Pregnancy in CKD Patients Asst. Prof. Naowanit Nata, MD Nephrology Division, Department of Medicine Phramongkutklao Hospital & College of Medicine
Outlines vPre-pregnancy care in CKD Patients vPregnancy care in CKD Patients vPeri and Post-partum care in CKD Patients
Physiological changes in the renal system in pregnancy v Kidney size increased by 1.0-1.5 cm v Kidney volume increased up to 30% v Hydronephrosis (80%, right > Left) v Serum Cr fall to 0.4-0.5 mg/dL v BUN fall to 8-10 mg/dL v Serum Na fall of 4-5 mEq/L Abnormal Serum Cr >0.8 mg/dL Wiles KS, et al. Reproductive health and pregnancy in women with chronic kidney disease. Nat Rev Nephrol. 2018 Mar;14(3):165-184.
Staging and Prognosis Indicate by eGFR and Albuminuria Categories Albuminuria stages, description and range (mg/g) A1 A2 A3 Normal to mildly Moderately increased Severely increased increased <30 30–300 >300 GFR categories, description G1 Normal or high ≥90 and range (ml/min/1.73 m2) G2 Mild decrease 60–89 G3a Mild–moderate 45–59 decrease G3b Moderate–severe 30–44 decrease G4 Severe decrease 15–29 G5 Kidney failure <15 Green: low CKD risk (if no other markers of kidney disease, no CKD); yellow: moderately increased risk; orange: high risk; red, very high risk. CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. Kidney Int Suppl 2013;3:1
Pregnancy in CKD Patients vWe recommend multidisciplinary teams (MDT; including a consultant obstetrician, consultant nephrologist/expert physician, and expert midwife or midwifery team) are established to offer advice and care for women with CKD who are pregnant or planning a pregnancy. All healthcare professionals caring for women with CKD should be able to access this MDT (1D) Wiles K, et al. Clinical practice guideline on pregnancy and renal disease. BMC Nephrology (2019) 20:401.
Pregnancy in CKD Patients Pre-pregnancy care Pregnancy care Post-partum care 1. Fertility 1. Assessment of renal Specific conditions: 1. Lactation 2. Contraception function 1. KT 2. Drugs 3. Conception: Pre- 2. Dialysis 3. Renal function 2. Antenatal care (ANC) 3. Lupus nephritis pregnancy 3. Pre-eclampsia 4. DN counselling and 5. UTI optimisation for prophylaxis 6. CAKUT pregnancy 4. BP management 5. Thromboembolism Wiles K, et al. Clinical practice guideline on pregnancy and prophylaxis renal disease. BMC Nephrology (2019) 20:401. 6. Anemia 7. Bone health 8. Renal biopsy 9. Peripartum care
Pre-pregnancy care in CKD Patients
Pregnancy in CKD Patients Pre-pregnancy care Pregnancy care Post-partum care v Fertility v Contraception v Conception
Endocrine effects of CKD on the hypothalamic–pituitary–ovarian axis Wiles KS, et al. Reproductive health and pregnancy in women with chronic kidney disease. Nat Rev Nephrol. 2018 Mar;14(3):165-184.
Endocrine effects of CKD on the hypothalamic–pituitary–ovarian axis Wiles KS, et al. Reproductive health and pregnancy in women with chronic kidney disease. Nat Rev Nephrol. 2018 Mar;14(3):165-184.
Mechanisms for decreased fertility in chronic kidney disease Burgner A, Hladunewich MA. Women's Reproductive Health for the Nephrologist. Am J Kidney Dis. 2019 Nov;74(5):675-681.
