1 Recommendations

The following guidance is based on the best available evidence. The full guideline gives details of the methods and the evidence used to develop the guidance.

The wording used in the recommendations in this guideline (for example, words such as 'offer' and 'consider') denotes the certainty with which the recommendation is made (the strength of the recommendation). See about this guideline for details.

Terms used in this guideline

Chronic kidney disease (CKD)

Defined as abnormalities of kidney function or structure present for more than 3 months, with implications for health. This includes all people with markers of kidney damage and those with a glomerular filtration rate (GFR) of less than 60 ml/min/1.73 m2 on at least 2 occasions separated by a period of at least 90 days (with or without markers of kidney damage).

Classification of CKD

CKD is classified according to estimated GFR (eGFR) and albumin:creatinine ratio (ACR) (see table 1), using 'G' to denote the GFR category (G1–G5, which have the same GFR thresholds as the CKD stages 1–5 recommended previously) and 'A' for the ACR category (A1–A3), for example:

  • A person with an eGFR of 25 ml/min/1.73 m2 and an ACR of 15 mg/mmol has CKD G4A2.

  • A person with an eGFR of 50 ml/min/1.73 m2 and an ACR of 35 mg/mmol has CKD G3aA3.

  • An eGFR of less than 15 ml/min/1.73 m2 (GFR category G5) is referred to as kidney failure.

Glomerular filtration rate (GFR)

This is abbreviated in the following way in this guideline:

  • GFR: either a measured or an estimated GFR

  • eGFR: estimated GFR (without indicating the method of estimation)

  • eGFRcreatinine: an estimation of GFR using serum creatinine

  • eGFRcystatinC: an estimation of GFR using cystatin C.

Markers of kidney disease

These include albuminuria (ACR more than 3 mg/mmol), urine sediment abnormalities, electrolyte and other abnormalities due to tubular disorders, abnormalities detected by histology, structural abnormalities detected by imaging, and a history of kidney transplantation.

Renin–angiotensin–aldosterone system antagonist

A drug that blocks or inhibits the renin–angiotensin–aldosterone system including angiotensin-converting enzyme (ACE) inhibitors, angiotensin‑receptor blockers (ARBs), direct renin inhibitors and aldosterone antagonists.

Renin–angiotensin system antagonist

A drug that blocks or inhibits the renin–angiotensin system including ACE inhibitors, ARBs and direct renin inhibitors. This group of drugs does not include aldosterone antagonists.

1.1 Investigations for chronic kidney disease

Measuring kidney function

Creatinine-based estimate of GFR

1.1.1 Whenever a request for serum creatinine measurement is made, clinical laboratories should report an estimate of glomerular filtration rate (eGFRcreatinine) using a prediction equation (see recommendation 1.1.2) in addition to reporting the serum creatinine result[2]. [2014]

1.1.2 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 (IDMS)

  • participate in a UK national external quality assessment scheme for creatinine. [new 2014]

    For more information about implementing this recommendation, see implementation: getting started.

1.1.3 Apply a correction factor to GFR values estimated using the CKD‑EPI creatinine equation for people of African-Caribbean or African family origin (multiply eGFR by 1.159). [new 2014]

1.1.4 In people with extremes of muscle mass – for example, in bodybuilders, people who have had an amputation or people with muscle wasting disorders – interpret eGFRcreatinine with caution. (Reduced muscle mass will lead to overestimation and increased muscle mass to underestimation of the GFR.) [2008]

1.1.5 Advise people not to eat any meat in the 12 hours before having a blood test for eGFRcreatinine. Avoid delaying the despatch of blood samples to ensure that they are received and processed by the laboratory within 12 hours of venepuncture. [2008]

Cystatin C-based estimate of GFR

1.1.6 Whenever a request for serum cystatin C measurement is made, clinical laboratories should report an estimate of glomerular filtration rate (eGFRcystatinC) using a prediction equation (see recommendation 1.1.7) in addition to reporting the serum cystatin C result. [new 2014]

