Transcript Document

Nephrology 2
Euan Green
Mr Betts
Assessment of renal function
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History and examination clues
Blood tests and associated formulae
Urine tests incl. 24h clearance
Nuclear medicine techniques
Chronic renal failure
• 1)How does autoregulation of renal blood flow work?
• 2) Why do you get hypertension in chronic renal failure?
• 3) What are the implications of chronic renal failure?
MCQ
1. CKD stage 5 equates to an eGFR <5mls/min
2. CKD stage 1 equates to an eGFR 75-90mls/min
3. Those identified with CKD stage 2 should be
referred to a nephrologist
4. The CKD classification is based solely on eGFR
5. CKD stage 3 has been subdivided into those
with an EGFR < or >= 45mls/min
MCQ
1. CKD stage 5 equates to an eGFR <5mls/min
2. CKD stage 1 equates to an eGFR 75-90mls/min
3. Those identified with CKD stage 2 should be
referred to a nephrologist
4. The CKD classification is based solely on eGFR
5. CKD stage 3 has been subdivided into those
with an EGFR < or >= 45mls/min
Chronic kidney disease
Kidney damage= persistent microalbuminuria, persistent proteinuria, persistent
haematuria, structural abnormalities of the kidneys demonstrated on ultrasound
scanning or other radiological tests, or biopsy-proven chronic glomerulonephritis)
Why should we detect kidney
disease
1. The scale of the problem
– 0.1% of the population on dialysis (40,000 in the
UK)
– Costing the NHS an average of £20,000 per patient
per year (3% of the NHS budget)
– 4.5% of the population have moderate or severe
renal failure but not yet on dialysis
2. Patients with renal failure are considered to
be in the highest risk category for heart
disease (20% per 10 years)
3. Death
– Patients with CKD are more likely to die
than require dialysis
– 27,998 CKD patients followed for 5 years:
Stage
GFR (ml/min)
RRT
Death
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60-89
1.1%
19.5%
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30-59
1.3%
24.3%
4
15-29
19.9%
45.7%
Keith DS, AIM 2004;164:659-663
4. Poor outcome of unreferred CKD
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East Kent study 601,000 population
Using opportunistic serum creatinine
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Males - serum creatinine  180 mol/L
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Females - serum creatinine  135 mol/l
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Approximate to GFR < 30-40ml/min/1.73m2
Prevalence 4708 unreferred
Outcome (over 31 months)
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Median survival 28 months
Cardiovascular 40%
Infection 26%
Cancer 16%
End stage renal failure <5%
Case 1
• A 45 year old man has been referred for a
vasectomy under GA
• His pre-op bloods show renal impairment
(eGFR 70) and he’s brought back to clinic
to assess this unexpected finding.
• How would you assess for evidence of renal
dyfunction?
Case 1
• History
– Age
– Co-morbidities
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Hypertension
Diabetes
Vascular disease
Obesity
Smoking
Structural urinary tract abnormalities
Liver disease
Cancers
Case 1
• Concurrent illness
– Dehydration from D&V
– Recent URTI
– Recent surgery
• Drugs
– Lots
– Remember X-ray contrast and other once offs
• Family history
Case 1
• Examination
– Blood pressure
– Abdominal masses (bladder, kidneys, ascites)
– Signs of fluid retention (peripheral oedema,
pulmonary oedema, JVP)
– Fluid balance
– Changes in weight
Bicohemistry Tests
• Tests
– Urine dipstick
– Urine tests
• Microscopy
• 24 hour urine collection
• Urinary Albumin:creatinine ratio
– Blood tests
MCQ
1. All proteins except albumin cause a colour
change on urine dipstick
2. Prolonged periods of standing can underestimate
proteinuria
3. A urinary albumin:creatinine ratio of
25mg/mmol is normal
4. Creatinine clearance is always an overestimate
of GFR
5. Creatinine is freely filtered at the glomerulus
and neither secreted, nor reabsorbed
MCQ
1. All proteins except albumin cause a colour
change on urine dipstick
2. Prolonged periods of standing can underestimate
proteinuria
3. A urinary albumin:creatinine ratio of
25mg/mmol is normal
4. Creatinine clearance is always an overestimate
of GFR
5. Creatinine is freely filtered at the glomerulus
and neither secreted, nor reabsorbed
Case 2
• Friday at 20:05 On call referral:
• A man has pitched up in A&E with a note.
