Slides courtesy of Matt Hall Nottingham University Hospitals February 2011 Slides courtesy of Matt...

Slides courtesy of Matt HallNottingham University HospitalsFebruary 2011






















Renal Disease and Pregnancy

Matt Hall

Nottingham Renal Unit

SpR Club Belfast























Sex

Drugs

Rock and roll























Sex























0

10

20

30

40

50

60

70

80

90

England andWales

CKD Transplant(Belfast)

Dialysis Dialysis inToronto

Conc

eptio

n ra

te (p

er 1

000

wom

en/y

ear)

?

National Statistics Online. Conception statistics 2008. http://www.statistics.gov.uk/downloads/theme_health/conceptions2008/conceptions08.pdfBrown JH, Maxwell AP, McGeown MG. Irish J Med. 2001

Barua M, Hladunewich M, Keunun J et al. Clin J Am Soc Nephrol. 2008;3:392/396

Pregnancy and CKD























Pregnancy and CKD

Dialysis, 20

CKD 3-4, 240

CKD 1-2, 960

UK, 800000

Approximate number of pregnancies per year in UK























Maternal and fetal risks

Maternal risks

Is pregnancy going to make my kidney disease worse?

Fetal risks

Will I take home a healthy baby?























Maternal and fetal risks























Factors associated with adverse outcomes

Baseline renal function?
























0

10

20

30

40

50

60

70

80

90

100

IUGR Preterm delivery Pre-eclampsia Perinatal death

%

<125

125-180

>180

Dialysis
























0

10

20

30

40

50

60

70

80

Loss of >25% renal functionduring pregnancy

Persistent loss of >25% renalfunction

ESRD after 1 year

%

<125

125-180

>180























0

20

40

60

80

100

120

140

Baseline serum creatinine

Base

line

seru

m cr

eatin

ine

(μm

ol/l

)

PALRF

No PALRFp=0.027

























0

20

40

60

80

100

120

Caesarean Section Preterm delivery Small for gestational age Neonatal ICU admission

ControlCKD 1CKD 2CKD 3CKD 4-5

*

*

** **
























Baseline renal function - yes

Baseline blood pressure?























Blood pressure?

Neonatal death

0

5

10

15

20

25

<70 70-80 80-90 >90 or treated

Diastolic blood pressure in early pregnancy (mmHg)

Odd

s ra

tio

Neonatal death risk

Diastolic BP Absolute risk

<70 0.9%

70-80 3.2%

80-90 3.6%

>90 or treated 15.3%























Blood pressure?

0

20

40

60

80

100

120

140

160

Systolic BP Diastolic BP

Mea

n bl

ood

pres

sure

(mm

Hg)

PALRFNo PALRF

p=0.08

p=0.009























Blood pressure?

• 43 pregnancies in 30 women with CKD (serum creatinine 110 to 490 μmol/l)• Hypertension was present from conception in 26 (60%).• Logistic regression identified uncontrolled hypertension at conception as an independent risk factor for fetal death• RR fetal death with MAP> 105mmHg at conception = 10.5• Accelerated loss of maternal renal function in 7 patients, all of whom had hypertension

• 168 pregnancies in 118 women with IgA nephropathy.• Perinatal mortality 33% in women with BP>140/90 versus 1% with BP<140/90• (Hypertension not identified as a risk factor for progression of maternal disease.)

Jungers P et al. Pregnancy in women with impaired renal function. Clin Nephrol 1997;47(5):218-288Abe S. Pregnancy in IgA nephropathy. Kidney International 1991;40:1098-1102

























Baseline blood pressure - yes

Proteinuria ?























Proteinuria

Women without CKD

Second trimester ACR>3mg/mmol

Second trimester ACR>20mg/mmol

OR 1.9 preterm delivery

OR 4.7 preterm deliveryXDiabetes and hypertension

Franceschini N et al. Maternal urine albumin excretion and pregnancy outcome. Am J Kindy Dis. 2005’45(6):1010-1018Jones DC, Hayslett JP. Outcome of pregnancy in women with moderate or severe renal insufficiency. New Engl J Med 1991;336(4):226-223

Hemmelder MH et al. Proteinuria: a risk factor for pregnancy-related renal function decline in primary glomerular disease? A,m J Kidney Dis 1995;2691):187-192

Women with CKDCreat > 124μmol /l

Proteinuria > 3g/d

Proteinuria < 3g/dNo impact on outcome

Women with CKD

Pregnancy (n=19)

No pregnancy (n=31)

Proteinuria andpregnancy assoc with

PALRF























Proteinuria?

