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
4. 0-10% 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. 1998
• 32 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 1.02 - 1.66

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 < 50
2. 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?
• 1963 150 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. 1998 Belgium
• American Jrnl Kid Diseases
• Spurred by the report of 5 pregnancies in 5 pts on chronic HD in 2 dialysis units bet 1989-1996
• 1st national survey of its kind which revealed a total of 15 pregnancies in HD - all dialysis centers in Belgium questioned for pts bet 1975-
1996

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
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Pt #12: initially treated in a ctr in which target Hb levels were lower than 10-12
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Pt #13, s/p parathyroidectomy just before conception
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Pt #14
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5 Highlighted Cases Are Those
Started on HD after Pregnancy
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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 14-44 yrs
• Pregnancies bet 1992 and 1995 were evaluated

Registry includes ~ 48% of women of childbearing years receiving HD in US 1992-1995
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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

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Women who conceived after start dialysis, 40.2% infants survived, c/w 73.6% in women who started dial after conception (p<.001)
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Frequency of Prematurity and Low Birth Rate is less in those conceived before beginning dialysis
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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

Hou, et al, 1998

Hou, et al, 1998

Survival Statistics
• One year survival of women 14-44 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