Pregnancy in End Stage Renal Disease Patients - Dr. Gawad

1. Pregnancy in End Stage Renal Disease Patients Mohammed Abdel Gawad Nephrology Specialist Kidney & Urology Center (KUC) Alexandria – EGY drgawad@gmail.com Mansoura MD Program – 25, Jul, 2016

2. To get the presentation with full animations please contact me on drgawad@gmail.com For more presentations visit www.NephroTubeCNE.com

3. Talk Outline  Sexual dysfunction / Incidence of pregnancy  Renal impairment effect on pregnancy outcome  Pre-Pregnancy Counseling / Contraception  Dialysis prescription  General Care  When to terminate pregnancy  Pregnancy Diagnosis  Pregnancy in Dialysis, When? How many times?  Lactation

5. Reproductive and sexual dysfunction in uremic women Dysregulation of the menstrual cycle, leading to amenorrhea by the time the patient reaches ESRD. Anovulation, even with preserved menstrual cycles. LH surge Absent. Abnormalities in endometrial morphology Decreased kidney prolactin clearance in advanced CKD. Kidney Int. 2016 May;89(5):995-1007 Hemodialysis International 2016; 20:339–348 Low levels of estrogen & progesterone.

6. The 6th International Hemodialysis Course, UNC, Mansoura University, Dec 23-7, 2013 Reproductive and sexual dysfunction in uremic women Dysregulation of the menstrual cycle, leading to amenorrhea by the time the patient reaches ESRD. Anovulation, even with preserved menstrual cycles. LH surge Absent. Abnormalities in endometrial morphology Decreased kidney prolactin clearance in advanced CKD. Kidney Int. 2016 May;89(5):995-1007 Hemodialysis International 2016; 20:339–348 Low levels of estrogen & progesterone. Actually, they do get pregnant !!

7. The incidence of pregnancy in women on hemodialysis has been documented to range from <1% to 7% Kidney Int. 2016 May;89(5)

8. Nephrol Dial Transplant (2015) 0: 1–20 n=90 pregnancies from 2000 to 2008 n=616 pregnancies from 2000 to 2014 Clin J Am Soc Nephrol (2010) 5: 62–71

11. Br Med J. 2008;336:311-5. Effect of Renal Function on Pregnancy Outcomes

12. Hippokratia. 2011 Jan; 15 (Suppl 1): 8–12. Effect of Renal Function on Pregnancy Outcomes

15. Pre-Pregnancy Counselling Hemodialysis International 2016; 20:339–348 Counseling about the possibility of pregnancy should occur in all women of reproductive age

16. Am J Kidney Dis. 2015 Dec;66(6):951-61 Pre-Pregnancy Counselling

19. ACKD Journal, Vol 20, No 3 (May), 2013 Complications of pregnancy are higher than those of using oral contraceptives. Pre-Pregnancy Counselling Contraception

20. Oral contraceptives is safe in most dialysis patients, but these drugs should be avoided in patients with lupus and patients with problems of clotting vascular access. Which Method to Use? Intrauterine devices may be associated with increased bleeding because of heparin use with hemodialysis. Commonly used barrier methods of contraception are safe. ACKD Journal, Vol 20, No 3 (May), 2013 Pre-Pregnancy Counselling Contraception

21. Hemodialysis International 2016; 20:339–48 J Perinat Med. 2015. Transplantation options should be reviewed with women while they are on dialysis, before attempting conception, because of better pregnancy outcomes Pre-Pregnancy Counselling Transplantation Advice

22. Hemodialysis International 2016; 20:339–48 There are no data as yet on the safety or effectiveness of assisted reproductive technologies in this patient population Pre-Pregnancy Counselling Assisted reproductive technologies??

