Chronic kidney disease (CKD) (Southampton pathway)

Background information Patient information Key messages for this pathway Definitions and abbreviations used in this pathway Classification of CKD Diagnosis of CKD Summary of referral criteria Screening for CKD in high risk groups Symptoms and signs suggestive of CKD Incidental finding Urinalysis and egfr Urinalysis result egfr result Assessment of isolated AMH Assessment of proteinuria with AMH Assessment of isolated proteinuria THRESHOLD for referral of patients with egfr <30ml/min Stage 4/5 CKD THRESHOLD for referral of patients with egfr 30-59ml/min Stage 3 CKD THRESHOLD for referral of patients with egfr 60ml/min Stage 1/2 CKD THRESHOLD for referral THRESHOLD for referral THRESHOLD for referral Are criteria for referral met? Consider Choose & Book Advice and Guidance Yes No Refer to Nephrology R Discharged to primary care Consider Choose & Book Advice and Guidance Go to CKD management in the community Go to CKD management in the community Refer to nephrology R Management by nephrology Discharged to primary care Go to CKD management in the community Page 1 of 13

1 Background information Since the introduction of egfr reporting in 2006 as part of the National Service Framework for Renal Services, an increasing number of patients with chronic kidney disease (CKD) have been identified. It is estimated that mild to moderate CKD (egfr >30ml/ min/1.73m²) has a prevalence of approximately 10% in the general population. Whilst the majority of patients with CKD have stable or slowly progressive disease, never reaching dialysis dependence, all have a significantly increased risk of cardiovascular (CV) disease, with a mortality rate approaching 40 times that of the general population. It is now well established that treatment of CKD from an early stage not only stabilises renal function but can also significantly reduce CV risk. In September 2008, NICE published guidelines for the management of CKD in primary care aimed at: earlier identification of CKD reducing the risk of progression to established renal failure reducing the risk of CV disease In light of these guidelines, this document provides local recommendations for the diagnosis, investigation and management of all stages of CKD in adults. The focus of these guidelines is to inform the assessment, investigation and management issues for all stages of CKD in adults, with particular emphasis on when and whom to refer for a specialist opinion. They are specific to CKD and do not cover acute kidney injury (AKI, previously known as acute renal failure), patients on dialysis or renal transplant patients. As with most guidelines, one size does not fit all and there may be circumstances where referral may seem inappropriate or unnecessary. For example, in patients with multiple co-morbidities, the primary care physician should make a judgement on how nephrological advice would impact upon the future of that individual. Similarly, while age should not be used to determine appropriateness of referral, any renal abnormality in a young adult warrants more concern than a similar abnormality in an elderly individual, bearing in mind that loss of renal function is expected with age. The renal service would be very happy to discuss any cases that are not clear-cut or that do not fall within the referral criteria. References: http://www.sign.ac.uk/guidelines/fulltext/103/index.html http://www.renal.org/whatwedo/informationresources/ckdeguide.aspx Department of Health (DH). National service framework for renal services. Part two: chronic kidney disease, acute renal failure and end of life care. London: DH; 2005. Renal Association (RA). Chronic kidney disease in adults: UK guidelines for identification, management and referral. London: RA; 2005. National Institute for Health and Clinical Evidence (NICE). Early identification and management of chronic kidney disease in adults in primary and secondary care. Clinical guideline 73. London: NICE; 2008. Kidney Disease Outcome Quality Initiative. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 2002; 39 Suppl 1: S1-S246. 2 Patient information Patient information on CKD can be found at http://www.kidney.org.uk/medical-info/ 3 Key messages for this pathway This pathway has been locally developed for South West Hampshire, taking 2008 NICE guidelines and current Renal Association guidelines into account. Key messages for this pathway: PCR should be measured for CKD rather than ACR, which is more expensive and does not add extra information ACR remains essential for screening and assessment of microalbuminuria in diabetic renal disease Contributors to this pathway: Dr Kirsty Armstrong, SUHT Page 2 of 13

