Dr Alan Begg reviews the guidelines on chronic kidney disease from NICE and SIGN, and highlights key clinical points for management in primary care

In June 2008, the Scottish Intercollegiate Guidelines Network (SIGN) published its guideline on Diagnosis and management of chronic kidney disease.1 This was followed in September 2008 by publication of the National Institute for Health and Care Excellence (NICE) guideline on Early identification and management of chronic kidney disease in adults in primary and secondary care.2 There are noticeable differences between the guidelines that could potentially result in variation in clinical care.

The SIGN guideline was developed according to its standard procedure, with recommendations graded according to the level and weight of evidence. The National Collaborating Centre for Chronic Conditions worked with a group of healthcare professionals, as well as patients, carers, and technical staff, who reviewed the evidence and drafted their recommendations, to produce the NICE guideline.

This paper compares the two guidelines on chronic kidney disease (CKD) and highlights the key clinical points for primary care. Articles on the individual guidelines were included in the October 2008 (SIGN) and February 2009 (NICE) issues of Guidelines in Practice.

Classification of CKD

The NICE and SIGN guidelines agree that an estimate of glomerular filtration rate (eGFR) using a prediction equation should be used to stratify CKD into different stages. They have both adopted the recommendation of the UK Consensus Conference on the subdivision of Stage 3 into 3A and 3B to reflect the different levels of risk.1–3 The suffix p is used to indicate proteinuria but the two guidelines use different threshold values, which will lead to a variation in staging:

  • NICE—albumin:creatinine ratio (ACR) ?30 mg/mmol or protein:creatinine ratio (PCR) ?50 mg/mmol
  • SIGN— >1 g/day equivalent to PCR >100 mg/mmol.

The SIGN guideline recommends adding the suffix T to indicate a patient with a functioning renal transplant and that those individuals on dialysis should be classified as Stage 5D.1

Quantifying proteinuria

The NICE guideline advises measurement of ACR as the best means of detecting proteinuria, in preference to PCR, because the former has greater sensitivity.2 An ACR of ?30 mg/mmol can be considered clinically significant proteinuria.
If ACR is ?30 mg/mmol but <70 mg/mmol, levels should be confirmed by an early morning sample. In patients who also have diabetes, the ACR should be measured to determine if microalbuminuria is present (>2.5 mg/mmol in men and >3.5 mg/mmol in women).2

The SIGN guideline recommends the measurement of ACR to exclude diabetic nephropathy (Grade B) in patients with diabetes, and to detect and monitor diabetic nephropathy (Grade C). It also recommends the use of PCR to exclude CKD in groups of patients who do not have diabetes, but who are at high risk of proteinuria (Grade B). In patients with CKD, measurement of PCR may be used to predict the risk of progressive disease (Grade D).1

Dietary advice

The NICE guideline suggests that when dietary interventions are indicated, an appropriately trained professional should discuss the risks and benefits of dietary protein restriction. This should occur within the context of education, detailed dietary assessment, and supervision.2 Patients with progressive CKD should be offered dietary advice on potassium, phosphate, protein, calorie, and salt intake. The SIGN guideline does not recommend dietary protein restrictions (<0.8 g/kg/day) in patients with stage 1–3 CKD. However, salt intake should be reduced to <6 g per day in those patients with stage 1–4 CKD and hypertension, as part of a comprehensive strategy to lower blood pressure and reduce cardiovascular (CV) risk.1

Statin therapy to reduce cardiovascular risk

For the majority of patients with CKD the risk of death from CV-associated causes is much greater than the risk of end-stage renal disease.4 Although patients with CKD can be assumed to have end-stage organ damage, the NICE guideline differentiates between those patients with a previous CV event and those without evidence of cardiovascular disease (CVD), with statins used appropriately for each of the two different categories in line with other NICE guidance.5,6 However, the guideline acknowledges that using existing risk prediction models that were developed in people without CKD, such as Framingham, is not ideal.2 The use of statins for the primary prevention of CVD in patients with CKD will be better informed when the SHARP trial (Study of Heart and Renal Protection) is published in 2010. This study has recruited 9438 patients with CKD who have been randomised to a combination of simvastatin 20 mg and ezetimibe 10 mg compared with placebo.7

