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Acute kidney injury (acute renal failure) in pregnancy

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Acute kidney injury (acute renal failure) in pregnancy Author Phyllis August, MD, MPH James N George, MD

Section Editor Charles J Lockwood, MD Paul M Palevsky, MD

Deputy Editor Alice M Sheridan, MD

Last literature review for version 17.1: enero 1, 2009 | This topic last updated: octubre 8, 2008 INTRODUCTION — Acute renal failure in pregnancy can be induced by any of the disorders leading to renal failure in the general population, such as acute tubular necrosis. There are, however, pregnancy complications characteristic of each trimester that can result in renal failure [1,2]. Early in pregnancy, for example, the most common problems are prerenal disease due to hyperemesis gravidarum or acute tubular necrosis, resulting from a septic abortion. Several different uncommon disorders can lead to acute renal failure later in pregnancy [1,2]. Mild to moderate preeclampsia is not part of this differential diagnosis, since renal function is generally maintained in the normal or near normal range. (See "Clinical features, diagnosis, and long-term prognosis of preeclampsia"). THROMBOTIC MICROANGIOPATHY — An important and difficult differential diagnosis is that of acute renal failure in late pregnancy in association with microangiopathic hemolytic anemia and thrombocytopenia. There are two main entities that must be considered: thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) and severe preeclampsia, usually with the HELLP syndrome (hemolysis with a microangiopathic blood smear, elevated liver enzymes, and a low platelet count) [1,3-7]. (See "HELLP syndrome"). The distinction between TTP-HUS and severe preeclampsia is important for therapeutic and prognostic reasons. However, the clinical and histologic features are so similar that establishing the correct diagnosis is often difficult. Most important are the history (eg, preceding proteinuria and hypertension favor preeclampsia) and the time of onset [3,4,7]: Preeclampsia typically develops in the late third trimester, including the intrapartum period; only a few percent of cases develop in the postpartum period, usually in the first 24 to 48 hours. Preeclampsia does not occur before twenty weeks gestation in non-molar pregnancies, except occasionally in the presence of thrombophilias, such as the antiphospholipid antibody syndrome. TTP and HUS had been considered by some as separate diseases. However, they have indistinguishable clinical and pathologic features and are best considered part of a spectrum of disease. (See "Causes of thrombotic thrombocytopenic purpura-hemolytic uremic syndrome in adults"). Women who present with a clinical picture usually associated with TTP (eg, fever, neurological symptoms, and microangiopathy) are more likely to present antepartum, whereas those with significant renal failure (which is more typical of classical HUS) more frequently present in the postpartum period. When TTP-HUS occurs antepartum, it may occur as early as the first or early second trimester (see below) [8]. Preeclampsia — Severe preeclampsia, which is much more common than TTP-HUS, is usually preceded by characteristic clinical features of hypertension, proteinuria, and severe edema. Renal failure is relatively unusual even with severe cases, unless there is significant bleeding with hemodynamic instability or marked disseminated intravascular coagulation (DIC) [5]. However, a mild

