Liver and Kidney diseases in pregnancy

Prepared by: Rita BattaSupervised by: Dr. Molham Al.Sukhon

Liver diseases during pregnancyThe liver diseases unique to

pregnancy include;Intrahepatic cholestasis of

pregnancy (ICP)Acute fatty liver of pregnancy

(AFP)HELLP syndrome. 

Intrahepatic cholestasis of pregnancy (ICP)

reversible type of hormonally influenced cholestasis

Is the most common pregnancy-related liver disorder

 usually develops during the last third of pregnancy, when hormone levels are highest in approx. 1% of pregnant women.

Risk factors include;twins or triplets or oral CCPs, previous ICP, sister or

mother with ICP.ICP has no clear etiology, and it is believed to be

a multifactorial disorder with environmental, hormonal, and genetic contributions

symptomsSudden onset of sever pruritus (without a rash) that

increase in intensity and characteristically starts in the soles of the feet and palms of the hands and progresses to the trunk and face and worsen at night

Loss of sleep, loss of appetite, and an inability to perform normal daily tasks can be a result of the intense itching. 

Less common symptoms (<10% of patients) include dark urine and/or pale stools (greyish in colour), jaundice abd. Pain and nausea. 

Steatorrhea and vitamin K deficiency may also occur due to fat malabsorption

If the vitamin K deficiency is not corrected by the time of delivery, a postpartum hemorrhage may ensue.

Lab. tests1. The most specific and sensitive marker of ICP is

total serum bile acid (BA) levels >10 micromol/L2.  The elevation of aminotransferases associated

with ICP varies from a mild increase to a 10- to 25-fold increase.

3. Elevated CA:CDCA4. Total bilirubin levels are also increased but

usually the values are less than 5 mg/d5. Alkaline phosphatase (AP) is elevated in ICP up

to 4-fold6. alanine aminotransferase (ALT) is the most

sensitive of the conventional liver tests for diagnosis of ICP in the presence of pruritus without a rash. (AST) values greater than 40 IU/L as partial criteria for the diagnosis of ICP.

7. Mild elevation of gamma glutamyltransferase (GGT) is seen with ICP but occurs in fewer than 30% of cases.

Impact on fetusincreased risk for infant stillbirth

(intrauterine death of the baby)premature labour fetal distress. If vit-K is deficient – bleeding in

both mother and child

ManagementAntenatal testing (umbilical artery Doppler

studies, biophysical profile (BPP), and NST ) to reduce the risk of stillbirth.

Delivery should be induced at 37 weeks’ without an amniocentesis for fetal lung maturity due to increased risk of fetal mortality, or after an amniocentesis for delivery prior to 37 weeks’ gestation.

If meconium is present at the time of amniocentesis, delivery is indicated regardless of the fetal lung maturity results.

Delivery can proceed without an amniocentesis if the fetal monitoring is nonreassuring.

Medications Drug of choice is Ursodeoxycholic

acid (UDCA) at a daily dose ranging from 600-2000 mg .

Others;phenobarbital (100 mg qd)hydroxyzine (25-50 mg qd) cholestyramine (8-16 g/d) dexamethasone (12 mg 4 times daily

for 7 days followed by a tapering dose).

Acute fatty liver of pregnancyA serious complication unique to pregnancyby

characterized by microvesicular fatty infiltration of hepatocytes

 It’s a rare condition (1 in 7000-20,000 deliveries). It is more common with multiple gestations and

possibly in women who are underweight.Acute fatty liver occurs typically in the third

trimester. The foremost cause of AFLP is thought to be due to

a mitochondrial dysfunction in the oxidation of fatty acids leading to an accumulation in hepatocytes

The infiltration of fatty acids causes acute liver insufficiency

Presentation Clinical presentation of acute fatty liver of

pregnancy (AFLP) is nonspecific, and the patient can present with the following complaints:

MalaiseNausea and vomiting (70%); this may present for the

first time in the third trimesterRUQ and epigastric pain (50-80%)Upper GI hemorrhageAcute renal failure InfectionPancreatitisHypoglycemiaFulminant liver failure with hepatic encephalopathy

Lab. Tests Elevated AST and ALT >300 IU/L Decreased blood glucose levels .Liver detoxification is also affected, resulting in

elevated levels of blood ammonia In addition, laboratory findings may be consistent

with disseminated intravascular coagulation (DIC)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.