Dr Patrick Terry, NHSSC Dr Tim Thurston, NHSH 4 Classification of CKD CKD is classified into 5 stages of severity based on the egfr and the presence or absence of other markers of kidney damage. It is diagnosed when there is: egfr 60ml/min/1.73m 2 for > 3 months with structural and / or functional abnormalities of the kidneys egfr < 60ml/min/1.73m 2 for > 3 months with or without structural and / or functional abnormalities of the kidneys Stage 1 egfr 90ml/min/1.73m 2 normal or increased GFR with other evidence of kidney damage* prevalence 3.3% Stage 2 egfr 60-89ml/min/1.73m 2 slightly decreased GFR with other evidence of kidney damage* prevalence 3% Stage 3 egfr 45-59ml/min/1.73m 2 (Stage 3A) egfr 30-44ml/min/1.73m 2 (Stage 3B) moderately decreased GFR prevalence 4.3% Stage 4 egfr 15-29ml/min/1.73m 2 severe decrease in GFR prevalence 0.2% Stage 5 egfr <15ml/min/1.73m 2 established (end-stage) renal failure prevalence 0.2% *Other evidence of kidney damage may be one or more of the following: persistent microalbuminuria in diabetics persistent proteinuria; PCR 50mg/mmol (or ACR 30mg/mmol) persistent asymptomatic microscopic haematuria (AMH) and urological causes excluded (if > 50 years) see Asymptomatic microscopic haematuria pathway structural abnormalities of the renal tract eg polycystic kidneys, reflux nephropathy with scarring, single kidney biopsy-proven chronic glomerulonephritis Points to note: patients with egfr 60ml/min/1.73m 2 without other evidence of kidney damage do NOT have CKD and should not be subjected to further investigation patients with egfr 60ml/min/1.73m 2 and a normal urine dip do NOT need an ultrasound scan UNLESS there is a family history of renal disease (e.g. ADPKD), or a history of reflux nephropathy patients > 70 with Stage 3A CKD (egfr 45-59ml/min/1.73m²), stable renal function and no other evidence of kidney damage are unlikely to develop CKD-related complications Page 3 of 13

patients with Stage 3B CKD (egfr 30-44ml/min/1.73m²) are at far higher risk of CV disease and end-stage kidney disease than those with Stage 3A disease and should therefore be regarded as an important target group, particularly if there are risk factors for progression eg hypertension, diabetes, significant proteinuria or inherited kidney disease 5 Definitions and abbreviations used in this pathway Abbreviations ACEI: angiotensin-converting enzyme inhibitor ACR: albumin creatinine ratio ADPKD: autosomal dominant polycystic kidney disease AKI: acute kidney injury (previously acute renal failure) AMH: asymptomatic microscopic haematuria ARB: angiotensin-ii receptor blocker BP: blood pressure CKD: chronic kidney disease CV: cardiovascular egfr: estimated glomerular filtration rate NSAID: non-steroidal anti-inflammatory drug PCR: protein creatinine ratio PTH: parathyroid hormone RRT: renal replacement therapy (dialysis or transplant) SLE: systemic lupus erythematosis USS: ultrasound scan Definitions microalbuminuria: ACR > 2.5mg/mmol in men or > 3.5mg/mmol in women with diabetes nephrotic range proteinuria: PCR > 300mg/mmol (or ACR > 250mg/mmol) nephrotic syndrome: PCR>300mg/mmol, albumin<30g/l and oedema persistent AMH: 1+ blood on 2 out of 3 urine dip tests persistent proteinuria: 1+ protein on 2 out of 3 urine dip tests progressive CKD: sustained and progressive decline in egfr of > 10% from baseline over 6 months or less referral criteria for isolated proteinuria: PCR > 100mg/mmol (or ACR > 70mg/mmol) (unless known to be due to diabetes and already appropriately treated) refractory hypertension: Blood pressure > 150/90 despite the use of 4 anti-hypertensive agents at therapeutic doses significant proteinuria: PCR>50mg/mmol (or ACR>30mg/mmol) 6 Summary of referral criteria Summary of referral criteria and information required with referral can be found in this document CKD referral summary 7 Diagnosis of CKD Chronic kidney disease (CKD) is usually picked up in the following situations: during screening of patients deemed at high risk of developing CKD during screening of patients in whom there is a clinical suspicion of CKD as an incidental finding on a routine blood test, urine test or imaging test Page 4 of 13