25. Multidisciplinary Team ObstetricianNephrologist NeonatologistNutritionist The Patient The Patient Family

26. Dialysis Prescription Item How to deal with? Duration, Frequency & Efficacy >24h/w, Urea<50 Dialysate K 3mEq/L Dialysate Bicarbonate 25mEq/L Ca, Pi & PTH balance Ca 1.75-2.5mmol/L,↑ dialysate P Dialysate Na 135mEq/L Heparnization heparin if no vaginal bleeding Blood Flow Gradual increase High vs Low flux ?? AVF Cannulation Rope Ladder Dialysis Decubitus left lateral decubitus Minerals and water soluble vitamins Increase Supplements Fetal Assessment Every session, esp at the end of session UF & Dry weight Assessment Assess regularly Big challenge

27. The 6th International Hemodialysis Course, UNC, Mansoura University, Dec 23-7, 2013 Dialysis Prescription Item How to deal with? Duration, Frequency & Efficacy >24h/w, Urea<50 Dialysate K 3mEq/L Dialysate Bicarbonate 25mEq/L Ca, Pi & PTH balance Ca 1.75-2.5mmol/L,↑ dialysate P Dialysate Na 135mEq/L Heparnization heparin if no vaginal bleeding Blood Flow Gradual increase High vs Low flux ?? AVF Cannulation Rope Ladder Dialysis Decubitus left lateral decubitus Minerals and water soluble vitamins Increase Supplements Fetal Assessment Every session, esp at the end of session UF & Dry weight Assessment Assess regularly Big challenge

29. 36 h or more of HD weekly for pregnant women with established ESRD without residual renal function Hemodialysis International 2016; 20:339–348

30. J Am Soc Nephrol. 2014; 25:1103–1109.

31. J Am Soc Nephrol. 2014; 25:1103–1109.

32. J Am Soc Nephrol. 2014; 25:1103–1109.

33. J Am Soc Nephrol. 2014; 25:1103–1109.

34. Nephrol Dial Transplant (2015) 0: 1–20

35. Nephrol Dial Transplant (2015) 0: 1–20

36. Nephrol Dial Transplant (2015) 0: 1–20 Dichotomized analysis

40. Nephrol Dial Transplant (2015) 0: 1–20 Meta-regression analysis

43. Case Rep Nephrol. Volume 2016 (2016)

44. Provision of intensified dialysis offers improved management of uremic toxins and blood volume, which may decrease the incidence of polyhydramnios and, as a result, decrease the likelihood of premature delivery and its complications J Ultrasound Med. 2013; 32:851–863. Target: BUN ??

45. Target: BUN < 50 mg/dL or even < 45 mg/dL Hemodialysis International 2016; 20:339–348

46. Kidney Int. 2009 Jun;75(11)

47. Kidney Int. 2009 Jun;75(11)

48. Percentage of Polyhydraminos Target BUN: Canada: Clin JAmSoc Nephrol. 2008;3(2):392-396. Singapore: Int J Gynaecol Obstet. 2006;94(1):17-22. France: Nephrologie. 2004;25(7):287-292. Italy: Ren Fail. 2002;24(6):853-862.

49. Dialysis Prescription Item How to deal with? Duration, Frequency & Efficacy >36h/w, BUN<50 Dialysate K 3mEq/L Dialysate Bicarbonate 25mEq/L Ca, Pi & PTH balance Ca 1.75-2.5mmol/L,↑ dialysate P Dialysate Na 135mEq/L Heparnization heparin if no vaginal bleeding Blood Flow Gradual increase High vs Low flux ?? AVF Cannulation Rope Ladder Dialysis Decubitus left lateral decubitus Minerals and water soluble vitamins Increase Supplements Fetal Assessment Every session, esp at the end of session UF & Dry weight Assessment Assess regularly Big challenge

