CHRONIC RENAL FAILURE DURING

PREGNANCY

Stephan Eisenschenk, MDDepartment of Neurology

DEFINITION

CRF is by definition distinguished from ARF by the fact that the patient has had loss of kidney function over a more prolonged period of time( more than 3 months and often a process that has been going on for years.

STAGES

Mild: 60 - 80% of normal function, serum creatinine of 1.4mg/ dl or less

Moderate: 30 - 60% of normal function, serum creatinine of 1.5-2.4 mg/ dl

Severe: 15 - 29%, serum creatinine of 2.5 mg/ dl or greater

End stage Renal Disease: < 15 % (these patients require renal replacement therapy: Hemodialysis; Peritoneal Dialysis or Kidney Transplantation)

Anatomic changes in the kidney during pregnancy

• Dilatation of the ureters and pelvis occurs secondary to the smooth muscle–relaxing effect of progesterone.

• An increase in overall kidney size by about 1-1.5 cm due to increase in the renal vascular volume

Physiological changes

• Renal plasma flow increases by 50-70% in pregnancy

• The GFR peaks around the 13th week of pregnancy and can reach levels up to 150% of normal. Therefore, both BUN and creatinine levels, the plasma markers of GFR, are decreased.

• Clinically, the plasma creatinine falls significantly and should not be greater than 0.8 mg/dL during pregnancy.

• B P falls shortly after conception due to peripheral vasodilation, mediated by nitric oxide synthesis and relaxin, and is resistance to the action of angiotensin II.

• There is a compensatory increase in heart rate and activation of the renin-angiotensin-aldosterone axis. Blood volume increases by 20%, and sodium retention of up to 900 mEq occurs.

• A change in tubular function with increased glucosuria also occurs.

• In addition, a reset in the osmostat occurs, resulting in increased thirst and decreased serum sodium levels (by approximately 5 mEq/L)

EPIDEMIOLOGY• Fertility is substantially decreased in

women with GFR’s < 50%• 85% of women with mild renal disease

will have a surviving infant• 1/3 of women with pre-existing

moderate to severe renal insufficiency will develop end stage renal disease within an year of delivery

• Uncontrolled hypertension is the single most important indicator of poor pregnancy outcome

• Of woman with renal disease requiring dialysis, 2% with hemodialysis will conceive over a four year period versus 1% of woman treated with peritoneal dialysis.

ETIOLOGY

• Diabetes mellitus 33%

• Hypertension-24%

• Glomerulonephritis -17%

• Polycystic kidney disease- 5%: Autosomal dominant polycystic kidney disease - Women with this disorder who are hypertensive have a high risk for fetal and maternal complications

• Specific kidney diseases –Glomerular diseases –Membranoproliferative

glomerulonephritis–Focal glomerulosclerosis –Reflux nephropathy– Immunoglobulin A nephropathy

Systemic lupus erythematosus (SLE) is a multiorgan system autoimmune disease with numerous immunological and clinical manifestations. It is characterized by an autoantibody response to nuclear and cytoplasmic antigens. The disease mainly involves the skin, joints, kidneys, blood cells, and nervous system.

• Approximately half of patients experience an exacerbation of lupus during pregnancy, although it is much less common in patients who have been in remission for more than 6 months. Fetal loss occurs in up to 50% of patients.

• Screen all lupus patients for the presence of lupus anticoagulant and the anticardiolipin antibody.

• Treatment for lupus flares includes prednisone or azathioprine. Cyclophosphamide is avoided because it is teratogenic in the first trimester, and it may cause bone marrow suppression in the child

PATHOPHYSIOLOGY • Impairment of the acid base

regulation predisposes the fetus to acedemia

• Inadequate BP control is associated with a dismal obstetric prognosis

• Hypertension secondary to renal disease places the fetus at risk due to

Uteroplacental insufficiency Decreased perfusion Decreased oxygen availability

Signs and smptoms

High blood pressure

Swelling or numbness of hands and feet

HaemeturiaProteinurea

Loss of appetite Nausea Back, side or abdominal pain

Fatigue Muscle cramps

Pregnancy Risk Factors

Hypertension Preeclampsia Premature labor Miscarriage Decreased kidney function Greater risk of urinary tract infections Acute renal failure

Effect of renal insufficiency on pregnancy

Fetal survival rates are good, approaching 95% in most studies.

Complications, including SGA infants, preterm labor, and stillbirth, are increased even in mild renal insufficiency.

