Download Guidelines on chronic kidney disease

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Clinical Review
Guidelines on chronic
kidney disease
The relationship between CKD and cardiovascular disease is very
important, write Liam Glynn et al
CHRONIC KIDNEY DISEASE (CKD) is becoming an increasingly
common diagnosis. In the US alone, there are over 400,000
patients with end-stage renal disease (ESRD) with nearly 10
times this number having mild CKD defined as a glomerular filtration rate (GFR) < 60ml/min/1.73m2.1 Even more
disturbingly, the current number of patients with early CKD
– the pool from which future ESRD patients will emerge –
exceeds the present number with ESRD by a factor of 30 to
60.2
Risk factors for the development of CKD include age,
smoking, hypertension and diabetes. The relationship
between CKD and cardiovascular disease is a very important
one. Cardiovascular disease is frequently associated with
CKD, and individuals with CKD are more likely to die of cardiovascular disease than to develop kidney failure.
Cardiovascular disease in CKD is treatable and potentially
preventable, and CKD appears to be a significant risk factor
for cardiovascular disease.3
It is now recognised that even mild degrees of renal insufficiency are strongly associated with adverse cardiovascular
outcomes and that CKD goes unrecognised in many individuals due to the asymptomatic nature of the condition.
Indeed, where CKD is recognised in this population, patients
are often nihilistically treated.4, 5
Despite the recognised association between reduced estimated GFR and poorer prognosis, risk factor management
is often not optimised for such patients in the community
setting5 while screening for CKD is frequently limited to a
measurement of serum creatinine which does not accurately
reflect GFR,6-7 the best indicator of renal function in health
and disease.8
Physicians worldwide recognise the importance of cardiovascular risk factors and strive to identify and improve them
in their patients. Despite the high prevalence of CKD in this
population,9 it remains outside the group of well-recognised
cardiovascular risk factors in many healthcare settings. This
is despite the growing body of evidence demonstrating
increased cardiovascular risk associated with CKD in the
general population,10, 11 as well as in patients post-myocardial infarction,9, 12-14 post cardiac intervention15 and those
with diabetes.16 However, the health systems of only a
minority of countries have emphasised the importance of
CKD screening (using estimated GFR) within primary
care.17, 18
Remarkably, with CKD representing the group at highest
risk from cardiovascular complications, even above diabetes,
there has been a systematic exclusion of patients with CKD
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from therapeutic trials.19 Most primary and secondary prevention of cardiovascular disease happens in the community
and therefore it is important that we as primary care physicians become proactive in diagnosing and managing CKD in
its most relevant setting.
In an effort to support this process, a group of Irish
nephrologists, GPs and endocrinologists, using several internationally recognised sources,18, 20, 21 have developed CKD
guidelines for primary care which are summarised below:
Why is CKD important to you and your patients?
CKD is common and is often unrecognised in many
patients due to the asymptomatic nature of the condition.
CKD is strongly associated with adverse cardiovascular outcomes. Estimated glomerular filtration rate (eGFR) is a
useful measure of renal function and can be calculated
easily in clinical practice using serum creatinine, age,
gender and race.
Reduced eGFR is a potent marker for cardiovascular morbidity and mortality, and should be regarded as a risk factor
for cardiovascular disease just like hypertension, cholesterol
level, diabetic status, etc. The vast majority of patients with
mild to moderate CKD will not require dialysis and can be
managed in primary care. Appropriate management of
patients with CKD in primary care may reduce overall cardiovascular risk and delay progression to renal failure.
Classification of CKD
Table 1 describes the classification of CKD as outlined by
the National Kidney Foundation Kidney Disease Outcomes
Quality Initiative.20
The classification of CKD is based on the use of an ‘estimated Glomerular Filtration Rate’ (eGFR) which is usually
represented in the units of ml/min/1.73m2. eGFR can be
calculated simply by using the patient variables of age,
gender, serum creatinine and race. As a result, an increasing number of clinical biochemistry laboratories nationally
are automatically calculating eGFR as part of each urea and
electrolytes (U+E) request.
