother and child. Urinary tract infections and sepsis may cause AKI.

Urinary Tract Infections

Asymptomatic bacteriuria is present in 2–10 % of women, both in the general popu-lation and in pregnant women. In diabetics and patients with sickle cell trait as well as women from a lower socioeconomic status the percentage is higher. Approximately 40 % of this group will develop cystitis or pyelonephritis. Urine sediment and cul-ture will help in selecting directed therapy to prevent development of sepsis or severe sepsis with multiple organ failure. Symptomatic urinary tract infections are usually caused by Escherichia coli bacteria. Resistant bacteria may cause perineph-ric abscess, kidney carbuncle, or cortical abscess, although rare.

Sepsis/Multiple Organ Failure

Sepsis is an infrequent cause of severe AKI in pregnancy. In 2009 the H1N1 infl u-enza unexpectedly caused severe illness and death in pregnant and postpartum women. During the infl uenza season, evaluation and antiviral treatment of infl uenza- like illnesses should be considered early in this patient population [ 29 ].

7.5.2.6 Urinary Tract Obstruction and Nephrolithiasis

The physiologic hydronephrosis of pregnancy seldom promotes ureteral obstruction due to the growing uterus or polyhydramnios. Stenting of the ureters may be indicated if delivery is not yet recommended. Obstruction may be induced by kidney stones, but is usually unilateral and presents with acute fl ank pain, hematuria and not with AKI.

7.6 Prevention

Care for pregnant women with AKI requires a multidisciplinary approach including maternal–fetal medicine, nephrology, critical care, and neonatal care specialists.

Renal replacement therapy may be indicated in a select group of women. There is little evidence in the literature for optimal modality selection. The choice of modal-ity should largely be predicated on the hemodynamic profi le of the patient and its availability. There is also a paucity of literature describing the RRT utilization rates for pregnancy-related AKI and outcomes for either mother or baby. Maternal preex-isting hypertension and kidney disease are considered risk factors for incident chronic kidney disease and progression to long-term renal replacement therapy [ 30 ].

Key Messages

• Pregnancy-related acute kidney injury (AKI) is an unusual clinical chal-lenge and requires a multidisciplinary approach

• Pregnancy-related AKI is associated with signifi cant maternal and fetal morbidity and mortality

• Physiological changes hamper normal laboratory testing of kidney function

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