Imbasciati E et al. AJKD 2007;49:753























Proteinuria?PALRF

Yes No p value

n 6 21

Maternal age (years) Mean (SD) 33.0 (3.7) 30.4 (3,3) 0.103

Gravidity Median (range) 3 (1-4) 3 (1-5) 0.057

Underlying glomerular disease n (%) 2 (33%) 13 (69%) 0.357

Baseline serum creatinine (μmol/l) Mean (SD) 111 (46) 81 (20) 0.027

Baseline eGFR (ml/min) Mean (SD) 63 (28) 79 (16) 0.077

Baseline protein:creatinine ratio

(mg/mmol creatinine)

Median (IQR) 29 (206) 46 (272) 0.345

Rate of decline in eGFR prior to conception (ml/min/year)

Median (IQR) 0.44 (4.15) -0.50 (3.52) 0.932

Baseline systolic BP (mmHg) Mean (SD) 143.1 (18.3)

136.6 (20.8)

0.08

Baseline diastolic BP (mmHg) Mean (SD) 81.0 (4.7) 71.6 (9.7) 0.009

Receiving antihypertensives n (%) 5 (83.3%) 7 (33.3%) 0.003

Table. Demographic and clinical parameters of study cohort























Proteinuria

0

10

20

30

40

50

60

70

80

90

100

Fetal Survival Low birth weight Preterm delivery

%

Proteinuria<100mg/mmol creatinineProteinuria>100mg/mmol creatinine

p=0.60

p=0.86

p=0.03


























Proteinuriamaternal? no

fetal? yes

Aetiology of kidney disease?























Aetiology of kidney disease?Perinatal

lossPretermdelivery

Renal function decline

Permanent blood pressure increase

FSGS (n=85) 23% 32% 13% 10%

Membranous GN (n=110) 4% 35% 3% 3%

IgA nephropathy (n=268) 15% 21% 12% 12%

MC GN (n=278) 12% 9% 2% 7%

Diabetic nephropathy (n=97) 6% 36% 32% 58%

Polycystic disease (n=464) 3% 10% 3% 14%

Reflux nephropathy (n=137) 7% 15% 0.7% 11%

Comparison of pregnancy outcomes by aetiology of CKD. FSGS, focal segmental glomerulosclerosis; GN, glomerulonephritis; MC, mesangiocapillary.No co

nvincin

g evidence

of effe

ct

of aetio

logy on outco

mes
























SLE

Hypertension

Medication

Anti-Roantibodies

Antiphospholipidsyndrome

Renaldysfunction

All associated with adverseoutcomes

Not the “SLE” label itself
























Reflux nephropathy

Increased riskof pyelonephritis

Maternalmortality

Pretermlabour

Neonatal morbidityand mortality

Increased riskof UTI
























Diabetes

0

5

10

15

20

25

30

35

Unknown

Glomerulonephriti

s

Pyelonep

hritis

Diabetes

Renal va

scular

disease

Hypert

ension

Polycysti

c dise

ase Other

Perc

enta

ge o

f cas

es

End stage renal disease

CKD and pregnancy























Aetiology of renal disease?


























Proteinuriamaternal? no

fetal? yes

Aetiology of kidney disease – not really























Management of CKD and hypertension in pregnancy

Hawk-like observation Masterful inactivity























Management of CKD in pregnancy

Limited interventions

Medicinesmanagement

Blood pressurecontrol

Pre-eclampsiaprophylaxis

Thrombo-prophylaxis

Urinary tract infectiontreatment

Timing of delivery

Preconceptioncounselling

Imm

unos

uppr

essa

nt

twea

kage

Dialysismanipulation























Management of CKD and hypertension in pregnancyPre-eclampsia prophylaxis























Aspirin 75mg odSystematic review

37560 women

All women

17% relativerisk reduction

High risk women

25% relativerisk reduction

NNT = 72 NNT = 19

Duley L, Henderson-Smart DJ, Meher S, King JF. Antiplatelet agents for preventing pre-eclampsia and its complications. Cochrane Database Syst.Rev. 2007 Apr 18;(2)(2):CD004659.

