Courtesy of Matt Hall Nottingham Renal Unit February 2011 Courtesy of Matt Hall Nottingham Renal...
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Courtesy of Matt Hall Nottingham Renal Unit February 2011 Courtesy of Matt Hall Nottingham Renal Unit February 2011 Courtesy of Matt Hall Nottingham Renal Unit February 2011 Courtesy of Matt Hall Nottingham Renal Unit February 2011 Courtesy of Matt Hall Nottingham Renal Unit February 2011 Courtesy of Matt Hall Nottingham Renal Unit February 2011 Courtesy of Matt Hall Nottingham Renal Unit February 2011 Courtesy of Matt Hall Nottingham Renal Unit February 2011 Courtesy of Matt Hall Nottingham Renal Unit February 2011 Courtesy of Matt Hall Nottingham Renal Unit February 2011 Courtesy of Matt Hall Nottingham Renal Unit February 2011 Courtesy of Matt Hall Nottingham Renal Unit February 2011 Courtesy of Matt Hall Nottingham Renal Unit February 2011 ourtesy of Matt Hall ottingham Renal Unit February 2011 Pre-eclampsia “A common human-specific disease of pregnancy characterised by novel and progressive hypertension and proteinuria after 20 weeks gestation.”
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Transcript of Courtesy of Matt Hall Nottingham Renal Unit February 2011 Courtesy of Matt Hall Nottingham Renal...
Courtesy of Matt HallNottingham Renal Unit
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February 2011 Pre-eclampsia
“A common human-specific disease of pregnancy characterised by novel and
progressive hypertension and proteinuria after 20 weeks gestation.”
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February 2011 Clinical features• Hypertension
• Proteinuria
• Fetal growth restriction
• Abdominal pain
• Headaches
• Visual scotoma
• Deranged LFTs
• Thrombocytopenia
• Haemolysis
• DIC
• Hyperreflexia
• Seizures
• Renal failure
• Death
εκ-λαμψια
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February 2011Demographic and clinical risk factors
1. Older mothers (>40 years, RR=2)2. Primigravidae (RR=3)3. Previous pre-eclampsia (RR=7)4. Family history of pre-eclampsia (RR=3)5. Obesity (BMI>35, RR=4)6. New sexual partner7. Diabetes mellitus (RR=4)8. Chronic hypertension (40x higher prevalence in cases)9. Chronic kidney disease10. Thrombophilia11. Connective tissue diseases (RR=6)12. Multiple pregnancies (RR=3)
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February 2011 Diagnosis
• No gold standard diagnostic test
• No (reliable) animal models
• Variable diagnostic criteria used
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February 2011Diagnosis
International Society for the Study of Hypertension in Pregnancy (ISSHP, 2001)
Research definition
De novo hypertension (systolic blood pressure >140mmHg, diastolic blood pressure >90mmHg) after 20 weeks’ gestation plus proteinuria (greater than 300mg/d or protein:creatinine ratio >30mg/mmol).
Clinical definition
As above but “in the absence of proteinuria the disease is highly suspect when increased blood pressure is accompanied by:
• Headache• Blurred vision• Abdominal pain• Low platelets• Abnormal liver enzymes.”
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February 2011 Epidemiology
Incidence
• 2-8% of pregnancies– 32,000 affected pregnancies/year in UK– 6,500,000 affected pregnancies/year
worldwide
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February 2011 Epidemiology
• Directly led to the death of 18 mothers in the UK from 2002-2005
• Implicated in 135 stillbirths in the UK in 2006
Lewis.G editor. The Confidential Enquiry into Maternal and Child Health (CEMACH). Saving Mothers’ Lives: Reviewing maternal deaths to make motherhood safer - 2003-2005. London: CEMACH; 2007
Acolet D editor. Confidential Enquiry into Maternal and Child Health (CEMACH) Perinatal Mortality 2006: England,Wales and Northern Ireland. London: CEMACH; 2008
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February 2011 Epidemiology
Directly implicated in 68,000 maternal deaths per year
worldwide.
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February 2011Treatment of pre-eclampsia
Deliver the fetusand placenta
Serial monitoringof fetal growth
Blood pressurecontrol
Clinical surveillanceof impending
eclampsia or HELLP
Magnesiumsulphate + betamethasone
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February 2011Prevention of pre-eclampsia
What is the pathological process?
