**2.1.9 Acute Fatty Liver of Pregnancy (AFLP)**

It is a rare complication of pregnancy. AFLP is unique to pregnancy. There is no predilection for any geographical area or race. It occurs more commonly in nullipara and primipara than

routine microscopy and culture are needed. Urinalysis with culture should be performed on a monthly basis after resolution. Treatment with a course of oral antibiotics (Nitrofurantoin 100 mg orally every 12 hours for five to seven days, Ampicillin ,Amoxicillin (500 mg orally every 12 hours for three to seven days), Amoxicillinclavulanate (500 mg orally every 12 hours for three to seven days),Cephalexin (500 mg orally every 12 hours for three to seven days) and Fosfomycin (3 g orally as a single dose)and sulphonamides are some of the safe regimes. Treatment reduces incidence of pyelonephritis to 3%. Fluoroquinolones should be avoided in pregnancy. The safest course is to avoid using nitrofurantoin in the first trimester if another antibiotic that is safe and effective is available. Sulfonamides should be avoided in the last days before delivery because they can increase the level of unbound bilirubin in the neonate. Trimethoprim (FDA category C) is generally avoided in the first trimester because it is a folic acid antagonist, has caused abnormal embryo development in experimental animals, and some case control studies have reported a possible association with a variety of birth defects. Ceftrioxone should be avoided the day before parturition because it displaces bilirubin and may cause kernicterus. Recurrence occurs in 35%. If bacteriuria is persistent, suppressive therapy (Nitrofurantoin

Cystitis (3%) is associated with dysuria, urgency and frequency, without systemic signs. It usually occurs in 2nd trimester and is common even in patients with negative urine cultures. Though cystitis recurs in 17% it does not progress to acute pyelonephritis. It should be aggressively treated with oral antibiotic regimens. The symptoms of cystitis and pyuria accompanied by a "sterile" urine culture finding may be due to *Chlamydia trachomatis* urethritis. There may be mucopurulent cervicitis, hence erythromycin therapy is effective.

Majority (70%) patients with PN have asymptomatic bacteriuria. 50% cases occur in 2 nd trimester. Onset is abrupt with fever, chills, flank pain, anorexia, nausea, vomiting and costovertebral tenderness. The etiologic organisms include *Escherichia coli*, *Klebsiella, Enterobacter* and *Proteus* . 10% are due to Gram+ organsisms. 15% patients have concurrent bacteremia. Other complications include hemolysis, sepsis, adult respiratory distress syndrome, hepatic dysfunction and death. Pyelonephritis requires hospitalization and intravenous antibiotics and fluids till fever resolves. Effective regimens include ampicillin plus gentamicin or a third-generation cephalosporin followed by oral administration of antibiotics for 14 days .This leads to complete resolution of infection in 70%. Antibiotics can be further adjusted according to culture sensitivity results. In infections recurring in 2 weeks, 2-3 wks of treatment and suppressive therapy throughout the pregnancy should be given. Post coital cephalexin 250mg or NFT 50 mg may be preventive. Perinephric or cortical abscesses may be seen. Although renal function is well maintained during acute pyelonephritis, some pregnant women develop acute renal failure. Renal biopsy may reveal focal microabscesses and recovery after antimicrobial therapy may be incomplete due to

It is a rare complication of pregnancy. AFLP is unique to pregnancy. There is no predilection for any geographical area or race. It occurs more commonly in nullipara and primipara than

50-100 mg at night , cephalexin 250-500 mg or amoxycillin) is indicated.

**2.1.8.2 Cystitis** 

**2.1.8.3 Pyelonephritis-(3%)** 

irreversible injury.

