Early identification and management of chronic kidney disease in adults: summary of updated NICE guidance
BMJ 2014; 349 doi: https://doi.org/10.1136/bmj.g4507 (Published 24 July 2014) Cite this as: BMJ 2014;349:g4507
- Serena Carville, associate director1,
- David Wonderling, head of health economics1,
- Paul Stevens, consultant nephrologist2
- on behalf of the Guideline Development Group
- 1National Clinical Guideline Centre, Royal College of Physicians, London NW1 4LE, UK
- 2East Kent Hospitals University NHS Foundation Trust, Canterbury CT1 3NG, UK
- Correspondence to: P Stevens pstevens{at}nhs.net
The publication of an internationally accepted definition and classification of chronic kidney disease (CKD) 12 years ago precipitated a proliferation of research and literature surrounding the identification of CKD, risk factors for progression, and important prognostic factors.1 It also stimulated continuing debate concerning the criteria used for definition of CKD and exactly how ageing influences CKD and its sequelae.2 3 The National Institute for Health and Care Excellence (NICE) has modified its previous recommendations on the classification of CKD,4 partly based on Kidney Disease Improving Global Outcomes (KDIGO)5 and driven by prognostic data from large observational studies. NICE has also recognised a requirement for better identification of people at risk of adverse outcome and covers some key areas relating to the management of CKD, including frequency of monitoring, progression of CKD, acute kidney injury, and renin-angiotensin system blockade. This article summarises the most recent recommendations from NICE.6
Recommendations
NICE recommendations are based on systematic reviews of best available evidence and explicit consideration of cost effectiveness. When minimal evidence is available, recommendations are based on the Guideline Development Group’s experience and opinion of what constitutes good practice. Evidence levels for the recommendations are given in italic in square brackets.
Investigations for chronic kidney disease
Clinical laboratories should:
-Use the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation to estimate GFRcreatinine, using creatinine assays with calibration traceable to standardised reference material
-Use creatinine assays that are specific (for example, enzymatic assays) and zero biased compared with isotope dilution mass spectrometry and
-Participate in a UK national external quality assessment scheme for creatinine.
(New recommendation.) [Based on high quality observational studies and the experience and opinion of the GDG]
Consider using eGFRcystatinC at initial diagnosis to confirm or rule out CKD in people with:
-An estimated GFRcreatinine of 45-59 mL/min/1.73 m2, sustained for at least 90 days and
-No proteinuria (albumin:creatinine ratio <3 mg/mmol) or other marker of kidney disease.
(New recommendation.) [Based on moderate to high quality observational studies, a cost analysis, and the experience and opinion of the GDG]
Markers of kidney disease include albuminuria (albumin:creatinine ratio >3 mg/mmol), urine sediment abnormalities (haematuria, red blood cell casts, white blood cell casts, oval fat bodies or fatty casts, granular casts, and renal tubular epithelial cells), electrolyte and other abnormalities caused by tubular disorders, abnormalities detected by histology, structural abnormalities detected by imaging, and previous kidney transplantation. Cystatin C is an alternative endogenous filtration marker that can be used to estimate glomerular filtration rate. In people with GFR above 45 mL/min/1.73 m2, GFR estimates based on cystatin C are more powerful predictors of clinical outcomes than is creatinine based estimated GFR, especially in people with no proteinuria.7 8
Do not diagnose CKD in people with:
-An estimated GFRcreatinine of 45-59 mL/min/1.73 m2 and
-An estimated GFRcystatinC of more than 60 mL/min/1.73 m2 and
-No other marker of kidney disease.
(New recommendation.) [Based on moderate to high quality observational studies, a cost analysis, and the experience and opinion of the GDG]
To detect and identify proteinuria, use urine albumin:creatinine ratio in preference to protein:creatinine ratio, because it has greater sensitivity for low levels of proteinuria. For quantification and monitoring of high levels of proteinuria (albumin:creatinine ratio ≥70 mg/mmol), protein:creatinine ratio can be used as an alternative. Albumin:creatinine ratio is the recommended method for people with diabetes. (Updated recommendation.) [Based on the experience and opinion of the GDG]
Offer testing for CKD using estimated GFRcreatinine and albumin:creatinine ratio to people with any of the following risk factors:
-Diabetes
-Hypertension
-Acute kidney injury
-Cardiovascular disease (ischaemic heart disease, chronic heart failure, peripheral vascular disease, or cerebral vascular disease)
-Structural renal tract disease, renal calculi, or prostatic hypertrophy
-Multisystem diseases with potential kidney involvement—for example, systemic lupus erythematosus
-Family history of end stage kidney disease (GFR category G5) or hereditary kidney disease
-Opportunistic detection of haematuria.