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February 2011Prevention of pre-eclampsia
Geneticpredisposition
Immunologicaldysfunction
Abnormalplacentation
Endothelialdysfunction
Coagulationabnormalities
Cardiovascularmaladaptation
Abnormaltrophoblast
invasion
Decreaseduteroplacental
perfusion
Disorderedendothelinmetabolism
Cytokines and growth factors
Cardiovascularor renal disease
ADMA / nitric oxideimbalance
Imbalancedprostaglandinmetabolism
Relaxin/metalloprotease-2
deficiency
Anti-AT2 IgG
Anti-cardiolipinIgG and IgM
Anti-spermatazoaantibodies
STOX-1mutation
ACEpolymorphisms
NOSpolymorphisms
TNF-α
IL-6
IL-1α
Fasligand VEGF PlGF
s-Flt-1
Endoglin
COMT deficiency
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February 2011Prevention of pre-eclampsia
Diuretics
Progesterone
Vitamin C and E
GTN
Calcium supplements
GarlicAspirin
L-arginine
Vitamin B6
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February 2011Prevention of pre-eclampsia
Calcium supplements Systematic review
14949 women
All women
52% relativerisk reduction
High risk women
78% relativerisk reduction
Hofmeyr GJ, Atallah AN, Duley L. Calcium supplementation during pregnancy for preventing hypertensive disorders and related problems. Cochrane Database Syst.Rev. 2006 Jul 19;3:CD001059.
Dietary calcium is adequate in most patients.Supplementation only recommended with dietary insufficiency
Hofmeyr GJ, Duley L, Atallah A. Dietary calcium supplementation for prevention of pre-eclampsia and related problems: a systematic review and commentary. BJOG 2007 Aug;114(8):933-943.
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February 2011Prevention of pre-eclampsia
AspirinSystematic 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%
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February 2011Prevention of pre-eclampsia
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February 2011The kidney in pre-eclampsia
Hypertension
Increased risk of ESRD
AKI
Proteinuria
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February 2011Pre-eclampsia and the kidney
Glomerular endotheliosis
Capillary endothelial oedema Vasospasm Microthrombi
Light microscopy normal by40 days post-partum
GBM thickening can persist on EM
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February 2011Pre-eclampsia and AKI
Intraglomerularthrombosis
Systemicvasoconstriction
Intravascularfluid depletion
Endothelialdysfunction
Antihypertensivemedication
Loss of autoregulation
Haemorrhage
DIC Placental abruption Emergency Caesarean
AKI Affects 1-2%
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February 2011Pre-eclampsia – renal treatment
Keep them dry
Dialyse when needed
Wait for it all to go away
Encourage baby extraction
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AnaesthetistsBeing unlucky
Patients die from fluid overloadPatients don’t die from kidney failure
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February 2011What’s new in pre-eclampsia?
Angiogenic factors
Podocyturia
Predicting pre-eclampsia
Biomarkers
Laboratory Imaging
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February 2011Angiogenic factors and pre-eclampsia
Gene expression profiling of placental tissue from women
with and without pre-eclampsia (PE)1
Up-regulation of soluble fms-like
tyrosine kinase-1(s-Flt-1)1
s-Flt-1 increased in serum in PE2
s-Flt-1 increased in urine in PE3
Binds to VEGF and Placental Growth Factor (PlGF) antagonising their function
Serum PlGF decreased in PE2 Urine PlGF decreased in PE3
1 Maynard S, Min J-Y et al. J. Clin. Invest 2003;111:6492 Levine RJ, Maynard SE et al. NEJM 2004;350:672
3 Buhimsci CS, Magloire L et al. Obstet Gynecol 2006;107:1103
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February 2011
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sVEGF-R1
sFlt-1
sVEGF-R1
sFlt-1
VEGF
VEGF
VEGF-R1
Flt-1VEGF-R2
Flk-1
VEGF-R2
sVEGF-R1
sFlt-1
Survival, migration and differentiation of
endothelial cells
Tyrosine kinase
No signal
VEGF
VEGFVEGF
PlGF PlGF
PlGF
Activation of VEGF-R2 by transphosphorylation
Displacement of VEGF from inactive receptors
Destabilise inactive VEGF-R heterodimers
Endothelial cell
VEGF-R1
Placenta
Normal pregnancyPre-eclampsia
AngiogenesisAnti-angiogenesis
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011Other supportive evidence
s-Flt-1
Hypertension Proteinuria
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011Other supportive evidence
Hypertension Proteinuria
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011Other supportive evidence
…in humans?