Pre-pregnancy care: Fertility in CKD patient Guideline 3.2.1 v We suggest fertility preservation is considered for women of Guideline 3.2.2 reproductive age who require treatment with cyclophosphamide (2C). v We suggest women who have had previous treatment with cyclophosphamide have early investigation of infertility (2D). Guideline 3.2.3 v We recommend women with CKD are referred for pre-pregnancy counselling before receiving assisted reproduction (1D). Guideline 3.2.4 v We recommend single-embryo transfer is performed to reduce risk of complications associated with multifetal pregnancies in women with CKD (1C). Wiles K, et al. BMC Nephrology (2019) 20:401 https://doi.org/10.1186/s12882-019-1560-2
Pregnancy in CKD Patients Pre-pregnancy care Pregnancy care Post-partum care v Fertility v Contraception v Conception
Contraceptive Method in CKD Patients Type of Contraception Risk Benefits IUDs - Risk of expulsion and perforation - Most effective contraceptive category - Increased risk of ectopic pregnancy - Long acting and reversible - No evidence for increased risk of pelvic inflammatory disease - No increased risk of HTN, vascular disease, or VT Copper IUD - Change in menstrual bleeding pattern: - Contains no hormones heavier IUD with progestin - Change in menstrual bleeding pattern: lighter - Contains levonorgestrel, Lighter periods to amenorrhea Combined estrogen-progestin hormonal Highly effective contraceptive category methods Combined estrogen-progestin oral - Worsening of HTN, worsening of proteinuria, - Improved cycle control contraceptive pills (COC) and increased risk of VT, stroke, and MI - Needs to be taken daily Transdermal contraceptive patch (ethinyl - Application site reactions - Convenient weekly application estradiol and norelgestromin) - Higher overall estrogen dose and risk of VT - No increased risk of HTN or vascular disease, compared with COC because it does not stimulate the RAAS Contraceptive vaginal ring - Increased risk of venous thrombosis, stroke, - Once a month self-administered use (etonogestrel/ethinyl estradiol) and myocardial infraction similar to COC Bramham K, et al. Nephrol Self Assess Program 2016; 15:141.
Contraceptive Method in CKD Patients Type of Contraception Risk Benefits Progestin-only hormonal methods Etonogestrel implant - Change in bleeding pattern with unscheduled - Most effective contraceptive category bleeding - Possible increased risk of thrombotic events Depot medroxyprogesterone acetate - Change in bleeding pattern with unscheduled - Highly effective contraceptive category bleeding - Administration every 3 months - Decreased bone density - Should not be used in patients with CV risk factors Progestin-only preparations - Change in bleeding pattern with unscheduled - Highly effective contraceptive category bleeding - No increased risk of HTN, vascular disease, - Higher failure rate if not taken consistently or VT within 3 hours each day Pericoital methods - Least effective contraceptive method - Contain no hormones - Used only when needed Condoms with or without spermicides - Least effective category of contraceptive methods - Protection against STIs Diaphragms - No protection against STIs Spermicide and spermicidal sponge - No protection against STIs Sterilization procedures - Surgical risk - Most effective contraceptive category and Permanent Bramham K, et al. Nephrol Self Assess Program 2016; 15:141.
Pre-pregnancy care: Contraception in CKD patient Guideline 3.1.1 v We recommend advice on safe and effective contraception is offered to all women of reproductive age with CKD (1D). Guideline 3.1.2 v We recommend safe and effective contraception is offered to women of reproductive age who are taking teratogenic medication, have active glomerulonephritis, are within one year of renal transplantation or acute graft rejection, and for any woman who does not wish to conceive (1D). Guideline 3.1.3 v We recommend that the progesterone only-pill, a progesterone subdermal implant, and the progesterone intra-uterine system are safe and effective for women with CKD (1C) Guideline 3.1.4 v We recommend that progesterone-only emergency contraception is safe for women with CKD (1C) Wiles K, et al. BMC Nephrology (2019) 20:401 https://doi.org/10.1186/s12882-019-1560-2
Contraceptive Method in Glomerular Disease Patients Contraceptive method Unintended pregnancy rate Contraindications in Other considerations within 1st year of use (%) glomerular disease Estrogen-containing Perfect use Typical use methods (pill, patch, ring) Lupus - Breast cancer risk 0.3 9 Progesterone-only pill VTE - Cervical cancer risk with 0.3 9 Progesterone IUD (Mirena) Vascular disease immunosuppression 0.2 0.2 Progesterone implant - VTE risk in nephrotic syndrome (Nexplanon) 0.05 0.05 Copper IUD 0.6 0.8 None - Longest re-dosing interval with Male condom 2 18 Female condom 5 21 desogestrel (may improve typical use) - Possible breast cancer risk, especially >40 years Non - Possible breast cancer risk, especially >40 years - Effective with immunosuppression, no evidence of increased infection None - Possible breast cancer risk, especially >40 years None - No associated hormonal risk Ineffective for long-term use - Protects against HIV and STI Wiles K, Lightstone L. Kidney Int Res. 2018 Mar; 3(2): 258–270.
