**2.1.8.1 Asymptomatic bacteriuria**

Bacteriuria occurs in 2 to 7 % of pregnancies, particularly in multiparous women, a similar prevalence as seen in nonpregnant women. A clean-voided specimen containing more than 1 lakh organisms per milliliter suggests infection. Bacteriuria often develops in the first month of pregnancy and is frequently associated with a reduction in concentrating ability. 30% of patients develop pyelonephritis if asymptomatic bacteriuria is left untreated. Universal screening is therefore recommended in all pregnant females. Screening for asymptomatic bacteriuria should be performed at 12 to 16 weeks gestation (or the first prenatal visit, if that occurs later). Rescreening is generally not performed in low risk women, but can be considered in women at high risk for infection (eg, presence of urinary tract anomalies, hemoglobin S, or preterm labor). Dipstick has a sensitivity of <50% and

Acute Kidney Injury in Pregnancy 167

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

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

#### **2.1.8.2 Cystitis**

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.

### **2.1.8.3 Pyelonephritis-(3%)**

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 irreversible injury.