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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Romero R, Nien JK, Espinoza J, Todem D, Fu W, Chung H, et al. A longitudinal study of angiogenic (placental growth factor) and anti-angiogenic (soluble endoglin and soluble vascular endothelial growth factor receptor-1) factors in normal pregnancy and patients destined to develop preeclampsia and deliver a small for gestational age neonate. J.Matern.Fetal.Neonatal Med. 2008 Jan;21(1):9-23.
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011Diagnosis of pre-eclampsia will change
International Society for the Study of Hypertension in Pregnancy (ISSHP, 2001)
Research definition
De novo hypertension (systolic blood pressure >140mmHg, diastolic blood pressure >90mmHg) after 20 weeks’ gestation plus proteinuria (greater than 300mg/d or protein:creatinine ratio >30mg/mmol).
Clinical definition
As above but “in the absence of proteinuria the disease is highly suspect when increased blood pressure is accompanied by:
• Headache• Blurred vision
• Abdominal pain• Low platelets• Abnormal liver enzymes.”
Elevated serumsFlt1:PlGF ratio
Elevated urinesFlt1:PlGF ratio
Elevated serumendoglin
Presence of podocyturiaor podocyte-specific mRNA
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February 2011
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February 2011
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February 2011Predicting pre-eclampsia
Pre-eclampsia affects5% of pregnancies
50% of patients with pre-eclampsiahave no risk factors
90% of patients with risk factorsdo not develop pre-eclampsia
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February 2011
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February 2011Current clinical practice
Demographic and clinical risk factors Frequent monitoring
Aspirin
Uterine artery doppler(20-24 weeks)
High risk – 14.4%
No uterine artery notch – 9.2%Uterine artery notch – 30%
Conde-Agudelo A, Villar J, Lindheimer M. World Health Organization Systematic Review of Screening Tests for Preeclampsia. Obs. Gynecol. 2004;104(6),1367-1391
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February 2011Predicting pre-eclampsia
Conde-Agudelo A, Villar J, Lindheimer M. World Health Organization Systematic Review of Screening Tests for Preeclampsia. Obs. Gynecol. 2004;104(6),1367-1391
Uterine artery dopplerHuman chorionic gonadotrophin
Alpha-fetoproteinInhibin A
Pregnancy-associated plasma protein A
Corticotrophin releasing hormone
Oestriol
Urinary calcium excretion Activin A
MicrotransferrinuriaUrine kallikrein
Homocysteine
N-acetyl-β-glucosaminidase
Fibronectin
Antiphospholipid antibodies
“As of 2004,there is no clinically usefulscreening test to predict
the developmentof pre-eclampsia.”
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February 2011
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February 2011Combining biomarkers
Giguère Y, Charland M, Bujold E et al. Combining biochemical and ultrasonographic markers in predicting preeclampsia: a systematic review. Clin Chem 2010;56(3):361-374
AFP > 2.5MoM + hCG > 2.5MoM + PI > 95% centile + bilateral uterine artery notches@ 20-24 weeks
Sensitivity 64%Specificity 97%
PlGF + PAPP-A + PI + mean arterial pressure + “multiple maternal demographic factors”@ 11-13 weeks
Sensitivity 93%Specificity 95%
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February 2011
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February 2011
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February 2011Combining biomarkers
Giguère Y, Charland M, Bujold E et al. Combining biochemical and ultrasonographic markers in predicting preeclampsia: a systematic review. Clin Chem 2010;56(3):361-374
“Numerous papers have been published on potential biomarkers for identifying women predisposed to
development of PE before the onset of clinical symptoms…
…new tests that will contribute to better predictive performance characteristics of a PE-risk model need to be
developed.”