Factors associated with increased perinatal mortality and preterm labor were impaired renal function, early or severe hypertension, and nephrotic-range proteinuria.

PREGNANCY IN PATIENTS RECEIVING DIALYSIS

Only 23-55% of pregnancies result in surviving infants, and a large number of second-trimester spontaneous abortions occur.

Approximately 85% of surviving infants are born premature, and 28% are born SGA. Hypertension worsens in more than 80% of pregnant females

Diagnosis of pregnancy is difficult because levels of beta-hCG are normally elevated in patients receiving dialysis.

General recommendations • Place the patient on a transplant list because

outcomes with allograft transplant patients are markedly better.

• During hemodialysis, pursue uterine and fetal monitoring and make every attempt to avoid dialysis-induced hypotension.

• Erythropoietin can also increase hypertension and must be used cautiously.

• Aggressive dialysis to keep BUN levels <50 mg/dL may be pursued with daily dialysis.

PREGNANCY IN PATIENTS AFTER TRANSPLANTATION

• Poor pre pregnancy renal function are important prognostic indicators for the risk of renal function deterioration.

• An elevated pre pregnancy creatinine level (ie, >1.4 mg/dL) is not only associated with a higher risk of renal decline but also with a decreased fetal survival rate.

• The fetal survival rate is approximately 74% in patients with a creatinine level of more than 1.4 mg/dL, while it increases to about 96% in patients with a creatinine level of less than 1.4 mg/dL.

Diagnostic tests• History and Physical

Exam • Urine Total Protein • Creatinine Clearance

Test • Blood Urea Nitrogen• Serum Potassium Test • Serum Creatinine Test • Serum Chloride Test • Serum Bicarbonate

Test • Electrolyte Panel • Erythropoietin Test

• Glucose Measurement • Serum Total Calcium

Test • Serum Magnesium

Test • Abdominal Ultrasound • Abdominal CT Scan • Kidney Scan • Serum Parathyroid

Hormone (PTH) Level Test

• Urinalysis • Biopsy

MANAGEMENT

• General management • A multidisciplinary approach• Prenatal visits every 2 weeks until 28 weeks'

gestation and then weekly. • Check blood pressure. Measure protein excretion,

usually by dipstick. If any worsening proteinuria is discovered, obtain a 24-urine collection

• Patients who have had a transplant to wait a year after a living relative donor transplant and 2 years after a cadaveric renal transplant before attempting pregnancy

• Stable Renal function, with a serum creatinine level of <2.0 mg/dL.

• Discontinue ACE inhibitors, and make every attempt to decrease prednisone to 15 mg/d or less, azathioprine to 2 mg/kg/d or less, and cyclosporine to 5 mg/kg/d or less.

• Check of immune status for hepatitis B virus, herpes simplex virus (HSV), cytomegalovirus (CMV), and Toxoplasma species

• If rubella titers are low, administer the vaccine before transplant

• Laboratory work consist of CBC counts, electrolytes, BUN and creatinine levels, and (if indicated) a cyclosporin level.

• Perform monthly ultrasounds and urine cultures.

• Biweekly fetal surveillance with a biophysical profile is indicated in the third trimester.

OBSTETRIC MANAGEMENT

• Preterm labor. Magnesium can be cautiously used to avoid toxicity and respiratory depression.

• The literature reflects a debate about elective early delivery (34-36 wk) in patients with chronic renal insufficiency or those receiving dialysis, especially when fetal lung maturity is present.

• In patients who have had a transplant, delaying delivery until the onset of labor provided, of course, that the mother and fetus show no signs of distress.

Fetal Surveillance and Timing of delivery:

• Cesarean section should be necessary only for purely obstetric reasons.

• In fact, preterm labor is generally the rule and may commence during hemodialysis. The role of cesarean section in this situation needs to be carefully considered

• Anemia management

DIALYSIS

• Early dialysis is necessary in pregnant women and should be considered when the serum creatinine reaches 3.5 mg/dL or the GFR is less than 20 mL/min.

• Conti– Longer, more frequent dialysis (20 hrs/week)

is associated with the best fetal outcome. Hemodialysis may therefore be necessary at least 5 days per week

– Careful avoidance of hypotension is important.

– Peritoneal dialysis with smaller volumes and frequent exchanges is another option.

– Premature labor and fetal size that is small for the fetus' gestational age are typical in women who deliver on dialysis.

• Nutritional support that allows weight gains of 0.3 to 0.5 kg/wk should be maintained in the second and third trimesters.