(Updated recommendation.) [Based on high quality individual patient data meta-analyses]
-Decreased GFR is associated with increased risk of adverse outcomes
-Increased albumin:creatinine ratio and decreased GFR in combination multiply the risk of adverse outcomes.
(New recommendation.) [Based on high quality individual patient data meta-analyses and the experience and opinion of the GDG]
Classification of chronic kidney disease
Classify CKD by using a combination of GFR and albumin:creatinine ratio (ACR) categories (as illustrated in figure 1⇓). Be aware that:
Fig 1 Classification of chronic kidney disease by using glomerular filtration rate (GFR) and albumin:creatinine ratio categories. *Consider using estimated GFRcystatinC for people with CKD G3aA1. Adapted with permission from reference 5
-Increased albumin:creatinine ratio is associated with increased risk of adverse outcomes
An incidental finding of clinically important proteinuria should always be considered in the context of GFR category.
Indications for renal ultrasound
Offer a renal ultrasound scan to all people with CKD who:
-Have accelerated progression of CKD (see “Defining progression of CKD”)
-Have visible or persistent invisible haematuria
-Have symptoms of urinary tract obstruction
-Have a family history of polycystic kidney disease and are aged over 20 years
-Have a GFR of less than 30 mL/min/1.73 m2 (GFR category G4 or G5)
-Are considered by a nephrologist to require a renal biopsy.
(Updated recommendation.) [Based on the experience and opinion of the GDG]
-Past patterns of estimated GFR and albumin:creatinine ratio (but be aware that progression of CKD is often non-linear)
-Comorbidities, especially heart failure
-Changes to their treatment (such as renin-angiotensin-aldosterone system antagonists, non-steroidal anti-inflammatory drugs, and diuretics)
-Intercurrent illness
-Whether they have chosen conservative management of CKD.
(New recommendation.) [Based on indirect evidence from low to high quality retrospective cohort studies and the experience and opinion of the GDG]
Frequency of monitoring
Use figure 2⇓ to guide the frequency of GFR monitoring for people with or at risk of CKD, but tailor it to the person according to:
Monitor people for the development or progression of CKD for at least two to three years after acute kidney injury, even if serum creatinine has returned to baseline. (New recommendation.) [Based on moderate quality evidence from retrospective cohort studies]
Fig 2 Frequency of monitoring of glomerular filtration rate for people with or at risk of chronic kidney disease. Albumin:creatinine ratio is an important indicator of cardiovascular risk and progression. Intensity of shading reflects risk of progression. Adapted with permission from reference 5
-The underlying cause of CKD
Defining progression of CKD
Define accelerated progression of CKD as:
-A sustained decrease in GFR of 25% or more and a change in GFR category within 12 months or
-A sustained decrease in GFR of 15 mL/min/1.73 m2 per year.
(New recommendation.) [Based on high quality evidence from retrospective cohort studies and the experience and opinion of the GDG]
Self management
Ensure that systems are in place to:
-Inform people with CKD of their diagnosis
-Enable people with CKD to share in decision making about their care
-Support self management (this includes providing information about blood pressure, smoking cessation, exercise, diet, and medicines) and enable people to make informed choices. (New recommendation.) [Based on high quality evidence from one qualitative study, cost effectiveness evidence, and the experience and opinion of the GDG]
People should be encouraged to take exercise, achieve a healthy weight, stop smoking, and restrict salt intake to less than 6 g/day according to existing guidance (see www.nice.org.uk/guidance/PH25).
Indications for referral
People with CKD in the following groups should normally be referred for specialist assessment:
-GFR less than 30 mL/min/1.73 m2 (GFR category G4 or G5), with or without diabetes*
-Albumin:creatinine ratio 70 mg/mmol or more, unless known to be caused by diabetes and already appropriately treated
-Albumin:creatinine ratio 30 mg/mmol (category A3) or more, together with haematuria
-Sustained decrease in GFR of 25% or more and a change in GFR category or sustained decrease in GFR of 15 mL/min/1.73 m2 or more within 12 months
-Hypertension that remains poorly controlled despite the use of at least four antihypertensive drugs at therapeutic doses (see also NICE clinical guideline 127 on hypertension (www.nice.org.uk/Guidance/CG127))
-Known or suspected rare or genetic causes of CKD
-Suspected renal artery stenosis.
