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Chronic kidney disease
Juliet Bell
Introduction
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CKD is common and frequently unrecognised
More common with increasing age.
Often exists together with other conditions
More common in south asian, and afro-caribbean
Lack of specific symptoms are often not diagnosed,
or diagnosed late when CKD is at an advanced
stage.
Definition
• CKD (or renal failure) is characterised by a gradual
decline in kidney function over time.
• Can be categorised into
– Kidney damage: indicated by persistent proteinuria,
haematuria or anatomical abnormality
– Decreased kidney function: indicated by a glomerular
filtration rate (GFR) of less than 60ml/min/ 1.73m2 which
persists for more than 3 months
At risk groups
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Diabetes
Hypertension
Cardiovascular disease
Structural renal tract disease, renal calculi or prostatic
hypertrophy
Multisystem diseases with potential kidney involvement
– eg SLE
Family history of stage 5 CKD or hereditary kidney
disease.
Opportunistic detection of haematuria or proteinuria
Patient on nephrotoxic drugs
Early Detection
• Early treatment of CKD and its complications can
delay or prevent progression to ESRD
• Annual SrCr checks recommended for estimation of
GFR, urine dipstick for patients known to have a
high risk of developing CKD.
Assessing Renal function
• Inulin – excreted unchanged in the urine,
– provides accurate GFR assessment.
– Expensive, time consuming
• Serum creatinine (SrCr)
– Simple to measure, Inexpensive
– Routinely used to assess renal function
– Not always accurate and can be influenced by many
factors.
• Equations use SrCr to estimate GFR
Estimated eGFR
• Current clinical standards recommend using the
modification of diet in renal disease (MDRD)
equation to estimate GFR.
GFR (ml/min/1.73m2) = 175 x (SrCr [umol/L]/88.4)-1.154 x age(years)-0.203
x 0.742 if female,
x 1.21 if african or african caribbean
Normal GFR is roughly 100ml/min/1.73m2
Testing kidney function
• DoH recommends that eGFR is reported alongside serum
creatinine to allow physicians to detect renal impairment.
• Correct for ethnicity: multiply eGFR by 1.21 for african or
african-caribbean ethnicity
• Make allowance for biological and analytical variance of
serum creatinine (+5%) when interpreting changes in egfr
• Advise no meat for 12 hours before the test
• Interpret with caution in people with extreme muscle mass.
[Also in pregnancy, oedematous states, muscle wasting disorders,
amputees and malnourished people, and in acute renal failure.]
• Test annually in all at risk groups
Cockgroft and Gault
Creatinine Clearance
CrCl (ml/min) = F x (140 – age[years]) x weight (kg)
SrCr (umol/L)
Where F = 1.23 in males and 1.04 in females
• No evidence to demonstrate that these are
interchangeable.
• Used for drug dosing in patients with renal function
Kidney Damage
• Haematuria
• Proteinuria
• Albuminuria
• Can be determined by dipstick test
• Haematuria can be classified as nephrological or urological
and will require further investigation if there is no obvious
cause – eg uti
• Proteinuria – sign of kidney disease and associated with a
more rapid decline in kidney function.
Testing for haematuria
Persistent invisible haematuria
Action
To differentiate, in the absence of
proteinuria, from transient haematuria.
Confirm persistent invisible haematuria
by 2 out of 3 positive reagent strips.
With or without proteinuria
Investigate for urinary tract malignancy in
appropriate age group
Without proteinuria
Follow up annually with repeat testing for
haematuria, proteinuria/albuminuria,
GFR and blood pressure monitoring as
long as the haematuria persists.
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Use reagent strips rather than urine microscopy
Evaluate further if there is a result of 1 + or more
Do not use urine microscopy to confirm a positive result
Testing for proteinuria
• Use ACR in preference to PCR as it has greater sensitivity.
• Do not use reagent strips
• If ACR > 30mg/mmol and < 70mg/mmol, confirm by
subsequent early morning sample.