Preterm delivery RRR 8%

Perinatal death RRR 14%

SGA RRR 10%

Management of CKD and hypertension in pregnancyPre-eclampsia prophylaxis























• Not evidence based

• Different practices between (and within) centres.

Management of CKD and hypertension in pregnancyThrombo-prophylaxis

Nephrotic syndromeRR VTE = 1.7

PregnancyRR VTE = 4.3

?Heavy proteinuriaRR VTE = ?

PregnancyRR VTE = 4.3























Management of CKD and hypertension in pregnancyThrombo-prophylaxis

Add-up risk factors

Prophylactic LMWH No treatment

Treat until 6 weekspostpartum

If renal impairment,monitor Factor Xa levels

Low threshold forinvestigating suspected VTE























Management of CKD and hypertension in pregnancyUrinary tract infection

Asymptomatic bacteruria Pyelonephritis4x increased risk

in pregnancy

21% risk of progression if untreated

Treatment of asymptomatic bacteruria in pregnancy reduces the incidence of

pyelonephritis by 75%
























…Antibiotic treatment of asymptomatic bacteruria is indicated to reduce the risk of pyelonephritis in pregnancy…

Based on studies from 1960-1970s

…Antibiotic treatment of asymptomatic bacteruria was associated with a reduction in the incidence of low birth weight babies (RR 0.66 (0.49-0.89))…
























Asymptomatic bacteruria PyelonephritisNon-pyelonephriticUTI

Preterm birth7.2%

Preterm birth7.7%

Preterm birth8.3%

Small for gestational age16.1%



n=85,484

After adjusting for confounding covariates, no increased risk of preterm birth orsmall infant in women exposed to urinary tract infection.

Chen YK et al. Acto Obstet Gynecol Scand 2010;89(7):882-888
























Asymptomatic bacteruria

Pyelonephritis

Non-pyelonephriticUTI

In pregnancy

Treat

Asymptomatic bacteruria

Pyelonephritis

Non-pyelonephriticUTI

Treat

Second or more episode in pregnancy?

Prophylaxis























Management of CKD and hypertension in pregnancyBlood pressure control
























Chronic hypertension Target BP <150/100

Chronic hypertension+ CKD

Target BP <140/90

Do not treat to DBP<80mmHg

Chronic hypertension+ proteinuric CKD

Target BP ?and treat with what?























Chronic hypertension+ proteinuric CKD

Target BP <140/90
























0

10

20

30

40

50

60

70

80

90

England andWales

CKD Transplant(Belfast)

Dialysis Dialysis inToronto

Conc

eptio

n ra

te (p

er 1

000

wom

en/y

ear)

?

National Statistics Online. Conception statistics 2008. http://www.statistics.gov.uk/downloads/theme_health/conceptions2008/conceptions08.pdfBrown JH, Maxwell AP, McGeown MG. Irish J Med. 2001

Barua M, Hladunewich M, Keunun J et al. Clin J Am Soc Nephrol. 2008;3:392/396

Pregnancy and dialysis
























An average sized renal unit in the UKwould expect to treat one pregnant patient

on dialysis every four years
























How do you diagnosispregnancy in a woman on dialysis?

Amenorrhoea? Pregnancy test from Boots?
























How do you diagnosispregnancy in a woman on dialysis?

Intradialytic hypotension?

Serum βhCG Early ultrasound

Elevated Serum βhCG but no fetal heart beat?

Serial βhCG Repeat ultrasoundin 1-2 weeks
























Target weight Increase by 1.5kg over first trimester

0.2-0.4 kg/week from week 15

Weekly clinical evaluation

Blood pressure Target blood pressure <140/90

Do not treat to DBP<80mmHg

Anaemia ESA requirement increases by 85% at 28 weeks

Target Hb 10-11g/dl

Nutrition Protein intake >1.8g/kg/day

Energy intake 30kcal/kg/day

Water soluble vitamin and folic acid supplementation
























Befriend an obstetrician

• Fetal growth monitoring every 1 – 2 weeks• Liquor volume monitoring every 1 -2 weeks• CTG monitoring every dialysis session from 25 weeks
























PD?

Yes!• Conception rates may be lower• Infection rates no higher• No contraindication to Caesarean
























HD?

Yes!