The two common methods for detecting CKD are: 1. Estimated glomerular filtration rate (egfr) 2. Urinalysis 8 Screening for CKD in high risk groups Screen for occult CKD (egfr and urinalysis) at least annually in all adult patients with: conditions associated with a high risk of development of CKD, e.g. hypertension, diabetes mellitus, CV disease and heart failure conditions requiring long-term treatment with recognised nephrotoxins, e.g. ACE inhibitors (ACEIs) and angiotensin-ii receptor blockers (ARBs), non-steroidal anti-inflammatory drugs (NSAIDS), lithium, mesalazine and calcineurin inhibitors such as cyclosporin or tacrolimus multisystem diseases with potential kidney involvement, e.g. SLE, vasculitis, myeloma and rheumatoid arthritis family history of hereditary renal disease, e.g. autosomal dominant polycystic kidney disease (ADPKD) or Stage 5 CKD urological conditions including neurogenic bladder (e.g. spina bifida), surgical urinary diversion, renal stone disease, benign prostatic hypertrophy or lower urinary tract symptoms including recurrent UTIs history of nephritis in childhood 9 Symptoms and signs suggestive of CKD Patients presenting with any of the following symptoms and/or signs should have an egfr and urinalysis as part of their preliminary investigations: non-specific symptoms including anorexia, nausea, vomiting, lethargy, shortness of breath, weight loss, itching signs of fluid overload including unexplained weight gain, peripheral oedema, pleural effusions, hypertension 10 Incidental finding Occult CKD may be detected as an incidental finding on a routine blood test, urine dipstick or renal imaging such as an ultrasound. Abnormalities should prompt further investigation 11 Urinalysis and egfr The two common methods for detecting CKD are: 1. Urinalysis 2. egfr (estimated glomerular filtration rate) Urinalysis Urinalysis should be performed alongside measurement of creatinine and egfr in anyone being evaluated for CKD. A positive urinalysis, defined as: asymptomatic microscopic haematuria (AMH) ( 1+ on urine dipstick), proteinuria with AMH ( 1+ on urine dipstick) or isolated proteinuria which may be an indicator of CKD and should prompt further investigation egfr The egfr is now the routine test of renal function and is reported alongside creatinine. It is much better at identifying early renal disease compared to serum creatinine alone (up to 50% of renal function can be lost before the creatinine exceeds the reference range, particularly in the elderly). The egfr is estimated from the serum creatinine, gender and age. It should be multiplied by a correction factor of 1.2 for African- Caribbean patients. In broad terms, the egfr equates to the percentage of normal kidney function that someone has. Page 5 of 13

The egfr is not validated in the following patient groups, in whom results should be interpreted with caution. patients with AKI patients < 18 years of age during pregnancy patients with extremes of muscle mass e.g. malnutrition or muscle wasting disorders, amputees, body builders oedematous states e.g. congestive cardiac failure, chronic liver disease certain ethnic groups e.g. Asians and Chinese NB: allow for biological and analytical variability of serum creatinine (± 5%) when interpreting changes in the egfr over time. 12 Urinalysis result A negative urinalysis is defined as: absence or trace of blood absence of proteinuria Note: absence of proteinuria on a dipstick does NOT exclude microalbuminuria, and an ACR should be requested in all patients with diabetes, even when the urine dip is negative for protein A positive urinalysis may be any of the following and should prompt further investigations: 1. Isolated asymptomatic microscopic haematuria (AMH) ( 1+) 2. Proteinuria ( 1+) with AMH ( 1+) 3. Isolated proteinuria ( 1+) egfr should be measured in anyone being evaluated for Chronic Kidney Disease, regardless of the urinalysis result, to determine whether nephrology referral is indicated. See egfr result box. 13 egfr result egfr should be measured in anyone being evaluated for CKD even if the urinalysis is negative. CKD is classified into 5 stages of severity, based on the egfr and the presence or absence of other markers of kidney damage (refer to Classification of CKD box above). Points to note: patients with egfr 60mls/min/1.73m 2 without other evidence of kidney damage do NOT have CKD and should not be subjected to further investigation patients with egfr 60mls/min/1.73m 2 and a normal urine dip do NOT need an ultrasound scan UNLESS there is a family history of renal disease (e.g. ADPKD), or a history of reflux nephropathy patients > 70 years with Stage 3A CKD (egfr 45-59mls/min/1.73m²), stable renal function and no other evidence of kidney damage are unlikely to develop CKD-related complications patients with Stage 3B CKD (egfr 30-44mls/min/1.73m²) are at far higher risk of CV disease and end-stage kidney disease than those with Stage 3A disease and should therefore be regarded as an important target group, particularly if there are risk factors for progression eg hypertension, diabetes, significant proteinuria or inherited kidney disease 14 THRESHOLD for referral of patients with egfr 30-59ml/min Stage 3 CKD Refer to nephrology if: progressive CKD (see definition of progression below) refractory hypertension with Stage 3B CKD (egfr <45ml/min/1.73m 2) Page 6 of 13