As the maternal kidneys become affected, blood creatine and uric acid can become elevated, leading to metabolic acidosis.

Impact on fetusThe toxic products accumulate in the

mitochondria and can cause degeneration and fatty infiltration of muscle fibres. This affects both skeletal and cardiac muscle development. The liver becomes enlarged with lipid depositions within the hepatocytes. There may be progressive jaundice associated with impaired bilirubin metabolism.

 At the time of diagnosis, infants frequently have severe liver failure, severe cardiomyopathy and hypoketotic hypoglycemic hepato-encephalopathy

ManagementDelivery of the fetus, regardless of gestational age, is

the only treatment for acute fatty liver of pregnancy (AFLP) once the diagnosis has been made. And the mode of delivery depends on :

Fetal status: Many fetuses demonstrate evidence of asphyxia and hypoxia; therefore, close monitoring of fetal status is necessary, along with the ability to expedite delivery should fetal compromise be evident.

Maternal coagulation status: Due to coagulation abnormalities that can accompany AFLP, patients may need to have replacement of their coagulation factors should cesarean delivery be necessary.

Likelihood of success with IOL : If delivery cannot be safely accomplished within 24 hours from the time of diagnosis, then cesarean delivery may be optimal.

Management of sever hypoglycemia (5% dextrose)

Fluid replacement (hemorrhage affect Renal- ATN)

using postpartum plasma exchange ( plasmapheresis) to treat severe cases of AFLP in the postpartum period (esp. encephalopathy or multi-irgan damage)

Renal disease during pregnancy Renal disease can affect the outcome of pregnancy,

pregnancy can affect the progression of pre-existing renal disease, and pregnancy can itself cause renal impairment

Physiologic changes on renal system:◦ Anatomical;

o increase in overall kidney size by about 1-1.5 cmo dilation of the urinary collecting system ; stasis

◦ Renal plasma flow increases by 50-70%◦ Increased GFR by 50%.◦ Therefore, both urea and creatinine levels are decreased.◦ A change in tubular function with increased glycosuria.◦ Increase urine pH

In general, the physiological changes peak by the end of the second trimester and then start to return to pre-pregnancy levels; anatomical changes generally take up to three months postpartum to subside.

Generally; UTIs incidence increases in pregnant women due to the physiologic changes mentioned earlier, in addition to the difficulty with hygiene due to a distended pregnant belly the already short urethra

untreated asymptomatic bacteriuria (15%) is an important risk factor for pyelonephritis (25-30%).

Acute pyelonephritis An inflammation of the

renal parenchyma ,calyces, and pelvis.

It is commonly caused by bacterial infection (ascending or descending).

It’s an upper UTI one of the most common

medical complications of pregnancy (1-2)%

Pathogenes:a. E.coli (75-90)%b. Klebsiella (10-15)%c. Proteaus species (5%)d. Others; Pseudomonas, staph. and strep.

groups B and DClinical Findings:

Fever, chills, malaise, dysuria, frequencyCVA pain/tenderness50% unilateral right sided flank pain25% bilateral or unilateral left sided flank pain

Laboratory Findings:Pyuria, bacteriuriaWhite blood cell casts highly predictivePositive urine culture10 – 20% bacteremic

Pyelonephritis in PregnancyComplications

Multi-organ system involvement in 20% Anemia due to hemolysis in up to 66% DIC with severe sepsis Transient renal dysfunction in 20% ARDS in 2 – 8%, especially with:• Tachycardia >110 BPM• Fever >38.5 in first 24 hours• Fluid overload• Tocolytic therapy

Preterm Labor

Pyelonephritis in PregnancyDisease Categorization

Outpatient management after inpatient observation and initial parenteral Rx. can be considered with 14 day oral antibiotic therapy (Amoxicillin/Clavulanat )

Inpatient management is requiredIV fluids and parentral;

Ceftriaxone, Cefotetan, Cefotaxime, Gentamicin, Ampicillin/Sulbactam, Piperacillin/Tazobactam.