Pregnancy in CKD Patients Pre-pregnancy Pregnancy Post-partum v Fertility 1. Pre-pregnancy counselling before conception is strongly recommended v Contraception v Conception 2. Ensure disease and/or transplant stability before conception 3. Remove or substitute teratogens before conception 4. Consider risks and/or benefits to remaining on angiotensin- converting enzyme inhibitors until conception
Outcome of Pregnancy in CKD Patient CKD patients with pregnancy outcomes: Pregnancy outcomes: v Worsening kidney function v Preterm birth v Stillbirth or neonatal death and/or proteinuria v Low birth weight v Potential flare of underlying disease v Fetal growth restriction v Hypertensive disorders of pregnancy v Small for gestational age v Gestational hypertension v Preeclampsia 1. Holley JL, et al. Am J Kidney Dis.1997;29:685–690. v HELLP syndrome 2. Hou S, et al. Handbook of Dialysis 5th ed, Philadelphia 2015. p.690-704. v Complications of immunosuppression 3. Gonzalez Suarez ML, et al. Am J Kidney Dis. 2019 Jun;73(6):897. v Miscarriage 4. Holley JL, et al. Adv Chronic Kidney Dis 2013; 20:240. 5. Shah S, et al. J Am Soc Nephrol 2019; 30:2437.
Forest plots of studies of the association between CKD and maternal complications Pre-eclampsia (crude estimates) ￪ 8.13 (4.41-14.97) Pre-eclampsia (adjusted estimates) ￪ 2.58 (1.33-5.01) Al Khalaf S, et al. Am J Obstet Gynecol. 2022 May;226(5):656-670.e32.
Forest plots of studies of the association between CKD and maternal complications Cesarean section (crude estimates) ￪ 1.66 (1.34-2.06) Cesarean section ((adjusted estimates) ￪ 1.65 (1.21-2.25) Al Khalaf S, et al. Am J Obstet Gynecol. 2022 May;226(5):656-670.e32.
Forest plots of studies of the association between CKD and fetal or neonatal outcomes Preterm birth <37 weeks (crude estimates) ￪ 3.07 (2.27-4.16) Preterm birth <37 weeks (adjusted estimates) ￪ 1.73 (1.31-2.27) Al Khalaf S, et al. Am J Obstet Gynecol. 2022 May;226(5):656-670.e32.
Forest plots of studies of the association between CKD and fetal or neonatal outcomes Small for gestational age (crude estimates) ￪ 2.69 (1.70-4.24) Small for gestational age (adjusted estimates) ￪ 1.93 (1.06-3.52) Al Khalaf S, et al. Am J Obstet Gynecol. 2022 May;226(5):656-670.e32.
The association between subtypes of CKD and perinatal outcomes Pre-eclampsia ￪ 1.59 - 8.45 ￪ 1.55 – 3.98 Al Khalaf SY, et al. Am J Obstet Gynecol. 2021 Sep;225(3):298.e1-298.e20.
The association between subtypes of CKD and perinatal outcomes Spontaneous preterm birth <37 weeks ￪ 1.59 - 8.45 ￪ 1.55 – 3.98 Al Khalaf SY, et al. Am J Obstet Gynecol. 2021 Sep;225(3):298.e1-298.e20.
The association between subtypes of CKD and perinatal outcomes Small for gestational age ￪ (1.39 – 4.28) ￪ 1.25 – 4.50 Al Khalaf SY, et al. Am J Obstet Gynecol. 2021 Sep;225(3):298.e1-298.e20.