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February 2011
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A two stage pathological process
0 5 10 15 20 25 30 35 40 weeks
Impairedtrophoblastinvasion of
myometrium
Poor spiralartery adaptation
Placentalischaemia
Abnormalimplantation
Clinical manifestationsof pre-eclampsia
Generalisedmaternal
endothelialdysfunction
Systemic release ofpro-inflammatory
and antiangiogenicmediators
Hypertension Proteinuria
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February 2011
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February 2011
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February 2011Participants
155 patients assessedfor eligibility
129 patients enrolled
126 patients provided≥ 1 urine sample
27 were excluded16 identified as chronic hypertension7 declined consent2 identified as diabetes mellitus1 leaving country during pregnancy
Normal pregnancy91 patients
3 patients did notprovide 1 urine sample
Pregnancy-inducedhypertension22 patients
Pre-eclampsia11 patients
<20 weeks: 81 samples <20 weeks: 11 samples
Lost to follow-up2 patients
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February 2011
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0
10
20
30
40
50
60
70
80
90
100
110
120
130
140
150
160
<20 weeks 20-25 weeks 26-31 weeks 32-37 weeks 37+ weeks
Mea
n (S
EM) B
lood
Pre
ssur
e (m
mH
g)
1
10
100
1000
10000
100000
1000000
10000000
Mea
n (S
EM) P
rote
in:C
reati
nine
Rati
o (m
g/m
mol
cre
atini
ne)
Proteinuria
Diastolic blood pressure
Systolic blood pressure
Urin
e sp
ecim
en c
olle
ction
0
10
20
30
40
50
60
70
80
90
100
110
120
130
140
150
160
<20 weeks 20-25 weeks 26-31 weeks 32-37 weeks 37+ weeks
Mea
n (S
EM) B
lood
Pre
ssur
e (m
mH
g)
1
10
100
1000
10000
100000
1000000
10000000
Mea
n (S
EM) P
rote
in:C
reati
nine
Rati
o (m
g/m
mol
cre
atini
ne)
Proteinuria
Diastolic blood pressure
Systolic blood pressure
Urin
e sp
ecim
en c
olle
ction
Outcomes
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Demographic and clinical details
Total(n=102)
Pregnancy complicated by pre-
eclampsia(n=11)
Normal pregnancy
(n=91)
p value
Age at conception (years) 28.8±5.8
29.2±4.3 28.8±6.0 0.83
EthnicityWhite EuropeanOther
89 (86%)
14 (14%)
10 (91%)1 (9%)
78 (86%)13(15%)
0.06
Primigravida (n (%)) 26 (26%)
4 (36%) 22 (24%) 0.46
Past history of pre-eclampsia (n (%)) 35 (46%)
4 (57%) 31 (45%) 1.00
Family history of pre-eclampsia (n (%))
15 (15%)
3 (27%) 12 (13%) 0.20
BMI at booking (kg/m2) 30.8±8.4
33.4±10.2 30.5±8.1 0.30
Systolic blood pressure at booking (mmHg)
123±12 124±13 123±12 0.67
Diastolic blood pressure at booking (mmHg)
77±11 79±9 77±11 0.54
Prescription of aspirin prophylaxis (n (%))
15 (15%)
1 (9%) 14 (15%) 1.00
Participants
No differences indemographic and clinical details at recruitment between normal and pre-eclamptic pregnancies
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February 2011
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SELDI spectra
Participant 1
Participant 2
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February 2011ANN results
ANN modelling selected a panel of 5 protein peaks
9080 Da8020 Da 4648 Da 4813 Da
11320 Da
Cross validation model results:
• Normal pregnancy correctly classified: 100%• Pre-eclampsia correctly classified: 92%