suspected renal artery stenosis ie acute deterioration in kidney function after starting an ACEI or ARB (defined as a rise in serum creatinine 30% or a fall in egfr 25% within 2 weeks of ACEI or ARB introduction / dose increase (see Indications for ACEIs and ARBs in CKD management in the community) known or suspected genetic cause of renal disease eg ADPKD haemoglobin < 110g/L and non-renal causes excluded ( particularly if egfr <45ml/min/1.73m 2 ) (see Management of suspected renal anaemia in CKD management in the community) severe hyperkalaemia (K + > 6.0mmol/L) and unresponsive to changes in therapy(see Management of hyperkalaemia in CKD management in the community) NB: If K + > 7.0mmol/L, patient requires urgent referral to AMU for assessment Definition of progression The definition of progressive CKD is highly contentious. South West Hampshire Trusts have elected to follow the criteria for progression recommended by the Wessex Renal and Transplant Unit at Portsmouth, i.e. a sustained and progressive decline in egfr of > 10% from baseline over a 6 month period. To assess for progression in a patient with an abnormal egfr: 1. Review previous creatinine/egfr levels over as long a time as possible to assess trend 2. Obtain a minimum of 3 egfr readings over a period of 3-6 months Points to note: take into consideration risk factors for progression, e.g. significant proteinuria (PCR > 50mg/mmol), inherited kidney disease, diabetes or poorly controlled hypertension consider whether progression, if it should it continue at the same rate, would result in the patient reaching dialysis dependence in their lifetime in patients in whom you suspect an abnormal egfr may be due to AKI, rather than CKD, repeat egfr within 2 weeks or less depending on clinical scenario The following information should accompany the referral letter: full medical history including relevant renal history current (and recently changed) medications examination including blood pressures (previous and current), oedema etc urinalysis results including PCR (or ACR) (if relevant) a list of the dates and results of previous measurements of serum creatinine / egfr (particularly if not undertaken in Southampton lab) recent biochemical and haematological profile to include (if relevant) calcium, phosphate, bicarbonate, albumin, glucose, lipid profile, haemoglobin and haematinics results of a recent USS (within 6 months) if relevant. 15 Assessment of isolated AMH Isolated asymptomatic microscopic haematuria (AMH) ( 1+): exclude menstruation and UTI (by dipstick) repeat urinalysis if persistent AMH ( 2 out of 3 positive results) see THRESHOLD for referral 16 Assessment of proteinuria with AMH Proteinuria ( 1+) with asymptomatic microscopic haematuria (AMH) ( 1+): exclude menstruation and UTI (by dipstick) repeat urinalysis if persistent proteinuria ( 2 out of 3 positive results), send spot urine for PCR (or ACR) and see THRESHOLD for referral Page 7 of 13

Points to note: PCR (or ACR) should be measured preferably on an early morning mid-stream urine sample PCR is the better (and cheaper) test for monitoring patients with proteinuria as well as detecting proteinuria in non-diabetic patients multiplying the PCR by 10 approximates to the amount of protein per day e.g. PCR 100mg/mmol=proteinuria of 1g/24hr) ACR is the test of choice in patients with diabetes and should be requested even when the urine tests negative for protein (a negative dipstick for protein does not exclude microalbuminuria) for a diagnosis of microalbuminuria 2 abnormal results from 3 specimens are required 17 Assessment of isolated proteinuria Isolated proteinuria( 1+): exclude UTI by dipstick repeat urinalysis if persistent proteinuria ( 2 out of 3 positive results), send spot urine for PCR (or ACR) and see THRESHOLD for referral Points to note: PCR (or ACR) should be measured preferably on an early morning mid-stream urine sample PCR is the better (and cheaper) test for monitoring patients with proteinuria as well as detecting proteinuria in non-diabetic patients multiplying the PCR by 10 approximates to the amount of protein per day e.g. PCR 100mg/mmol=proteinuria of 1g/24hr) ACR is the test of choice in patients with diabetes and should be requested even when the urine tests negative for protein (a negative dip for protein does not exclude microalbuminuria) for a diagnosis of microalbuminuria 2 abnormal results from 3 specimens are required 18 THRESHOLD for referral of patients with egfr <30ml/min Stage 4/5 CKD As a general rule, all patients with newly diagnosed Stage 4 (egfr 15-29 ml/min/1.73m 2 ) CKD or Stage 5 (egfr <15 ml/ min/1.73m 2 ) CKD should be referred or at least formally discussed with a nephrologist. This is to identify patients who may require renal replacement therapy (RRT) in the future and to ensure that an agreed and understood management plan is in place that can be activated as and when necessary. The only exceptions to this rule would be: patients in whom you deem further investigations / dialysis therapy to be inappropriate because of advanced age and / or significant comorbidities patients in whom severe renal impairment is part of another terminal illness patients who have specifically declined any further investigations or treatment In such individuals specialist assessment is unlikely to influence further management, and ongoing care in the community may be more appropriate (CKD management in the community pathway). In patients being referred the following information should accompany the referral letter: full medical history including relevant renal history current (and recently changed) medications examination including blood pressures (previous and current), oedema etc urinalysis results including PCR (or ACR) (if relevant) a list of the dates and results of previous measurements of serum creatinine / egfr (particularly if not undertaken in Southampton lab) recent biochemical and haematological profile to include calcium, phosphate, bicarbonate, albumin, glucose, lipid profile, haemoglobin and haematinics results of a recent USS (within 6 months) if available. Page 8 of 13

