Dialysis and Pregnancy: Nephrology Perspectives

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Dialysis and Pregnancy: Nephrology Perspectives h Prenatal Nephrology Care h Dialysis Regimen & Precautions :

Dialysis and Pregnancy: Nephrology Perspectives h Prenatal Nephrology Care h Dialysis Regimen & Precautions Mohammed Abdel Gawad Nephrology Specialist Kidney & Urology Center (KUC) Alexandria

Pregnancy in Pre-Existing Kidney Disease:

Pregnancy in Pre-Existing Kidney Disease CKD ND CKD 5D

Is pregnancy with pre-existing kidney disease is a common problem?:

Is pregnancy with pre-existing kidney disease is a common problem? What is the frequency or incidence of conception & pregnancy in a woman with pre-existing kidney disease?

Is Pregnancy with Pre-Existing Kidney disease is a Common Problem?:

Is Pregnancy with Pre-Existing Kidney disease is a Common Problem? Country Years Period Number of Patients on HD % of conception per year European Transplant & Dialysis Association (13 European countries) (1) 1970-1980 13,000 <1% USA (2) 1992-1995 6230 women (age14-44) 0.5% Belgium (3) 1989 -1996 4,545 0.3% Japan (4) 1977-1996 38,889 (age 32.7 ± 5.0) 3.4% (1) Br J Obstet Gynaecol.1980;87(10):839-845. (2) Okundaye I et al. Am J Kidney Dis. 1998;31(5):766-773. (3) Jacques A et al. Am J Kidney Dis. Vol 31, No 5 (May), 1998 (4) Toma H et al. 1999;14(6): 1511-1516.

Is Pregnancy with Pre-Existing Kidney disease is a Common Problem?:

Is Pregnancy with Pre-Existing Kidney disease is a Common Problem? Plant L et al. Renal disease in pregnancy. London: RCOG Press; 2008:272. 1 in 200 women of childbearing age on dialysis become pregnant

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Reproductive dysfunction in uremic women CKD – Pregnancy Relationship Effect of CKD on Pregnancy Effect of Pregnancy on CKD CKD Classification in Pregnancy Pre-Pregnancy Counseling in CKD Contraception in Childbearing Age General Principles of Prenatal Care CKD ND CKD 5D When to dialyse ? Dialysis Regimen & Precautions When to Terminate Pregnancy Normal Physiology during pregnancy Talk Outline

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Normal Physiology during pregnancy Talk Outline

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- David Williams, John Davison2 BMJ 2008;336:211-5 - J Prakash . Indian Journal of Nephrology, Vol. 22, No. 3, May-June, 2012 Normal Physiological Renal Changes During Pregnancy

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Reproductive dysfunction in uremic women Normal Physiology during pregnancy Talk Outline

Reproductive and sexual dysfunction in uremic women:

Reproductive and sexual dysfunction in uremic women Dysregulation of the menstrual cycle, leading to amenorrhea by the time the patient reaches ESRD.(1) Anovulation , even with preserved menstrual cycles.(1) LH surge Absent . (2) Abnormalities in endometrial morphology (3) Decreased kidney prolactin clearance in advanced CKD. (5) 1. Holley JL et al. Am J Kidney Dis. 1997;29(5):685-690. 2. Lim VS et al. Ann Intern Med. 1980;93(1):21-27. 3. Matuszkiewicz-Rowinska Jet al. Nephrol Dial Transplant. 2004;19(8):2074-2077. 4. Mantouvalos H et al. Int J Gynaecol Obstet.1984;22(5):367-370. 5. Gomez F et al. Am J Med. 1980;68(4):522-530. Low levels of estrogen & progesterone. (4) Actually, they do get pregnant !!

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Reproductive dysfunction in uremic women CKD Classification in Pregnancy Normal Physiology during pregnancy Talk Outline

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CKD Classification & GFR Estimation in Pregnancy None of the eGFR formulas is valid for pregnancy. S.Cr remains the standard for assessment of renal function during pregnancy. Kavitha Vellanki. Advances in Chronic Kidney Disease, Vol 20, No 3 (May), 2013 Which eGFR formula to use in Pregnant CKD?