How much?
























0

10

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30

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50

60

70

80

90

100

IUGR Preterm delivery Pre-eclampsia Perinatal death

%

<125

125-180

>180

Dialysis
























0%

10%20%

30%

40%50%

60%

70%

80%90%

100%

<14 hours/week 15-19 hours/week >20 hours/week

Dialysis duration

Infa

nt s

urvi

val

Hou S. Hemodialysis International 2004;8:167-171

p<0.05
























0%

10%20%

30%

40%50%

60%

70%

80%90%

100%

<14 hours/week 15-19 hours/week >20 hours/week

Dialysis duration

Pret

erm

del

iver

y

Hou S. Hemodialysis International 2004;8:167-171
























0%10%20%30%40%50%60%70%80%90%

100%

<14hours/week

15-19hours/week

>20hours/week

48±5hours/week

Dialysis duration

Infa

nt s

urvi

val

Hou S. Hemodialysis International 2004;8:167-171Barua M et al. Clin J Am Soc Nephrol 2008;3:392-396
























0%10%20%30%40%50%60%70%80%90%

100%

<14hours/week

15-19hours/week

>20hours/week

48±5hours/week

Dialysis duration

Pret

erm

del

iver

y

Hou S. Hemodialysis International 2004;8:167-171Barua M et al. Clin J Am Soc Nephrol 2008;3:392-396
























Historic observations Nocturnal HD

Preterm delivery 90% 50%

IUGR/SGA 90% 17%

Pre-eclampsia 75% 0%

Perinatal death 50% 17%

Williams D, Davison J. BMJ 2008;336:211-215Barua M et al. Clin J Am Soc Nephrol 2008;3:392-396
























As much dialysis as you can facilitate and certainly >20 hours/week

Maintain pre-dialysis urea < 15mmol/l

How much?























0

5

10

15

20

25

Dia lys is Transplant (Bel fast)

Conc

eptio

n ra

te (p

er 1

000

wom

en/y

ear) Fertility returns

within 1 -2 monthsof transplant

Transplant and pregnancy























Renal disease and pregnancy – renal transplant

Pregnancy outcomes following transplant are

vastly better than if still on dialysis

- 95% success

General guidelines1. Wait 2 years post-transplant (some say 12-18 months)

2. Stable renal function

3. Minimal proteinuria

4. Minimal or well-controlled hypertension

5. No transplant rejection

6. Minimal levels of appropriate immunosuppression























Renal disease and pregnancy – renal transplant

Pregnancy outcomes are predicted

by baseline kidney function

Baseline creatinine Complicated pregnancy

Successful outcome

<125 μmol/l 30% 97%

>125 μmol/l 82% 75%

Persistent post pregnancy kidney function

impairment develops in 15% of transplant patients























Renal disease and pregnancy – renal transplant; children

Children born to mothers with a renal

transplant do well in general

Complications are due mainly to

preterm delivery and low birth weight

Overall, 16% of children have specialeducational needs (cf. 11% in USA general population)























Transplant dysfunction in pregnancy

• Same causes• Same investigations (caution but not contraindication to

radiation exposure)

• Different treatment

Infection Rejection Obstruction Medication

Biopsy if indicated.























Drugs























Drugs, CKD and pregnancy

• Altered pharmacodynamics

• Potential teratogenicity

Check the BNF

Learn what you can use

ImmunosuppressantsAntibioticsAntihypertensives
























Antihypertensives

1. Labetalol2. Methyldopa3. Nifedipine4. Hydralazine

1. ACE inhibitors2. ARBs

3. Spironolactone4. Aliskiren

5. Moxonidine6. Minoxidil7. Diltiazem
























Antibiotics

1. Cephalosporins2. Penicillins3. Gentamicin4. Erythromycin

1. Quinolones2. Tetracyclines

1. Trimethoprim(not in 1st trimester)2. Nitrofurantoin(not in 3rd trimester)
























Immunosuppressants

1. Prednisolone2. Cyclosporine3. Tacrolimus4. Azathioprine

1. Mycophenolate mofetil2. Mycophenolic acid

3. Sirolimus4. Methotrexate

5. Cyclophosphamide6. ATG / OKT3























Rock and roll























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Slides courtesy of Matt Hall Nottingham University Hospitals February 2011 Slides courtesy of Matt...

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