1.1.7 When an improved assessment of risk is needed (see recommendation 1.1.14), clinical laboratories should use the CKD‑EPI cystatin C equation to estimate GFRcystatinC. [new 2014]

1.1.8 Clinical laboratories should use cystatin C assays calibrated to the international standard to measure serum cystatin C for cystatin C-based estimates of GFR. [new 2014]

1.1.9 Interpret eGFRcystatinC with caution in people with uncontrolled thyroid disease because eGFRcystatinC values may be falsely elevated in people with hypothyroidism and reduced in people with hyperthyroidism. [new 2014]

Reporting and interpreting GFR values

1.1.10 Clinical laboratories should report GFR either as a whole number if it is 90 ml/min/1.73 m2 or less, or as 'greater than 90 ml/min/1.73 m2'. [new 2014]

1.1.11 If GFR is greater than 90 ml/min/1.73 m2, use an increase in serum creatinine concentration of more than 20% to infer significant reduction in kidney function. [new 2014]

1.1.12 Interpret eGFR values of 60 ml/min/1.73 m2 or more with caution, bearing in mind that estimates of GFR become less accurate as the true GFR increases. [2014]

1.1.13 Confirm an eGFR result of less than 60 ml/min/1.73 m2 in a person not previously tested by repeating the test within 2 weeks. Allow for biological and analytical variability of serum creatinine (±5%) when interpreting changes in eGFR. [2008]

When to use a cystatin C-based estimate of GFR for diagnosis of CKD

1.1.14 Consider using eGFRcystatinC at initial diagnosis to confirm or rule out CKD in people with:

  • an eGFRcreatinine of 45–59 ml/min/1.73 m2, sustained for at least 90 days and

  • no proteinuria (albumin:creatinine ratio [ACR] less than 3 mg/mmol) or other marker of kidney disease. [new 2014]

    For information about implementing this recommendation, see implementation: getting started.

1.1.15 Do not diagnose CKD in people with:

  • an eGFRcreatinine of 45–59 ml/min/1.73 m2 and

  • an eGFRcystatinC of more than 60 ml/min/1.73 m2 and

  • no other marker of kidney disease. [new 2014]

When highly accurate measures of GFR are required

1.1.16 Where a highly accurate measure of GFR is required – for example, during monitoring of chemotherapy and in the evaluation of renal function in potential living donors – consider a reference standard measure (inulin, 51Cr‑EDTA, 125I‑iothalamate or iohexol). [2008]

Proteinuria

1.1.17 Do not use reagent strips to identify proteinuria unless they are capable of specifically measuring albumin at low concentrations and expressing the result as an ACR. [2008]

1.1.18 To detect and identify proteinuria, use urine ACR in preference to protein:creatinine ratio (PCR), because it has greater sensitivity than PCR for low levels of proteinuria. For quantification and monitoring of levels of proteinuria of ACR 70 mg/mmol or more, PCR can be used as an alternative. ACR is the recommended method for people with diabetes. [2008, amended 2014]

1.1.19 For the initial detection of proteinuria, if the ACR is between 3 mg/mmol and 70 mg/mmol, this should be confirmed by a subsequent early morning sample. If the initial ACR is 70 mg/mmol or more, a repeat sample need not be tested. [2008, amended 2014]

1.1.20 Regard a confirmed ACR of 3 mg/mmol or more as clinically important proteinuria. [2008, amended 2014]

1.1.21 Quantify urinary albumin or urinary protein loss as in recommendation 1.1.18 for:

  • people with diabetes

  • people without diabetes with a GFR of less than 60 ml/min/1.73 m2. [2008, amended 2014]

1.1.22 Quantify by laboratory testing the urinary albumin or urinary protein loss of people with a GFR of 60 ml/min/1.73 m2 or more if there is a strong suspicion of CKD (see also recommendation 1.1.28). [2008]