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CKD Classification & GFR Estimation in Pregnancy CKD Classification in Pregnancy - Davison JM et al. Clin Perinatol. 1985;12:497-519. - Kavitha Vellanki. Advances in Chronic Kidney Disease, Vol 20, No 3 (May), 2013 Mild Moderate Sever S.Cr < 1.5 mg/ dL S.Cr 1.5-2.5 mg/ dL S.Cr > 2.5 mg/ dL This classification based on the difference between these category levels regarding: 1- CKD progression. 2- Maternal outcome. 3- Fetal outcome.

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Reproductive dysfunction in uremic women CKD – Pregnancy Relationship Effect of CKD on Pregnancy Effect of Pregnancy on CKD CKD Classification in Pregnancy Normal Physiology during pregnancy Talk Outline

CKD – Pregnancy Relationship:

CKD – Pregnancy Relationship Etiology (other than lupus nephritis) is probably not a major determinant of worsening renal disease if above factors are well controlled (4) (1) Kavitha Vellanki. Advances in Chronic Kidney Disease, Vol 20, No 3 (May), 2013 (2) Galdo T et al. Transplant Proc. 2005;37(3):1577-1579. (3) Imbasciati E et al Nephrol Dial Transplant. 2009;24(2):519-525. (4) Jungers P et al. Am J Kidney Dis. 1991;17(2):116

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Mark A. Brown. Comprehensive Clinical Nephrology. 4 th edition, chapter 43, p517 CKD – Pregnancy Relationship Effect of CKD on Pregnancy Outcome % in all stages is highly affected by level of control of hypertension

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Williams D, Davison JM . Br Med J. 2008;336:311-5. Outcomes in mild & moderate stages are highly affected by level of control of hypertension CKD – Pregnancy Relationship Effect of CKD on Pregnancy

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CKD – Pregnancy Relationship Effect of Pregnancy on CKD Renal Outcome Mild S. Cr < 1.5 g/dl <10% → decline in renal function (1) Moderate S.Cr 1.5-3 g/dl 30 % → GFR decline in 3 rd trimester or early postpartum (2) Risk of an irreversible loss of GFR > 50 % if uncontrolled hypertension (3) 10% → progresses to ESRD within 6-12 months after delivery. (2) Sever S.Cr > 3 g/dl Progression to ESRD is high. (3) Jungers P et al. Lancet. 1995;346(8983):1122. Jungers P et al. Am J Kidney Dis. 1991;17(2):116. Mark A. Brown. Comprehensive Clinical Nephrology. 4 th edition, chapter 43, p517 Outcome % in all stages is highly affected by level of control of hypertension

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CKD – Pregnancy Relationship Effect of Pregnancy on CKD Imbasciati E et al Nephrol Dial Transplant. 2009;24(2):519-525.

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CKD – Pregnancy Relationship Effect of Pregnancy on CKD Once a decline in renal function has occurred Okundaye IB, Abrinko P, Hou S. Am J Kidney Dis. 1998;31(5):766-773. It cannot be predictably reversed even by terminating the pregnancy. Women who start dialysis for progressive renal insufficiency during pregnancy Usually require continued dialysis postpartum

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Reproductive dysfunction in uremic women CKD – Pregnancy Relationship Effect of CKD on Pregnancy Effect of Pregnancy on CKD CKD Classification in Pregnancy Pre-Pregnancy Counseling in CKD Normal Physiology during pregnancy Talk Outline

Pre-Pregnancy Counseling in CKD :

Pre-Pregnancy Counseling in CKD Discuss with the patient the possible adverse events which may arise during or as a consequence of her pregnancy Mark A. Brown. Comprehensive Clinical Nephrology. 4 th edition, chapter 43, p517

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Reproductive dysfunction in uremic women CKD – Pregnancy Relationship Effect of CKD on Pregnancy Effect of Pregnancy on CKD CKD Classification in Pregnancy Pre-Pregnancy Counseling in CKD Normal Physiology during pregnancy Talk Outline General Principles of Prenatal Care

Multidisciplinary Team:

Multidisciplinary Team Obstetrician Nephrologist Neonatologist Nutritionist The Patient The Patient Family

Multidisciplinary Team:

Multidisciplinary Team Obstetrician Nephrologist Neonatologist Nutritionist The Patient The Patient Family All must have the same perspectives

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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

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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 Jungers P, Chauveau D. Kidney Int.1997;52(4):871-885. 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

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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

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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

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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 AVOID Diuretics may cause reduction in maternal plasma volume, uteroplacental or renal perfusion. General Principles of Prenatal Care & Management