50. The 6th International Hemodialysis Course, UNC, Mansoura University, Dec 23-7, 2013 Dialysis Prescription Item How to deal with? Duration, Frequency & Efficacy >36h/w, BUN<50 Dialysate K 3mEq/L Dialysate Bicarbonate 25mEq/L Ca, Pi & PTH balance Ca 1.75-2.5mmol/L,↑ dialysate P Dialysate Na 135mEq/L Heparnization heparin if no vaginal bleeding Blood Flow Gradual increase High vs Low flux ?? AVF Cannulation Rope Ladder Dialysis Decubitus left lateral decubitus Minerals and water soluble vitamins Increase Supplements Fetal Assessment Every session, esp at the end of session UF & Dry weight Assessment Assess regularly Big challenge

51. Dialysis Prescription The potassium concentration in dialysate must also be adjusted to reflect the more intensive HD regimen, Advances in Chronic Kidney Disease, Vol 20, No 3 (May), 2013 usually with a concentration of 3.0 mEq/L. Dialysate K

52. Dialysis Prescription ↑ circulating progesterone Kidney Int. 2016 May;89(5) Advances in Chronic Kidney Disease, Vol 20, No 3 (May), 2013 Relative hyperventilation Mild respiratory alkalosis Subsequent reduction in serum bicarbonate of approximately 4 mEq/L To ensure the physiologic expression of respiratory alkalosis that is associated with pregnancy, dialysate bicarbonate usually reduced to 25 mEq/L to maintain serum bicarbonate in the usual pregnancy range of 18 to 22 mmol/l Normal Pregnancy Physiology Dialysate Bicarbonate

53. Dialysis Prescription Intensive dialysis and increased phosphate requirements for fetal bone formation Decrease S.Phosphate levels (hypophosphatemia) Phosphate levels need to be monitored frequently Supplement with oral phosphate increased dialysate phosphate Hemodialysis International 2016; 20:339–348 Nat Rev Nephrol. 2012;8(9):515-522. Stop phosphate binders Dialysate P

54. Dialysis Prescription Increase dialysate calcium to 1.75 - 2.5 mmol/L Predialysis and postdialysis calcium levels should be measured to avoid hyper- and hypocalcaemia oral calcium (1.5-2g/d) Hemodialysis International 2016; 20:339–348 Clin JAmSoc Nephrol. 2008;3(2):392-396. Take care of Hypercalcemia Occasionally placental production of vitamin D–like substances and PTHrP Dialysate Ca

55. Dialysis Prescription Vit D Occasionally placental production of vitamin D–like substances and PTHrP

58. Dialysis Prescription Dialysate Na Indian Journal of Nephrology, Vol. 22, No. 3, May-June, 2012

59. The 6th International Hemodialysis Course, UNC, Mansoura University, Dec 23-7, 2013 Dialysis Prescription Dialysate Na Indian Journal of Nephrology, Vol. 22, No. 3, May-June, 2012 Reduction in serum sodium during pregnancy necessitates a concomitant reduction in dialysate sodium concentration to around 135 mmol/l.

62. Dialysis Prescription Dialysis heparin requirements are often increased because of the hypercoagulable state of pregnancy (this is not the situation for every pregnant woman and is assessed by monitoring dialysis adequacy and dialyser clotting) Hemodialysis International 2016; 20:339–348 Piccoli GB et al. Clin J Am Soc Nephrol. 2010;5(1):62. Heparinization should be minimal to prevent obstetric bleeding. Heparin is a safe and effective anticoagulation therapy that prevents circuit clotting Heparnization

65. Dialysis Prescription At each HD session, blood flow gradually increased over 1st 30 minutes of HD, from 180 to 300 ml/min Blood Flow

68. Dialysis Prescription High vs Low flux Dialyzers High flux

71. Dialysis Prescription High vs Low flux Dialyzers Low flux

72. Dialysis Prescription High vs Low flux Dialyzers Low flux

75. Dialysis Prescription AVF Cannulation Risk for vascular access dysfunction because of increased frequency of dialysis Avoided by rotating the needle sites using rope ladder technique

78. Dialysis Prescription Dialysis in left lateral decubitus position Dialysis Decubitus

81. Dialysis Prescription Hemodialysis International 2016; 20:339–348 Give at increased doses, because they can be partially removed by intensive dialysis. Folic acid at a higher dose of 5 mg daily if on dialysis Minerals and water soluble vitamins

