Transcript 2._Chronic_Kidney_Diseasex

Chronic Kidney Disease
Dr Dana Ahmed Sharif
MRCP UK/ MRCP London
Each kidney has:
• a renal artery
• a renal vein
• a ureter
which enter the kidney at the
hilum.
The kidney has:
• an outer cortex layer
• an inner medullary pyramid
layer
• fine branches of the ureter
which form the calyx
The NEPHRON is the functional
unit of the kidney.
Each kidney has nearly a million
of nephrons
Each nephron:
• is supplied with an afferent
arteriole.
• produces urine which drains
into a collecting duct.
The collecting ducts fuse together
to make larger and larger tubes
until they join together as the
ureter
Each nephron consists of:
• a glomerulus & Bowman’s
capsule
• a proximal convoluted tubule
• a loop of Henle
• a distal convoluted tubule
Chronic Kidney Disease
• Longstanding and irreversible decline in renal
function
• Injured nephrons replaced by extensive
fibrosis
• Normal nephrons gradually fail due to
‘hyperfilteration’
• Is mainly TUBULAR scarring, so urine output
usually normal, though urine quality reduced
• Any cause of AKI can eventually lead to CKD
Assessment of renal function
• 60 years old woman
- Creatinine 1.1 (0.4-1.1mg/dl)
- Wt 48 Kg
• 20 years old man
- Creatinine 1.3 (0.7-1.2mg/dl)
- Wt 98 Kg
How do we assess renal function?
• Serum urea and creatinine
- Small molecules
- Filtered by glomerulus – measure of GFR
- But creatinine also depends on:
+ Muscle mass
+ Body size
+ Sex and race
• Measurement of GFR
- Direct measurement
- Estimation of GFR (eGFR)
Shenmesh, O., Golbetz, H., Kriss, J. P., and Myers, B. D. (1985). Kidney
International 28 , 830–838
Staging of chronic kidney disease
K/DOQI guideline
stage
GFR (ml/min)
Description
1*
≥90
Normal kidney function but other evidence of
kidney damage
2*
60-89
Mild reduction in kidney function with other
evidence of kidney damage
3
30-59
Moderate kidney damage
4
15-29
Severe kidney damage
5
<15
Established renal failure or end stage renal failure
*Only considered to be CKD stage 1 or 2 if proteinuria and/or haematuria or structural renal
disease are present
CKD prevalence
Stage 5: 0.2%
Stage 4: 0.2%
Stage 3: 4.3%
Stage 2: 3.0%%
Stage 1: 3.3%
Coresh J. Astor BC, Greene T, et al. (2003) Prevalence of chronic kidney disease and decreased kidney function in the adult US population:
Third National Health and Nutrition Examination Study. Am J Kidney Dis, 41(1), 1-12
Why is it important to identify patients
with CKD?
• CKD predispose to increased cardiovascular risk
(modify risk factors such as Hypertension)
• Some patient may benefit from other
investigations ( such as renal biopsy)
• It may be possible to slow down the progression
• Complications of CKD can be identified and
treated early
• Preparation for dialysis or transplantation once
they reach end-stage.
?Acute or Chronic kidney impairment
• History and duration of symptoms
• Previous urinalysis or measurement of renal
function
• Rapid changes in renal function
• Normocytic, normochromic anaemia( but
haemorrhage, haemolysis)
• Ultrasound: small kidneys and increased
echogenicity
• Evidence of renal osteodystrophy ( ie digital
subperiosteal erosions)
Who is at risk?
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Known CKD
Hypertension
Diabetes
Unexplained oedema
Congestive cardiac failure
Atherosclerotic disease ( coronary, cerebral, peripheral)
Multi systemic disease ( myeloma, SLE)
Bladder outflow obstruction, neurogenic bladder, renal
stone disease, recurrent UTI
• Chronic nephrotoxic use ( NSAID, ACEI, ARBII, ciclosporin,
lithium)
• Urologically unexplained haematuria
Why chronic renal failure tends to
progress?
• Once CKD established, inexorable progression
is likely
• While only 10% of those with CKD stage 3 may
progress, all are at risk
• Therefore life-long follow up is desirable
Mechanism of progression
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Raised intraglomerular pressure
Glomerular damage
Proteinuria
Tubulo-intestitial scarring
Importance of proteinuria
• Normal glomeruli do not leak protein
• Proteinuria is a sign of glomerular dysfunction
• Proteinuria is also risk factor for progression of
CKD
Importance of proteinuria
• Normal glomeruli do not leak protein
• Proteinuria is a sign of glomerular dysfunction
• Proteinuria is also risk factor for progression of
CKD
• Measures which reduce proteinuria slow down
the progression of CKD*
• Albuminuria is a marker of cardiovascualr risk**
*GISEN Group (1997). Lancet 349 , 1857–1863
**Hebert, L. A., Spetie, D. N., and Keane, W. F. (2002). Postgraduate Medicine 111 , 23.
Causes of End Stage Renal Disease*
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Diabetes
Glomerulonephritis
Reflux nephropathy
Renovascular disease
Hypertension
Polycystic kidney disease
*UK renal data registry
Case 1
• 55 years old male
• History of diabetes for 15 years
• He has CKD with eGFR 35ml/min( checked 6
months ago).