The SIGN guideline recommends statin therapy for all patients with stage 1–3 CKD, and a predicted 10-year CVD risk ?20%.1 The same risk threshold is also used by SIGN to recommend low-dose antiplatelet therapy in this group of patients. The NICE guideline states that antiplatelet drugs should be offered for the secondary prevention of CVD and that low-dose aspirin can be used, although clinicians need to be aware of the increased risk of minor bleeding in people with CKD who are given multiple antiplatelet drugs.2

ACE inhibitors and ARBs

The NICE guideline uses ACR or PCR equivalent values to indicate when an angiotensin-converting enzyme (ACE) inhibitor or angiotensin-II receptor blocker (ARB) should be offered to different patient types (see Table 1).2 The guideline from SIGN recommends (Grade A) an:

  • ACE inhibitor for all patients with CKD and type 1 diabetes with microalbuminuria
  • ACE inhibitor or ARB for all patients with CKD and type 2 diabetes with microalbuminuria
  • ACE inhibitor or ARB to reduce proteinuria in patients who have CKD and proteinuria without diabetes
  • ACE inhibitor or ARB in those with CKD and proteinuria (PCR >50 mg/mmol) to reduce the rate of progression of disease.

The SIGN guideline also recommends that a non-dihydropyridine calcium channel blocker should be considered in those with CKD and proteinuria who are intolerant of ACE inhibitors or ARBs (Grade A).1

Table 1: NICE parameters for treating patients who have CKD with an ACE inhibitor or ARB

Concomitant condition Gender ACR
(mg/mmol)
PCR equivalent
(mg/mmol)
Diabetes Male >2.5
Female >3.5
No diabetes but with hypertension Either ?30 ?50
No diabetes with or without hypertension or CVD Either ?70 ?100
CKD=chronic kidney disease; ACE=angiotensin-converting enzyme; ARB=angiotensin-II receptor
blocker; ACR=albumin:creatinine ratio; PCR=protein:creatinine ratio; CVD=cardiovascular disease

Practicalities of treatment

The guideline from NICE also includes practical comments on the accepted management of patients with CKD, which do not lend themselves to graded recommendations. These points need to be taken into account when prescribing ACE inhibitors or ARBs for a patient with CKD. They include:

  • serum potassium and eGFR should be measured before starting therapy, and these measurements should be repeated between 1 and 2 weeks after starting treatment and after any increase in dose
  • drug therapy should not be initiated if serum potassium is >5 mmol/l and any pre-existing hyperkalaemia should be investigated
  • drugs that increase hyperkalaemia can be used, but in these situations more frequent monitoring of serum potassium may be required
  • if the serum potassium concentration rises to >6 mmol/l, treatment with an ACE inhibitor or ARB should be stopped, along with any other hyperkalaemia-inducing drugs
  • if, after the introduction of an ACE inhibitor or ARB, the eGFR decreases by up to 25% or the plasma creatinine increases by up to 30%, then the dose should remain the same and the eGFR measurement should be repeated after a period of 1–2 weeks
  • following on from introduction of an ACE inhibitor or ARB, if the eGFR is 25% or more, or the plasma creatinine rises by more than 30%, other causes of the deterioration in renal function should be investigated, such as volume depletion or concurrent drug treatment (non-steroid anti-inflammatory drugs are most likely to be implicated)
  • in cases where no cause for the deterioration is found, then the ACE inhibitor or ARB should be reduced to a previously tolerated dose or stopped, with alternative antihypertensive therapy used as required.

The SIGN guideline recommends checking potassium and renal function after initiating and changing dosage of ACE inhibitors or ARBs.

Blood pressure control

Lowering blood pressure reduces CV risk and progression of CKD and is a major target for intervention.1 The NICE guideline development group searched for, and appraised evidence on blood pressure control but did not set out to establish definitive safe ranges for blood pressure in CKD.2 The levels given within their recommendations are those that in their clinical experience will inform good practice in CKD. The NICE and SIGN recommendations on blood pressure control in patients with CKD are shown in Table 2.