Mild / Moderate• Low-grade Fever• Normal or slightly

elevated white blood cell count

• Absence of Nausea or Vomiting

Severe • High Fever• Respiratory Insufficiency• Poor urine output• Sepsis• Unable to tolerate oral intake or

antibiotics• No improvement during initial /

observational phase

ACUTE RENAL FAILURE

The underlying causative factors may be;

prerenal : a history of blood or fluid

loss.Renal: direct damage to kidney

by inflammation, toxins, drugs or infections

Postrenal: urologic obstructive

conditions.

Acute renal failure

Pro

Acute renal failure in pregnancy

challenging clinical problem that requires understanding normal physiology of the kidney in pregnancy and the natural history of different underlying renal diseases

prerenal hyperemesis gravidarum and uterine hemorrhage, as in

abruptio placentae , hemorrhage folloing spontaneous abortion

Renal causes in the pregnant woman include acute pyelonephritis

and septic abortion. Renal cortical necrosis, hypercoagulable state, such as TTP or HUS. Prolonged hypotension can lead to acute cortical necrosis or ATN.

Post-renal The most likely causes are the gravid uterus,

polyhydramnios, kidney stones, and enlarged uterine fibroids. Obstructive uropathy usually resolves with delivery, although ureteral stenting may be required preterm.

Those conditions that cause renal failure unique to pregnancy must always be considered when renal function deteriorates in the last trimester or the postpartum period.

Severe preeclampsia, acute fatty liver of pregnancy, and idiopathic postpartum acute renal failure may all present similar complications.

Impact on fetus :

classificationEarly pregnancyPrerenal azotemia, ATN, RCN,

pyelonephritis,TTP, HUS.Late pregnancySever pre-eclampsia, HELLP, ATN,

acute fatty liver disease.Post partumDays to wks. Retained placental

fragments

symptoms bloody stools breath odor slow, sluggish movements swelling - generalized

(fluid retention) fatigue pain between ribs and hips hand tremor

• prolonged bleeding• seizures• nausea• vomiting• elevated blood pressure• metallic taste•decreased sensation, especially in your hands or feetLab. Tests:

BUN Creatinine clearance Serum creatinine Serum potassium Urinalysis (WBCs,RBCs or hyaline

casts) tubular cells.

CHRONIC RENAL FAILURE

The outcome of pregnancies complicated by chronic renal disease is less favorable.

High fetal/maternal morbidity and mortality

Low liklihood of successful outcome

Pregnancy is discouragedPoor prognosis

Pregnancy in patients receiving dialysis

Although fertility is significantly impaired in women with end-stage renal disease, pregnancy may still occur.

Most women on dialysis are anovulatory, with either irregular or no menses, which can result in significant delays in the diagnosis of pregnancy in those who do conceive.

In addition, the spontaneous abortion rate for pregnant women who require dialysis is approximately 50%.

For pregnancies that continue, however, the fetal survival rate is as high as 71%.

Pregnancy in women with kidney transplants

Pregnancy in women following renal transplantation has become commonplace.

Transplantation restores fertility, and although most women with kidney transplants can deliver successfully, there is a higher risk of miscarriage, therapeutic abortion, stillbirth, ectopic pregnancy, preterm birth, low birthweight babies, and neonatal death.

Guidelines for pregnancy in kidney transplant recipients include the

following:

Good general health for 2 years post-transplantation, with serum creatinine levels below 2.0 mg/dL (preferably < 1.5 mg/dL)

No recent acute rejection or ongoing rejection

Normotension, or hypertension controlled with minimal antihypertensive agents

No or minimal proteinuriaNo evidence of pelvicaliceal dilatation on

renal ultrasonogram

The following are complication risks in kidney transplant recipients:

Immunosuppressive agents increase the risk of hypertension during pregnancy

Preeclampsia occurs in approximately one third of kidney-transplant recipients

Almost 50% of pregnancies in these women end in preterm delivery due to hypertension

Blood levels of calcineurin inhibitors need to be frequently monitored due to changes in volumes of distribution of extracellular volume

There is an increased risk of cytomegalovirus, toxoplasmosis, and herpes infections, which raise concern for the fetus