The association between subtypes of CKD and perinatal outcomes Stillbirth ￪ 0.84 – 5.75 ￪ 0.80 – 2.73 Al Khalaf SY, et al. Am J Obstet Gynecol. 2021 Sep;225(3):298.e1-298.e20.
Associations between maternal chronic disease and adverse pregnancy outcomes over time (Adjusted estimates) Al Khalaf SY, et al. Am J Obstet Gynecol. 2021 Sep;225(3):298.e1-298.e20.
Associations between maternal chronic disease and adverse pregnancy outcomes over time (Adjusted estimates) Al Khalaf SY, et al. Am J Obstet Gynecol. 2021 Sep;225(3):298.e1-298.e20.
Adverse pregnancy outcomes according to chronic kidney disease stage Wiles KS, et al. Nat Rev Nephrol. 2018 Mar;14(3):165-184.
Selected renal disorders during pregnancy Berry C, Atta MG. World J Nephrol. 2016 Sep 6;5(5):418-28.
Summary of Pregnancy Counselling by CKD Stage Burgner A, Hladunewich MA. Women's Reproductive Health for the Nephrologist. Am J Kidney Dis. 2019 Nov;74(5):675-681.
Renal disorders and associated maternal and fetal health risks: Maternal and fetal risk by degree of renal impairment Berry C, Atta MG. World J Nephrol. 2016 Sep 6;5(5):418-28. Guideline 3.3.7We suggest women with CKD stages 4 and 5 contemplating pregnancy are offered pre-dialysis education (2D). Wiles K, et al. BMC Nephrology (2019) 20:401.
Pregnancy in CKD Patients Pre-pregnancy Pregnancy Post-partum v Fertility 1. Ensure disease and/or transplant stability before conception v Contraception v Conception 2. Pre-pregnancy counselling before conception is strongly recommended 1. No active disease 2. Normal/controll BP 3. Remove or substitute teratogens before conception 3. Serum Cr <1.4 mg/dL 4. Minimal proteinuria 4. Consider risks and/or benefits to remaining on angiotensin- converting enzyme inhibitors until conception
Considerations for drugs commonly used in nephrology during conception, pregnancy and lactation Conception Fetal considerations Wiles KS, et al. Reproductive health and pregnancy in women with chronic kidney disease. Nat Rev Nephrol. 2018 Mar;14(3):165-184.
Considerations for drugs commonly used in nephrology during conception, pregnancy and lactation Conception Fetal considerations ACEi Wiles KS, et al. Reproductive health and pregnancy in women with chronic kidney disease. Nat Rev Nephrol. 2018 Mar;14(3):165-184.
Considerations for drugs commonly used in nephrology during conception, pregnancy and lactation Conception Fetal considerations ARB Wiles KS, et al. Reproductive health and pregnancy in women with chronic kidney disease. Nat Rev Nephrol. 2018 Mar;14(3):165-184.
Medication in pregnancy v Guideline 3.3.5 We recommend women with CKD who are taking angiotensin converting enzyme inhibitors have a plan for discontinuation/conversion guided by the strength of indication for renin-angiotensin blockade and the likelihood of pregnancy confirmation in the first trimester (1B). v Guideline 3.3.6 We recommend angiotensin receptor antagonists are discontinued in advance of pregnancy (1D). Wiles K, et al. BMC Nephrology (2019) 20:401 https://doi.org/10.1186/s12882-019-1560-2
Considerations for drugs commonly used in nephrology during conception, pregnancy and lactation Wiles KS, et al. Reproductive health and pregnancy in women with chronic kidney disease. Nat Rev Nephrol. 2018 Mar;14(3):165-184.
Considerations for drugs commonly used in nephrology during conception, pregnancy and lactation Conception Fetal considerations Wiles KS, et al. Reproductive health and pregnancy in women with chronic kidney disease. Nat Rev Nephrol. 2018 Mar;14(3):165-184.
Considerations for drugs commonly used in nephrology during conception, pregnancy and lactation Wiles KS, et al. Reproductive health and pregnancy in women with chronic kidney disease. Nat Rev Nephrol. 2018 Mar;14(3):165-184.