Table 2: Recommendations from NICE and SIGN on blood pressure control

Guideline Patient type Blood pressure (mmHg)
NICE   Systolic Diastolic
CKD Below <140
Target range 120–139
<90
CKD and diabetes with ACR ?70 mg/mmol (PCR of 100 mg/mmol) Below <130
Target range 120–129
<80
SIGN CKD with proteinuria ?1 g/day (PCR of 100 mg/mmol) Target maximum 130  
CKD=chronic kidney disease; ACR=albumin:creatinine ratio; PCR=protein:creatinine ratio

Invisible haematuria

The NICE guideline gives clear advice on the subject of haematuria—it advises that reagent strips, rather than urine microscopy, should be used for detection. Patients should be evaluated further if there is a result of 1+ or more, but urine microscopy should not be used for confirmation. Some patients may have transient haematuria, and in these cases, two out of three positive reagent strip tests provide confirmation of persistent invisible haematuria. Regardless of whether it is associated with proteinuria or not, confirmation warrants further investigation using cystoscopy and renal ultrasound in the appropriate age groups to exclude urinary tract malignancy.2

If there is persistent invisible haematuria but no proteinuria, annual follow-up should take place, with repeat testing for haematuria, urine ACR, GFR, and measurement of blood pressure, for as long as the haematuria persists.2 The SIGN guideline recommends that persisting isolated microscopic haematuria should be evaluated initially for urinary tract infection and malignancy (Grade D). Table 3 highlights the difference in emphasis between the NICE and SIGN guidelines on the use of renal ultrasound.

Table 3: Use of renal ultrasound according to NICE and SIGN1,2

NICE SIGN
Offer to those with CKD if:
  • progressive CKD
  • visible or persistent invisible haematuria
  • symptoms of urinary tract obstruction
  • family history of polycystic kidney disease and age >20 years
  • stage 4 or 5 CKD present
  • prior to renal biopsy
Ultrasound is the modality of choice in the evaluation of patients with suspected CKD
Use to identify:
  • obstructive uropathy
  • renal size and symmetry
  • renal scarring
  • polycystic disease
CKD=chronic kidney disease

Referral

The NICE guideline suggests that patients with stage 4 or 5 CKD should normally be referred for specialist assessment. Both NICE and SIGN agree that those with a rapidly progressive decline in kidney function requires specialist referral.1,2

Implementing the guidance

Both guidelines have their merits in line with the standard approach of the publishing bodies. The SIGN guideline illustrates the difficulties of making evidence-based recommendations in the absence of evidence. The NICE guideline provides a significant amount of practical advice on how to manage a patient with CKD that will be of immense use to those healthcare professionals working in primary care. Tips for good practice can be found in Box 1.

Box 1: Good practice tips on measuring estimated glomerular filtration rate

NICE on eGFR measurement

  • Advise patients not to eat any meat in the 12-hour period prior to measurement
  • Samples should be processed in the laboratory within 12 hours of venepuncture
  • A new finding of an eGFR <60 ml/min/1.732—retest within 2 weeks to exclude acute kidney failure
  • Increased muscle mass will lead to underestimation of eGFR and vice versa
SIGN on eGFR measurement
  • Assess renal function at least annually in patients on antihypertensive or lipid-lowering therapy
  • Do not ‘stage’ on a sample collected after consumption of a meal containing cooked meats—take fasting confirmatory sample
eGFR=estimated glomerular filtration rate

  1. Scottish Intercollegiate Guidelines Network. Diagnosis and management of chronic kidney disease. SIGN 103. Edinburgh: SIGN, 2008. Available at: www.sign.ac.uk/guidelines/fulltext/103/index.html
  2. 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
  3. Archibald G, Bartlett W, Brown A et al. UK Consensus Conference on Early Chronic Kidney Disease—6 and 7 February 2007. Nephrol Dial Transplant 2007; 22 (9): 2455–2457.
  4. Hallan S, Dahl K, Oien C et al. Screening strategies for chronic kidney disease in the general population: follow-up of cross sectional health survey. BMJ 2006; 333 (7577): 1047.
  5. National Institute for Health and Care Excellence. Statins for the prevention of cardiovascular events. Technology Appraisal 94. London: NICE, 2006. Available at: www.nice.org.uk/Guidance/TA94
  6. National Institute for Health and Care Excellence. Lipid modification: cardiovascular risk assessment and the modification of blood lipids for the primary and secondary prevention of cardiovascular disease. Clinical Guideline 67. London: NICE, 2008. Available at: www.nice.org.uk/Guidance/CG67
  7. Baigent C, Landry M. Study of Heart and Renal Protection (SHARP). Kidney Int Suppl 2003; (84): S207–210.G