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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 - Khalafallah AA et al. BMJ Open. 2012;2(5). pii:e000998. - BaruaM et al. Clin JAmSoc Nephrol. 2008;3(2):392-396. ESAs at doses higher than needed before pregnancy (Doubling of the baseline EPO requirements is not infrequent) Intravenous iron as required General Principles of Prenatal Care & Management

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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 - Khalafallah AA et al. BMJ Open. 2012;2(5). pii:e000998. - BaruaM et al. Clin JAmSoc Nephrol. 2008;3(2):392-396. General Principles of Prenatal Care & Management

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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 Stover J. Adv Chronic Kidney Dis. 2007;14(2):212-214. General Principles of Prenatal Care & Management

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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 Askie LM et al. Lancet. 2007;369(9575):1791-1798. General Principles of Prenatal Care & Management

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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 Askie LM et al. Lancet. 2007;369(9575):1791-1798. The aim of aspirin is for the prevention of preeclampsia or perinatal death General Principles of Prenatal Care & Management

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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) c reatinine > 1.5 mg/dl previous pregnancy complications Heparin Protein Diet Identification and management of urinary tract infection Assessment of fetal well-being Identification of superimposed preeclampsia Askie LM et al. Lancet. 2007;369(9575):1791-1798. General Principles of Prenatal Care & Management

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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) c reatinine > 1.5 mg/dl previous pregnancy complications Heparin Nephrotic Syndrome Serum Albumin of <2.5 g/l Protein Diet urinary tract infection Assessment of fetal well-being superimposed preeclampsia Davison JM, Nelson-Piercy C, Kehoe S, Baker P, eds. Renal disease in pregnancy. London: RCOG Press; 2008:21-30 General Principles of Prenatal Care & Management

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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) c reatinine > 1.5 mg/dl previous pregnancy complications Heparin Nephrotic Syndrome Serum Albumin of <2.5 g/l Protein Diet urinary tract infection Assessment of fetal well-being superimposed preeclampsia General Principles of Prenatal Care & Management

Protein diet:

Protein diet Pregnant females are counseled to have high protein intake. even when the ideal protein intake in normal pregnancy has not yet been assessed. Low-protein diet is an important tool in the management of CKD . - Piccoli GB et al. Nephrol Dial Transplant. 2011;26(1):196-205. - Hou S. Am J Kidney Dis 1999; 33: 235–252. Little is known about the risk and benefits of LPD in pregnant CKD . Supplementary of 20 g/day necessary for correct development of the fetus 1 g/kg/day related to a sufficient mother intake Recommended Protein Intake Pregnant CKD

Protein diet:

Protein diet Piccoli GB et al . Nephrol Dial Transplant. 2011;26(1):196-205.

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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) c reatinine > 1.5 mg/dl previous pregnancy complications Heparin Nephrotic Syndrome Serum Albumin of <2.5 g/l Protein Diet 1 g/kg/day + 20 g/day urinary tract infection Assessment of fetal well-being superimposed preeclampsia General Principles of Prenatal Care & Management

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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) c reatinine > 1.5 mg/dl previous pregnancy complications Heparin Nephrotic Syndrome Serum Albumin of <2.5 g/l Protein Diet 1 g/kg/day + 20 g/day Urinary tract infection Early identification & management Assessment of fetal well-being superimposed preeclampsia General Principles of Prenatal Care & Management

PowerPoint Presentation:

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) c reatinine > 1.5 mg/dl previous pregnancy complications Heparin Nephrotic Syndrome Serum Albumin of <2.5 g/l Protein Diet 1 g/kg/day + 20 g/day Urinary tract infection Early identification & management Assessment of fetal well-being Regular Assessment superimposed preeclampsia General Principles of Prenatal Care & Management

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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) c reatinine > 1.5 mg/dl previous pregnancy complications Heparin Nephrotic Syndrome Serum Albumin of <2.5 g/l Protein Diet 1 g/kg/day + 20 g/day Urinary tract infection Early identification & management Assessment of fetal well-being Regular Assessment Superimposed preeclampsia Difficult Challenge !!! General Principles of Prenatal Care & Management

Superimposed Preeclampsia:

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 - Kavitha Vellanki . Advances in Chronic Kidney Disease, Vol 20, No 3 (May), 2013 - Haase M et al. Nephrol Dial Transplant. 2005;20(11):2537-2542. - Napolitano R et al. Prenat Diagn . 2012;32(2):180-184.