(Updated recommendation.) [Based on the experience and opinion of the GDG]
*Where this is a stable isolated finding, formal referral may not be indicated and advice may be all that is required. The aim is to avoid late referral of those people likely to progress to requirement for renal replacement therapy within one year.
People with CKD and renal outflow obstruction should normally be referred to urological services, unless urgent medical intervention is required—for example, for the treatment of hyperkalaemia, severe uraemia, acidosis, or fluid overload.
Pharmacotherapy
Choice of antihypertensive agent and blood pressure control
Offer a low cost renin-angiotensin system antagonist to people with CKD and:
-Diabetes and an albumin:creatinine ratio of 3 mg/mmol or more (category A2 or A3)
-Hypertension and an albumin:creatinine ratio of 30 mg/mmol or more (category A3)
-An albumin:creatinine ratio of 70 mg/mmol or more (irrespective of hypertension or cardiovascular disease).
(New recommendation.) [Based on high to very low quality randomised controlled trial evidence and cost effectiveness evidence]
The evidence to support these criteria is limited in people aged over 70 years.
Do not offer a combination of renin-angiotensin system antagonists to people with CKD. (New recommendation.) [Based on moderate to very low quality randomised controlled trial evidence]
Follow the treatment recommendations in NICE clinical guideline 127 (www.nice.org.uk/Guidance/CG127) (on hypertension) for people with CKD, hypertension, and an albumin:creatinine ratio of less than 30 mg/mmol (categories A1 and A2) if they do not have diabetes. (New recommendation.) [Based on high to very low quality randomised controlled trial evidence and cost effectiveness evidence]
Blood pressure control recommendations for people with CKD and diabetes and an albumin:creatinine ratio of greater than 3 mg/mmol (categories A2 and A3) and hypertension were not updated.
In people with CKD, aim to keep the systolic blood pressure below 140 mm Hg (target range 120-139 mm Hg) and the diastolic blood pressure below 90 mm Hg.
In people with CKD and diabetes, and also in people with an albumin:creatinine ratio of 70 mg/mmol or more (category A3), aim to keep the systolic blood pressure below 130 mm Hg (target range 120-129 mm Hg) and the diastolic blood pressure below 80 mm Hg.
Oral antiplatelets and anticoagulants
Offer antiplatelet drugs to people with CKD for the secondary prevention of cardiovascular disease, but be aware of the increased risk of bleeding. (New recommendation.) [Based on observational studies and the experience and opinion of the GDG]
Overcoming barriers
The use of thresholds for diagnosis of CKD and the definition of progression remain contentious areas. In the whole adult population, the CKD-EPI creatinine equation reduces bias in GFR estimation, affords greater precision, and is better at categorising people at higher risk of all cause mortality, cardiovascular mortality, myocardial infarction, progression of CKD, and end stage kidney disease.9 10 Categorisation by GFR in the new classification is complemented by categorisation of urinary albumin:creatinine ratio. Strong evidence shows that both lower GFR and greater albumin:creatinine ratio are independently related to mortality, cardiovascular events, progression to end stage kidney disease, and also acute kidney injury. This is important, although intervention trials in the different albumin:creatinine ratio categories are lacking, albuminuria increases the risk of acute kidney injury, and acute kidney injury predicts progression of CKD. The diagnosis of CKD in people without significant proteinuria in the GFR category 45-59 mL/min/1.73 m2 (G3aA1), especially older people, continues to raise concerns regarding over-diagnosis. Use of cystatin C identifies those at higher risk of adverse outcomes, including end stage kidney disease, and overcomes some of the concerns relating to potential over-diagnosis and disease labelling. Another contentious area is the definition of progression of CKD. The recommendation is supported by more recent evidence and attempts to recognise both the inherent variability of serum creatinine in the assessment of GFR and the fact that progression of kidney disease is often not linear.11 12 13 We used the term “accelerated progression” in the knowledge that reported decline in GFR among people with CKD may be lower (reviewed extensively in reference 5). Finally, categorisation by GFR and albumin:creatinine ratio also provides a template for frequency of monitoring in people with established CKD and aids decision making regarding referral.
