Renal Failure and Dialysis in Pregnancy

Renal Failure and Dialysis in Pregnancy
By:David Shure

Differential Diagnosis
* FSGS -
Pro: HTN, non-remitting, albumin close to NL
Con: expected creatinine to be higher after several years

* Membranous Nephropathy -
Pro: wax/waning course
Con: often with lower albumin, edema

* Diabetic Nephropathy -
Pro: proteinuria, time course
Con:poor evidence for DM
4. FMD - Pro: unequal sized kidneys, young female, HTN hx, renal arteries not commented on in US

Nephrology Consult
* Is there any indication and/ or benefit to the fetus if we begin HD at this time?
* Can we preserve any residual maternal renal function?
* OB team trying to prolong in-utero growth/ length of pregnancy, not sure if pt is masking severe preeclampsia

Why did Ob Deliver the Baby?
* 7/21 pt c/o HA, and 7/23 severe RUQ tenderness and epigastric pain, decision made to deliver fetus based on:
* Severe superimposed Preeclampsia in setting of chronic HTN
* Also, mild thrombocytopenic further led to diagnosis of severe preeclampsia

Normal Physiologic Alterations of Pregnancy
Normal Renal Alterations in Pregnancy

Changes in GFR
* GFR and RBF rise markedly
* Glomerular hyperfiltration results in normal reduction in the plasma creatinine concentration to about 0.4 to 0.5 mg/dL
* Blood urea nitrogen (BUN) and uric acid levels fall for the same reason

Effects of Pregnancy on Renal Disease
* ― cases proteinuria worsen
* ž cases HTN develops
* Worsening edema if nephrotic
* 0-10% women with NL or mild reduction in GFR have permanent decline in renal function

Views on Pregnancy and Dialysis
* ‘Children of women with renal disease used to be born dangerously or not at all - not at all if their doctors had their way’, Lancet, 1975
* ‘Show me a method of birth control more effective than end stage renal disease’, Roger Rodby MD, 1991
* ‘Even if a woman on CAPD ovulates, doesn’t the egg just float away?’, Rodby, 1992

Why don’t uremic women get pregnant?
* Most beyond child bearing age
* Libido/ frequency of intercourse reduced
* Don’t ovulate
* Absence of increase in basal body temperature during the luteal phase of cycle
* Elevated circulating prolactin concentrations
* Elevated PRL impairs hypothalamic-pit function

Actually, they do get pregnant!
* 1st successful term pregnancy in 35 y/o dialysed pt in 1971, Confortini, et al.
* Yr 2000: >15,000 women of childbearing age getting dialysis
* For every person w/CKD 5, 20 have CKD 3 or 4 w/GFR <60, suggesting ~300,000 women w/CKD potentially able to bear children Course of Renal Disease in Pregnancy * Baseline azotemia = more rapid deterioration * As renal dz progresses, ability to maintain nl pregnancy deteriorates, and presence of HTN incr likelihood of renal deterioration * Renal dysfunction - greater risk for complications incl preeclapsia, premature delivery, IUGR Pregancy during dialysis: case report and management guidelines; Giatras, et al. 1998 * 32 y/o AA woman, G4, P2, A1 * FSGS and chronic interstitial nephritis * Renal/obstetric protocol implemented * Increased HD to 4 hrs/ 4 sessions/ week maintain prediaysis BUN <50 * At each HD session, blood flow gradually increased over 1st 30 minutes of HD, from 180 to 300 ml/min * Kt/V 1.02 - 1.66 Giatras Protocol * Dialysis performed in left lateral decubitus position * Est maternal dry wt incrased by 500 g every 10d * EPO administered at each HD session, to maintain HCT 32-34% * Vit D, folic acid and MVI admin * Evid of malnutrition prior to pregnancy, so 3000kcal/day diet w>100g protein/ day

Obstetric Surveillance
* From 25 wks gestation
* Serial BP
* Uterine and umbilical artery perfusion evaluation
* Cont fetal heart rate tracing before, during and after HD
* There were no signif changes in uterine or umbilical artery S/D ratios at any time of HD, and no sig alteration in maternal MAP during HD
* Pt delivered at 32 wks gestation, due to PROM

