26/09/2014 1 Pathophysiology- diagnosis and clinical management Kathleen Claes Core curriculum BVN-SBN 2014 PREGNANCY AND RENAL DISEASE Pregnancy and renal disease • Physiological changes • Renal complications of “normal” pregnancy • Pregnancy in a renal patient – Chronic Kidney Disease – Transplantation • The role of the kidney in pre-eclampsia BMJ 2008; 336: 211-215; Williams D, and Davison J
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26/09/2014
1
Pathophysiology- diagnosis and clinical management
Kathleen Claes
Core curriculum BVN-SBN 2014
PREGNANCY AND RENAL DISEASE
Pregnancy and renal disease
• Physiological changes
• Renal complications of “normal”
pregnancy
• Pregnancy in a renal patient
– Chronic Kidney Disease
– Transplantation
• The role of the kidney in pre-eclampsia
BMJ 2008; 336: 211-215; Williams D, and Davison J
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In renal grafts,male kidneys show equal changes
Changes independent of graft age.
Kidney function and disease in pregnancy. Lindheimer, Katz, 1977
BMJ 2008; 336: 211-215; Williams D, and Davison J
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BMJ 2008; 336: 211-215; Williams D, and Davison J
BMJ 2008; 336: 211-215; Williams D, and Davison J
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METHOD TO ASSESS RENAL
FUNCTION
Smith MC, BJPG, 2008
Pregnancy and renal disease
• Physiological changes
• Renal complications of “normal”
pregnancy
• Pregnancy in a renal patient
– Chronic Kidney Disease
– Transplantation
Renal complications
• Urinary tract infections/pyelonephritis
• Urolithiasis
• Hypertension
• Novel renal diagnosis/ Acute kidney
injury
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INFECTIONS: UTI
• Untreated30-40%
pyelonefritis
• Risk 70-80% after R/
• Treat if
– >100.000 CFU if
asymptomatic
– w/ symptoms
• Pre-eclampsia:
– OR 1.22 (1.03-1.45)
• Preterm delivery
– OR 1.3 (1.2-1.5)
Nicolle LE, Clin Infect Dis. 2005
Minassian C, Plos One 2013
Wing DA, Am J Obstet Gynecol 2000
Amoxyclav: risk for necrotising enterocolitis end of
pregnancy
Quinolones: CI do not use
UROLITHIASIS
• Same prevalence as in non-pregnant population
• DD with the physiological dilatation
HYPERTENSION
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HYPERTENSION(6%-8%)
• Pre-existing hypertension
• Pregnancy induced hypertension
• Pre-eclampsia/eclampsia
Target blood pressure < 160/105 mm Hg
Renal patients ≤ 140/90 mm Hg
HYPERTENSION
Drug Mechanism of
action
Dose Comments
Relative rest
No salt restriction
Low dose ASA in
all
80-100 mg/d Start 12 weeks
Labetolol
(Trandate)
a+ß-adrenergic
receptor
antagonists
100-400 mg (2-4/d)
maximum dose
1200 mg
First choice
No long term follow-up
children
hepatotoxicity
Methyldopa
(Aldomet)
a2-adrenergic
receptor agonists
250-500 mg (2/d)
maximum dose 2
g/d
Maternal side effects:
fatigue, nasal
congestion, dry mouth,
postural hypotension,
…
Nifedipine LA
(Adalat)
Ca2+-block 30-120 mg/d Mildly tocolytic?
Aggrevate oedema
Ketanserin serotinine-2-
receptor blocker
In combination w/
aspirinPET
HYPERTENSION: NOT RECOMMENDED
Drug Mechanism of action Comments
Atenolol ß-adrenergic receptor antagonists Side effects: bradycardia,
apnoe, hypoglycemia,
IUGR, …
ACE-inhibitor or
ARB
May be used till pregnant
Recent data no increase in
teratogenicity if stopped in first
trimester
Teratogenic in second and
third trimester
Diuretics May be continued if intake
prepregnancy
Avoid (may limit
physiological increase in
plasma volume)
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ACUTE KIDNEY INJURY
• Any renal disorder similar to non-pregnant
patients
• Early in pregnancy
– Prerenal: hyperemesis gravidarum
– Acute tubular necrosis: septic abortion
• Late in pregnancy
– Severe pre-eclampsia w/ or wo/ HELLP
– Acute fatty liver of pregnancy
– Thrombotic micro-angiopathy (HUS)
– Cortex necrosis (abruptio placenta/placenta
praevia)
– Pyelonephritis
NOVEL RENAL DISEASES
Evaluation during pregnancy
• Immunological testing
• Ultrasound
• Biopsy <32 weeks
– Complication rate similar as non-pregnant? <->
morbid procedure (7% complications in
pregnancy)
– Limited to women in need for diagnosis
– Rapidly progressive with active sediment
– Nephrotic syndrome eci ? Steroidresponsive?
– No coagulation abnormalities
Piccoli Bjog 2013
NOVEL RENAL DISEASES
• ADPKD
• Focal Sclerosis
• Refluxnephropathy
• IgA nephropathy
• HUS
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TMA
“Acute post-partum renal failure is one of the strongest complications of an apparantly uncomplicated pregnancy and delivery …. Occasionally the same syndrome strikes during pregnancy… Renal failure is usually irreversible although Finkelstien saw 2 patients make an excellent recovery… heparin improved some cases but not others”
Lancet, 1975,801-802
DIFFERENTIAL DIAGNOSIS
Thrombotic microangiopathy/ HUS Severe PET/HELLP
mostly PP, every trimester
(TTP mostly 3rd trim(ADAMTS13)/
HUS postpregnancy)
>20/40, third trimester, intrapartum
No pre-existing hypertension Pre-existing hypertension at higher risk
No DIC DIC
Hemolysis, thrombocytopenia,
LDH>1000 U/L
Hemolysis, thrombocytopenia,
LDH<800 U/L
Liverfunction tests: normal Liverfunction tests abnormal,
subcapsular hematoma
DIAGNOSTICS PREECLAMPSIA
Guidelines of ACOG
Blood pressure ≥140 mm Hg Systolic or
≥90 mm Hg diastolic on two occasions
(4 h apart)
>20/40 w with previous normal blood
pressure
≥160 mm Hg systolic or ≥110 mm Hg
diastolic
and
Proteinuria >300 mg/24 h or P/C ratio ≥0,3
(Dipstick 1+)
Or in the absence of proteinuria, new-onset hypertension with the onset of any of
the following
Thrombocytopenia <100,000/µl
Renal insufficiency >1,1 mg/dl or doubling
Impaired liver function Transaminases >2times ULN
Pulmonary oedema or cerebral or visual
symptoms
www.acog.org
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DIFFERENTIAL DIAGNOSIS
Signs Intrinsic renal problem Pre-eclampsia
Creatinine >1 mg/dl (variable)
0.8-1.2 mg/dl
Proteinuria variable
>300 mg/d
Uric acid variable >5.5 mg/dl
Blood pressure
variable >140/90 mm Hg
Liver function tests
normal ()
Blood platelets normal ()
Angiogenic factors sFlt-1 low/PIGF high S-Flt-1 high/PIGF low