• His BP was 140/90 and his doctor started him
on Ramipril 2.5 mg two weeks ago.
• Lab results: eGFR of 25ml/min otherwise well,
HbA1c 6.0%, urinary protein excretion of
0.5g/24hrs( no changes from previous results).
What is the most likely cause of his
renal deterioration?
1- Progression of his diabetic nephropathy
2- Uncontrolled hypertension
3- Infection
4- Drug induced
What is the most likely cause of his
renal deterioration?
1- Progression of his diabetic nephropathy
2- Uncontrolled hypertension
3- Infection
4- Drug induced
Reversible causes of deteriorating
renal function
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Blood pressure control
Diabetes control
Obstruction
Drug, contrast agent
Intercurrent illness
Exacerbation of underlying kidney disease
(sarcoidosis, lupus)
Preventing progression
• Blood pressure and diabetes
- Uncontrolled Hypertension and diabetes makes
proteinuria worse
- Controlling hypertension and diabetes is vital
• ACE inhibitors and ARBs have anti-proteinuric
effects over and above their effects via blood
pressure
- Agents of choice in proteinuric renal disease
- Even if blood pressure ‘normal’
Blood pressure targets*
• CKD with no proteinuria: <140/90 mmHg
• CKD with proteinuria: <130/80 mmHg
• Diabetic nephropathy: <130/80mmHg (aim for
125/75 mmHg).
* NICE guideline for management of Chronic Kidney Disease, Sept 2008
Managing CKD
1- General advice:
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Smoking cessation
Weight reduction if obese
Encourage aerobic exercise
Aspirin 75mg od ( if 10 years cardiovascular risk>20%)
Treat hyperlipidaemia
Avoid NSAID and other nephrotoxic drugs
Limit alcohol intake( <21units/wk in male, <14units/wk
in female
• Vaccination against influenza and pneumococcus
Managing CKD
2- CKD stages 1-3:
• Monitor eGFR, urinalysis and protein
creatinine ratio
• Meticulous BP and diabetes control
• If Hb < 11g/dl check ferritin, B12 and folate( if
ferritin <100mg/dl start on oral or IV iron)
• Annual check of PTH, Calcium and phosphate
Managing CKD
3- CKD stages 4-5:
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Refer to nephrologist
Full dietary assessment
Optimize PTH, Calcium and phosphate
Correct acidosis
Hepatitis B immunization
Discuss future treatment (dialysis, transplant or
conservative/palliative)
Complications of CKD
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Uraemia
Anaemia
Renal bone disease
Salt and water retention
Electrolyte imbalance
Acidosis
Cardiovascular disease and lipids
Salt and water retention
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Dietary salt restriction ( aim <5g/day)
Fluid intake restriction
Diuretics such as furosemide, titrate up
Add thiazide ( metolazone)
Those with fluid overload and on diuretics monitor:
- Weight ( loss of 1kg/day)
- BP control
- Monitor electrolyte
- if Ur > 70mg/dl consider reducing diuretics
- Refractory volume overload = dialysis
Hyperkalaemia
• Common and potentially fatal
• Rapid rise of K+ is more dangerous than gradual ones, as
cell membrane stability is more vulnerable to acute
changes
• ↑K+ → depolarization of the membrane resting potential
→ Na+ channel inactivation → ↓membrane excitability →
neuromuscular depression and cardiac dysrhythmias.
• When to treat:
- K+: 5.5-6.0 mmol/l: recheck routinely. Review medications
and arrange dietary advice
- K+: 6.1-6.5 mmol/l: recheck urgently, review med, stop
ACEI/ARB2 and arrange dietary advice.
- K+: >6.5 mmol/l: admit for emergency management
Measures to prevent ↑K+
- Dietary restriction: diary products, potatoes and some
fruits (such as banana ,grapes, pineapple), fresh fruit juice,
tomatoes, sweet corn, mushrooms, chocolate and coffee.
- Loop diuretics: promote urinary K+ excretion.
- Drug withdrawal or dose reduction (ACEI, ARB2), review
other contributory drugs (spironolactone, NSAID and Bblockers)
- Correct acidosis.