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degree of azotemia may occur, due in part to reduced permeability of the glomerular capillary wall [9]. Severe preeclampsia is an indication for urgent delivery. The renal and extrarenal abnormalities typically begin to resolve spontaneously within two to three days postpartum and virtually complete recovery occurs within eight weeks postpartum [6,10]. In some cases, however, preeclampsia begins in the postpartum period without prior proteinuria and may be difficult to initially differentiate from postpartum HUS [3,7]. Only the subsequent spontaneous recovery will point toward preeclampsia in this setting. Generalized coagulopathy may be present when severe abruptio placentae, hepatic rupture, or liver failure complicate preeclampsia. Low levels of clotting factors, if present, are important diagnostically since they are almost always absent in TTP-HUS in which increased platelet consumption and thrombocytopenia are the primary abnormalities. (See "Clinical features, diagnosis, and long-term prognosis of preeclampsia" and see "Causes of thrombotic thrombocytopenic purpura-hemolytic uremic syndrome in adults"). Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome — TTP-HUS is characterized by the otherwise unexplained combination of thrombocytopenia and microangiopathic anemia, generally in association with a renal thrombotic microangiopathy [3,4,7]. The association of TTP-HUS with pregnancy is suggested by observations in all case series with 10 or more patients reported since 1966 that the diagnosis is made during pregnancy or postpartum in 13 percent of all women with TTP-HUS [11]. Patients have been traditionally considered to have TTP when neurologic abnormalities are dominant and acute renal failure is minimal or not present, and considered to have HUS when acute renal failure is dominant and neurologic abnormalities are minimal or absent; however, these distinctions are frequently unclear and may not be important for management decisions. (See "Treatment of thrombotic thrombocytopenic purpura-hemolytic uremic syndrome in adults"). This clinical distinction may represent a true pathogenetic difference, as severe deficiency in the von Willebrand factor cleaving protease (ADAMTS13) is rarely present in patients with acute renal failure [12]. The thrombotic state in some patients antiphospholipid antibodies may be indistinguishable from TTP-HUS. (See "Clinical manifestations of the antiphospholipid syndrome"). The time of onset is variable. In one report of 13 pregnancies complicated by TTP-HUS, three developed before midpregnancy, eight peripartum, and two several weeks postpartum [13]. Postpartum disease may follow a normal pregnancy or be preceded by findings indistinguishable from preeclampsia [3,4,7]. ADAMTS13 levels tend to fall during the last two trimesters of pregnancy, which could contribute to the time course of development of TTP-HUS [14]. In addition to de novo disease, TTP-HUS that initially occurred in nonpregnant women has relapsed during a subsequent pregnancy and recurrent TTP-HUS has developed during successive pregnancies [13,15,16]. However, most subsequent pregnancies are uncomplicated and most children survive [17]. (See "Treatment of thrombotic thrombocytopenic purpura-hemolytic uremic syndrome in adults"). The distinction between the HELLP variant of severe preeclampsia and TTP-HUS is difficult since both are characterized by microangiopathy and low platelet count. The presence of elevated liver enzymes is strongly suggestive of HELLP syndrome, and is an uncommon feature of TTP-HUS. In contrast to patients with typical TTP, who have severe deficiencies of ADAMTS13, plasma levels of ADAMTS13 are only mildly or moderately reduced in patients with HELLP syndrome [18]. Acute fatty liver of pregnancy (see below), a late pregnancy syndrome, has many features of both HUS-TTP and HELLP syndrome, and can be particularly difficult to identify. Women with this disorder will have elevated liver enzymes, similar to those with HELLP syndrome; however, they frequently develop more severe azotemia and consumptive coagulopathy.