Further information on the guidance
This guideline is a partial update of NICE clinical guideline CG73.4 Areas prioritised for update included investigation of chronic kidney disease (CKD), specifically measurement of kidney function, markers of kidney damage, and the frequency of monitoring; classification; self management with low protein diets and self management support systems; the choice of renin-angiotensin-aldosterone system antagonists in managing blood pressure; antiplatelet and antithrombotic treatment to reduce cardiovascular disease; and management of asymptomatic hyperuricaemia and renal bone disease with vitamin D. New topics that were not covered in the 2008 guideline were the risk of developing CKD after an episode of acute kidney injury and the management of acidosis with bicarbonate supplementation in people with CKD.
Methods
The Guideline Development Group followed standard NICE methods in the update of this guideline (www.nice.org.uk/aboutnice/howwework/developingniceclinicalguidelines/developing_nice_clinical_guidelines.jsp). The GDG comprised three consultant nephrologists (including the chair), a consultant renal nurse and renal community nurse specialist, a general practitioner, two lay members, a consultant clinical scientist, a consultant in geriatric and general medicine, a renal pharmacist, and a professor of public health.
The group developed clinical questions, collected and appraised clinical evidence, and evaluated the cost effectiveness of proposed interventions and management strategies through literature review and economic analysis. The draft guideline went through a rigorous reviewing process, in which stakeholder organisations were invited to comment; the group took all comments into consideration when producing the final version of the guideline. Quality ratings of the evidence were based on GRADE methodology (www.gradeworkinggroup.org). These relate to the quality of the available evidence for assessed outcomes rather than the quality of the clinical study. Where standard methods could not be applied, a customised quality assessment was done. These were either presented as a narrative summary of the evidence or in customised GRADE tables (for example, for observational studies and individual patient data meta-analysis).
NICE has produced three different versions of the guideline: a full version; a summary version known as the “NICE guideline;” and a version for people who have chronic kidney disease, their family and carers, and the public. All of these versions, as well as a pathway, are available from the NICE website. Updates of the guideline will be produced as part of NICE’s guideline development programme.
Economic analysis
A cost analysis was conducted to compare different diagnostic strategies for CKD, using diagnostic accuracy data from the guideline’s systematic review. Twelve month costs were calculated for each strategy, including the cost of tests, healthcare visits, and drugs. The addition of a one-off cystatin C test was found to be cost saving for people without diabetes who have a creatinine based glomerular filtration rate of 45-59 mL/min/1.73 m2.
Future research/remaining uncertainties
The GDG identified some priority areas for research:
Does the provision of educational and supportive interventions to people with CKD by healthcare professionals increase patients’ skills and confidence in managing their condition and improve clinical outcomes?
For people with CKD at the highest risk of cardiovascular disease, what is the clinical effectiveness of low dose aspirin compared with placebo for primary prevention of cardiovascular disease?
For people aged over 75 years with CKD, what is the clinical effectiveness of renin-angiotensin-aldosterone system antagonists?
In people with CKD who are at high risk of progression, what is the clinical and cost effectiveness of uric acid lowering agents on the progression of CKD and on mortality?
In people with hyperparathyroidism secondary to CKD, does treatment with vitamin D or vitamin D analogues improve patient related outcomes?
Notes
Cite this as: BMJ 2014;349:g4507
Footnotes
This is one of a series of BMJ summaries of new guidelines based on the best available evidence; they highlight important recommendations for clinical practice, especially where uncertainty or controversy exists.
Contributors: All authors contributed to the conception and drafting of this article and to revising it critically. They have all approved this version. PS is the guarantor.
Competing interests: We have read and understood BMJ policy on declaration of interests and declare the following interests: SC is a member of the Kidney Disease Improving Global Outcomes (KDIGO) Methods Committee (no reimbursement is received); SC and DW are employees of the Royal College of Physicians, National Clinical Guideline Centre, which is commissioned by NICE to develop clinical guidelines; PS is a co-investigator on an NIHR funded research project in progress, which is a multicentre study examining the accuracy of glomerular filtration rate estimation using creatinine and cystatin C and albuminuria for monitoring disease; he has given lectures on guidelines, chronic kidney disease, and measurement of kidney function for the International Society of Nephrology, American Society of Nephrology, German Society of Nephrology, Renal Association, British Renal Society, US National Kidney Foundation, and Japanese Society of Nephrology (all professional societies in kidney disease; no reimbursement was received). The authors’ statements can be viewed at www.bmj.com/content/bmj/349/bmj.g4507/related#datasupp.
Provenance and peer review: Commissioned; not externally peer reviewed.