Common Themes in Dialysing Pregnant Patients

1. Keeping BUN < 50 2. Increasing dialysis time and frequency 3. BP control 4. Managing anemia with increasing doses of ESA 5. Fetal monitoring once viability reached BUN <50 Hypothesis? * 1963 150 women varying degrees of CKD, none on dialysis, found the single most important factor influencing fetal outcome was BUN * Fetal mortality directly proportional to BUN * Hypothesis: intensive dialysis in pregnant women w/renal dz might improve fetal outcomes Increasing frequency and time on dialysis? * May be beneficial in reducing incidence of polyhydramnios by reducing urea and water load * Less dialysis-induced hypotension * More liberal diet * American Jrnl Kid Diseases * Spurred by the report of 5 pregnancies in 5 pts on chronic HD in 2 dialysis units bet 1989-1996 * 1st national survey of its kind which revealed a total of 15 pregnancies in HD - all dialysis centers in Belgium questioned for pts bet 1975-1996 Study Population Figures Case Characteristics/ Outcomes Dialysis Dosing * 15 pregnancies went beyond 1st trimester * Frequency of HD was increased immediately or progressively to 16 to 24 hrs * No difference bet successful pregnancies and failed ones for # mths on HD prior to conception or age at conception. * For successful pregnancies + correlation bet birth wt and excess dialysis hrs delivered over entire pregnancy. Success Rate * 80% (4/5) when HD initiated after onset of pregnancy (pregnancy first) * 50% (5/10) when HD was the first event * ‘‘Pregnancy first’ cases have a significant residual renal function and even may benefit from ‘preventive dialysis’, to be taken on dialysis at a stage of renal failure that would not justify dialysis in the eyes of many were it not for the very special setting of a pregnant state’’ Obstetrical Problems * Main Problem: premature births * In this study 3 died due to severe prematurity * Polyhydramnios present in almost all cases, may be cause of preterm labor * Growth retarded babies at highest risk for intrauterine death * Maternal prognosis is good Should we Initiate Dialysis in Pts w/Low Cr Clearance? * Hou, S., Pregnancy in Women on Hemodialysis, 1994, revealed better outcomes of pregnancy in women w/ significant residual renal function or who initiate pregnancy before they need dialysis. * May reduce incidence of polyhydramnios, lower urea and lowers water load, also reducing risk of dialysis-induced hypotension Registry of Pregnancy in Dialysis Patients USRDS Frequency of Prematurity and Low Birth Rate is less in those conceived before beginning dialysis Women who Start Dialysis During Pregnancy * Likelihood of infant surviving is good * Termination of a pregnancy after renal function has begun to deteriorate rarely rescues the kidneys * NEJM, Jones and Hayslett, 1996, looked at 82 pregnancies in 67 women w/CRI, only 15% of those w/deteriorating renal function had a return of renal function to baseline in 6 mths post partum Survival Statistics Renal Failure and Dialysis in Pregnancy.ppt

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Hemolytic Disease of the Newborn

Hemolytic Disease of the Newborn, Current Methods of Diagnosis and Treatment
By:Terry Kotrla, MS, MT(ASCP)BB

Objectives
* List the classifications of Hemolytic Disease of the Newborn and the most antibody specificities involved.
* State the testing to perform on the mother to monitor the severity of HDN.
* List the laboratory tests and values which indicate that an infant is affected by HDN both in the fetus and newborn.
* State the treatment options for intrauterine treatment of HDN.
* State the treatment options for HDN in the moderately and severely affected newborn.
* State the requirements of blood to be used for transfusion of the fetus and newborn.

Cause of Hemolytic Disease
* Maternal IgG antibodies directed against an antigen of paternal origin present on the fetal red blood cells.
* IgG antibodies cross the placenta to coat fetal antigens, cause decreased red blood cell survival which can result in anemia.
* Produced in response to previous pregnancy with antigen positive fetus OR exposure to red blood cells, ie transfusion.

Three Classifications of HDN
* ABO
* “Other” – unexpected immune antibodies other than anti-D – Jk, K, Fy, S, etc.
* Rh – anti-D alone or may be accompanied by other Rh antibodies – anti-C, -c, -E or –e.