Outlines vPre-pregnancy care in CKD Patients vPregnancy care in CKD Patients vPeri and Post-partum care in CKD Patients
Pregnancy in CKD Patients Pre-pregnancy care Pregnancy care Post-partum care 1. Fertility 1. Assessment of renal Specific conditions: 1. Lactation 2. Contraception function 1. KT 2. Drugs 3. Conception: Pre- 2. Dialysis 3. Renal function 2. Antenatal care (ANC) 3. Lupus nephritis pregnancy 3. Pre-eclampsia 4. DN counselling and 5. UTI optimisation for prophylaxis 6. CAKUT pregnancy 4. BP management 5. Thromboembolism Wiles K, et al. Clinical practice guideline on pregnancy and prophylaxis renal disease. BMC Nephrology (2019) 20:401. 6. Anemia 7. Bone health 8. Renal biopsy 9. Peripartum care
การวนิ จิ ฉยั ภาวะตงั. ครรภ:์ CKD patients v อาการทส'ี งสยั ภาวะตง0ั ครรภใ์ นผปู้ ่ วยลา้ งไตทางชอ่ งทอ้ งหรอื ฟอกเลอื ดดว้ ยเครอ'ื งไตเทยี ม คอื การขาดประจาํ เดอื น อาการคลน'ื ไสอ้ าเจยี น มคี วามผดิ ปกตทิ างเมทาบอลกิ เชน่ ระดบั นํา0 ตาล ในเลอื ดสงู ขน0ึ การวนิ จิ ฉยั การตง0ั ครรภใ์ นผปู้ ่ วยลา้ งไตทง0ั สองวธิ จี ะยากกวา่ ปกตเิ พราะการตรวจ การตง0ั ครรภด์ ว้ ยการตรวจปสั สาวะไมส่ ามารถทาํ ไดใ้ นกรณีผปู้ ่ วยไมม่ ปี สั สาวะ การตรวจเลอื ด เพอื' วดั ระดบั beta-human chorionic gonadotropin (beta-hCG) พบผลบวกลวงไดแ้ มไ้ มม่ ี การตงั0 ครรภ์ โดยอาจพบระดบั beta-hCG สงู ขน0ึ เล็กนอ้ ยในภาวะไตวายระยะสดุ ทา้ ย (borderline positive) ทไี' มไ่ ดต้ งั0 ครรภ์ ดงั นนั0 กรณีสงสยั การตง0ั ครรภแ์ นะนําใหต้ รวจอลั ตรา ซาวดร์ ว่ มดว้ ยเพอ'ื ดตู วั ทารกในครรภเ์ พอ'ื วนิ จิ ฉยั การตงั0 ครรภแ์ ละประเมนิ อายคุ รรภร์ ว่ มดว้ ย เพราะระดบั beta-hCG มกั สงู กวา่ อายคุ รรภจ์ รงิ จนบางครงั0 อาจตอ้ งวนิ จิ ฉยั แยกโรคกบั ภาวะ ครรภแ์ ฝดหรอื ครรภไ์ ขป่ ลาอกุ ในผปู้ ่ วยลา้ งไตแนะนําการประเมนิ อายคุ รรภค์ วรทาํ อลั ตราซาวด์ เหมาะสมกวา่ ใชว้ ธิ อี นื' กรณีตรวจพบระดบั α-fetoprotein ในเลอื ดสงู อาจเกดิ พบผลบวกลวง ในผปู้ ่ วยโรคไตเรอ0ื รงั หรอื จากโรค Down syndrome กรณีสงสยั ควรวนิ จิ ฉยั แยกโรคและไดร้ บั การยนื ยนั จากการตรวจ karyotyping v โดยสรปุ การวนิ จิ ฉยั และการประเมนิ การตงั0 ครรภใ์ นผปู้ ่ วยลา้ งไตทงั0 การลา้ งไตทางชอ่ งทอ้ งและ ฟอกเลอื ดดว้ ยเครอ'ื งไตเทยี มควรใชก้ ารตรวจรว่ มกนั ระหวา่ งการตรวจระดบั beta-hCG ใน เลอื ดและการตรวจอลั ตราซาวดเ์ พอื' ประเมนิ ทารกในครรภ์
Assessment of renal function in pregnancy in CKD patients 1. Guideline 4.1.1 We recommend renal function in pregnancy is assessed using serum creatinine concentrations as estimated GFR (eGFR) is not valid for use in pregnancy (1C). 2. Guideline 4.1.2 We recommend women with CKD have formal quantification of proteinuria in pregnancy (1D). 3. Guideline 4.1.3 We recommend quantification of pro- teinuria is undertaken by protein:creatinine ratio (uPCR) or albumin:creatinine ratio (uACR). Twenty-four hour urine collection for quantification of protein is not re- quired (1B). Wiles K, et al. BMC Nephrology (2019) 20:401 https://doi.org/10.1186/s12882-019-1560-2