Superimposed Preeclampsia:

Superimposed Preeclampsia Diagnosis of superimposed preeclampsia in CKD pregnant is difficult - Kavitha Vellanki . Advances in Chronic Kidney Disease, Vol 20, No 3 (May), 2013 - Haase M et al. Nephrol Dial Transplant. 2005;20(11):2537-2542. - Napolitano R et al. Prenat Diagn . 2012;32(2):180-184. 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 ).

Superimposed Preeclampsia:

Superimposed Preeclampsia

Superimposed Preeclampsia:

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, 2009 Levine RJ et al. Gynecol Obstet Invest. 2012;74(4):274-281. PIGF Placental development sFlt1 Endothelial damage New hope for diagnosis

Superimposed Preeclampsia:

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

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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) c reatinine > 1.5 mg/dl previous pregnancy complications Heparin Nephrotic Syndrome Serum Albumin of <2.5 g/l Protein Diet 1 g/kg/day + 20 g/day Urinary tract infection Early identification & management Assessment of fetal well-being Regular Assessment S uperimposed preeclampsia Difficult Challenge !!! General Principles of Prenatal Care & Management

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Reproductive dysfunction in uremic women CKD – Pregnancy Relationship Effect of CKD on Pregnancy Effect of Pregnancy on CKD CKD Classification in Pregnancy Pre-Pregnancy Counseling in CKD Normal Physiology during pregnancy Talk Outline General Principles of Prenatal Care CKD 5D Dialysis Regimen & Precautions

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Pregnant CKD 5D 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

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Pregnant CKD 5D Dialysis Prescription Intensive HD : average dialysis time of more than 24 hours per week or switching to long nightly dialysis Target: BUN < 50 mg/ dL or even < 45 mg/ dL   What is the Evidence? Nadeau-Fredette et al. Advances in Chronic Kidney Disease, Vol 20, No 3 (May), 2013: pp 246-252 Duration, Frequency & Efficacy

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Pregnant CKD 5D Dialysis Prescription Nocturnal dialysis program . All women conceived during chronic NHD treatment after a NHD vintage of 3 ± 2 years. None of them had conceived during previous conventional HD. 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. Duration, Frequency & Efficacy

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Pregnant CKD 5D Dialysis Prescription Duration, Frequency & Efficacy 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.

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Pregnant CKD 5D Dialysis Prescription Duration, Frequency & Efficacy 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.

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Pregnant CKD 5D Dialysis Prescription Percentage of Living Infants Spontaneous Abortion Neonatal & Infant Death Preterm Preterm IUGR IUGR IUGR Duration, Frequency & Efficacy Preterm Preterm Stillbirth 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. IUGR not reported

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Pregnant CKD 5D Dialysis Prescription Percentage of Pre- eclampsia Not Reported Duration, Frequency & Efficacy 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.

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Pregnant CKD 5D Dialysis Prescription Percentage of Polyhydraminos Target BUN: Duration, Frequency & Efficacy 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.

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Pregnant CKD 5D Dialysis Prescription Duration, Frequency & Efficacy 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.

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Pregnant CKD 5D 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

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Pregnant CKD 5D Dialysis Prescription The potassium concentration in dialysate must also be adjusted to reflect the more intensive HD regimen, Nadeau-Fredette et al. Advances in Chronic Kidney Disease, Vol 20, No 3 (May), 2013 usually with a concentration of 3.0 mEq/L. Dialysate K

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Pregnant CKD 5D Dialysis Prescription ↑ circulating progesterone - Wolfe LA et al. Can J Physiol Pharmacol 1998. Nadeau-Fredette et al. Advances in Chronic Kidney Disease, Vol 20, No 3 (May), 2013: pp 246-252 Smith WT, Int Urol Nephrol 2005;37(1):145–51. 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

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Pregnant CKD 5D 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 Tennankore KK et al.. Nat Rev Nephrol. 2012;8(9):515-522. Stop phosphate binders Dialysate P

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Pregnant CKD 5D 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) BaruaM et al. Clin JAmSoc Nephrol. 2008;3(2):392-396. Hou S. N Engl J Med. 1985;312(13):836 Take care of Hypercalcemia Occasionally placental production of vitamin D–like substances and PTHrP Dialysate Ca

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Pregnant CKD 5D Dialysis Prescription Vit D Occasionally placental production of vitamin D–like substances and PTHrP

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Pregnant CKD 5D 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

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Pregnant CKD 5D Dialysis Prescription Dialysate Na J Prakash . Indian Journal of Nephrology, Vol. 22, No. 3, May-June, 2012 van Es PN et aI. Clin Sci 1996; 91:163-168 Reduction in serum sodium during pregnancy necessitates a concomitant reduction in dialysate sodium concentration to around 135 mmol/l .

