Acute Kidney Injury in Pregnancy: The Changing Landscape for the 21st Century

Abstract

Pregnancy-related acute kidney injury (Pr-AKI) remains a large public health problem, with decreasing incidences in developing countries but seemingly increasing incidences in the United States and Canada. These epidemiologic changes are reflective of the advances in medical and obstetric care, as well as changes in underlying maternal risk factors. The risk factors associated with advanced maternal age, such as hypertension, diabetes, chronic kidney disease, and those associated with reproductive technologies such as multiple gestations, are increasing. Traditional causes of Pr-AKI, such as septic abortions and puerperal sepsis, have been replaced by hypertensive diseases, such as preeclampsia and thrombotic microangiopathies comprising thrombotic thrombocytopenic purpura (TTP) and atypical hemolytic uremic syndrome (aHUS). In this review, we discuss the global impact of Pr-AKI on maternal and fetal outcomes, the predominant etiologies, and key clinical features to distinguish diagnoses, such as preeclampsia/hemolysis elevated liver function test and low platelet (HELLP) syndrome, acute fatty liver disease of pregnancy (AFLP), and other thrombotic microangiopathies. New insights into the pathogenesis of preeclampsia, TTP/aHUS, and AFLP that have unearthed possible therapeutic targets are summarized. We also delve into special consideration needed to give to pyelonephritis and postobstructive causes of Pr-AKI. With each diagnosis, we offer the latest treatment recommendations, such as the positive reports from the use of eculizumab to treat aHUS. In the end, we hope to arm the clinician with the best tools to understand and address this morbid problem that does not seem to be disappearing.

Keywords: acute fatty liver of pregnancy; acute kidney injury; atypical hemolytic uremic syndrome; preeclampsia; pregnancy; pyelonephritis.

Figure 1

Main causes of pregnancy-related acute kidney injury with overlapping clinical features. ADAMTS-13, ADAM metallopeptidase with thrombospondin type 1 motif 13; aHUS, atypical hemolytic-uremic syndrome; ATN, acute tubular necrosis; D, delivery; HELLP, hemolysis, elevated liver function test, and low platelets; LCHAD, long-chain 3-hydroxyl coenzyme A dehydrogenase; LDH, low-density lipoprotein; TTP, thrombotic thrombocytopenic purpura. ∗Updated diagnostic criteria of preeclampsia: New onset hypertension after 20 weeks of gestation (defined by blood pressure ≥140 mm Hg systolic or ≥90 mm Hg diastolic on 2 occasions at least 4 hours apart or blood pressure ≥ 160 mm Hg or ≥ 110 mm Hg confirmed within a short period [minutes] to facilitate timely antihypertensive therapy) AND proteinuria (defined by ≥ 300 mg/24 h urinary collection, protein/creatinine ratio of ≥ 0.3, or urine dipstick reading of 1+) OR in the absence of proteinuria with thrombocytopenia (platelet count of <100,000/µl), renal insufficiency (serum creatinine ≥ 1.1 mg/dl or doubling of serum creatinine), impaired liver function (transaminases elevated to twice the normal concentration), pulmonary edema, or cerebral or visual symptoms.