84. Fetal Assessment Serial ultrasound examinations are importantfor the early detection fetal growth restriction Assessment of the fetal heart rate (particularly during the last portion of a session) Kidney Int. 2016 May;89(5)

85. Fetal Assessment J Matern Fetal Neonatal Med. 2016 Jul 12:1-16.

86. Fetal Assessment J Matern Fetal Neonatal Med. 2016 Jul 12:1-16. There may be no fetal benefit of EFM during HD for gravid women with renal disease attributed to hypertensive and diabetic nephropathy. There may be cost savings by shifting HD to the outpatient setting.

89. Body weight gain 1 to 2 kg during the first three months Institute of Medicine and National Research Council. Weight Gain During Pregnancy: Reexamining the Guidelines. The National Academies Collection: Reports Funded by National Institutes of Health. Washington, DC: National Academies Press; 2009. then 0.5 kg a week during the rest of pregnancy Normal body weight gain in pregnancy How to assess intravascular volume in pregnancy? Tools to asses intravascular volume during pregnancy Dialysis Prescription UF & Dry weight Assessment

90. Blood pressure out of target Respiratory compromiseClinical signs of hypervolemia Edema is an unhelpful sign in pregnancy Advances in Chronic Kidney Disease, Vol 20, No 3 (May), 2013 How to assess intravascular volume in pregnancy? Tools to asses intravascular volume during pregnancy Dialysis Prescription UF & Dry weight Assessment

91. Measure Hematocrit & Albumin at the initial first- trimester visit. A rise in either value strongly suggests intravascular volume contraction. Hematocrit & Albumin levels Opposite is not true How to assess intravascular volume in pregnancy? Tools to asses intravascular volume during pregnancy Dialysis Prescription UF & Dry weight Assessment

95. General Principles of Prenatal Care & Management Problem How to manage? Hypertension Anemia Folic acid Aspirin (75–150 mg/day) Heparin Protein Diet Urinary tract infection Assessment of fetal well-being Superimposed preeclampsia

96. Problem How to manage? Hypertension Target BP 110-140/80-90 mmHg Anemia Folic acid Aspirin (75–150 mg/day) Heparin Protein Diet Identification and management of urinary tract infection Assessment of fetal well-being Identification of superimposed preeclampsia This range of treatment is not based on solid pregnancy outcome data But is thought to be the range that reduces maternal risk for severe hypertension while providing sufficient systemic BP to maintain placental perfusion General Principles of Prenatal Care & Management Hemodialysis International 2016; 20:339–348

97. Problem How to manage? Hypertension Target BP 110-140/80-90 mmHg Anemia Folic acid Aspirin (75–150 mg/day) Heparin Protein Diet Identification and management of urinary tract infection Assessment of fetal well-being Identification of superimposed preeclampsia Ines et al. Clinical Medicine 2013, Vol 13, No 1: 57–62 General Principles of Prenatal Care & Management

98. Problem How to manage? Hypertension Target BP 110-140/80-90 mmHg Anemia Folic acid Aspirin (75–150 mg/day) Heparin Protein Diet Identification and management of urinary tract infection Assessment of fetal well-being Identification of superimposed preeclampsia Ines et al. Clinical Medicine 2013, Vol 13, No 1: 57–62 General Principles of Prenatal Care & Management

99. Problem How to manage? Hypertension Target BP 110-140/80-90 mmHg Anemia Folic acid Aspirin (75–150 mg/day) Heparin Protein Diet Identification and management of urinary tract infection Assessment of fetal well-being Identification of superimposed preeclampsia Take Care Diuretics may cause reduction in maternal plasma volume, uteroplacental or renal perfusion. General Principles of Prenatal Care & Management