– “Dear urologist, This 60 year old chap had dipstick
haematuria so I sent him for a CT urogram yesterday. The
report says ‘mild bilateral hydronephrosis, images in the
pelvis are uninterpretable due to streak artefact from bilateral
hip replacements. Clinical correlation advised’. His creatinine
is 150 today. Please clinically correlate as discussed with your
SHO.”
Case 2
• A&E have helpfully done a urine dipstick which
shows
– Blood ++
– Protein ++
• They’ve done a post void bladder scan which is
normal
• They’ve confirmed the creatinine result
• In doing so he’s reached 3 hours and 59 minutes in
the department and the bed manager has admitted
him under urology after discussing with the SHO.
Urine dipstick
• Protein
– Tetrabromophenol reaction with albumin causes a colour change
(yellow to blue/green)
• Trace 5-20mg/dL
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~30mg/dL
• ++
~100 mg/dL
• +++ ~300mg/dL
• ++++ >2000mg/dL
– False +ve
• Orthostatic proteinuria
• Iodinated contrast
• Alkaline urine
• Blood
– Peroxidase reaction
– (See BAUS consenus statement on haematuria)
Case 2
• You take a history and examine him and there’s
nothing to find
• He’s a medical negligence lawyer whose best
friends is your trusts chief exec. and refuses to go
home until this is all sorted.
• The med reg says he won’t see the patient over the
weekend unless you can convince him this is more
likely to be medical than surgical
• X-ray won’t scan him at the weekend as he’s well
• What tests can you do to help?
Urine microscopy
• RBCs
• Infection, glomerular disease, malignacy
• WBCs
• Infection, glomerulopnehritis, malignancy, TB, intersitial nephritis, inflammation
• Crystals
• Seen with stones, cystinuria, gout
• Casts
– Hyaline casts (clear and colourless)
• Seen with exercise, fever, concentrated urine (often in normal subjects)
– Red cell casts
• Seen in GN, vasculitis, malignant hypertension
– White cell casts
• Pyelonephritis, proliferative glomerulonephritis
– Epithelial casts
• Acute tubular necrosis, acute glomerulonephritis
– Granular casts
• GN, diabetic nephropathy, amyloidosis, intersitial nephritis
Urine electrolytes
Prerenal/GN
<20
ATN/Obstruction
>40
Urine to plasma
creatinine
Renal failure index
>30
<20
<1
>1
FE Na
<1
>1
>500
<400
Urinary Na
Urine osmolality
Urine electrolytes
WBC
Granular
Casts
RBC
Hyaline
24 Hour urine collection
• Void , discard urine, note time
• Collect all urine 24 hours
• Exactly 24 hours later empty bladder and
collect urine
• Provide serum sample for creatinine
• Measure volume, protein, creatinine, sodium
Protein
• Excrete 80-150mg/day
• Minimum concentration for dipstick detection 2030 mg/dl
• Glomerular disease
– suspected >1g/24 hours
– certain > 3g/24 hours
• Tubular disease - <3g/24 hours
• Overflow – abnormal immunoglobins
– Myeloma – bence jones protein
Urinary Albumin:Creatinine ratio
• Proteinuria is a measure of renal disease
• 24 urinary protein estimation is a pain
– 3 samples over 2 months
• Spot microalbuminuria test is subject to variability
• Comparing with creatinine improves its accuracy
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Normal <2.5mg/mmol
<30 ‘acceptable’
30-70 warrants a retest
>70mg/mmol NICE suggests referral to nephrology
Case 3
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60 yr old woman
Mild renal impairment (eGFR 59)
Hypertension
4 cm exophytic, enhancing, solid, left renal
mass
• Has a partial nephrectomy
• Seen for follow-up 3 months later
Case 3
• She wants to know how much kidney
function has she got left?