Haematuria

1.1.23 When testing for the presence of haematuria, 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. [2008]

Managing isolated invisible haematuria

1.1.24 When there is the need to differentiate persistent invisible haematuria in the absence of proteinuria from transient haematuria, regard 2 out of 3 positive reagent strip tests as confirmation of persistent invisible haematuria. [2008]

1.1.25 Persistent invisible haematuria, with or without proteinuria, should prompt investigation for urinary tract malignancy in appropriate age groups. [2008]

1.1.26 Persistent invisible haematuria in the absence of proteinuria should be followed up annually with repeat testing for haematuria (see recommendations 1.1.24 and 1.1.25), proteinuria or albuminuria, GFR and blood pressure monitoring as long as the haematuria persists. [2008]

Who should be tested for CKD

1.1.27 Monitor GFR at least annually in people prescribed drugs known to be nephrotoxic, such as calcineurin inhibitors (for example, cyclosporin or tacrolimus), lithium and non-steroidal anti-inflammatory drugs (NSAIDs). [2008, amended 2014]

1.1.28 Offer testing for CKD using eGFRcreatinine and ACR to people with any of the following risk factors:

  • diabetes

  • hypertension

  • acute kidney injury (see recommendation 1.3.9)

  • cardiovascular disease (ischaemic heart disease, chronic heart failure, peripheral vascular disease or cerebral vascular disease)

  • structural renal tract disease, recurrent 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. [new 2014]

1.1.29 Do not use age, gender or ethnicity as risk markers to test people for CKD. In the absence of metabolic syndrome, diabetes or hypertension, do not use obesity alone as a risk marker to test people for CKD. [2008, amended 2014]

1.2 Classification of chronic kidney disease

1.2.1 Classify CKD using a combination of GFR and ACR categories (as described in table 1). Be aware that:

  • increased ACR is associated with increased risk of adverse outcomes

  • decreased GFR is associated with increased risk of adverse outcomes

  • increased ACR and decreased GFR in combination multiply the risk of adverse outcomes. [new 2014]

    For information about implementing this recommendation, see implementation: getting started.

Table 1 Classification of chronic kidney disease using GFR and ACR categories

Table 1 Classification of chronic kidney disease using GFR and ACR categories

1.2.2 Do not determine management of CKD solely by age. [new 2014]

Investigating the cause of CKD and determining the risk of adverse outcomes

1.2.3 Agree a plan to establish the cause of CKD during an informed discussion with the person with CKD, particularly if the cause may be treatable (for example, urinary tract obstruction, nephrotoxic drugs or glomerular disease). [new 2014]

1.2.4 Use the person's GFR and ACR categories (see table 1) to indicate their risk of adverse outcomes (for example, CKD progression, acute kidney injury, all-cause mortality and cardiovascular events) and discuss this with them. [new 2014]

Indications for renal ultrasound

1.2.5 Offer a renal ultrasound scan to all people with CKD who:

  • have accelerated progression of CKD (see recommendation 1.3.3)

  • 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. [2008, amended 2014]

1.2.6 Advise people with a family history of inherited kidney disease about the implications of an abnormal result before a renal ultrasound scan is arranged for them. [2008]

1.3 Frequency of monitoring

1.3.1 Agree the frequency of monitoring (eGFRcreatinine and ACR) with the person with, or at risk of, CKD; bear in mind that CKD is not progressive in many people. [new 2014]

1.3.2 Use table 2 to guide the frequency of GFR monitoring for people with, or at risk of, CKD, but tailor it to the person according to:

  • the underlying cause of CKD

  • past patterns of eGFR and ACR (but be aware that CKD progression is often non-linear)

  • comorbidities, especially heart failure

  • changes to their treatment (such as renin–angiotensin–aldosterone system [RAAS] antagonists, NSAIDs and diuretics)

  • intercurrent illness

  • whether they have chosen conservative management of CKD. [new 2014]

Table 2 Frequency of monitoring of GFR (number of times per year, by GFR and ACR category) for people with, or at risk of, CKD