- Dialysis ( especially in refractory ↑K+)
Acidosis
Leads to:
• Bone: increase bone resorption and impaired
mineralization, contributing to renal
osteodystrophy.
• Over ventilation (compensatory mechanism)
• Hyperkalaemia
• Increased ionized Calcium (acidosis lead to
reduced albumin bound fraction)
• Malnutrition: acidosis promotes catabolism
How to correct acidosis?
• Treat when venous HCO3- is <21 mmol/l
• Give NaHCO3 tablet 0.5-1.5g/tds
• Refractory acidosis: dialysis
Uraemia
• Clinical syndrome caused by substantial fall in GFR
• Failure to eliminate potentially toxic small and middle size
molecules.
• NOT a result of high blood urea concentration.
• Ur and Cr are not directly toxic.
• Leads to:
- Chronic inflammation and ↑oxidative stress
- Accumulation of metabolic end products
- Accelerated atherogenesis
- Disruption of immune system
- phosphate is retained: leads to ↑PTH, arteriosclerosis and
vascular calcification
Uraemia
Symptoms:
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Nausea/ vomiting
Anorexia and weight loss
Malaise, fatigue
Confusion, fits and coma
Pericarditis
Anaemia
• Erythropoietin(EPO) is essential for the
terminal maturation of erythrocyte
• EPO deficiency occur in most advanced CKD (
eGFR < 35ml/min) with exception:
- Adult polycystic kidney disease
- Benign renal cysts
- Renal cell carcinoma
Differential diagnosis of anaemia in
CKD
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EPO deficiency
Iron deficiency anaemia
Blood loss ( GI tract, Haemodialysis)
Folate deficiency
B12 deficiency
Haemolysis
Myelodyplasia
Myeloma
Case 2
• 54 years old male with CKD stage 4
• History or recurrent chest infection for the last
3months
• On oral co-amoxiclav, Erythropoietin injection
6000 iu sc weekly( increased recently)
• Lab results: Hb 8.5g/dl(no changes), WBC: 14,
eGFR:16, CRP:75, ferritin: 600
What is the most likely cause of EPO
non-responsiveness
1- Non-compliance
2- Inadequate dose of EPO
3- High CRP
4- Iron deficiency anaemia
What is the most likely cause of EPO
non-responsiveness
1- Non-compliance
2- Inadequate dose of EPO
3- High CRP
4- Iron deficiency anaemia
EPO non-response
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Iron deficiency
Chronic blood loss
Infection/inflammation
Severe hyperparathyroidism (causes bone
marrow fibrosis)
B12 and folate deficiency
Haemolysis
Malnutrition
Inadequate dosing
Poor compliance
Renal bone disease
(Osteodystrophy)
• Heterogeneous disorder leading to diminished bone
strength
• Is a function of bone turnover, density, mineralization and
architecture
• Mostly occur beyond CKD stage 3
• High turnover( PTH > 450ng/L*) : caused by secondary
hyperparathyroidism leads to increased bone resorption
and formation (osteitis fibrosa cystica)
• Low turnover (Adynamic bone disease)( PTH < 100ng/L):
paucity of cells with decreased bone resorption and
formation.
• Osteomalacia: defect in mineralization, deficiency of
1,25(OH)2D
• Osteoporosis: reduced bone density
Renal bone disease: clinical features
1- Secondary hyperparathyroidism:
• Usually asymptomatic
• Bone pain and arthralgia
• Muscle weakness
• Pruritis (cutaneous calcium phosphate deposition)
• Bone deformity
• Increased fracture risks (hip fracture x5 in Dialysis)
• Marrow fibrosis contribute to anaemia
2- Adynamic bone disorder: asymptomatic and may have twice
increase in fracture risk than dynamic bone disease.
3- Increased cardiovascular risk
Renal bone disease: treatment
• Measures to reduce serum phosphate:
- Dietary PO4 restriction( meat, egg, milk, cereals)
- Dialysis
- Oral phosphate binders( prevent absorption)such as Ca+2 and non-Ca+2
containing phosphate binder
• Measures to increase serum calcium and suppress PTH:
- Ca+2 salts ( also act as PO4 binder)
- Vit D analogues (calciterol, alfacalcidol)
• Measures to suppress PTH directly:
- Calcimimetic agents(cinacalcet)
- Parathyroidectomy( tertiary PTH= PTH, Ca2,PO4 and
ALP)
Malnutrition
Causes:
• Anorexic uraemic toxins(↑leptin)
• Chronic low grade inflammation and oxidative
stress.
• Dietary restriction (low protein diet)
• Medications (iron, PO4 binders)
• Acidosis
• Dialysis itself (protein loss during dialysis)
• Biochemical indicators: s. albumin, transferrin
and cholesterol