1. NICE CKD Guideline Update Karen Jenkins Consultant Nurse Chair Kent & Medway Renal Collaborative Kent Kidney Care Centre EKHUFT

2. Background NICE (2008) guidance on the early identification and management of chronic kidney disease (CKD) in adults in primary and secondary care has been updated using new available evidence (NICE,2014) Published July 2014 http://www.nice.org.uk/guidance/cg182 http://www.nice.org.uk/guidance/cg182

3. What’s new? New information focussing on: – Identification and investigation of people who have or are at risk of developing CKD – Classification of CKD and identification of people at risk of CKD complications and progression – Definition of CKD progression – Relationship between acute kidney injury (AKI) and CKD – Self-management of CKD – Pharmacotherapy

4. Investigations Equation used to calculate eGFR is due to change from MDRD (Modification of Diet in Renal Disease) to the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation CKD-EPI is expected to diagnose fewer people with CKD than MDRD If there is a need to confirm diagnosis in someone with eGFR creatinine 45–59 ml/min/1.73 m² for at least 90 days who has no proteinuria, consider using a one-off eGFRCystatin-C test

5. Consider factors affecting eGFR results Muscle mass & medications influence creatinine levels; – extremes of muscle mass (e.g. bodybuilders or people with muscle wasting disorders or amputations). – Reduced muscle mass leads to overestimation and increased muscle mass to underestimation of the GFR. People advised not to eat any meat in the 12 hours before blood test for eGFR. Exogenous creatinine from the diet enters the blood affecting the assay. Dehydration can lower eGFR Blood samples should be received and processed by the laboratory within 12 hours of venepuncture Trimethoprim interferes with creatinine secretion by the kidneys and can lower eGFR Therefore creatinine-based eGFR may not always be reliable as a basis for the diagnosis of CKD

6. eGFR Cystatin C Why another test? – Creatinine based formulas can under estimate eGFR especially with near normal/normal creatinine levels; leading to over estimation of people with stage 3CKD Test Cystatin C not influenced by muscle mass or medication - better marker of kidney function and prognosis. At present assay is not available in all laboratories. Although more costly than eGFR creatinine it is estimated that reduced medical costs of over diagnosis will make it cost effective. KEY MESSAGE Those with an eGFRcreatinine 45–59 ml/min/1.73 m², an eGFRcystatinC >60 ml/ min/1.73 m² and no other marker of kidney disease should not be diagnosed with CKD Cystatin C estimation can be used as a “one off” to confirm or refute a diagnosis of CKD

7. Who should be screened for Kidney Disease? People should be offered testing for eGFR and urinalysis if they have the following risk factors: – Cardiovascular disease (ischaemic heart disease, cerebral vascular disease, peripheral vascular disease, chronic heart failure) – Hypertension – Diabetes – Structural renal tract disease, recurrent renal calculi or prostatic hypertrophy – Family history of stage 5 CKD or hereditary kidney disease. – Nephrotoxic medications e.g. mesalazine NSAIDs (>12 mths), lithium, calcineurin inhibitors – Multisystem diseases with potential kidney involvement e.g. Lupus – Opportunistic detection of haematuria Note that although the incidence of CKD is increased in Asian and black race and age, these in isolation are not reasons for screening tests

8. Proteinuria Terms proteinuria and albuminuria are often used interchangeably 2014 NICE guideline has chosen to use the term proteinuria recommending albumin: creatinine ratio (ACR) as the best means of measuring this Urine dipsticks can’t reliably detect an ACR less < 30mg/mmols Term microalbuminuria used to describe range 3- 70mg/mmol now obsolete Upper limit of the normal range for ACR was different in males and females now the same >3mg/mmol.

9. Proteinuria Fresh morning sample recommended (misleading ↑ACR exercise/active) If ACR>3mg/mmol on non morning sample repeat using am sample to confirm, if >70mg/mmol don’t repeat A confirmed ACR of >3 mg/mmol should be regarded as clinically significant proteinuria and trigger regular monitoring Categories of ACR:

10. CKD classification Slight change from the 2008 NICE classification Stages 1-5 of CKD are now described as categories G1-5(G, defined by eGFR) which are each subdivided into A1-3 (A, defined by ACR) Using categories of increasing proteinuria is intended to reflect the increase in risk associated with increasing proteinuria

11. CKD classification eGFR & Albuminuria GFR ml/min/1.73m² AlbuminuriaCategoriesmg/mmol A 1A 2A 3 G1 ≥ 90No CKDG1 A2G1 A3 G2 60-89No CKDG2 A2G2 A3 G3a 45-59G3a A1G3b A2G3a A3 G3b A2 G3b 30-44G3b A1G2b A2 G4 15-29G4 A1G4 A2G4 A3 G5 <15G5 A1G5 A2G5 A3 Lower eGFR higher ACR = increased CV risk

12. Risk & Progression Progression defined as: sustained decrease in eGFR of ≥25% in a year or a decrease in eGFR 15 ml/min/1.73m² Minimum of 3 eGFR estimations over a period of <90 days unchanged Finding a new ↓ eGFR repeat within 2 weeks to exclude causes of acute deterioration in kidney function (e.g. AKI) or staring a renin-angiotensin system antagonist therapy (RAAS anti- hypertensive).