• If ACR > 70mg/mmol repeat sample not needed
• Proteinuria defined as ACR > 30mg/mmol
• If ACR > 70mg/mmol – consider specialist referral
• In patients with diabetes consider microalbuminuria as
clinically significant:
– Men: ACR > 2.5mg/mmol
– Women: ACR > 3.5mg/mmol
Investigation
• If eGFR < 60ml/min/1.73m2 in first test:
– Repeat within 2 weeks
– Quantify ACR (early morning sample)
– Check for haematuria
• If eGFR > 60ml/min/1.73m2
– Interpret with caution as estimates of GFR become less accurate as
true GFR increases.
– Strong suspicion of CKD
• Check for haematuria
• Quantify ACR (early morning sample)
• Repeat Test (significant reduction in renal function if rise in serum creatinine
concentration of > 20%)
Stages of CKD
Stage
Egfr
(ml/min/1.73m2)
Description
Typical
testing
frequency
1
> 90
Normal or increased GFR, with
other evidence of kidney damage.
12 monthly
2
60-89
Slight decrease in GFR, with other
evidence of kidney damage
12 monthly
3a
3b
45-59
30-44
Moderate decrease in GFR, with or
without other evidence of kidney
damage.
6 monthly
4
15-29
Severe decrease in GFR, with or
without other evidence of kidney
damage.
3 monthly
5
<15
Established renal failure
6 weekly
* Monitor more closely for all patients with CKD during intercurrent illness
Read Coding
• Code as:
– CKD 3a, 3b, 4 and 5
• Use the QOF guideline to ensure patients are correctly
coded and entered on the register.
• On receipt of ACR results code as CKD disease
– with or
– without proteinuria.
Symptoms
• Early stages tend to be asymptomatic.
• As kidney function worsens patients will accumulate
uraemic toxins and develop symptoms such as
– fatigue, nausea, anorexia, lethargy, weight loss and
pruritis
• In stages 4 and 5 patients are likely to experience
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Hyperkalaemia
Uraemia
Anaemia
Impaired Vitamin D metabolism leading to
hyperparathyroidism which in turn affects bone turnover.
Early intervention
3 key interventions
• Glycaemic control (for diabetics)
• Blood pressure control
• Reducing proteinuria
Progression will depend on the cause.
• Tubulointestinal diseases progress more slowly
than glomerular, diabetic, hypertensive and
polycystic diseases.
Glycaemic control
• Hyperglycaemia is an independent risk factor for
nephropathy
• Glycaemic control has been shown to reduce the
development of microalbuminuria and therefore
reduces the progression of diabetic renal disease.
• Angiotensin converting enzyme inhibitors and
angiotensin II receptor blockers have been shown
to have renoprotective effects in early and late
nephropathy caused by type 2 diabetes, by
reducing microalbuminuria.
Blood Pressure Control
• Control of blood pressure has been demonstrated
to slow the progression of CKD in several trials.
• Aim to keep blood pressure below 140/90mmHg
• In Diabetes and CKD or if ACR is > 70mg/mmol aim
to keep blood pressure below 130/80mmHg
Anti-hypertensives in CKD
Diabetes
No proteinuria
1st line ACE inhibitor
No diabetes
As per NICE
2nd line ARB
Proteinuria
ACR > 70mg/mmol
As above
As diabetes
As above
As diabetes
ACE inhibitors and ARBs are the preferred treatments because they
reduce interglomerular pressure and lower proteinuria.
Some patients will experience an initial rise in SrCr and mild increase in
potassium levels.
Monitoring ACE/ARB Therapy
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Measure U&Es
– before starting treatment with ACE
– 1-2 weeks after treatment starts and
– after each dose increase
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Titrate to maximum tolerated dose before adding 2nd agent.
• If egfr falls by < 25% or creatinine rises by < 30% continue
to monitor, do not adjust doses.
• If egfr falls by > 25% or creatinine rises by > 30%
• investigate for other causes of decreasing renal function
• If no other cause stop drug.
• If potassium rises above 5.6mmol/L – stop
Cardiovascular Risk
• Cardiovascular disease is the most common cause
of death in patients with CKD.
• Risk of CVD and associated mortality increases as
GFR decreases.
• Prophylaxis
– Offer statin for primary prevention depending on
calculated cardiovascular risk
– Offer statin for secondary prevention regardless of
baseline lipid
– Aspirin should only be offered as secondary prevention.