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Pregnant CKD 5D 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

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Pregnant CKD 5D 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) (1) Piccoli GB et al. Clin J Am Soc Nephrol. 2010;5(1):62. Smith WT et al. Int Urol Nephrol 2005;37(1): 145–51. Hou S. N Engl J Med. 1985;312(13):836 Heparinization should be minimal to prevent obstetric bleeding. (2) It is safe to use heparin whenever there is no vaginal bleeding. (3) Heparnization

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Pregnant CKD 5D 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

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Pregnant CKD 5D Dialysis Prescription At each HD session, blood flow gradually increased over 1st 30 minutes of HD, from 180 to 300 ml/min Blood Flow

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Pregnant CKD 5D 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

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Pregnant CKD 5D Dialysis Prescription High vs Low flux Dialyzers High flux

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Pregnant CKD 5D Dialysis Prescription High vs Low flux Dialyzers High flux

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Pregnant CKD 5D Dialysis Prescription High vs Low flux Dialyzers High flux

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Pregnant CKD 5D Dialysis Prescription High vs Low flux Dialyzers Low flux

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Pregnant CKD 5D Dialysis Prescription High vs Low flux Dialyzers Low flux

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Pregnant CKD 5D 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

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Pregnant CKD 5D 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

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Pregnant CKD 5D 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

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Pregnant CKD 5D Dialysis Prescription Dialysis in left lateral decubitus position Dialysis Decubitus

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Pregnant CKD 5D 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

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Pregnant CKD 5D Dialysis Prescription Stover J. Adv Chronic Kidney Dis. 2007;14(2):212-214. Hou S. N Engl J Med. 1985;312(13):836 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

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Pregnant CKD 5D 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

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Pregnant CKD 5D Dialysis Prescription Giatras I et al. Nephrol Dial Transplant. 1998;13(12):3266. Careful uterine and fetal monitoring during hemodialysis Assessment of the fetal heart rate (particularly during the last portion of a session ) Fetal Assessment

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Pregnant CKD 5D 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

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Pregnant CKD 5D Dialysis Prescription What is the importance of maintaining adequate intravascular volume? Avoid dialysis hypotension and volume contraction which may result in hemodynamic compromise, reduced uteroplacental perfusion, and premature labor. Preservation of GFR and good pregnancy outcome for mother and baby Piccoli GB et al. Clin J Am Soc Nephrol. 2010;5(1):62. UF & Dry weight Assessment

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Pregnant CKD 5D Dialysis Prescription 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 UF & Dry weight Assessment How to assess intravascular volume in pregnancy? Tools to asses intravascular volume during pregnancy

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Pregnant CKD 5D Dialysis Prescription Blood pressure out of target Respiratory compromise Clinical signs of hypervolemia Edema is an unhelpful sign in pregnancy Nadeau-Fredette et al. Advances in Chronic Kidney Disease, Vol 20, No 3 (May), 2013: pp 246-252 UF & Dry weight Assessment How to assess intravascular volume in pregnancy? Tools to asses intravascular volume during pregnancy

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Pregnant CKD 5D Dialysis Prescription 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 UF & Dry weight Assessment How to assess intravascular volume in pregnancy? Tools to asses intravascular volume during pregnancy

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Pregnant CKD 5D 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

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Normal Physiological Renal Changes during Pregnancy Reproductive and sexual dysfunction in uremic women CKD – Pregnancy Relationship Effect of CKD on Pregnancy Effect of Pregnancy on CKD CKD Classification in Pregnancy Pre-Pregnancy Counseling in CKD General Principles of Antenatal Care & Management CKD ND CKD 5D When to dialyse ? Dialysis Regimen & Precautions

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It is generally recommended to commence dialysis at eGFR 20 ml/min BUN 50 mg/dl S.Cr 3.5-5 mg/dl - Lindheimer MD et al. Medical Disorders in Pregnancy. St. Louis: Mosby; 2000:39-70. Asamiya Y et al. Kidney Int. 2009;75;1217-1222. Hou S. N Engl J Med. 1985;312(13):836 Pregnant CKD ND When to Initiate Dialysis? Better outcomes of pregnancy . May reduce incidence of polyhydramnios , lower urea and lowers water load, also reducing risk of dialysis-induced hypotension.

