Renal Failure and Dialysis in Pregnancy David Shure

Differential Diagnosis 1.FSGS - Pro: HTN, non-remitting, albumin close to NL Con: expected creatinine to be higher after several years 2.Membranous Nephropathy - Pro: wax/waning course Con: often with lower albumin, edema 3.Diabetic Nephropathy - Pro: proteinuria, time course Con:poor evidence for DM 4.FMD - Pro: unequal sized kidneys, young female, HTN hx, renal arteries not commented on in US

Nephrology Consult 1.Is there any indication and/ or benefit to the fetus if we begin HD at this time? 2.Can we preserve any residual maternal renal function? OB team trying to prolong in-utero growth/ length of pregnancy, not sure if pt is masking severe preeclampsia

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

Normal Physiologic Alterations of Pregnancy

Normal Renal Alterations in Pregnancy

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

Effects of Pregnancy on Renal Disease 1.½ cases proteinuria worsen 2.¼ cases HTN develops 3.Worsening edema if nephrotic % women with NL or mild reduction in GFR have permanent decline in renal function

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

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

Actually, they do get pregnant! 1st successful term pregnancy in 35 y/o dialysed pt in 1971, Confortini, et al. Yr 2000: >15,000 women of childbearing age getting dialysis For every person w/CKD 5, 20 have CKD 3 or 4 w/GFR <60, suggesting ~300,000 women w/CKD potentially able to bear children

Course of Renal Disease in Pregnancy Baseline azotemia = more rapid deterioration As renal dz progresses, ability to maintain nl pregnancy deteriorates, and presence of HTN incr likelihood of renal deterioration Renal dysfunction - greater risk for complications incl preeclapsia, premature delivery, IUGR

Pregancy during dialysis: case report and management guidelines; Giatras, et al y/o AA woman, G4, P2, A1 FSGS and chronic interstitial nephritis Renal/obstetric protocol implemented Increased HD to 4 hrs/ 4 sessions/ week maintain prediaysis BUN <50 At each HD session, blood flow gradually increased over 1st 30 minutes of HD, from 180 to 300 ml/min Kt/V

Giatras Protocol Dialysis performed in left lateral decubitus position Est maternal dry wt incrased by 500 g every 10d EPO administered at each HD session, to maintain HCT 32-34% Vit D, folic acid and MVI admin Evid of malnutrition prior to pregnancy, so 3000kcal/day diet w>100g protein/ day

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

Common Themes in Dialysing Pregnant Patients 1. Keeping BUN < Increasing dialysis time and frequency 3. BP control 4. Managing anemia with increasing doses of ESA 5. Fetal monitoring once viability reached

BUN <50 Hypothesis? women varying degrees of CKD, none on dialysis, found the single most important factor influencing fetal outcome was BUN Fetal mortality directly proportional to BUN Hypothesis: intensive dialysis in pregnant women w/renal dz might improve fetal outcomes

Increasing frequency and time on dialysis? May be beneficial in reducing incidence of polyhydramnios by reducing urea and water load Less dialysis-induced hypotension More liberal diet

Pregnancy and Dialysis Bagon, et al Belgium American Jrnl Kid Diseases Spurred by the report of 5 pregnancies in 5 pts on chronic HD in 2 dialysis units bet st national survey of its kind which revealed a total of 15 pregnancies in HD - all dialysis centers in Belgium questioned for pts bet

Study Population Figures 32 Belgian HD Centers - Nationwide 4,135 pts on HD Jan 1, 1975 and Dec 31, 1996, 17,618 pts 7,982 female Among female pts, 1,472 were of childbearing years (18-44) In addition to the 5 pts identified in the authors clinics, 10 others identified. All preterm, all w/low birth rate, 3 intrauterine deaths, 3 neonatal deaths; 9 survived.

Characteristics of Personal Cases

Pt #12: initially treated in a ctr in which target Hb levels were lower than 10-12

Pt #13, s/p parathyroidectomy just before conception

Pt #14

5 Highlighted Cases Are Those Started on HD after Pregnancy

Case Characteristics/ Outcomes 4/5 cases survived, 1 in-utero death All deliveries preterm All w/ low birth wt (<2500 gm) No congenital malformations Polyhydramnios very common Most cases received steroids for FLM Case 15 hospitalized for severe HTN, and IUGR, creat clear 18 ml/ min, at 29 wks fetus w/severe acidosis, bradycardia and death

Dialysis Dosing 15 pregnancies went beyond 1st trimester Frequency of HD was increased immediately or progressively to 16 to 24 hrs No difference bet successful pregnancies and failed ones for # mths on HD prior to conception or age at conception. For successful pregnancies + correlation bet birth wt and excess dialysis hrs delivered over entire pregnancy.

Success Rate 80% (4/5) when HD initiated after onset of pregnancy (pregnancy first) 50% (5/10) when HD was the first event ‘‘Pregnancy first’ cases have a significant residual renal function and even may benefit from ‘preventive dialysis’, to be taken on dialysis at a stage of renal failure that would not justify dialysis in the eyes of many were it not for the very special setting of a pregnant state’’

Obstetrical Problems Main Problem: premature births In this study 3 died due to severe prematurity Polyhydramnios present in almost all cases, may be cause of preterm labor Growth retarded babies at highest risk for intrauterine death Maternal prognosis is good

Should we Initiate Dialysis in Pts w/Low Cr Clearance? Hou, S., Pregnancy in Women on Hemodialysis, 1994, revealed better outcomes of pregnancy in women w/ significant residual renal function or who initiate pregnancy before they need dialysis. May reduce incidence of polyhydramnios, lower urea and lowers water load, also reducing risk of dialysis-induced hypotension

Registry of Pregnancy in Dialysis Patients Okundaye, I., Abrinko, P., Hou S., 1998 Am Jrnl Kid Ds Questionnaires to 2,299 dialysis centers in US Women yrs Pregnancies bet 1992 and 1995 were evaluated

Registry includes ~ 48% of women of childbearing years receiving HD in US

USRDS In 1992: 12,992 women under age 44 receiving dialysis in US This registry covers approx 48% of women of childbearing age receiving dialysis in US

Women who conceived after start dialysis, 40.2% infants survived, c/w 73.6% in women who started dial after conception (p<.001)

Frequency of Prematurity and Low Birth Rate is less in those conceived before beginning dialysis

Women who Start Dialysis During Pregnancy Likelihood of infant surviving is good Termination of a pregnancy after renal function has begun to deteriorate rarely rescues the kidneys NEJM, Jones and Hayslett, 1996, looked at 82 pregnancies in 67 women w/CRI, only 15% of those w/deteriorating renal function had a return of renal function to baseline in 6 mths post partum

Hou, et al, 1998

Survival Statistics One year survival of women yrs on dialysis is 90% Risk of death for dialysis pt who becomes pregnant is not increased by the pregnancy Extreme vigilance required to safeguard health of pregnant dialysis pts