100. Problem How to manage? Hypertension Target BP 110-140/80-90 mmHg Anemia Maintain Hemoglobin 10–11 g/dl Folic acid Aspirin (75–150 mg/day) Heparin Protein Diet Identification and management of urinary tract infection Assessment of fetal well-being Identification of superimposed preeclampsia Kidney Int. 2016 May;89(5) Hemodialysis International 2016; 20:339–348 Khalafallah AA et al. BMJ Open. 2012;2(5). ESAs at doses higher than needed before (Doubling of the baseline EPO requirements is not infrequent) Intravenous iron as required (Currently, the US Food and Drug Administration classifies only iron sucrose as a pregnancy category B drug) General Principles of Prenatal Care & Management

101. Problem How to manage? Hypertension Target BP 110-140/80-90 mmHg Anemia Maintain Hemoglobin 10–11 g/dl Folic acid for every pregnant woman (5 mg daily if on dialysis) Aspirin (75–150 mg/day) Heparin Protein Diet Identification and management of urinary tract infection Assessment of fetal well-being Identification of superimposed preeclampsia Kidney Int. 2016 May;89(5) Adv Chronic Kidney Dis. 2007;14(2). General Principles of Prenatal Care & Management

102. Problem How to manage? Hypertension Target BP 110-140/80-90 mmHg Anemia Maintain Hemoglobin 10–11 g/dl Folic acid for every pregnant woman (5 mg daily if on dialysis) Aspirin (75–150 mg/day) Heparin Protein Diet Identification and management of urinary tract infection Assessment of fetal well-being Identification of superimposed preeclampsia Use Low-dose aspirin (75-150 mg/day) if if there is no obvious contraindication serum creatinine above 1.5 mg/dl If one of the following in a previous pregnancy: A- early-onset severe preeclampsia B- fetal loss General Principles of Prenatal Care & Management Ann Intern Med. 2014 May 20;160(10) Kidney Int. 2016 May;89(5)

103. Problem How to manage? Hypertension Target BP 110-140/80-90 mmHg Anemia Maintain Hemoglobin 10–11 g/dl Folic acid for every pregnant woman (5 mg daily if on dialysis) Aspirin (75–150 mg/day) Heparin Protein Diet Identification and management of urinary tract infection Assessment of fetal well-being Identification of superimposed preeclampsia The aim of aspirin is for the prevention of preeclampsia or perinatal death General Principles of Prenatal Care & Management Ann Intern Med. 2014 May 20;160(10) Kidney Int. 2016 May;89(5)

104. Problem How to manage? Hypertension Target BP 110-140/80-90 mmHg Anemia Maintain Hemoglobin 10–11 g/dl Folic acid for every pregnant woman (5 mg daily if on dialysis) Aspirin (75–150 mg/day) creatinine > 1.5 mg/dl previous pregnancy complications General Principles of Prenatal Care & Management

105. Problem How to manage? Hypertension Target BP 110-140/80-90 mmHg Anemia Maintain Hemoglobin 10–11 g/dl Folic acid for every pregnant woman (5 mg daily if on dialysis) Aspirin (75–150 mg/day) creatinine > 1.5 mg/dl previous pregnancy complications Superimposed preeclampsia General Principles of Prenatal Care & Management

106. Superimposed Preeclampsia Diagnosis of superimposed preeclampsia in CKD pregnant is difficult Already patient has renal impairment ± proteinuria ± the absence of significant urine output if late stage CKD or 5D ↑ BP, ↓ GFR, ↑ serum urate, or ↑ protein excretion can be due to progression the renal disorder rather than superimposed preeclampsia Kidney Int. 2016 May;89(5) Advances in Chronic Kidney Disease, Vol 20, No 3 (May), 2013 Prenat Diagn. 2012;32(2):180-184.