ABO Hemolytic Disease
* Mother group O, baby A or B
* Group O individuals have anti-A, -B and –A,B in their plasma, fetal RBCs attacked by 2 antibodies
* Occurs in only 3%, is severe in only 1%, and <1:1,000 require exchange transfusion. * The disease is more common and more severe in African-American infants. “Other” Hemolytic Disease * Uncommon, occurs in ~0.8% of pregnant women. * Immune alloantibodies usually due to anti-E, -c, -Kell, -Kidd or -Duffy. * Anti-K o disease ranges from mild to severe o over half of the cases are caused by multiple blood transfusions o is the second most common form of severe HDN * Anti-M very rare Rh Hemolytic Disease * Anti-D is the commonest form of severe HDN. The disease varies from mild to severe. * Anti-E is a mild disease * Anti-c can range from a mild to severe disease - is the third most common form of severe HDN * Anti-e - rare * Anti-C - rare * antibody combinations (ie anti-c and anti-E antibodies occurring together) - can be severe HDN * Maternal antibodies destroy fetal red blood cells o Results in anemia. o Anemia limits the ability of the blood to carry oxygen to the baby's organs and tissues. * Baby's responds to the hemolysis by trying to make more red blood cells very quickly in the bone marrow and the liver and spleen. o Organs enlarge - hepatosplenomegaly. o New red blood cells released prematurely from bone marrow and are unable to do the work of mature red blood cells. * As the red blood cells break down, bilirubin is formed. o Babies unable to get rid of the bilirubin. o Builds up in the blood (hyperbilirubinemia ) and other tissues and fluids of the baby's body resulting in jaundice. o The placenta helps get rid of some of the bilirubin, but not all. Complications During Pregnancy * Severe anemia with enlargement of the liver and spleen When these organs and the bone marrow cannot compensate for the fast destruction of red blood cells, severe anemia results and other organs are affected. * Hydrops Fetalis This occurs as the baby's organs are unable to handle the anemia. The heart begins to fail and large amounts of fluid build up in the baby's tissues and organs. A fetus with hydrops is at great risk of being stillborn. Hydrops Fetalis Clinical Presentation * Varies from mild jaundice and anemia to hydrops fetalis (with ascites, pleural and pericardial effusions) * Chief risk to the fetus is anemia. * Extramedullary hematopoiesis due to anemia results in hepatosplenomegaly. * Risks during labor and delivery include: o asphyxia and splenic rupture. * Postnatal problems include: o Asphyxia o Pulmonary hypertension o Pallor (due to anemia) o Edema (hydrops, due to low serum albumin) o Respiratory distress o Coagulopathies ( platelets & clotting factors) o Jaundice o Kernicterus (from hyperbilirubinemia) o Hypoglycemia (due to hyperinsulinemnia from islet cell hyperplasia) Kernicterus * Kernicterus (bilirubin encephalopathy) results from high levels of indirect bilirubin (>20 mg/dL in a term infant with HDN).
* Kernicterus occurs at lower levels of bilirubin in the presence of acidosis, hypoalbuminemia, prematurity and certain drugs (e.g., sulfonamides).
* Affected structures have a bright yellow color.
* Unbound unconjugated bilirubin crosses the blood-brain barrier and, because it is lipid soluble, it penetrates neuronal and glial membranes.
* Bilirubin is thought to be toxic to nerve cells
* The mechanism of neurotoxicity and the reason for the topography of the lesions are not known.
* Patients surviving kernicterus have severe permanent neurologic symptoms (choreoathetosis, spasticity, muscular rigidity, ataxia, deafness, mental retardation).

Laboratory Findings
* Vary with severity of HDN and include:
* Anemia
* Hyperbilirubinemia
* Reticulocytosis (6 to 40%)
* nucleated RBC count (>10/100 WBCs)
* Thrombocytopenia
* Leukopenia
* Positive Direct Antiglobulin Test
* Hypoalbuminemia
* Rh negative blood type or ABO incompatibility
* Smear: polychromasia, anisocytosis, no spherocytes

Blood Smear
* Polychromasia
* Anisocytosis
* Increase NRBCs
* no spherocytes

Blood Bank Testing
Bilirubin Nomogram
* Total Serum Bilirubin (TSB) monitored to determine risk of kernicterus.
* Measure bilirubin in cord blood and at least every 4 hours for the first 12 to 24 hours. Plot bilirubin concentrations over time.

