Transcript Proteinuria - St Helier VTS

Proteinuria
Judy Tyrrell BA, MB, MRCP
Clinical Champion for Diabetes
Sutton and Merton PCT
Microproteinuria
(Microalbuminuria)
Urinary albumin loss of between 30mg and
300mg/day which is
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persistent – in at least two out of three
consecutive samples
in the absence of infection
In practice
An early morning urine (EMU) sample in
which the
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Albumin/creatinine ratio (ACR) is
>2.5mg/mmol (for men)
>3.5mg/mmol (for women)
or
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Urinary albumin concentration >20mg/l
is diagnostic
Proteinuria
(Macroproteinuria)
Urinary protein excretion of >
300mg/24 hours
Diabetic Nephropathy
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Persistent albuminuria (>300mg/24 hours or
an ACR > 30mg/mmol) in an individual who
has had
diabetes for >5 years and who has
concomitant retinopathy
in the absence of urinary infection, other
renal disease or heart failure
Proteinuria – other causes
Factors suggesting a non-diabetic cause for
proteinuria include
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no retinopathy
normal blood pressure
sudden onset
significant haematuria
systemically unwell
Epidemiology of Diabetic
Nephropathy
Type 1 diabetes
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Rare <10years or >35years of disease
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Microalbuminuria develops in about 40%
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20% have proteinuria after 25 years of disease
Epidemiology of Diabetic
Nephropathy
Type 2 Diabetes
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25-30% develop some degree of nephropathy
Related to duration of disease - 20% surviving 10
years develop proteinuria
Risk varies with ethnic origin – 25% in Europeans
to 50% in other ethnic groups
Equal numbers of Type 1 and Type 2 entering ESRF
programmes (early mortality from CVD in Type 2)
Risk Factors for Diabetic
Nephropathy
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Hypertension
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Poor glycaemic control
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Genetic susceptibility
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Ethnicity
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Biochemical factors eg increased prorenin activity
Diabetic Nephropathy
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Leading cause of ESRF
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Responsible for more than one third of all
patients starting renal replacement therapy
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Strong predictor of cardiovascular disease
(most common cause of death in this group)
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Extensive co-morbidities such as
retinopathy, neuropathy and autonomic
dysfunction
Clinical Course - Early
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Clinically silent
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Increased glomerular filtration rate (GFR)
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Increased renal blood flow
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Hypertrophy of kidney
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Microalbuminuria
Glycaemic Control and the
Development of Microalbuminuria
Poor glycaemic control is an important determinant
for the development of micoalbuminuria.
UKPDS – for each 1% drop in the HbA1c there was
a reduction in risk of
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25% for any microvascular end-point
33% for albuminuria at 12 years
Clinical Course - Late
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Onset of persistent macroproteinuria
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Decline in GFR (creatinine clearance)
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Uraemia
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End stage renal disease (ESRD)
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Renal replacement therapy (RRT)
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Increased CVD morbidity and mortality
Factors Affecting Progression
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Correlation between BP and rate of progression of
established nephropathy
Improved glycaemic control has variable impact on
progression
Degree of proteinuria is related to disease
progression
Beneficial effects of reduction of proteinuria with
ACE and A11A beyond doubt
Pathology
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Glomerular hyperfiltration and hyperperfusion
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Thickening of the glomerular basement membrane
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Mesangial expansion
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Kidneys normal or increased in size
Screening
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Annual EMU for albumin/creatinine ratio
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If raised, repeat twice more
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Exclude infection by sending MSU for culture
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Annual serum creatinine
Management
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Aggressive treatment of hypertension with therapy that
includes ACE inhibitor or A11A to achieve BP <135/75.
UKPDS - 37% reduction in microvascular endpoints in tight
control group
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Multiple Rx often required to achieve target
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UKPDS - an average of 3 drugs were needed to achieve tight
control
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In normotensive patients reduce albumin excretion rate (AER)
by using ACE inhibitor
Management contd
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Optimise glycaemic control
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Reduce risk macrovascular disease by
 treatment
with aspirin
 smoking cessation assistance
 aggressive treatment of abnormal lipid
profiles
Ace Inhibitors / A11A
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Reduce the progression of microalbuminuria to
overt proteinuria
Slow the decline in GFR
They work by
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Lowering systemic blood pressure
Lowering intraglomerular pressure
Care with ACE Inhibitors
Precipitation of acute renal failure by ACE inhibitors
is usually associated with severe bilateral renal
artery stenosis (RAS)
A degree of RAS is common in people with
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intermittent claudication
absent pedal pulses
history of coronary angiography
long history of hypertension
femoral bruits
Precautions with ACE Inhibitors
Measure serum creatinine
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one week after initiation of treatment
one week after increasing dose
A rise of 10-20% in serum creatinine is common
and should not result in ACE being stopped unless
rise continues
Monitoring Progress
If microalbuminuria is present
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Measure urinary microalbumin or ACR 6 monthly
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Intensify treatment if continues to rise
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Measure serum creatinine annually
Monitoring Progress
If ACR>20mg/mmol measure
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24 hour urinary protein excretion
creatinine clearance
Perform annually to monitor progress
Current Referral Criteria
Guidelines currently suggest referral when serum
creatinine >150umols/l
but
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rise in serum creatinine late manifestation of
diabetic nephropathy
affected by age, gender, race and body size
Suggested Referral Criteria
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24 hour urinary protein >1gm
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Serum creatinine >150umols/l
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Creatinine clearance < 60ml/min
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Rapidly increasing proteinuria despite treatment
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Factors suggesting a non-diabetic cause for
proteinuria