Referral
• CKD Stage 4 or 5 (with or without diabetes)
• ACR > 70mg/mmol unless known diabetic and appropriately
treated
• ACR > 30mg/mmol and haematuria
• Rapidly declining eGFR (> 5ml/min/1.73m2in 1 year, or > 10ml
within 5 years)
• Poorly controlled hypertension despite the use of at least 4
antihypertensive drugs at therapeutic doses.
• People with, or suspected of having, rare or genetic causes of
CKD
• Suspected renal artery stenosis.
• Refer to urology if CKD and outflow obstruction, unless urgent
medical intervention is needed.
Other Complications
• Anaemia
• Mineral Bone disorder
Anaemia
• In the UK CKD is the most common cause of
anaemia.
• EPO deficiency – produced by the peritubular cells
in the kidney.
• Other factors include:
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Blood loss (during dialysis)
Shortened lifespan of red blood cells
Impaired iron haemostasis
Secondary hyperparathyroidism
Inflammation
Mineral and bone disorder
• Begins to appear from stage 3 onwards
Manifests as
• Abnormalities in calcium, phosphate, parathyroid
hormone and vitamin d metabolism
• Abnormalities of bone turnover, mineralisation,
volume, linear growth and strength
• Vascular or soft tissue calcification
Mineral and bone disorder
• Initially phosphate
excretion is reduced
• This triggers an increase in
PTH, stimulating the kidney
to excrete more phosphate.
• This ability diminishes with
disease progression and
phosphate levels rise.
• Renal hydroxylation of
inactive calcidiol to the
active form of vitamin D
(calcitriol) is reduced.
• Low levels of calcitriol lead
to reduced intestinal
absorption of calcium
resulting in hypocalcaemia.
Net result of hyperphosphataemia, hypocalcaemia and low levels of
calcitriol is the stimulation of PTH synthesis and secretion. 2ry
hyperparthyroidism and is treated by correcting the imbalance of
calcium, phosphate and calictriol.
Bone conditions
• Offer biphosphonates if indicated for prevention and
treatment of osteoporosis in CKD stages 1,2,3a,3b
• If vitamin D supplementation is indicated
– cholecalciferol or ergocalciferol for CKD stages 1,2,3a,3b
– alfacaldidol or calcitriol for CKD stages 4 and 5
• Serum Calcium, phosphate and parathyroid
hormone concentrations should be monitored in
CKD stages 4 and 5 (but not routinely in stages 1-3b)
Biochemical Targets
Biochemistry Test
Target Range
Albumin corrected calcium
CKD stages 1 to 4
2.2 to 2.5 mmol/litre
Phosphate
CKD stages 3 to 4
0.9 to 1.5 mmol/litre
Calcium x Phosphate
product
Less than 4.8 mmol/litre and ideally less than
4.2 mmol/litre
PTH
CKD stages 1 to 3
0.9 to 5.4 pmol/litre
Ongoing management
• Consider discussing management issues with a specialist in
cases where it may not be necessary for the patient to be
seen.
• Consider routine follow up at surgery rather than specialist
clinic, specifying criteria for re-referral.
Drug induced –
renal impairment
• 5 to 20% of cases of acute kidney injury can be
attributed to drugs and chemicals.
• Common nephrotoxic drugs:
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ACE inhibitors, ARBs
NSAIDs
Lithium
Tacrolimus, Ciclosporin
Gold, Pencillamine
Mesalazine
Drug induced hyperkalaemia
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Potassium sparing diuretics
ACE inhibitors, ARBs
Digoxin overdose
NSAIDs
Ciclosporin
Trimethoprim
Drug dosing in renal
impairment
• eGFR is only an estimate of renal function
• Cockgroft and Gault equation is more accurate and
provides creatinine clearance which is quoted in all
renal dosing references.
• It should be used for patients with extreme body
weight or where egfr is close to the borders
between stages.
• REF sources: BNF, Renal drug handbook
• www.bnf.org – to calculate creatinine clearance
• www.ukmicentral.nhs.uk/resource/culo.htm -ibw
Useful Websites
• NICE Guidance no 73. Chronic Kidney Disease –
Early identification and management of chronic
kidney disease in adults in primary and secondary
care.
• British Renal Society – www.britishrenal.org
• British Kidney patient association –
www.britishkidney-pa.co.uk
• Quality outcomes framework – www.qof.ic.nhs.uk
• www.bnf.org
Questions