Transcutaneous Monitoring
* Transcutaneous bilirubinometry can be adopted as the first-line screening tool for jaundice in well, full-term babies.
* This leads to about 50% decrease in blood testing.
* http://tinyurl.com/36jazx

Intrauterine Transfusion (IUT)
* Given to the fetus to prevent hydrops fetalis and fetal death.
* Can be done as early as 17 weeks, although preferable to wait until 20 weeks
* Severely affected fetus, transfusions done every 1 to 4 weeks until the fetus is mature enough to be delivered safely. Amniocentesis may be done to determine the maturity of the fetus's lungs before delivery is scheduled.
* After multiple IUTs, most of the baby’s blood will be D negative donor blood, therefore, the Direct Antiglobulin test will be negative, but the Indirect Antiglobulin Test will be positive.
* After IUTs, the cord bilirubin is not an accurate indicator of rate of hemolysis or of the likelihood of the need for post-natal exchange transfusion.

Intrauterine Transfusion
* An intrauterine fetal blood transfusion is done in the hospital. The mother may have to stay overnight after the procedure.
* The mother is sedated, and an ultrasound image is obtained to determine the position of the fetus and placenta.
* After the mother's abdomen is cleaned with an antiseptic solution, she is given a local anesthetic injection to numb the abdominal area where the transfusion needle will be inserted.
* Medication may be given to the fetus to temporarily stop fetal movement.
* Ultrasound is used to guide the needle through the mother's abdomen into the fetus's abdomen or an umbilical cord vein.
* A compatible blood type (usually type O, Rh-negative) is delivered into the fetus's abdominal cavity or into an umbilical cord blood vessel.
* The mother is usually given antibiotics to prevent infection. She may also be given tocolytic medication to prevent labor from beginning, though this is unusual.
* Increasingly common and relatively safe procedure since the development of high resolution ultrasound particularly with colour Doppler capability.
* MCA Doppler velocity as a reliable non-invasive screening tool to detect fetal anemia.
o The vessel can be easily visualized with color flow Doppler as early as 18 weeks’ gestation.
o In cases of fetal anemia, an increase in the fetal cardiac output and a decrease in blood viscosity contribute to an increased blood flow velocity
* The risk of these procedures is now largely dependent on the prior condition of the fetus and the gestational age at which transfusion is commenced.
* Titer greater than 32 for anti-D and 8 for anti-K OR four fold increase in titer indicates need for analysis of amniotic fluid.
* Amniocentesis
o Perform at 28 wks if HDN in previous child
o Perform at 22 wks if previous child severely affected
o Perform if maternal antibody increases before 34th wk.
* High values of bilirubin in amniotic fluid analyses by the Liley method or a hemoglobin concentration of cord blood below 10.0 g/mL.
* Type fetus -recent development in fetal RhD typing involves the isolation of free fetal DNA in maternal serum. In the United Kingdom, this technique has virtually replaced amniocentesis for fetal RhD determination in the case of a heterozygous paternal phenotype
* Maternal plasma exchange may be instituted if the fetus is too young for intrauterine transfusion.