• Biochemical tests
• Nuclear medicine tests
Case 3
• Biochemical tests
– Assess overall function
– Various methods for refining assessment, but
none perfect
• Radiological tests
– Can assess overall and relative function
– Can give additional information eg Scars,
drainage
Blood tests
• Urea
– Varies with protein and catabolic states
– Freely filtered
– Reabsorbed at variable rate dependant on water
reabsorption
– Not a reliable indicator of function
• Creatinine
– Freely filtered and secreted into distal tubule
– Varies with muscle mass
140
Creatinine Clearance ml/min
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100
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Serum Creatinine mmol/L
• Serum creatinine not sensitive indicator in early renal impairment
• Need GFR to fall below 60-80ml/min before there is rise in
Serum Cr
• An abnormal creatinine indicates a loss of 50% of renal function
MCQ
1. MDRD formula is not valid for children
2. The Cockcroft & Gault formula is an alternative
to MDRD for calculating eGFR
3. MDRD formula uses 3 variables to calculate
eGFR
4. Your path lab should use the same formula as the
online MDRD calculator
5. eGFR is accurate an reproducible in acute renal
failure
MCQ
1. MDRD formula is not valid for children
2. The Cockcroft & Gault formula is an alternative
to MDRD for calculating eGFR
3. MDRD formula uses 3 variables to calculate
eGFR
4. Your path lab should use the same formula as the
online MDRD calculator
5. eGFR is accurate an reproducible in acute renal
failure
Formulae
• Used to improve on serum creatinine, but
all suffer from its limitations
• Estimated creatinine clearance
– Cockcroft-Gault
• Estimated GFR
– MDRD (4 and 6 variable)
– CKD-EPI
– Mayo
Cockcroft and Gault formula
• Creatinine clearance =
(140-age) x body weight in Kg
72 x serum creatinine in mg/dL
• Multiply by 0.85 for women
• May be more accurate than timed urine collections
• Assumptions:
– Lean body weight (hence in obesity, will overestimate)
– Volume distribution and Creatinine production is in steady state (hence
will overestimate in low protein diet)
MDRD
• 4 variable (Creatinine, Age, Gender, Race)
• 6 variable (Albumin, Urea)
• eGFR=32788 x [creatinine in μmol/L]-1.154 x Age-0.203
• x 1.212 if black
• x 0.742 if female
• Should be automatically reported by your lab every time serum
creatinine is checked.
• Be aware of its limitations
Limitations of MDRD
• It is only an estimate, significant error is possible. Likely to
be inaccurate in extremes of body type
• malnourished,
• amputees,
• It is not valid in pregnant women
• Some racial minorities may not fit the MDRD equation
well. Originally validated for US white and black patients.
• Not so good near normal: The MDRD equation tends to
underestimate normal or near-normal function.
Routine reporting of eGFR values >90 is not recommended.
Limitations of MDRD
• Creatinine level must be stable: eGFR calculations assume
that the level of creatinine in the blood is stable over days
or longer. They are not valid if it is changing.
• The MDRD equation is not valid for under-18s. Use the
Counahan-Barrat method for children
• Different equations: from April 2006 in the UK, local
laboratories should calculate eGFR on all samples sent for
creatinine measurement. The equation they use will take
into account local variations in accuracy of creatinine
assays, so eGFR values obtained in this way should be a
little more accurate than those generated by any of the
online calculators
CKD-EPI
• eGFR = 141 x min([creat]/κ,1)α x max([creat]/κ,1)-1.209 x 0.993Age x 1.018
[if female] x 1.159 [if black]
• κ = 0.7 if female.
κ = 0.9 if male.
• α = -0.329 if female
α = -0.411 if male
• min = the minimum of Scr/κ or 1
max = the maximum of Scr/κ or 1
• Probably more accurate than MDRD
• Certainly better if GFR > 60mls/min
• New (2009) and MDRD remains the NICE approved formula
There’s an app for that!
EMQ
A. Inulin clearance
B. Cr51 EDTA
C. Tc99m DTPA
D. MDRD 6 variable
E. Cockcroft and Gault
F. Tc99m DMSA
G. 24hr urinary creatinine clearance
H. eGFR
Which of the above:
1.
Could be used to assess GFR and renal drainage at the same time
2.
Is the gold standard for assessment of glomerular filtration rate
3.
Is not an assessment of overall renal function
EMQ
A. Inulin clearance
B. Cr51 EDTA
C. Tc99m DTPA
D. MDRD 6 variable
E. Cockcroft and Gault
F. Tc99m DMSA
G. 24hr urinary creatinine clearance
H. eGFR
Which of the above:
1.
Could be used to assess GFR and renal drainage at the same time
B
2.
Is the gold standard for assessment of glomerular filtration rate
A
3.
