Acute Kidney Injury in Pregnancy

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Summary: Pregnancy-related acute kidney injury (AKI) has declined in incidence in the last three decades, although it remains an important cause of maternal and fetal morbidity and mortality. Pregnancy-related causes of AKI such as preeclampsia, acute fatty liver of pregnancy, HELLP (Hemolysis, Elevated Liver function tests, Low Platelets) syndrome, and the thrombotic microangiopathies (thrombotic thrombocytopenic purpura, atypical hemolytic-uremic syndrome [HUS]) exhibit overlapping features and often present as diagnostic dilemmas. Differentiating among these conditions may be difficult or impossible based on clinical criteria only. In difficult and rare cases, a renal biopsy may need to be considered for the exact diagnosis and to facilitate appropriate treatment, but the risks and benefits need to be carefully weighed. The use of eculizumab for the treatment of atypical HUS has demonstrated efficacy in early case reports. Non–pregnancy related causes such as volume depletion and pyelonephritis require early and aggressive resuscitative as well as antibiotic measures respectively. We will discuss in this review the various etiologies of AKI in pregnancy, current diagnostic approaches, and the latest treatment strategies. Given the recent trends of increasing maternal age at the time of pregnancy, and the availability of modern reproductive methods increase the risks of AKI in pregnancy in the coming years.

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Renal Outcomes

Renal outcomes complicated by AKI are determined by cause, demographics, and availability of health care resources. A recent Canadian report showed that AKI resulting in the need for dialysis occurred in 1 per 10,000 pregnant women, where 4.3% of these women died compared to 0.01% of pregnant women who did not experience kidney injury; 3.9% who remained on dialysis for up to four months after delivery.5 The most common reasons for AKI in this study included preeclampsia, thrombotic

Diagnosis

The diagnosis of AKI in pregnancy has not been standardized either in practice or research. The definitions can range from an increase in the serum creatinine to the need for dialysis. This is further confounded by the physiologic decrease in serum creatinine seen in pregnancy. The frequently cited RIFLE (Risk, Injury, Failure, Loss and End stage)7 and the AKIN (Acute Kidney Injury Network) criteria8 for the nonpregnant population have not been well validated in pregnancy. More recent obstetric

Differential Diagnosis

There are numerous etiologies for AKI in pregnancy; the majority are pregnancy-related, but some are not. It is useful to categorize the types of AKI into prerenal, renal, and postrenal etiologies, as in the nonpregnant population. For prerenal causes, it is generally a hemodynamic disturbance that starts with a reversible reduction in the glomerular filtration rate, leading to ischemic acute tubular damage and resulting in irreversible cortical necrosis in the most extreme cases. These insults

Timing of AKI

The timing of AKI during pregnancy may serve as an important clue as to the underlying etiology (Fig. 1). In developing countries, AKI that occurs in the first trimester frequently is due to septic abortions or lupus nephritis. The vast majority of AKI occurring in the second and third trimesters is due to hypertensive complications such as preeclampsia/HELLP, TTP/HUS, abruptio placentae, severe hemorrhage or disseminated intravascular coagulation, or AFLP. Atypical HUS, however, generally

Atypical Hus in Pregnant Patients in the Age of Eculizumab

Ninety percent of HUS cases are associated with diarrhea, typically due to Shiga-like toxin–producing Escherichia coli.16 The remaining 10% are classified as atypical HUS and are caused by the activation of the alternative complement pathway (ACP) that can be either familial (due to mutations in genes that code for proteins in the ACP pathway) or more commonly be sporadic (~80% of cases). Although pregnancy is one of several known triggers of abnormal complement activation leading to sporadic

Preeclampsia/HELLP

AKI as a complication of preeclampsia affects only about 1% of cases.25 However, when it is associated with HELLP, AKI is much more common, occurring in 7% to 15% of cases.26, 27 Although the diagnosis of preeclampsia is commonly based on new-onset hypertension and proteinuria after 20 weeks’ gestation, other conditions such as AFLP, TTP, atypical HUS, and lupus nephritis, may also exhibit these findings. The clinical clues to help make an accurate diagnosis are listed in Table 2. Furthermore,

Acute Fatty Liver of Pregnancy

AFLP is a rare entity that occurs in ~1 in 10,000 deliveries.33 Its pathogenesis is attributed to a fetal deficiency of long-chain 3-hydroxyl coenzyme A dehydrogenase (LCHAD), which leads to excess fetal free fatty acids that cross the placenta and are hepatotoxic to the mother.34 Women usually present in the third trimester with fatigue, vomiting, headache, hypoglycemia, and lactic acidosis. Laboratory abnormalities include hepatic derangements such as increases in the transaminases, alkaline

Pyelonephritis

Pyelonephritis, although neither specific nor more frequent45 in pregnancy, may be much more severe. The high incidence of asymptomatic bacteriuria during pregnancy may occur due to anatomic and physiologic changes of the urinary tract. When bacteriuria becomes symptomatic, it is likely to progress to cystitis, pyelonephritis, or even sepsis with severe maternal complications. Untreated bacteriuria has also been shown to lead to low birth weight and preterm delivery, whereas its eradication has

Postrenal AKI

Postrenal causes of AKI are uncommon in pregnancy. Ureteral and bladder outlet obstruction should always be considered as with the nonpregnant population. However, iatrogenic injuries to the bladder and ureters are extremely rare and are usually a result of emergent cesarean sections. The incidences of iatrogenic injuries range from 0.0016% to 0.94% in different parts of the world.61, 62, 63 Women who are at highest risk are those with ectopic kidneys or duplication of ureters. Another rare

Management of AKI

General measures to treat pregnancy-related AKI include identification of the underlying source of injury, volume resuscitation, prevention of further injury, timely initiation of renal replacement therapy, and prompt delivery of fetus, if necessary. Volume repletion is crucial in prerenal states although the rate of volume replacement needs to be carefully monitored, as women with either endotoxin-mediated injury or preeclampsia can easily develop pulmonary edema. Complications of AKI can be

Conclusion

Although the overall incidence of AKI in pregnancy in most of the world is declining, the absolute numbers of deaths from AKI remain unacceptably high. Diagnosis of pregnancy-related AKI is not always straightforward and can be quite challenging in those with overlapping features such as preeclampsia/HELLP, AFLP, HUS/TTP, atypical HUS, and lupus nephritis. Clinical judgment and experience become paramount in making an accurate diagnosis. Measuring angiogenic factors may prove to be helpful in

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