Liley Graph
Selection of Blood
* CPD, as fresh as possible, preferably <5 days old. * A hematocrit of 80% or greater is desirable to minimize the chance of volume overload in the fetus. * The volume transfused ranges from 75-175 mL depending on the fetal size and age. * CMV negative * Hemoglobin S negative * IRRADIATED * O negative, lack all antigens to which mom has antibodies and Coomb’s compatible. Treatment of Mild HDN * Phototherapy is the treatment of choice. * Phototherapy process slowly decomposes/converts bilirubin into a nontoxic isomer, photobilirubin, which is transported in the plasma to the liver. * HDN is judged to be clinically significant (phototherapy treatment) if the peak bilirubin level reaches 12 mg/dL or more. Bilirubin Degradation by Phototherapy Phototherapy * The therapy uses a blue light (420-470 nm) that converts bilirubin so that it can be excreted in the urine and feces. * Soft eye shields are placed on the baby to protect their eyes from damage that may lead to retinopathy due to the bili lights. Phototherapy * Lightweight, fiberoptic pad delivers up to 45 microwatts of therapeutic light for the treatment of jaundice while allowing the infant to be swaddled, held and cared for by parents and hospital staff. * Compact unit is ideal for hospital and homecare. Exchange Transfusion * Full-term infants rarely require an exchange transfusion if intense phototherapy is initiated in a timely manner. * It should be considered if the total serum bilirubin level is approaching 20 mg/dL and continues to rise despite intense in-hospital phototherapy. * The procedure carries a mortality rate of approximately 1% and there may be substantial morbidity Goals of Exchange Transfusion * Remove sensitized cells. * Reduce level of maternal antibody. * Removes about 60 percent of bilirubin from the plasma, resulting in a clearance of about 30 percent to 40 percent of the total bilirubin. * Correct anemia by providing blood that will have normal survival. * Replacement with donor plasma restores albumin and any needed coagulation factors. * Rebound – usually a 2 volume exchange is needed as bilirubin in tissues will return to blood stream. Testing Baby * Antibody elution testing from cord red blood cells. * ABO/D typing o If baby received intrauterine transfusions will type as O negative o If baby’s Direct Antiglobulin Test is strongly positive due to anti-D may get FALSE NEGATIVE immediate spin reaction with reagent anti-D (blocking phenomenon), weak D (Du) test will be STRONGLY positive * Antibody screen * Coomb’s crossmatch antigen negative donor. Testing Mom * Type and screen on mom. * Identification of unexpected antibodies. * More than 40 antigens have been identified as causing HDN. * Select blood that lacks antigens to which mom has antibodies. * Perform coomb’s crossmatch with Mom and baby’s blood. Selection of Donor Blood * CPD, as fresh as possible, preferably <5 days old. * CMV negative * Hemoglobin S negative * Irradiated if possible Preparation of Donor Unit * Physician will specify a hematocrit. * Reconstitute donor unit with plasma. * Most facilities prefer to use group O red cells and AB plasma. * Reference for procedure at end of this presentation. Summary * Three types of HDN vary in severity. * Laboratory testing key to diagnosing and monitoring- great care to be taken when interpreting ABO/D typing on affected infants. * Therapy dependent on severity: phototherapy alone or with transfusion. References Hemolytic Disease of the Newborn, Current Methods of Diagnosis and Treatment.ppt

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Hemolytic Disease of the Newborn and Fetus

Hemolytic Disease of the Newborn and Fetus
By:Renee Newman Wilkins, MS, MT(ASCP), CLS(NCA)
CLS 325/435 Clinical Immunohematology
School of Health Related Professions
University of Mississippi Medical Center

What is HDN?
* Destruction of the RBCs of the fetus and newborn by antibodies produced by the mother
* Only IgG antibodies are involved because it can cross the placenta (not IgA or IgM)
Mother’s antibodies
Pathophysiology
* Although transfer of maternal antibodies is good, transfer of antibodies involved in HDN are directed against antigens on fetal RBCs inherited by the father
* Most often involves antigens of the Rh and ABO blood group system, but can result from any blood group system
* Remember: The fetus is POSITIVE for an antigen and the mother is NEGATIVE for the same antigen

Pathophysiology
* HDN develops in utero
* The mother is sensitized to the foreign antigen present on her child’s RBCs usually through some seepage of fetal RBCs (fetomaternal hemorrhage) or a previous transfusion
* HDN occurs when these antibodies cross the placenta and react with the fetal RBCs

