The new NICE CKD Guideline
Dr Paul Stevens
Chair of the CKD Guideline Update Group
East Kent Hospitals, University NHS Foundation Trust
NICE published its first clinical practice guideline for the early identification and management of Chronic Kidney Disease (CKD) in 2008, some two years after the implementation of universal estimated glomerular filtration rate (eGFR) reporting and the introduction of CKD indicators in the primary care quality and outcomes framework. These combined initiatives have led to improved awareness and confidence in managing CKD in primary care, and a sustained reduction in late referral of patients with end stage renal disease (ESRD). However, some would contend that in certain groups of patients, particularly older adults with eGFR 45-59 mL/min/1.73m2 and no other marker of CKD, there has been a degree of 'disease-mongering', raising unnecessary anxiety amongst people whose overall risk of requiring renal replacement therapy (RRT) is low. The 2014 update for NICE CKD guidance attempts to address some of these concerns and also considers new evidence of particular relevance to primary care, including relating to identification, investigation, and classification of CKD, definition of CKD progression, the relationship between acute kidney injury (AKI) and CKD, and certain areas of pharmacotherapy.
- Identification and investigation of CKD
NICE recommends that clinical laboratories use a new equation of estimating GFR (the CKD-EPI equation) in place of the modification of diet in renal disease (MDRD) equation which is currently used. The new equation has less bias and improved accuracy in the population as a whole and has additional advantage of identifying those people at greater risk of adverse outcome from CKD. The consequence of switching to CKD-EPI would be a reduction in the overall prevalence of CKD diagnosed by a GFR of <60 mL/min/1.73m2, although paradoxically because the new equation has a superior performance to the MDRD equation in older Caucasians there would be a small increase in prevalence in people over the age of 75.
NICE suggests considering using an additional measure (cystatin C) to estimate GFR at initial diagnosis to confirm or rule out CKD in people with an eGFRcreatinine of 45-59 ml/min/1.73m2, sustained for at least ninety days and no proteinuria (albumin:creatinine ratio [ACR] less than 3 mg/mmol) or other marker of kidney disease. The rationale behind this is two-fold. Firstly, some people with a creatinine-based eGFR<60 may be re-classified to eGFR>60mL/min/1.73m2 by eGFRcystatinC and in the absence of any other marker of CKD should not be diagnosed as such, and secondly, those who are confirmed to have an eGFR<60 are at increased risk of subsequent adverse outcome.
NICE recommends regarding a sustained urinary albumin to creatinine ratio (ACR) of >3mg/mmol as clinically important proteinuria. This is on basis of large epidemiological studies (n>1 million subjects) that quite clearly demonstrate a continuum of increased risk of adverse outcome with increasing urinary ACR.
The original 2008 recommendation concerning which groups of people should be tested for CKD has been updated to include people who have had an episode of AKI. NICE also specifically recommends that anybody sustaining an episode of AKI should be monitored for at least 2.3 years after recovery from AKI for either progression CKD or new onset CKD. The rationale behind this is the strong evidence from longitudinal studies of both progression of existing CKD and new onset CKD following recovery from an episode of AKI.
2. Classification and monitoring of CKD
The classification of CKD has been updated to include urinary ACR categories in addition to GFR categories. The reasons behind this are that large population studies clearly demonstrate increased risk of adverse outcome (all cause mortality, cardiovascular mortality, ESRD, AKI) with decreasing eGFR and increasing ACR. GFR and ACR categories have also been used to suggest frequency of monitoring in people with CKD, although this is still largely an opinion-based area.
3. Definition of progression of CKD
NICE recommends defining accelerated progression of CKD as a sustained decrease in GFR of 25% or more and a change in GFR category with 12 months; or a sustained decrease in GFR of 15 ml/min/1.73 m2 per year. This is still an area of work in progress, in part because of the inherent intra-individual variability of creatinine-based eGFR and also because of the non-linearity of progression of CKD in certain subjects. This may be particularly apparent in people who have sustained an episode of AKI.
4. Specific pharmacotherapy in CKD
NICE recommends offering a low cost renin-angiotensin system antagonist to people with CKD and diabetes and an ACR of 3 mg/mmol or more (irrespective of hypertension or cardiovascular disease). However, combinations of renin-angiotensin system antagonists are actively discouraged.
The CKD guidance refers to the recommendations in Lipid modification (NICE clinical guideline 181) for the use of statins in CKD but essentially it is recommended that treatment with statin therapy should be offered to people with CKD for both primary prevention and secondary prevention of cardiovascular disease. The lipid guidance does not apply and age limitation to this recommendation.
NICE also recommends offering antiplatelet drugs to people with CKD for the secondary prevention of cardiovascular disease, but counsels awareness of the increased risk of bleeding.
In people with a confirmed eGFR of 30-50 ml/min/1.73m2 and non-valvular atrial fibrillation who have one or more of the following risk factors:
- Prior stroke or transient ischaemic attach.
- Age 75 years or older.
- Diabetes mellitus.
- Symptomatic heart failure NICE suggests considering Apixaban to Warfarin because of the reduced risk of bleeding.
Finally, NICE considers oral sodium bicarbonate supplementation for people with both an GFR less than 30 ml/min/1.73m2 (GFR category G4 or G5) and a serum bicarbonate concentration of less than 20 mmol/litre.