793 peaks differentially expressed between normal pregnancy and pre-eclampsia
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February 2011
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ANN results
9080 Da 8020 Da 4648 Da 4813 Da 11320 Da
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February 2011
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0.00
0.10
0.20
0.30
0.40
0.50
0.60
0.70
0.80
0.90
1.00
Norm
alNo
rmal
Norm
alNo
rmal
Norm
al
Norm
alNo
rmal
Norm
al
Norm
alNo
rmal
Norm
al
Norm
alNo
rmal
Norm
al
Norm
alNo
rmal
Norm
al
Pre-
ecla
mps
iaNo
rmal
Norm
al
Norm
alNo
rmal
Norm
al
Norm
alNo
rmal
Norm
al
Norm
alNo
rmal
Pre-
ecla
mps
ia
Norm
alPr
e-ec
lam
psia
Pre-
ecla
mps
ia
Norm
alPr
e-ec
lam
psia
Pre-
ecla
mps
ia
Pre-
ecla
mps
iaPr
e-ec
lam
psia
Pre-
ecla
mps
ia
Pre-
ecla
mps
iaPr
e-ec
lam
psia
Prob
abili
ty o
f Pre
ecla
mps
ia
Sensitivity: 87%Specificity: 82%
Model performance
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February 2011 Summary
1. Pre-eclampsia is common2. AKI from pre-eclampsia is rare and
managed by timely delivery and supportive care
3. Pregnant patients with CKD should receive aspirin from 12 weeks to delivery
4. Improved knowledge re: pathophysiology may lead to new treatments to delay or prevent pre-eclampsia
5. Predictive tests for pre-eclampsia are on the horizon.
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February 2011
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February 2011 Case studies
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February 2011 Case 1
• 23 year old
• G2 P0+1
• Chronic pyelonephritis/reflux
• No recent infections
• 10 weeks pregnant
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February 2011
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February 2011 Case 1
• No medication
• BP 125/78
• Urine dip: Prot +, Leu -, Nit –
• Urine P:CR 43 mg/mmol
• Serum creatinine: 138 µmol/l
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February 2011
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February 2011
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February 2011
Courtesy of Matt HallNottingham Renal Unit
February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011 Case 1
Will pregnancy affect kidney disease?
Will she have asuccessful pregnancy?
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011Baseline 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
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011Blood 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%
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011 Case 1
What to do?
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011 Case 1
Aspirin 75mg od from 12 weeksto delivery
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011 Case 1
• 20 weeks• No symptoms• Aspirin 75mg od
• BP 110/72• Creat 119 µmol/l• Urine pro +, leu +, nit +• P:CR 55 mg/mmol
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011 Case 1
MC+S
• Coliforms
• Sensitive to ciprofloxacin, trimethoprim, nitrofurantoin, cefalexin and co-amoxiclav
• Resistant to amoxicillin
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011Drugs, CKD and pregnancy
Antibiotics
1. Cephalosporins2. Penicillins3. Gentamicin4. Erythromycin
1. Quinolones2. Tetracyclines
1. Trimethoprim(in 1st trimester)
2. Nitrofurantoin(in 3rd trimester)
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011 Case 1
• 26 weeks gestation
• Aspirin 75mg od
• Dysuria x 2 days
• BP 131/81
• Urine: Pro +, Bld ++, Leu +, Nit +
• MC+S: Coliforms again
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011 Case 1
What to do?
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011Management of CKD and hypertension in pregnancyUrinary tract infection
Asymptomatic bacteruria
Pyelonephritis
Non-pyelonephriticUTI
In pregnancy
Treat
Asymptomatic bacteruria
Pyelonephritis
Non-pyelonephriticUTI
Treat
Second or more episode in pregnancy?
Prophylaxis
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011 Case 1
• 33 weeks
• Well
• Aspirin 75mg od, cefalexin 125mg nocte
• BP 153/91
• Creat 143 µmol/l
• P:CR 80 mg/mmol
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011 Case 1
• Repeat BP 154/92, 166/88, 149/90
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011 Case 1
What to do?
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011Management 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 <140/90
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011Drugs, CKD and pregnancy
Antihypertensives
1. Labetalol2. Methyldopa3. Nifedipine4. Hydralazine
1. ACE inhibitors2. ARBs
3. Spironolactone4. Aliskiren
5. Moxonidine6. Minoxidil7. Diltiazem
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011 Case 1
• 34 weeks• Abdominal pain – RUQ• Headache• Aspirin 75mg od, cefalexin 125mg od, labetalol
200mg tds
• BP 173/105• PCR 205 mg/mmol• Serum creatinine 192 µmol/l
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011 Case 1
What to do?
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011 Case 1
• Admit to maternity unit
• Add nifedipine or methyldopa
• CTG
• FBC, LFTs, clotting
• Consider magnesium sulphate
• Plan for delivery
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011 Case 2
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011 Case 2
• Preconception counselling
• 35 year old.
• Nulliparous
• FSGS
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011 Case 2
• Ramipril 10mg od• Simvastatin 40mg od
• BP 118/64• Serum creatinine 84 µmol/l, eGFR 73
ml/min• Urine PCR 342 mg/mmol• Serum albumin 38g/l
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011 Case 1
Will pregnancy affect kidney disease?
Will she have asuccessful pregnancy?
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011 Proteinuria?
Imbasciati E et al. AJKD 2007;49:753
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011 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
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011 Case 2
What to do?
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011 Case 2
• Stop statin• Stop ACEi• Advise to commence aspirin from 12
weeks• Folic acid
?
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011 Case 2
• 6 months later
• Oedema x 2 months• Cellulitis left leg
• BP 163/91• Urine PCR 854 mg/mmol• Serum albumin 21 g/l• Serum creatinine 114 µmol/l, eGFR 54ml/min
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011 Case 2
• 2 weeks later
• Acute dyspnoea, pleuritic chest pain, left flank pain, episode of haematuria.