ABO HDN
* ABO incompatibilities are the most common cause of HDN but are less severe
* Usually, the mother is type O and the child has the A or B antigen…Why?
* ABO HDN can occur during the FIRST pregnancy b/c prior sensitization is not necessary
* ABO HDN is less severe than Rh HDN because there is less RBC destruction
o Fetal RBCs are less developed at birth, so there is less destruction by maternal antibodies
Diagnosis of ABO HDN
* Infant presents with jaundice 12-48 hrs after birth
* Testing done after birth on cord blood samples:
Treatment of ABO HDN
* Only about 10% require therapy
* Phototherapy is sufficient
* Rarely is exchange transfusion needed
* Phototherapy is exposure to artificial or sunlight to reduce jaundice
* Exchange transfusion involves removing newborn’s RBCs and replacing them with normal fresh donor cells

Phototherapy
Fluorescent blue light in the 420-475 nm range
Exchange transfusion
* CMV negative
* Irradiated
* Fresh Whole Blood (to avoid Ca++)
* Maternal blood if possible
* Leukoreduced

What type of blood to give fetus:

Rh HDN
* Mother is D negative (d/d) and child is D positive (D/d)
* Most severe form of HDN
* 33% of HDN is caused by Rh incompatibility
* Sensitization usually occurs very late in pregnancy, so the first Rh-positive child is not affected
o Bleeds most often occur at delivery
o Mother is sensitized
o Subsequent offspring that are D-positive will be affected

About 1 in 10 pregnancies involve an Rh-negative mother and an Rh-positive father
FetoMaternal Hemorrhage
* Sensitization occurs as a result of seepage of fetal cells into maternal circulation as a result of a fetomaternal hemorrhage

Risk
* Rh-negative women can be exposed to Rh-Positive cells through transfusion or pregnancy
* Each individual varies in their immune response (depends on amount exposed to)
Pathogenesis
* Maternal IgG attaches to antigens on fetal cells
o Sensitized cells are removed by macrophages in spleen
o Destruction depends on antibody titer and number of antigen sites
o IgG has half-life of 25 days, so the condition can range from days to weeks
* RBC destruction and anemia cause bone marrow to release erythroblasts, hence the name “erythroblastosis fetalis”)

Increased immature RBCs
Pathogenesis
* When erythroblasts are used up in the bone marrow, erythropoiesis in the spleen and liver are increased
Bilirubin
* Hemoglobin is metabolized to bilirubin
Diagnosis & Management
* Serologic Testing (mother & newborn)
* Amniocentesis and Cordocentesis
* Intrauterine Transfusion
* Early Delivery
* Phototherapy & Newborn Transfusions

Serologic testing on mother
* ABO and Rh testing
* Antibody Screen
* Antibody ID
* Paternal phenotype
* Amniocyte testing
* Antibody titration
Marsh score
Example:
Amniocentesis & Cordocentesis
* About 18-20 weeks’ gestation
* Cordocentesis takes a sample of umbilical vessel to obtain blood sample
* Amniocentesis assesses the status of the fetus using amniotic fluid
Analysis of amniotic fluid (example)
Liley graph
What to do?
* Intrauterine transfusion is done if:
* Removes bilirubin
* Removes sensitized RBCs
* Removes antibody

Other treatments
* Early Delivery
* Phototherapy (after birth)
* Newborn transfusion

Postpartum testing
* ABO – forward only
* Rh grouping – including weak D
* DAT
* Elution
Prevention
* RhIg (RhoGAM®) is given to the mother to prevent immunization to the D antigen

Postpartum administration of RhIg
Dose
Rosette Test
* A qualitative measure of fetomaternal hemorrhage

Fetomaternal Hemorrhage:
Kleihauer-Betke acid elution
Calculating KB test
Step 1) stain and count the amount of fetal cells out of 1000 total cells counted
Step 2) calculate the amount of fetal blood in cirulation by multiplying %fetal cells by 50 mL
Step 3) divide mL of fetal blood by 30 (each vial protects against a 30 mL bleed
Step 4) Round the calculated dose up and add one more vial for safety

Considerations
* RhIg is of no benefit once a person has formed anti-D
* It is VERY important to distinguish the presence of anti-D as:
o Residual RhIg from a previous dose OR
o True immunization from exposure to D+ RBCs
* RhIg is not given to the mother if the infant is D negative (and not given to the infant)

* Make sure presence of anti-D is not due to antenatal administration of Rh immune globulin
Hemolytic Disease of the Newborn and Fetus.ppt

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