Is not an assessment of overall renal function
F
Creatinine Clearance
• 24 urinary creatinine measurement allows
calculation of creatinine clearance
• Clearance = UV/P
(U = urine concentration, V = flow rate, P = plasma concentration)
• Usually adjusted for body surface area
• Normal >120ml/min/1.73m2
• Creatinine clearance is 20% higher than GFR due
to tubular excretion of creatinine
Glomerular filtration rate
• GFR determined by using substance
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Neither metabolised nor synthesised
Secreted into plasma at constant rate
freely filtered at glomerulus
Neither secreted or absorbed further down nephron
• Inulin clearance is the gold standard for GFR measurement
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Polysaccharide
Filtrated (not reabsorbed, secreted or metabolised by the kidney)
Continuous infusion
Measure Inulin in urine and blood until steady state reached
Expensive, time consuming, impractical
Isotopic GFR
• Cr51 EDTA (closest in clearance pattern to inulin)
• Tc99m DTPA (short half life, but can do a renogram
at the same time)
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Blood sample for background count
Known dose of radiopharmaceutical given
Time for equilibration
Samples at 2,3 and 4 hours
Volume of distribution worked out
Rate of clearance calculated by slope intercept
Renography
• A study of the uptake, transit and elimination by
the kidney of an intravenous dose of a
radionucleotide
• Gives information on drainage and relative
function
• Limited anatomical information
• Use of diuretic improves discrimination between
obstructed and non-obstructed patterns
• Tc99m MAG-3
• I131 Hippuran
• T99m DTPA
• See nephrology 1 for renograms in detail
DMSA scan
• Dimercaptosuccinic acid
• Bound in proximal tubules
• Excellent imaging of functioning areas of cortex
• IV injection with imaging 3 hours later
• Multiple views to allow better visualisation
• Can calculate relative function
• Look for areas of poor function ie scars
• May need to wait 6 months after last insult for
areas to recover
Summary of nuclear medicine
Renography
Rel. funct.
Scarring
Imaging
GFR
MAG3
Yes
Yes
No
Yes
No
DMSA
No
Yes
Yes
Yes
No
DTPA
Yes
Yes
No
Yes
Yes
EDTA
No
No
No
No
Yes
Hipp
Yes
Yes
No
Yes
No
Chronic kidney disease
Kidney damage= persistent microalbuminuria, persistent proteinuria, persistent
haematuria, structural abnormalities of the kidneys demonstrated on ultrasound
scanning or other radiological tests, or biopsy-proven chronic glomerulonephritis)
Case 4
• 65 yr old man
• Cystectomy + ileal conduit urinary diversion for
refractory CIS
• eGFR 39 mls/min pre-op
• Has looked at his consent form after the op and
wants to talk to you about the fact that someone
has written ‘decline in renal function on it’ He
wants to know how you’re going to monitor it?
Case 4
• Renal surveillance post diversion
– Isotopic GFR
– Renography
– Regular BP check
• Slow decline in function over the 5 years
following his surgery
• Disease free
• GFR now 28mls/min/1.73m2
• What are you going to do?
Case 4
• Make sure it’s not post renal
– Renogram
– Loopogram
• Not obstructed
• What next ?
MCQ
Which of the following should be referred for a nephrology
opinion?
1. CKD stage 3B
2. Hypertension that remains poorly controlled after 2nd
line therapy
3. ACR >30mg/mmol
4. Those with a decline in GFR of > 5 ml/min/1.73 m2
within 1 year
5. Those with a decline in GFR of > 10 ml/min/1.73 m2
within 5 years
MCQ
Which of the following should be referred for a nephrology
opinion?
1. CKD stage 3B
2. Hypertension that remains poorly controlled after 2nd
line therapy
3. ACR >30mg/mmol
4. Those with a decline in GFR of > 5 ml/min/1.73 m2
within 1 year
5. Those with a decline in GFR of > 10 ml/min/1.73 m2
within 5 years
Who should be referred for
nephrology assessment
• Stage 4 and 5 CKD (with or without diabetes)
• Higher levels of proteinuria (ACR ≥ 70 mg/mmol) unless
known to be due to diabetes and already appropriately treated
• Proteinuria (ACR ≥ 30 mg/mmol) together with haematuria
• Rapidly declining eGFR (> 5 ml/min/1.73 m2 in 1 year, or >
10 ml/min/1.73 m2 within 5 years)
• Hypertension that remains poorly controlled despite the use of
at least four antihypertensive drugs at therapeutic doses
• People with, or suspected of having, rare or genetic causes of
CKD
• Suspected renal artery stenosis.
