Dr Ivan Benett outlines the key recommendations from the NICE guideline on chronic kidney disease that can be implemented in primary care
Chronic kidney disease (CKD) is a common but frequently unrecognised condition, the age standardised prevalence of which is 8.5%; this increases significantly with age.1 Although CKD is usually asymptomatic, it is possible to test for this condition. The National service framework for renal services emphasised the importance of early detection and treatment of established kidney disease.2 This is because end-stage renal disease incurs huge costs, in terms of economic impact and quality of life, to individuals, their families, and to the NHS;3 furthermore, patients with CKD are at a greater risk of cardiovascular events including death.4 Early identification of CKD can therefore lessen this burden. The guideline developed by NICE on Early identification and management of chronic kidney disease in adults in primary and secondary care aims to reduce the risk of both end-stage renal disease and cardiovascular disease (CVD) through identification and management of patients who:1,5
- are at risk of developing CKD or who already have this condition
- require interventions to reduce cardiovascular risk
- will develop progressive kidney disease and/or complications from kidney disease
- require referral to a specialist.
This article aims to summarise the important interventions and demonstrate that they are not too onerous to be implemented in general practice.
Classification of CKD
Chronic kidney disease is defined as kidney damage or a glomerular filtration rate (GFR) of <60 ml/min/1.73m2 on at least two occasions in a period of over 3 months.1,5 The US National Kidney Foundation Kidney Disease Outcomes Quality Initiative (KDOQI) classification of CKD was adopted by the National service framework for renal services, and has been modified by the NICE guideline (see Table 1). In addition to GFR measurement, stage 1 and 2 CKD also require other evidence of kidney disease such as haematuria, proteinuria, albuminuria, or structural abnormalities. Stages 3–5 can be defined by GFR alone but other features, such as those listed above, may also be present and should be looked for.
The prevalence of complications as a result of CKD begins to rise as the GFR falls below 45 ml/min/1.73m2. Therefore, stage 3 has been divided into two groups based on GFR values:1,5
- CKD 3A: 45–59 ml/min/1.73m2
- CKD 3B: 30–44 ml/min/1.73m2.
Significant proteinuria (>0.5 g/24 h) (see below) is also associated with adverse CKD outcomes, and the suffix ‘p’ should be added to the staging of CKD to indicate proteinuria.
Table 1: The US National Kidney Foundation’s KDOQI stages of CKD as
modified by NICE
This classification divides CKD into stages, defined by evidence of kidney damage and level of renal function as measured by GFR. Chronic kidney disease is defined as either kidney damage (proteinuria, haematuria, or anatomical abnormality) or GFR <60 ml/min/1.73m2 present on at least two occasions for ?3 months.
Kidney damage with normal or raised GFR
Kidney damage with mild decrease in GFR
Moderately lowered GFR
|4||Severely lowered GFR||15–29|
|5||Kidney failure (end-stage renal disease)||<15|
aUse the suffix (p) to denote the presence of proteinuria when staging CKD
*In order to diagnose stages 1 and 2 CKD, additional evidence of kidney damage must be present, e.g. persistent proteinuria, haematuria, or structural abnormalities
For the purposes of this classification define proteinuria as urinary ACR ?30 mg/mmol, or PCR ?50 mg/mmol (approximately equivalent to urinary protein excretion 0.5 g/24 h or more). For patients with diabetes, microalbuminuria is clinically significant if ACR >2.5 mg/mmol in men or >3.5 mg/mmol in women
At any given stage of CKD, management should not be influenced solely by age.
KDOQI=Kidney Disease Outcomes Quality Initiative; CKD=chronic kidney disease; GFR=glomerular filtration rate; ACR= albumin:creatinine ratio; PCR=protein:creatinine ratio
Adapted from the National Kidney Foundation, with permission. NKF KDOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification and Stratification. www.kidney.org/Professionals/Kdoqi/guidelines_ckd/p4_class_g1.htm
Diagnosis of CKD
As it is difficult to measure GFR directly, an estimated GFR (eGFR) should be used; this is based on serum creatinine and other factors, such as age and gender.6 (NB if the patient is of African origin, e.g. African-Caribbean ethnicity, the eGFR should be multiplied by a correction factor of 1.21.1,5) Serum creatinine can be increased artificially after eating meat, therefore patients should be advised not to eat it in the 12 hours before creatinine is measured.4
If the eGFR result is ?60 ml/min/1.73m2 the measurement should be repeated at an interval that is appropriate to the clinical context, usually 2 weeks. Providing this does not reveal a rapid decline, eGFR should be measured again after 3 months. A decline of >5 ml/min/1.73m2 per year or >10 ml/min/1.73m2 in 5 years indicates progressive CKD, and should prompt referral to a specialist. An eGFR ?60 ml/min/1.73m2 is inaccurate; therefore, significant reduction in renal function should be inferred from an increase in serum creatinine concentration of >20%.1,5
Testing for protein and blood in urine
The continual presence of protein, albumin, or red blood cells in urine is evidence of kidney damage. The degree of proteinuria can be assessed by collecting urine over a 24-hour period, but this is not usually practical, and so spot testing of urine is performed. Ideally the sample should be a ‘first pass’ morning specimen. Dipsticks are rarely accurate enough for this purpose. In patients with CKD but without diabetes, significant proteinuria is regarded as ?0.5 g/24 h. This is equivalent to an albumin:creatinine ratio (ACR) of ?30 mg/mmol or a protein:creatinine ratio (PCR) of ?50 mg/mmol. For patients with diabetes, microalbuminuria is considered to be clinically significant if the ACR is >2.5 mg/mmol in men or >3.5 mg/mmol in women.1,5
The presence of haematuria should be assessed by reagent strips; if there is a result of 1+ or more, further evaluation is required. Urine microscopy should not be used to confirm a positive result.
