acute kidney injury (acute renal failure) in pregnancy

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Acute kidney injury (acute renal failure) in pregnancy

AuthorPhyllis August, MD, MPHJames N George, MD

Section EditorCharles J Lockwood, MDPaul M Palevsky, MD

Deputy EditorAlice 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 leadingto 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 inpregnancy, for example, the most common problems are prerenal disease due to hyperemesisgravidarum or acute tubular necrosis, resulting from a septic abortion. Several different uncommondisorders can lead to acute renal failure later in pregnancy [1,2]. Mild to moderate preeclampsia isnot part of this differential diagnosis, since renal function is generally maintained in the normal ornear normal range. (See "Clinical features, diagnosis, and long-term prognosis of preeclampsia").

THROMBOTIC MICROANGIOPATHY — An important and difficult differential diagnosis is that ofacute renal failure in late pregnancy in association with microangiopathic hemolytic anemia andthrombocytopenia. There are two main entities that must be considered: thromboticthrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) and severe preeclampsia, usuallywith 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 prognosticreasons. However, the clinical and histologic features are so similar that establishing the correctdiagnosis is often difficult. Most important are the history (eg, preceding proteinuria and hypertensionfavor preeclampsia) and the time of onset [3,4,7]:

Preeclampsia typically develops in the late third trimester, including the intrapartumperiod; only a few percent of cases develop in the postpartum period, usually in the first 24to 48 hours. Preeclampsia does not occur before twenty weeks gestation in non-molarpregnancies, except occasionally in the presence of thrombophilias, such as theantiphospholipid antibody syndrome.

TTP and HUS had been considered by some as separate diseases. However, they haveindistinguishable clinical and pathologic features and are best considered part of aspectrum of disease. (See "Causes of thrombotic thrombocytopenic purpura-hemolyticuremic syndrome in adults").

Women who present with a clinical picture usually associated with TTP (eg, fever, neurologicalsymptoms, and microangiopathy) are more likely to present antepartum, whereas those withsignificant renal failure (which is more typical of classical HUS) more frequently present in thepostpartum period. When TTP-HUS occurs antepartum, it may occur as early as the first or earlysecond trimester (see below) [8].

Preeclampsia — Severe preeclampsia, which is much more common than TTP-HUS, is usuallypreceded by characteristic clinical features of hypertension, proteinuria, and severe edema. Renalfailure is relatively unusual even with severe cases, unless there is significant bleeding withhemodynamic 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 abnormalitiestypically begin to resolve spontaneously within two to three days postpartum and virtually completerecovery occurs within eight weeks postpartum [6,10]. In some cases, however, preeclampsia beginsin the postpartum period without prior proteinuria and may be difficult to initially differentiate frompostpartum HUS [3,7]. Only the subsequent spontaneous recovery will point toward preeclampsia inthis setting.

Generalized coagulopathy may be present when severe abruptio placentae, hepatic rupture, or liverfailure complicate preeclampsia. Low levels of clotting factors, if present, are important diagnosticallysince they are almost always absent in TTP-HUS in which increased platelet consumption andthrombocytopenia are the primary abnormalities. (See "Clinical features, diagnosis, and long-termprognosis of preeclampsia" and see "Causes of thrombotic thrombocytopenic purpura-hemolyticuremic syndrome in adults").

Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome — TTP-HUS ischaracterized by the otherwise unexplained combination of thrombocytopenia and microangiopathicanemia, generally in association with a renal thrombotic microangiopathy [3,4,7]. The association ofTTP-HUS with pregnancy is suggested by observations in all case series with 10 or more patientsreported since 1966 that the diagnosis is made during pregnancy or postpartum in 13 percent of allwomen with TTP-HUS [11]. Patients have been traditionally considered to have TTP when neurologicabnormalities are dominant and acute renal failure is minimal or not present, and considered to haveHUS 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 managementdecisions. (See "Treatment of thrombotic thrombocytopenic purpura-hemolytic uremic syndrome inadults").

This clinical distinction may represent a true pathogenetic difference, as severe deficiency in the vonWillebrand 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 fromTTP-HUS. (See "Clinical manifestations of the antiphospholipid syndrome").

The time of onset is variable. In one report of 13 pregnancies complicated by TTP-HUS, threedeveloped before midpregnancy, eight peripartum, and two several weeks postpartum [13].Postpartum disease may follow a normal pregnancy or be preceded by findings indistinguishable frompreeclampsia [3,4,7]. ADAMTS13 levels tend to fall during the last two trimesters of pregnancy, whichcould 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 relapsedduring 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 inadults").