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Pregnant CKD ND When to Initiate Dialysis? Matt Hall, Nigel J Brunskill. Renal disease in pregnancy. Obstetrics, Gynaecology and Reproductive medicine 23:2. 2012

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Normal Physiological Renal Changes during Pregnancy Reproductive and sexual dysfunction in uremic women CKD – Pregnancy Relationship Effect of CKD on Pregnancy Effect of Pregnancy on CKD CKD Classification in Pregnancy Pre-Pregnancy Counseling in CKD General Principles of Antenatal Care & Management CKD ND CKD 5D When to dialyse ? Dialysis Regimen & Precautions When to Terminate Pregnancy

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Mark A. Brown. Comprehensive Clinical Nephrology. 4 th edition, chapter 43, p517 When to Terminate Pregnancy?

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Normal Physiological Renal Changes during Pregnancy Reproductive and sexual dysfunction in uremic women CKD – Pregnancy Relationship Effect of CKD on Pregnancy Effect of Pregnancy on CKD CKD Classification in Pregnancy Pre-Pregnancy Counseling in CKD Contraception in Childbearing Age General Principles of Antenatal Care & Management CKD ND CKD 5D When to dialyse ? Dialysis Regimen & Precautions When to Terminate Pregnancy

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Contraception - Hou S. N Engl J Med. 1985;312(13):836 - Kavitha Vellanki. Advances in Chronic Kidney Disease, Vol 20, No 3 (May), 2013 Sexually active women who have normal periods should use contraception if they do not wish to become pregnant ( esp if S.Cr > 3g/dl ) Although the frequency of conception in dialysis patients is low Contraception is advisable because of poor pregnancy outcomes with advanced CKD Complications of pregnancy are higher than those of using oral contraceptives .

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Contraception 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. (1) Which Method to Use? Intrauterine devices may be associated with increased bleeding because of heparin use with hemodialysis. (2) Commonly used barrier methods of contraception are safe . (2) Kavitha Vellanki. Advances in Chronic Kidney Disease, Vol 20, No 3 (May), 2013 Hou S. N Engl J Med. 1985;312(13):836

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Diagnosis of Pregnancy in Dialysis Patients Difficult to Diagnose !!

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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 - Hou S. Am J Kidney Dis. 1999;33(2):235. - Buckner CL et al. Ann Clin Lab Sci. 2007;37(2):186-191.

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Pregnancy in Dialysis When? How many times?

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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 . Pregnancy in Dialysis When? How many times? Hou S. Am J Kidney Dis. 1999;33(2):235.

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Available Guidelines for Pregnancy & CKD

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Available Guidelines for Pregnancy & CKD

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Take Home Messages

CKD – Pregnancy Relationship:

CKD – Pregnancy Relationship (1) Kavitha Vellanki. Advances in Chronic Kidney Disease, Vol 20, No 3 (May), 2013 (2) Galdo T et al. Transplant Proc. 2005;37(3):1577-1579. (3) Imbasciati E et al Nephrol Dial Transplant. 2009;24(2):519-525. (4) Jungers P et al. Am J Kidney Dis. 1991;17(2):116

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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) c reatinine > 1.5 mg/dl previous pregnancy complications Heparin Nephrotic Syndrome Serum Albumin of <2.5 g/l Protein Diet 1 g/kg/day + 20 g/day Urinary tract infection Early identification & management Assessment of fetal well-being Regular Assessment Superimposed preeclampsia Difficult Challenge !!! General Principles of Prenatal Care & Management

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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

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Pregnant CKD ND When to Initiate Dialysis? Matt Hall, Nigel J Brunskill. Renal disease in pregnancy. Obstetrics, Gynaecology and Reproductive medicine 23:2. 2012

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Contraception - Hou S. N Engl J Med. 1985;312(13):836 - Kavitha Vellanki. Advances in Chronic Kidney Disease, Vol 20, No 3 (May), 2013 Sexually active women who have normal periods should use contraception if they do not wish to become pregnant ( esp if S.Cr > 3g/dl ) Contraception is advisable because of poor pregnancy outcomes with advanced CKD

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Diagnosis of Pregnancy in Dialysis Patients Challenging USS

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

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