Ultrasound can be used to assess structural changes to the kidneys. Renal ultrasound should be offered if:1,5
- there is visible or persistent invisible haematuria
- symptoms of urinary tract obstruction are present
- there is a family history of polycystic kidney disease and the patient is aged over 20 years
- patients have already been referred to secondary care.
Co-morbid conditions are common in CKD: in a large scale primary care study of patients with stages 3–5 CKD, the adjusted age and gender odds ratio for diabetes=1.33 (95% confidence interval [CI] 1.21–1.41); for hypertension=2.1 (95% CI 2.0–2.2); and for cardiovascular disease (CVD)=1.69 (95% CI 1.59–1.79).1 Patients with these conditions should be offered testing. General practitioners also need to be aware of at-risk groups and offer testing for CKD if patients have been prescribed nephrotoxic drugs (most commonly non-steroidal anti-inflammatory drugs) on a long-term basis or have any of the following risk factors:1,5
- structural renal tract disease, renal calculi (stones), prostatic hypertrophy
- multisystem diseases with possible kidney involvement
- a family history of stage 5 CKD or hereditary kidney disease
- incidental haematuria or proteinuria.
Management of CKD
It is important to establish the rate of decline of renal function as early as possible because this will indicate if referral is needed. At least two readings of eGFR are required for this purpose. Certain factors (e.g. CVD, smoking, black or Asian ethnicity) increase the risk of progression of CKD and these should be borne in mind.
People with CKD should be offered education and information that is tailored to their stage and cause of CKD. As the disease progresses, patients may require referral for specialist pre-dialysis education. Healthcare professionals should also be aware of the psychological impact of CKD and offer appropriate support.
Patients with CKD should be encouraged to exercise and maintain a healthy weight. Smoking increases the risk of progression for both CKD and CVD so advice and intervention in this area is a priority. Dietary interventions apply more to advanced stages of CKD.
The NICE guideline recommends that blood pressure (BP) should be controlled within a systolic range of 120–139 mmHg and the diastolic BP should be below 90 mmHg. If the patient has significant proteinuria, the target range for BP is within a systolic range of 120–129 mmHg and the diastolic blood pressure should be below 80 mmHg. The priority is to achieve the systolic range even if diastolic BP falls below its optimal range during treatment.
Angiotensin-converting enzyme (ACE) inhibitors/angiotensin II receptor blockers (ARBs) should be offered for the control of hypertension to all patients with significant proteinuria. Before initiating drug treatment, serum potassium, creatinine, and eGFR should be measured. These measurements should then be taken again (between 1 and 2 weeks after starting therapy) and after each dose increase, or at intervals indicated by clinical context.
Drug therapy should be stopped if serum potassium is ?6 mmol/l and other drugs known to promote hyperkalaemia have been discontinued. Initiation, and an increase in the dose of ACE inhibitor/ARB therapy may result in a decrease in GFR (or an increase in serum creatinine). If the change in GFR is less than 25% (increase in serum creatinine is <30%), measurements should be repeated in a further 1–2 weeks. A decrease in GFR of ?25% (or change in serum creatinine ?30%) should be investigated; this may be caused by volume depletion or concurrent drug treatment. If no other cause is found, the dose of ACE inhibitor/ARB therapy should either be stopped or reduced, and an alternative form of hypertensive pharmacotherapy added. If the fall is catastrophic, urgent referral should be considered to exclude renal artery stenosis.1,5
Prevention of CVD
Primary and secondary prevention of CVD in patients with CKD should not differ from normal practice in those patients without CKD. However, it should be noted that in people with CKD, the Framingham risk tables significantly underestimate risk.1,5
There was not enough evidence to recommend the use of drugs to lower uric acid in people with CKD who have asymptomatic hyperuricaemia.
Complications of CKD
Renal bone disease
There is no need to routinely measure calcium, phosphate, parathyroid hormone, or vitamin D levels at CKD stages 1, 2, or 3 (A or B) but they should be quantified in stages 4 and 5. At stages 1, 2 and 3 (A or B), prevention of osteoporosis and vitamin D supplementation is no different to that recommended for people without CKD, and should be offered if indicated.1,5
If haemoglobin (Hb) has not already been measured, it should be determined in people with CKD stage 3B or worse to identify anaemia (<11.0 g/dl). Healthcare professionals should refer to the NICE guideline on Anaemia management in people with chronic kidney disease for further guidance.7 If a patient with CKD is found to have anaemia, other causes should be considered apart from anaemia of CKD. Iron deficiency is a common problem and should be diagnosed if the patient has stage 5 CKD and serum ferritin is <100 µg/l; it can be considered a possible diagnosis if the patient has stage 3 or 4 CKD and if ferritin level is <100 µg/l.