13. Risk & Progression Risk factors – Cardiovascular disease – Proteinuria – Hypertension – AKI – Diabetes – Smoking – African Caribbean, Asian origin – Long term use of NSAIDs – Untreated urinary outflow obstruction

14. Monitoring Agreed with person & dependent on: – Underlying cause – Past patterns of eGFR and ACR – Comorbidities – Changes in treatment (RAAS, NSAIDs, diuretics) – Intercurrent illness – Whether they chose to have renal replacement therapy or be treated conservatively

15. Table Frequency of monitoring GFR Category GFR mL/min GFR Description Frequency of monitoring eGFR (times per year) A1A2A3 G1≥90Normal or high≤ 11≥1 G260-89Mildly decreased≤ 11≥1 G3a45-59Mildly to Moderately decreased112 G3b30-44Moderately to severely decreased≤ 22≥2 G415-29Severely decreased223 G5<15Kidney failure4≥ 4 ACR Categories: A1 (normal to mildly increased) 30 mg/mmol

16. Pharmacotherapy It is recommended drugs acting on Renin-Angiotensin- Aldosterone Sytstem (RAAS) be offered to people with: – CKD, diabetes and ACR ≥3 mg/mmol (A2/A3) – CKD, hypertension and ACR ≥30 mg/mmol (A3 – CKD and ACR ≥70 mg/mmol (irrespective of hypertension or cardiovascular disease) – Not used if renal artery stenosis A combination of RAAS antagonists (ACEI, ARBs) should not be offered to CKD patients Those with CKD, hypertension and ACR <3 mg/mmol without Diabetes follow BHS guidelines

17. Pharmacotherapy Sodium Bicarbonate – Consider oral supplementation to manage metabolic acidosis if eGFR is 30 ml/min/1.73 m² and serum bicarbonate concentrate is <20 mmol/L. Vitamin D – Do not routinely offer to treat CKD mineral bone disorder. Anti-platelet therapy – Offer to prevent secondary cardiovascular disease. Apixaban can be considered in preference to warfarin in people with a confirmed eGFR of 30–50 ml/min/1.73 m² with non-valvular atrial fibrillation and one or more of these risk factors: Prior stroke or transient ischaemic attack ≥75 years Hypertension Diabetes Symptomatic heart failure

18. Dietary Advice Advice should be offered appropriate to the severity of CKD about – potassium – phosphate – calorie and salt intake, Low-protein diets with a protein intake of <0.6–0.8 g/kg/day should not be offered to people with CKD

19. Managing people with CKD Receive up to date information Reduce cardiovascular risk: lifestyle changes Take active role in management Diabetes: good blood sugar & BP management reduces progression Access to blood results: Renal patient view

20. Referral to Kidney Doctors eGFR < 30ml/min with or without Diabetes ACR 70 mg/mmol or more, unless known to be caused by diabetes and already appropriately treated Sustained ↓ GFR of 25% or more and a change in GFR category or sustained ↓ GFR of 15 ml/min/1.73 m² or more ↓ eGFR of >25% after starting ACEi or ARB hypertension that remains poorly controlled despite the use of at least 4 antihypertensive drugs at therapeutic doses Known or suspected rare or genetic causes of CKD Suspected renal artery stenosis.

21. Summary The equation used to calculate eGFR due to change from the MDRD equation to the CKD-EPI creatinine equation There is a need to confirm CKD in someone with an eGFR creatinine 45–59 ml/min/1.73 m² for at least 90 days and no proteinuria One-off eGFRCystatin-C test can be used to confirm the diagnosis CKD will now be classified using a combination of eGFR and ACR categories The health of people with risk factors for CKD progression, such as cardiovascular disease, hypertension and smoking, should be optimised ACR and eGFR testing should be offered to at-risk patients, such as those with diabetes and a family history of CKD stage 5 Emphasis on relationship between proteinuria, risk of progression of CKD and cardiovascular events Informing patients about their diagnosis, involving them in decision- making and promote self management