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011 Case 2
• BP 181/104• Serum creatinine 434 µmol/l• US: Renal vein thrombosis• V/Q: Extensive mismatch. High probability
of PE.
• Heparin and warfarin commenced• Amlodipine 5mg od
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011 Case 2
• 2 months later
• BP 144/85• Serum creatinine 312 µmol/l• Urine PCR 443mg/mmol• Serum albumin 24 g/l
• Transplant work-up and dialysis planning
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011 Case 2
A little pessimistic…
…but a risk worth considering
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011 Quiz
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011 Quiz
No conferring
No Google
My word is final
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011 Question 1
Which of the following statements about pregnancy and haemodialysis is incorrect?
1. Target weight increases by about 300g/week from the second trimester
2. At least 20 hours/week dialysis is recommended3. ESA requirement increases by about 85%4. Preterm labour is commonly caused by
oligohydramnios5. Antihypertensive treatment should be titrated to
maintain blood pressure <140/90 mmHg
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011 Question 2
Approximately, how many pregnancies are there per year in the UK?
1. 4000002. 5000003. 6000004. 7000005. 800000
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011 Question 3
The risk of pre-eclampsia is increased with:
1. Aspirin
2. Calcium supplements
3. Cigarettes
4. Singleton pregnancies
5. First time pregnancies
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011 Question 4
Which of the following is safe to use in pregnancy?
1. Ciprofloxacin2. Cyclophosphamide3. Cyclosporine4. Chlorambucil5. Candesartan
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011 Question 5
A renal biopsy during pregnancy should be considered for which of the following:
1. De novo nephrotic syndrome at 37 weeks2. Persistent invisible haematuria, urine PCR 55
mg/mmol and serum creatinine 99 µmol/l from booking3. Severe de novo hypertension and proteinuria at 26
weeks4. ANCA positive, oliguric AKI with blood and protein and
a creatinine of 446 µmol/l at 33 weeks5. BP 141/89, urine blood ++, protein ++, creat 131
µmol/l, ANA +ve, dsDNA +ve at 23 weeks
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011 Question 6
What is the chance of a woman with serum creatinine 200 µmol/l at conception needing dialysis within a year of pregnancy?
1. 1 in 6
2. 1 in 5
3. 1 in 4
4. 1 in 3
5. 1 in 2
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011 Question 7
A woman on PD thinks she might be pregnant. Serum βHCG is equivalent to an 8 week old fetus. Ultrasound scanning does not show a fetal heart rate as expected. What advice should be given?
1. Molar pregnancy likely – requires hysteroscopy and curettage
2. Measure serum alfa-fetoprotein3. Repeat serum βHCG and ultrasound in 1 – 2 weeks4. Diagnosis of missed abortion – consolation5. Explain βHCG is elevated in ESRD
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011 Question 8
A 32 year old with asthma, previous depression and diabetic nephropathy develops gestational hypertension. Which treatment is most appropriate?
1. Methyldopa2. Valsartan3. Bendroflumethiazide4. Labetalol5. Nifedipine
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011 Question 9
You are asked to see a 26 year old following her first pregnancy which ended in severe pre-eclampsia yesterday at 35 weeks. She is oliguric and creatinine has climbed from 121 to 158 µmol/l in 24 hours. CVP is 4 mmHg and BP 185/83 mmHg on labetalol 200mg bd. Renal ultrasound shows mild left hydronephrosis.
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011 Question 9You are asked to see a 26 year old following her first pregnancy which
ended in severe pre-eclampsia yesterday at 35 weeks. She is oliguric and creatinine has climbed from 121 to 158 µmol/l in 24 hours. CVP is 4 mmHg and BP 185/83 mmHg on labetalol 200mg bd. Renal ultrasound shows mild left hydronephrosis.
What is the most appropriate management plan?
1.Ask how the baby is and repeat bloods in 6 hours
2. Oral magnesium glycerophosphate 2 tabs bd3. Aspirin 75mg od4. Nephrostomy left kidney5. IV colloid 500ml stat followed by 0.9% sodium
chloride – 1000ml/4 hours
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011 Question 10
How are babies made?
1. Nobody knows
2. When a mummy and a daddy love each other very much they give each other a special kiss
3. By a woman sitting on a seat warmed by a man’s bottom
4. Stork
5. By doing “the filthy thing”
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011 Congratulations
You have survived.
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
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February 2011
Slides available at
http://emrt.org.uk