Referral information
The following information should be included in any referral to secondary care:
• General medical history
• Urinary symptoms
• Medication history
• Examination, e.g. blood pressure, oedema, palpable bladder or other positive findings
• Urinalysis for blood and protein
• In all patients who have persistent dipstick – positive pro-
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Clinical Review
Table 1
Stages of chronic kidney disease
The stages of CKD as outlined by the National Kidney Foundation Kidney Disease Outcomes Quality Initiative
GFR (ml/min/1.73m 2)
Stage
Clinical Featur es
I
*Kidney damage with normal or increased GFR
≥ 90
II
*Kidney damage with a mild decrease in GFR
60-89
III
Moderate decrease in GFR
30-59
IV
Severe decrease in GFR
15-29
V
Kidney failure
< 15 or dialysis
*Other evidence of kidney damage may include any of the following:
• Persistent microalbuminuria/proteinuria/haematuria
• Structural abnormalities of the kidneys demonstrated on ultrasound scanning or other radiological tests, eg. polycystic
kidney disease, reflux nephropathy
• Biopsy-proven chronic glomerulonephritis
Patients found to have an eGFR of ≥ 60mL/min/1.73m2 without one of these markers:
• Should not be considered to have CKD and
• Should not be subjected to further investigation (unless there are additional reasons to do so, see ‘criteria for referral’)
In the following circumstances eGFR may not be accurate:
• Acute renal failure
• Patients less than 18 years of age
• Patients with advanced muscle-wasting and amputations
• Pregnancy
teinuria, check spot urine protein/creatinine (PCR) ratio.
In diabetes patients with negative dipstick, check spot
urine albumin/creatinine (ACR) ratio
• Relevant blood results: U+E: urea, creatinine, sodium,
potassium, chloride and bicarbonate; eGFR; liver profile
(albumin); bone profile: calcium, phosphate; fasting cholesterol and glucose; HbA1c (in diabetes); full blood count
• All previous serum creatinine results with dates
• Result of renal ultrasound scan if available.
Laboratory assessment of CKD
Calculation of eGFR
eGFR is calculated from the serum creatinine value and
patient variables such as age, gender, race. The most commonly used estimation equation is the abbreviated Modified
Diet in Renal Disease (MDRD) equation:22
Estimated GFR (ml/min) = 186 x (serum creatinine level
[in milligrams per deciliter]) – 1.154 x (age [in years]) –
0.203.
For women and those of Afro-Caribbean decent (ethnicity
data was collected during follow-up), the product of this
equation is multiplied by correction factors of 0.742 and
1.21, respectively.22
Urinalysis
Haematuria by dipstick is always significant and usually
does not need verification by other tests.
Proteinuria does need to be quantified so as to further
stratify patients, (ie. nephrotic versus subnephrotic range
proteinuria).
Urine dipsticks are a useful screening tool, although they
only provide a semi-quantitative assessment of level of proteinuria, as the reported value can vary according to the
hydration status of the patient. Spot urine samples can be
used to measure the PCR allowing the correction for hydra-
tion status. The ACR is useful for the detection of small
levels of proteinuria in diabetes patients and is not useful
for routine follow-up of patients who already have established macroalbuminuria.
Management and referral guidelines
The chief goals of management of CKD are to delay progression to renal failure, to reduce overall cardiovascular risk
and to avoid complications. Guidelines for CKD evaluation,
treatment goals and referral guidelines are summarised in
Table 2.
Regular reviews are recommended and should consist of
blood pressure measurement, assessment of kidney function, review of all medications, and immunisation with
influenza vaccine and pneumococcal vaccine.
Review all medications when renal insufficiency is first
identified and avoid potentially nephrotoxic medications (eg.
NSAIDs, COX inhibitors and contrast media). Risk factors
for the development of CKD such as hypertension and diabetes mellitus should be specifically targeted.
Cardiovascular complications can be reduced by attention
to smoking cessation, weight loss, regular aerobic exercise,
thrombotic risk (consider aspirin) and treatment of hypercholesterolemia. Anaemia is common and a target of
> 11.5gm/dl should be sought.
Hypertension
Target blood pressure is < 130/80mmHg and lower targets
may be appropriate in patients with diabetes or proteinuria.
A low salt diet (< 100mmol (2.4 grams) sodium per day) is
recommended and ACE inhibitors or ARBs are first choice
medication and should be increased to maximum tolerated
dose as necessary. Serum creatinine and potassium should
be monitored during treatment and most patients will need
more than two medications for optimal control.