Antenatal care in CKD patients v Guideline 4.2.1 We suggest pregnant women with CKD who have not had pre-pregnancy counselling by the MDT are referred to the MDT and receive the same counselling and optimisation as for women attending pre- pregnancy (2D). v Guideline 4.2.2 We recommend pregnant women with CKD receive routine antenatal care, in addition to specialist input (1D). v Guideline 4.2.3 We recommend pregnant women with CKD be referred for assessment by a consultant obstetrician (1D). v Guideline 4.2.4 We recommend pregnant women with CKD have access to usual trisomy screening with specialist interpretation of high-risk results (1C). v Guideline 4.2.5 We recommend women with CKD exposed to teratogenic drugs in the first trimester are referred to a specialist fetal medicine unit (1D). v Guideline 4.1.6 We recommend pregnant women with CKD have scans to assess fetal growth and wellbeing in the third trimester (1C). v Guideline 4.2.7 We recommend pregnant women taking prednisolone and/or calcineurin inhibitors are screened for gestational diabetes (1C). Wiles K, et al. BMC Nephrology (2019) 20:401 https://doi.org/10.1186/s12882-019-1560-2
Renal biopsy in Pregnancy vGuideline 4.8.1 We recommend if a histological diagno- sis will change management in pregnancy then renal biopsy can be performed in the first and early second trimester of pregnancy (1C) Wiles K, et al. BMC Nephrology (2019) 20:401 https://doi.org/10.1186/s12882-019-1560-2
Preg 3 Gestational Hypertension and Preeclampsia: ACOG Practice Bulletin, Number 222. Obstet Gynecol. 2020 Jun;135(6):e237-e260.
Risk Factors for Preeclampsia v Nulliparity v Multifetal gestations v Preeclampsia in a previous pregnancy v Chronic hypertension v Pregestational diabetes v Gestational diabetes v Thrombophilia v Systemic lupus erythematosus v Prepregnancy body mass index greater than 30 kg/m2 v Antiphospholipid antibody syndrome v Maternal age 35 years or older v Kidney disease v Assisted reproductive technology v Obstructive sleep apnea Gestational Hypertension and Preeclampsia: ACOG Practice Bulletin, Number 222. Obstet Gynecol. 2020 Jun;135(6):e237-e260.
Diagnostic Criteria for Preeclampsia ü Blood pressure: v SBP of 140 mmHg or more or DBP of 90 mm Hg or more on two occasions at least 4 hours apart after 20 weeks of gestation in a woman with a previously normal blood pressure v SBP of 160 mm Hg or more or DBP of 110 mm Hg or more. (Severe hypertension can be confirmed within a short interval (minutes) to facilitate timely antihypertensive therapy). AND ü Proteinuria: v 300 mg or more per 24 hour urine collection (or this amount extrapolated from a timed collection) or v Protein/creatinine ratio of 0.3 or more or v Dipstick reading of 2+ (used only if other quantitative methods not available) Gestational Hypertension and Preeclampsia: ACOG Practice Bulletin, Number 222. Obstet Gynecol. 2020 Jun;135(6):e237-e260.
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