Case 4
• Make sure it’s not post renal
– Renogram
– Loopogram
• Not obstructed
• What next ?
• Consider renal referral
• He wants to know what the possible problems
from poor kidneys are
Manifestations of CKD
Functions of the kidney
• Regulation of water and electrolytes
• Maintenance of acid/base balance
• Excretion of waste products, water soluble toxic substances and drugs
• Endocrine functions - erythropoietin and vitamin D
• Patients with CKD stage 3 or lower (GFR >30 mL/min) generally are
asymptomatic and do not experience clinically evident disturbances in
water or electrolyte balance or endocrine/metabolic derangements.
• Generally, they clinically manifest with CKD stages 4 and 5 (GFR <30
mL/min).
System
Clinical manifestations
Renal / Electrolytes
Oedema, hyponatremia, hyperkalemia, metabolic acidosis,
hyperuricemia, hyperphosphatemia, hypocalcemia (NB: symptoms
of uremia correlate only inconsistently with the level of urea)
Gastrointestinal
Anorexia, nausea, vomiting, malnutrition
Cardiovascular
Accelerated atherosclerosis, systemic hypertension, pericarditis
Haematological
Anaemia, immune dysfunction, platelet dysfunction
Musculoskeletal
Renal osteodystrophy, muscle weakness, growth retardation in
children, amyloid arthropathy caused by beta2-microglobulin deposition
Neurological
Encephalopathy, seizures, peripheral neuropathy
Endocrine
Hyperlipidemia, glucose intolerance caused by insulin resistance,
amenorrhea and infertility in women, impotence
Skin
Pruritus
Water and electrolyte disturbances
• Water retention - loss of concentrating ability, ADH
resistance thus polyuria initially
• Sodium balance remains virtually normal till late in CRF
as kidneys can markedly increase the amount of Na
excretion per nephron by reducing tubular reabsorption.
Subsequently, Hypertension and fluid overload develops
due to Na retention
• Potassium balance: plasma potassium level are also
maintained until very late in CKD, mainly because of an
increase in renal excretion of potassium per functioning
nephron and an increase in potassium output in the stool.
Acid base balance
• Metabolic acidosis
Reduced reabsorption of HCO3 (proximal tubules)
Reduced NH4 synthesis NH3 + H+  NH4 (proximal
tubules)
Reduced ability to excrete the hydrogen ions (distal
tubules)
• Chronic acidosis
Phosphate is used as a buffer. Associated with worsening
of hyperparathyroid-induced kidney bone disease and
negative calcium balance, enhanced skeletal muscle
breakdown and catabolism, growth retardation in children,
and probably faster progression of GFR loss
Cardiovascular disease
• Patients with renal failure are considered to be in the
highest risk category for heart disease, at least 20% per 10
years. Current cardiovascular guidelines now recommend
screening for reduced GFR in people over 40 years old as
part of their cardiovascular risk assessment.
• Left ventricular hypertrophy is a particularly common form
of heart disease and carries a high mortality. LVH tends to
develop relatively early in the course of the renal failure
and is normally established when dialysis starts.
• Heart disease accounts for over 70% of the mortality of
ESRF patients (commonest cause of death)
Cardiovascular disease
Anaemia of chronic renal disease
• Usually apparent when GFR <30 ml/min (or <45 in
diabetics as red cell survival is reduced)
• Anaemia is multifactorial in nature. Mostly due to
erythropoietin deficiency (which is produced by interstitial
cells of renal cortex), reduced RBC survival and uraemic
suppression of RBC synthesis
• NICE recommends checking for anaemia in those with
eGFR <45 and treating those with Hb <11g/dL
Renal osteodystrophy
• Causes include:
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Reduced Vitamin D availability
Increased serum phosphate
Reduced serum calcium
Reduced response to PTH.
Uraemia induced
(nodular) hyperplasia
Signs and symptoms of bone
disease
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Biomechanical bone pain
Soft tissue and tendon calcification
Tendon rupture/ avulsion
Calciphylaxis (ectopic calcification)
Pseudogout and pseudoclubbing
Vertebral fractures (with height loss)
Vascular calcification (enhancing cardiac risk)
Management of CKD
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Prevent progression
Modify risk factors (eg hypertension)
Drugs (eg ACE inhibitors)
Minimise adverse effects
– Phosphate binders
– Erythropoetin
– Primary prevention of Cardiac disease
• Renal replacement therapy
• Is covered in Nephrology 4