• A daily oral intake of 70 gm protein, 1,500 mg calcium, 50 mM potassium and 80 mM sodium is advised, with supplements of dialyzable vitamins.

• Vitamin D supplements can be difficult to judge in patients who have had parathroidectomy. In addition, the placenta produces hydroxyvitamin D, one reason why oral supplementation may have to be curtailed.

Renal TransplantationGuidelines for pregnancy in kidney

transplant recipient

Two years posttransplant, with good general health and serum creatinine less than 2.0 mg/dL (preferably <1.5 mg/dL)

No recent or ongoing rejection

Normotension, or minimal antihypertensives

Absent or minimal proteinuria

No evidence of pelvicalyceal dilation on renal ultrasonogram

Immunosuppression Prednisone - Less than 15 mg per day Azathioprine - Less than or equal to 2

mg/kg/d Calcineurin inhibitor–based therapy

- Therapeutic levels Mycophenolate mofetil and sirolimus

- Discontinue 6 weeks prior to conception

Methylprednisolone - The preferred agent for treatment of rejection during pregnancy

Immunosuppressive drugs in pregnancyPrednisone crosses the placenta with a

maternal-to-cord ration of 1:10. Fetal complications include neonatal adrenal insufficiency and thymic hypoplasia. These are unlikely to occur if the dose is less than 15 mg/d. If acute rejection of the kidney occurs during pregnancy, there is generally no hesitation in the use of high-dose steroids.

Azathioprine apparently crosses the placenta, the immature fetal liver cannot convert it to its active form, 6-mercaptopurine. Use of azathioprine is associated with SGA babies and dose-related myelosuppression in the fetus.

Cyclosporine has not been associated with an increase in congenital anomalies but has been associated with SGA babies.

Complication Risks Immunosuppressive agents increase the

risk of hypertension during pregnancy. Preeclampsia occurs in approximately one-

third of transplant recipients. Almost 50% of pregnancies in these

women end in preterm delivery due to hypertension.

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

COUNSELING AND EARLY PREGNANCY ASSESSMENT

PRECONCEPTION GUIDELINES

A wait of 18 months to 2 years post-transplant is advised before conception. Also, if function is well maintained at 24 months, there is a high probability of allograft survival at 5 years

Good general health about 2 years since transplantation

Stature compatible with good obstetric outcome

No or minimal proteinurea Absence of hypertension No evidence of graft rejection Stable renal function with plasma creatinine

of 2 mg/100 ml or less (preferably less than 1.5 mg/100 ml)

Drug therapy reduced to maintenance levels: prednisone 15 mg/day or less, and azathioprine 2 mg/kg body weight/day or less. Safe doses of cyclosporine-A, have not yet been established because of limited clinical experience, but 5 mg/kg body weight per day or less is quoted anecdotally

NURSING MANAGEMENT • Assess for risk for fluid overload• Fluid intake should be carefully

monitored & intake should equal output

• Evaluate the degree of edema.• Discuss the importance of

nutritional modifications and refer to dietician

• Teach family on home BP monitoring

• Instruct the patient & family on about importance of recognizing & reporting signs of fluid & electrolyte imbalance, HELLP syndrome, medicine induced side effects etc

• Modify home activities to reduce onset of dangerous hypertension & avoid added fatigue factors

• Teach patient to avoid infection• Teach the patient the signs &

symptoms of preterm labour & report it( 4 painless contractions per hour unrelieved by rest of 1 hour)

• Avoid using urinary catheters• Always run a clean catch urine

specimen • Start fetal surveillance with electronic

fetal monitoring , BPP, NST• After 24 weeks of gestation evaluate

for fetal IUGR• Assess for hypertensive disorders of

pregnancy & or DIC• Assess for signs of fluid, electrolyte,

acid base imbalance• Perform dialysis as ordered.• Weight the patient at each dialysis

exchange

NURSING DIAGNOSIS • Imbalanced nutrition less than

body requirement related to dietary restriction.

• Fluid volume excess related to compromised regulatory mechanism

• High risk for decreased cardiac output related to fluid volume overload, accumulated toxins

• High risk for injury ( hypocalcemia)related to increased phosphorus level, renal failure

• High risk for injury related to bone marrow suppression secondary to insufficient renal production of erythropoietic factor

• High risk for impaired skin integrity related to edema

• High risk for self esteem disturbance related to loss of body function, prolonged dialysis

• High risk for noncompliance related to lack of resources, knowledge deficit.

Page 42

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