Functional iron deficiency may be present in patients with CKD7 even if serum ferritin is >100 µg/l.7 In practice, iron supplementation should be given to patients with anaemia at least until serum ferritin exceeds 200 µg/l. If there is no response to iron supplementation, referral for erythropoietin treatment should be considered. In patients with anaemia of CKD, Hb levels should be maintained between 10.5 and 12.5 g/dl for adults.7
The age of the patient should not influence the use of any of these interventions, and the risks and benefits should be judged in a holistic assessment of each individual.
Referral of patients with CKD
Referral should be made when:
- there is doubt about the diagnosis
- the disease has reached an advanced stage
- specialised treatments are indicated.
The NICE guideline on early identification and management of CKD1,5 and its previous guideline on anaemia in CKD have identified criteria for referral as shown in Box 1. In all the listed cases the referral should be discussed with the patient and their family. Sometimes the decision may be made not to refer if the patient is in a palliative phase or has actively declined further intervention.
Box 1: Referral for specialist assessment
People with CKD in the following groups should be considered for referral:
|CKD=chronic kidney disease; ACR=albumin:creatinine ratio; PCR=protein:creatinine ratio; GFR=glomerular filtration rate; ACE=angiotensin-converting enzyme; ARB=angiotensin II receptor blocker|
Chronic kidney disease is an important and prevalent condition that leads to increased morbidity and mortality in people at all ages, but especially in those aged over 50 years who have CVD, diabetes and/or hypertension. It results in a significant burden to both individuals and society. The guideline development group for the NICE guideline on early identification and management of CKD reviewed interventions that have been found to reduce the decline of renal function and mitigate complications. Many of the recommendations in the guideline can be implemented in general practice; the main interventions that can be conducted in primary care include management of the underlying condition and BP control. The reduction of cardiovascular risk should also be optimised in patients through lifestyle changes, BP control, and the use of statins. Furthermore, it should be taken into account that the Framingham risk score underestimates the likelihood of CVD events in people with CKD.1,5
NICE implementation tools
NICE has developed the following tools to support implementation of its guideline on the Early identification and management of chronic kidney disease in adults in primary and secondary care. They are now available to download from the NICE website: www.nice.org.uk
National cost reports and local cost templates for the guideline have been produced:
The slides are aimed at supporting organisations to raise awareness of the guideline and resulting implementation issues at a local level and can be edited to cater for local audiences. This information does not supersede or replace the guidance itself.
Audit support has been developed to support the implementation of the NICE guideline on chronic kidney disease. The aim is to help NHS organisations with a baseline assessment and to assist with the audit process, thereby helping to ensure that practice is in line with the NICE recommendations. The audit support is based on the key recommendations of the guidance and includes criteria and data collection tools.
- The NICE guideline on the diagnosis and management of CKD is likely to increase workload in primary care and referrals to secondary care
- It is likely to create immediate referral and prescribing cost pressures, with potential savings and health benefits realised sometime in the future
- Many of the suggested interventions can be provided in primary care or the community
- A constructive and pragmatic dialogue between hospital and primary care clinicians is likely to craft local care pathways that can best meet the demands of this guideline
- CKD specialist nurses could be employed in primary care to avoid paying an expensive tariff charge when working for hospital trusts
- The majority of people with CKD will be elderly, often with complex co-morbidities. Sensitive and personalised interpretation of the NICE guideline in discussion with the patient is likely to be necessary
- Tariff costs general medical outpatient = £194 (new), £96 (follow up)1
- National Collaborating Centre for Chronic Conditions. Chronic kidney disease: national clinical guideline for early identification and management in adults in primary and secondary care. London: Royal College of Physicians, 2008. Available at: www.rcplondon.ac.uk/pubs/brochure.aspx?e=257
- Department of Health. National service framework for renal disease—Part Two, chronic kidney disease, acute renal failure and end of life care. London: DH, 2005. Available at: www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyAndGuidance/DH_4101902
- Ansell D, Feest T, Tomson C et al. UK Renal Registry Report 2006. Bristol: UK Renal Registry, 2006.
- Go A, Chertow G, Fan D et al. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med 2004; 351 (13): 1296–1305.
- National Institute for Health and Care Excellence. Chronic kidney disease—early identification and management of chronic kidney disease in adults in primary and secondary care. Clinical Guideline 73. London: NICE 2008. Available at: www.nice.org.uk/Guidance/CG73
- Levey A, Bosch J, Lewis J et al. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Int Med 1999; 130 (6): 461–470.
- National Institute for Health and Care Excellence. Anaemia management in chronic kidney disease. Clinical Guideline 39. London: NICE 2006. Available at: www.nice.org.uk/Guidance/CG39G