107. Superimposed Preeclampsia Diagnosis of superimposed preeclampsia in CKD pregnant is difficult When to suspect pre-eclampsia? after 20 weeks of pregnancy Unexplained rise in BP not responding to fluid removal & drugs Development of classic preeclampsia symptoms (visual abnormalities, severe headache, epigastric pain & hyper-reflexia) Laboratory abnormalities consistent with the HELLP syndrome & thrombocytopenia Fetal growth restriction and abnormal umbilical artery blood flow (uterine artery doppler). Kidney Int. 2016 May;89(5) Advances in Chronic Kidney Disease, Vol 20, No 3 (May), 2013

108. Superimposed Preeclampsia

109. Superimposed Preeclampsia fms-like tyrosine kinase-1 (sFlt1), a placental antiangiogenic factors to both vascular endothelial growth factor and placental growth factor (PIGF) Sharon E. Maynard et al. J Am Soc Nephrol 20: 14–22, 2009Levine RJ et al. Gynecol Obstet Invest. 2012;74(4):274-281. PIGF Placental development sFlt1 Endothelial damage New hope for diagnosis

110. Superimposed Preeclampsia PE CKD PIGF (placental development) Low Normal sFlt1 (endothelial damage) High Normal

111. Dis Markers. 2015; 2015: 127083.

112. Problem How to manage? Hypertension Target BP 110-140/80-90 mmHg Anemia Maintain Hemoglobin 10–11 g/dl Folic acid for every pregnant woman (5 mg daily if on dialysis) Aspirin (75–150 mg/day) creatinine > 1.5 mg/dl previous pregnancy complications Superimposed preeclampsia Difficult Challenge !!! General Principles of Prenatal Care & Management

115. Comprehensive Clinical Nephrology. 5th edition, When to Terminate Pregnancy?

118. Diagnosis of Pregnancy in Dialysis Patients A high degree of suspicion is required to make the diagnosis of pregnancy Difficult to Diagnose !! Amenorrhea is frequent in CKD 5D Nausea, vomiting, fatigue & soft signs of pregnancy are often attributed to the kidney condition, volume overload & erythropoietin deficiency. Because beta HCG is removed by the kidney, beta HCG levels are higher at each stage of gestation than in women with normal renal function. Borderline positive HCG levels can be seen in nonpregnant CKD 5D. The stage of gestation must be determined by ultrasound Hemodialysis International 2016; 20:339–348

121. J Med Case Rep. 2016; 10: 50.

122. Repeat pregnancies in women who become pregnant on dialysis are not uncommon. (In the 318 women whose pregnancies are recorded by the National Registry for Pregnancy in Dialysis Patients (NPDR), eight women became pregnant twice, eight women became pregnant three times, and one woman conceived four times.) Most pregnancies occur during first few years on dialysis, but conception rates as a function of time on dialysis have not been determined. Pregnancy has occurred in women who have been on dialysis for as long as 20 years. Hou S. Am J Kidney Dis. 1999;33(2):235.

125. PLoS One. 2015 Nov 16;10(11)

126. PLoS One. 2015 Nov 16;10(11) PLoS One. 2015 Nov 16;10(11)

127. PLoS One. 2015 Nov 16;10(11)

128. PLoS One. 2015 Nov 16;10(11)

129. PLoS One. 2015 Nov 16;10(11)

130. Take Home Messages

132. Problem How to manage? Hypertension Target BP 110-140/80-90 mmHg Anemia Maintain Hemoglobin 10–11 g/dl Folic acid for every pregnant woman (5 mg daily if on dialysis) Aspirin (75–150 mg/day) creatinine > 1.5 mg/dl previous pregnancy complications Superimposed preeclampsia Difficult Challenge !!! General Principles of Prenatal Care & Management

133. Contraception Contraception is advisable because of poor pregnancy outcomes with advanced CKD

134. Diagnosis of Pregnancy in Dialysis Patients Challenging USS

135. Diagnosis of Pre- eclampsia of Pregnancy in Dialysis Patients Challenging Hope – New Markers

136. Gawad Thank You

Pregnancy in End Stage Renal Disease Patients - Dr. Gawad

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