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Table 2
Summary of CKD evaluation, treatment goals and referral guidelines
CKD stage
eGFR
I
> 90ml/min/1.73m2
Frequency of eval.
Evaluation
12 months
Treatment
Referral
Exam + BP
Referral not
(with proteinuria or
U+E
warranted unless
haematuria)
eGFR
1) BP <130/80
other problems
present
60-89ml/min/1.73m2
II
12 months
(with proteinuria or
ACR/PCR
Urinalysis
haematuria)
III
30-59ml/min/1.73m2
2) ACEi/ARB if no CI
3) Statin if CVD risk >
20% over 10 years
6-12 months
As above +
FBC, PTH, Ca,
P, Albumin
4) Aspirin if no CI
5) Diabetics: optimise
glycaemic control
IV
15-29ml/min/1.73m2
V
< 15ml/min/1.73m2
3-6 months
1-3 months
Type 2 diabetes
Target HbA1C is < 7.0% and again, ACE inhibitors or
ARBs are the first choice in patients with hypertension
and/or (micro) albuminuria and should be increased to maximum tolerated dose as necessary. Target a reduction in
proteinuria and avoid the use of metformin when eGFR
< 60ml/min.
Conclusions
Automated searching of general practice computer records
can provide a reliable and valid way of identifying people
with CKD who could benefit from interventions readily available in primary care.23 However, poor physician awareness
of CKD and its association with excess cardiovascular morbidity and mortality remains a significant problem.24 The
very low rate of recording of CKD in patients found to have
CKD indicates scope for improving detection and early intervention.25
It appears that both traditional (diabetes mellitus, hypertension, and smoking etc) and non-traditional risk factors
(elevated inflammatory markers such as C-reactive protein
and interleukin-6;26 elevated plasma homocysteine and
abnormal apolipoprotein levels;27 anaemia;28 and arterial calcification29 among others) promote the frequent
development of cardiovascular disease in the CKD population. This means that therapies targeting both progression
of CKD and comorbidities such as cardiovascular disease
are required to reduce mortality among these patients.24
As chronic disease management moves to the community,
there are understandable concerns regarding the increasing
numbers of patients and associated workload. eGFR may be
a useful tool to prioritise the management of certain patients
with established heart disease in the community. As the cardiovascular disease/CKD population continues to rise,
strategies to improve survival for this group become increasingly critical.
In fact, several studies suggest that these individuals may
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As for III
h eGFR 15%/yr
i Creat. 15%/yr
BP > 150/90 on
3 meds
PCR ≥ 100
unexplained anaemia
Micro.haematuria
Discussion with
or urgent referral
to nephrologist
As for III
derive as much, if not more, benefit from evidence-based
cardiovascular therapies and strategies.30 This suggests that
estimated GFR should be added to the list of dyslipidemia,
hypertension, smoking, central obesity, and sedentary
lifestyle as a significant and potentially modifiable risk
factor for cardiovascular disease.
The fact that estimated GFR appears to discriminate prognosis emphasises the importance of including estimated
GFR in any cardiovascular risk factor profile for this group
of patients. This also highlights the potential role of primary
care physicians in risk factor assessment and management
decision-making for patients with CKD.
Liam G Glynn, GP principal, Ballyvaughan, Co Clare and lecturer in primary care, Department of General Practice, NUI,
Galway; Donal Reddan, consultant nephrologist, Department
of Medicine, Merlin Park Regional Hospital, Galway; Liam
Hayes, GP principal, Tralee, and GP specialist in nephrology,
Tralee General Hospital, Co Kerry; Liam Casserly, consultant
nephrologist, Mid-Western Regional Hospital, Limerick;
Austin Stack, consultant nephrologist, Regional Kidney Unit,
HSE North West Letterkenny, Co Donegal; George J Mellotte,
consultant nephrologist, Tallaght Hospital, Dublin
The CKD guidelines discussed above have been developed
by a group of Irish nephrologists, general practitioners and
endocrinologists with the support of Roche pharmaceuticals
and specifically with the help of Yvonne D’Arcy and Clare
Blaney.
The guidelines will be available for download from the ICGP
website (www.icgp.ie) after they are launched on the March
8, World Kidney Day, at the Royal College of Physicians in
Dublin.
References on request