The distinction between the HELLP variant of severe preeclampsia and TTP-HUS is difficult since bothare characterized by microangiopathy and low platelet count. The presence of elevated liver enzymesis strongly suggestive of HELLP syndrome, and is an uncommon feature of TTP-HUS. In contrast topatients with typical TTP, who have severe deficiencies of ADAMTS13, plasma levels of ADAMTS13 areonly 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 bothHUS-TTP and HELLP syndrome, and can be particularly difficult to identify. Women with this disorderwill have elevated liver enzymes, similar to those with HELLP syndrome; however, they frequentlydevelop more severe azotemia and consumptive coagulopathy.


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Although a kidney biopsy may distinguish TTP-HUS from preeclampsia, it is typically not initiallyconsidered because of thrombocytopenia and the anticipated complete recovery. If thethrombocytopenia and hemolysis resolve but renal failure persists, a kidney biopsy may beappropriate 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), orTTP-HUS, and careful consideration of the clinical presentation in association with the pattern oflaboratory abnormalities is usually sufficient to make an accurate diagnosis. Preeclampsia/HELLPsyndrome 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 whenrecovery is prolonged. However, since women with microangiopathic disorders are more prone tobleeding and may also be hypertensive, biopsy is more likely to be associated with complications, andthe risks and benefits must be carefully considered.

Treatment — The optimal therapy of TTP-HUS developing in association with pregnancy is thesame as for patients who are not pregnant [19]. One report evaluated 11 pregnant women, eight whowere considered to have TTP and three who were considered to have HUS [8]. The patients weretreated with plasma infusion with or without plasma exchange, similar to the regimen used in themanagement of other forms of TTP-HUS. Two women died, four had chronic renal insufficiency (onewith a residual neurologic deficit), and five recovered without significant residua. These relativelyencouraging results, which have also been noted in case reports [20], were much better than theapproximately 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, andalthough some of the laboratory features may worsen immediately after delivery, they usually resolvewithin one week postpartum, without any specific therapy. Corticosteroids have been utilized in onecenter, 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 withoutinflammation or necrosis) is a rare complication of pregnancy that is associated with acute renalfailure in up to 60 percent of cases [2,22]. The diagnosis should be suspected in a woman withpreeclampsia who has hypoglycemia, hypofibrinogenemia, liver function test abnormalities, and aprolonged PTT in the absence of abruptio placentae [23]. Most patients with renal failure haveevidence of decreased renal perfusion or acute tubular necrosis. Therapy consists of treatment of DICand immediate delivery of the fetus [2,23]. The laboratory abnormalities frequently begin to improvewithin 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, acutetubular necrosis) may be induced during pregnancy by abruptio placentae or other severecomplications 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 secondaryfibrin deposition) have been proposed as the initiating event in this disorder. When endothelial injurydoes occur, the local release of nitric oxide (endothelium-derived relaxing factor) normally minimizesthe degree of thrombus formation by diminishing platelet aggregation. If, however, the endothelialdysfunction is so great that nitric oxide release is impaired, then the tendency to thrombosis will beaccelerated [26].

Affected patients typically have one of the above complications of pregnancy and then develop theabrupt onset of oliguria or anuria, frequently accompanied by gross hematuria, flank pain, andhypotension [24,25]. The triad of anuria, gross hematuria, and flank pain is unusual in the othercauses of renal failure in pregnancy.

The diagnosis can usually be established by ultrasonography or CT scanning, which demonstratehypoechoic or hypodense areas in the renal cortex [24]. Renal biopsy or arteriography also can beperformed, 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 andis not visible for one to two months.

No specific therapy has been shown to be effective in this disorder. Many patients require dialysis, but20 to 40 percent have partial recovery with a creatinine clearance that stabilizes between 15 and 50mL/min [25].

ACUTE PYELONEPHRITIS — Although renal function is generally well maintained during episodesof acute pyelonephritis (in the absence of septicemia or hypotension), some pregnant women candevelop acute renal failure [2,27]. Renal biopsy in this setting may reveal focal microabscesses andrecovery after appropriate antimicrobial therapy may be incomplete due to irreversible injury.

URINARY TRACT OBSTRUCTION — Relaxation of ureteral smooth muscle and pressure on theureters 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 byultrasonography but is not usually associated with renal dysfunction. Rarely, the degree ofobstruction is sufficient to cause renal failure [28]. The diagnosis can be established in some cases bythe normalization of renal function in the lateral recumbent position (which relieves pressure on theureters by the uterus) and its recurrence when supine. In some cases, however, either insertion of aureteral catheter or delivery of the fetus is required [29].

Acute obstructive renal failure in pregnancy has also been reported in association with enlargeduterine 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 andmicroscopic or gross hematuria, rather than renal failure. The diagnosis can usually be established byrenal ultrasonography. Approximately 70 to 85 percent of stones pass spontaneously, due in part tothe normally relaxed and dilated collecting systems. Cystoscopy with insertion of a ureteral stent oruse of a thin, rigid ureteroscope to remove or fragment the stone may be required in the patient whois 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

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