**2.1.9 Acute Fatty Liver of Pregnancy (AFLP)** 

multipara. It was first described in 1940 by Sheehan as an "acute yellow atrophy of the liver". The incidence of AFLP is 1 case per 20,000 births in the UK. Incidence of AFLP from non-UK studies based on hospital case series estimate 1 in 4000 deliveries to 1 in 16000 births. AFLP is associated with AKI in 60%. AFLP occurs in the third trimester or the immediate period after delivery however it can be seen as early as 26 weeks of gestation. (Buytaert,1996) It is due to mutation in enzyme for long chain 3 hydroxy acyl CoA dehydrogenase leading to disordered metabolism of fatty acids by mitochondria in the mother. The most common mutation found in acute fatty liver of pregnancy is the E474Q missense mutation (IJlst L,1997) This gene mutation is recessive; therefore, in non pregnant state, women have normal fatty acid oxidation. However, if the fetus is homozygous for this mutation, it will be unable to oxidize fatty acids. These acids are passed to the mother, who, because of diminished enzyme function, cannot metabolize the additional fatty acids. This results in hepatic strain leading to the development of AFLP, which can be relieved by delivery of the infant. The accumulation of long-chain 3-hydroxyacyl metabolites produced by the fetus or placenta is toxic to the liver and may be the cause of the liver disease. It is characterized by jaundice, hypoalbuminemia, mild renal failure, DIC, PIH, hypoglycemia, pancreatitis and encephalopathy. Laboratory findings may be consistent with disseminated intravascular coagulation (DIC), specifically, prolongation of prothrombin time, low fibrinogen, and low antithrombin levels. This results in a clinical picture similar to DIC; however, in AFLP, the values are abnormal, not due to consumption of the clotting factors but rather to decreased production by the damaged liver. Bilirubin levels are elevated. This elevation is primarily the conjugated form, with levels exceeding 5 mg/dL. This can result in jaundice, which is rarely seen in patients with other forms of pregnancy-related hepatic injury, including preeclampsia. The diagnosis should be suspected in a woman with preeclampsia who has hypoglycemia, hypofibrinogenemia, and a prolonged PTT in the absence of abruptio placentae, high bilirubin, normal/ high transaminases, microvesicular steatosis and rarely liver necrosis. Criteria for diagnosis of AFLP include six or more of the following features in the absence of another explanation: Vomiting, abdominal pain, polydipsia / polyuria, encephalopathy, elevated bilirubin, hypoglycemia, elevated urate, leucocytosis (>11x109/l), ascites or bright liver on ultrasound scan, elevated transaminases (aspartate aminotransferase or alanine aminotransferase >42 IU/l ), elevated ammonia, renal impairment, coagulopathy (prothrombin time >14 s or activated partial thromboplastin time >34 s), microvesicular steatosis on liver biopsy. (Ch'ng,2002). The liver biopsy is diagnostic but is not always feasible especially in patients with severe coagulopathy (Bacq, 2006) and it seldom influences acute management. Ultrasound and computed tomography have been used but false negative results are common. Renal biopsy shows Acute tubular necrosis (ATN). Delivery of the fetus, regardless of gestational age, is the only treatment for acute fatty liver of pregnancy (AFLP) once the diagnosis has been made. Treatment includes intravenous fluids, cryoprecipitate, Fresh frozen Plasma and glucose. It reverses with delivery. C section is preferred over vaginal delivery. Liver transplant is the treatment of choice in patients with liver necrosis. There is 20-25% maternal and fetal mortality and the syndrome can recur in subsequent pregnancies with a calculated genetic risk of 25%.The other causes of jaundice during pregnancy include cholestasis, cholelithiasis, viral hepatitis and pre-eclampsia with or without HELLP syndrome. Intrahepatic cholestasis of pregnancy may present during the third trimester but itching is the characteristic symptom and serum bilirubin concentration is rarely higher than 6mg/ dl. Cholelithiasis may occur at any time during pregnancy and is accompanied by pain in the right upper quadrant, and fever, and

Acute Kidney Injury in Pregnancy 169

be silent or produce acute or chronic renal failure with proteinuria. APLS may cause glomerular lesions like membranous nephropathy, minimal change disease or proliferative

A history of a biologic false positive serologic test for syphilis (BFPTS) may be a clue to the presence of any type of aPL: aCL, ß2-GP-I antibodies, or an LA. However, because of the nonspecific nature of the BFPTS, the presence of one or more aPL should be confirmed with one of the tests (A)The presence of aPL may be demonstrated directly by: ELISA testing in the case of aCL and antibodies to ß2-GP-I and (B) Clotting assay that demonstrates effects of an aPL on the phospholipid-dependent factors in the coagulation cascade (LA test).The lupus anticoagulant phenomenon refers to the ability of aPL to cause prolongation of in vitro clotting assays such as the activated partial thromboplastin time (aPTT), the dilute Russell viper venom time (dRVVT), the kaolin clotting time or, the prothrombin time. This prolongation is not reversed when the patient's plasma is diluted 1:1 with normal platelet-

**Treatment** includes heparin, oral anticoagulants ie warfarin, antiplatelet drugs eg aspirin

The other miscellaneous causes of acute renal failure in pregnancy include Acute gastroenteritis, infections ,drugs and other causes similar to the varied causes of AKI in non

It is the typical finding in PIH. Glomeruli look enlarged and the endothelial cells are swollen. This lesion was first described by Spargo. It resolves by the end of post partum

It is one of the dreaded histopathological lesions . 50% of all cortical necrosis is pregnancy related. Causes include Abruptio (esp if concealed hemorrhage), septic abortion, placenta previa, prolonged IUD, or amniotic fluid embolism. It is commoner in post partum than antepartum AKI. Renal cortical necrosis may be patchy or total. The triad of anuria, gross hematuria, and flank pain seen in cortical necrosis is unusual in the other causes of renal failure in pregnancy. The diagnosis can be established by ultrasonography which shows a subcapsular hypoechoic band . Renal calcifications on plain film of the abdomen suggest

glomerulonephritis. **Laboratory diagnosis** 

free plasma.

pregnant states.

**2.2 Pathology** 

period.

and clopidogrel and hydroxyl chloroquin.

Pathology of pregnancy related AKI varies with etiology.

**2.1.12 Miscellaneous causes** 

**2.2.1 Glomerular endotheliosis** 

**2.2.2 Acute tubular necrosis** 

**2.2.3 Acute interstitial nephritis** 

**2.2.4 Cortical necrosis** 

May be seen in cases of ischemic or toxic insult.

May be commonly due to infection or drug.

USG is usually diagnostic. Acute viral hepatitis in pregnancy presents as a systemic illness with fever, nausea, vomiting, fatigue, and jaundice, however, aminotransferase concentrations are markedly elevated (>500U/liter). The manifestations of pre-eclampsia are usually observed in the second half of pregnancy, whereas the symptoms of HELLP syndrome and AFLP frequently appear in the third trimester. The incidence of HELLP syndrome is much higher (1:5,000). Morbidity of the infant includes increased risk of cardiomyopathy, neuropathy, myopathy, nonketotic hypoglycemia, hepatic failure, and death associated with fatty acid oxidation defects in newborns.