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Although a kidney biopsy may distinguish TTP-HUS from preeclampsia, it is typically not initially considered because of thrombocytopenia and the anticipated complete recovery. If the thrombocytopenia and hemolysis resolve but renal failure persists, a kidney biopsy may be appropriate to define the etiology and anticipate the prognosis for recovery of renal function. Renal biopsy is rarely, if ever, indicated to distinguish HELLP, acute fatty liver of pregnancy (AFLP), or TTP-HUS, and careful consideration of the clinical presentation in association with the pattern of laboratory abnormalities is usually sufficient to make an accurate diagnosis. Preeclampsia/HELLP syndrome usually resolves within days of delivery, and most women do not have permanent, detectable renal sequelae. Women with TTP/HUS may present diagnostic challenges, especially when recovery is prolonged. However, since women with microangiopathic disorders are more prone to bleeding and may also be hypertensive, biopsy is more likely to be associated with complications, and the risks and benefits must be carefully considered. Treatment — The optimal therapy of TTP-HUS developing in association with pregnancy is the same as for patients who are not pregnant [19]. One report evaluated 11 pregnant women, eight who were considered to have TTP and three who were considered to have HUS [8]. The patients were treated with plasma infusion with or without plasma exchange, similar to the regimen used in the management of other forms of TTP-HUS. Two women died, four had chronic renal insufficiency (one with a residual neurologic deficit), and five recovered without significant residua. These relatively encouraging results, which have also been noted in case reports [20], were much better than the approximately 90 percent mortality rate reported prior to the use of plasma exchange [21]. (See "Treatment of thrombotic thrombocytopenic purpura-hemolytic uremic syndrome in adults"). The treatment of the HELLP variant of preeclampsia is also controversial. Delivery is indicated, and although some of the laboratory features may worsen immediately after delivery, they usually resolve within one week postpartum, without any specific therapy. Corticosteroids have been utilized in one center, with some success; however, large randomized clinical trials have not been performed. (See "HELLP syndrome", section on Treatment). ACUTE FATTY LIVER OF PREGNANCY — Acute fatty liver (fatty infiltration of hepatocytes without inflammation or necrosis) is a rare complication of pregnancy that is associated with acute renal failure in up to 60 percent of cases [2,22]. The diagnosis should be suspected in a woman with preeclampsia who has hypoglycemia, hypofibrinogenemia, liver function test abnormalities, and a prolonged PTT in the absence of abruptio placentae [23]. Most patients with renal failure have evidence of decreased renal perfusion or acute tubular necrosis. Therapy consists of treatment of DIC and immediate delivery of the fetus [2,23]. The laboratory abnormalities frequently begin to improve within one to two days after delivery [23]. (See "Acute fatty liver of pregnancy"). RENAL CORTICAL NECROSIS — Bilateral renal cortical necrosis (or, in less severe cases, acute tubular necrosis) may be induced during pregnancy by abruptio placentae or other severe complications such as placenta previa, prolonged intrauterine fetal death, or amniotic fluid embolism [2,24,25]. Both primary DIC and severe renal ischemia (leading to endothelial damage and secondary fibrin deposition) have been proposed as the initiating event in this disorder. When endothelial injury does occur, the local release of nitric oxide (endothelium-derived relaxing factor) normally minimizes the degree of thrombus formation by diminishing platelet aggregation. If, however, the endothelial dysfunction is so great that nitric oxide release is impaired, then the tendency to thrombosis will be accelerated [26]. Affected patients typically have one of the above complications of pregnancy and then develop the abrupt onset of oliguria or anuria, frequently accompanied by gross hematuria, flank pain, and hypotension [24,25]. The triad of anuria, gross hematuria, and flank pain is unusual in the other causes of renal failure in pregnancy. The diagnosis can usually be established by ultrasonography or CT scanning, which demonstrate hypoechoic or hypodense areas in the renal cortex [24]. Renal biopsy or arteriography also can be performed, but these invasive procedures are not required in most cases. Renal calcifications on plain

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film of the abdomen also suggests renal cortical necrosis, but this is a late consequence of healing and is not visible for one to two months. No specific therapy has been shown to be effective in this disorder. Many patients require dialysis, but 20 to 40 percent have partial recovery with a creatinine clearance that stabilizes between 15 and 50 mL/min [25]. ACUTE PYELONEPHRITIS — Although renal function is generally well maintained during episodes of acute pyelonephritis (in the absence of septicemia or hypotension), some pregnant women can develop acute renal failure [2,27]. Renal biopsy in this setting may reveal focal microabscesses and recovery after appropriate antimicrobial therapy may be incomplete due to irreversible injury. URINARY TRACT OBSTRUCTION — Relaxation of ureteral smooth muscle and pressure on the ureters by the gravid uterus typically result in mild to moderate dilatation of the collecting systems [28,29]. (See "Renal and urinary tract physiology in pregnant women"). This functional hydronephrosis, which tends to be more prominent on the right, is detectable by ultrasonography but is not usually associated with renal dysfunction. Rarely, the degree of obstruction is sufficient to cause renal failure [28]. The diagnosis can be established in some cases by the normalization of renal function in the lateral recumbent position (which relieves pressure on the ureters by the uterus) and its recurrence when supine. In some cases, however, either insertion of a ureteral catheter or delivery of the fetus is required [29]. Acute obstructive renal failure in pregnancy has also been reported in association with enlarged uterine myomata [30]. Nephrolithiasis — Rarely, acute urinary tract obstruction in pregnancy is induced by a kidney stone [31,32]. Since this process is unilateral, affected women present with acute flank pain and microscopic or gross hematuria, rather than renal failure. The diagnosis can usually be established by renal ultrasonography. Approximately 70 to 85 percent of stones pass spontaneously, due in part to the normally relaxed and dilated collecting systems. Cystoscopy with insertion of a ureteral stent or use of a thin, rigid ureteroscope to remove or fragment the stone may be required in the patient who is septic, has severe pain, or has obstruction in a solitary functioning kidney [31,32].

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Acute kidney injury (acute renal failure) in pregnancy