19 THRESHOLD for referral of patients with egfr 60ml/min Stage 1/2 CKD Refer to nephrology if: isolated persistant AMH and <50 years 50 years and urological causes excluded proteinuria (PCR 50mg/mmol (or ACR 30mg/mmol)) and persistent AMH significant proteinuria (PCR 100mg/mmol (or ACR 70mg/mmol)) suspected renal artery stenosis ie acute deterioration in kidney function after starting an ACEI or ARB (defined as a rise in serum creatinine 30% or a fall in egfr 25% within 2 weeks of ACEI or ARB introduction / dose increase (see Indications for ACEIs and ARBs in CKD management in the community) known or suspected genetic cause of renal disease eg ADPKD severe hyperkalaemia (K + > 6.0mmol/L) and unresponsive to changes in therapy(see Management of hyperkalaemia in CKD management in the community) Nb. If K + > 7.0mmol/L, patient requires urgent referral to AMU for assessment Points to note: in patients in whom you suspect an abnormal egfr may be due to AKI, rather than CKD, repeat egfr within 2 weeks or less depending on clinical scenario patients with egfr 60ml/min/1.73m 2 without other evidence of kidney damage do not have CKD and should not be subjected to further investigation The following information should accompany the referral letter: full medical history including relevant renal history current (and recently changed) medications examination including blood pressures (previous and current), oedema etc urinalysis results including ACR / PCR (if relevant) a list of the dates and results of previous measurements of serum creatinine / egfr (particularly if not undertaken in Southampton lab) recent biochemical and haematological profile (if relevant) results of a recent USS (within 6 months) only if there is a family history of renal disease, e.g. ADPKD or a history of reflux nephropathy NB: many patients with egfr 60ml/min/1.73m 2 can be managed via Choose and Book advice in the first instance 20 THRESHOLD for referral Refer to nephrology if isolated persistent AMH ( 2 out of 3 positive results) and < 50 years, or 50 years and urological causes have been excluded The following information should accompany the referral letter: full medical history including relevant renal history current (and recently changed) medications examination including blood pressures (previous and current), oedema etc urinalysis results a list of the dates and results of previous measurements of serum creatinine / egfr (particularly if not undertaken in Southampton lab) recent biochemical and haematological profile to include (if relevant) calcium, phosphate, bicarbonate, albumin, glucose, lipid profile, haemoglobin and haematinics results of a recent USS (within 6 months) if relevant. NB: patients with AMH may not need to be seen in clinic and will first be investigated via the "virtual" renal AMH pathway. Page 9 of 13

21 THRESHOLD for referral Refer to nephrology if: PCR 50mg/mmol (or ACR 30mg/mmol) and persistant AMH If PCR < 50mg/mmol (or ACR < 30mg/mmol), see Assessment of isolated AMH box. The following information should accompany the referral letter: full medical history including relevant renal history current (and recently changed) medications examination including blood pressures (previous and current), oedema etc urinalysis results including PCR (or ACR) a list of the dates and results of previous measurements of serum creatinine / egfr (particularly if not undertaken in Southampton lab) recent biochemical and haematological profile to include (if relevant) calcium, phosphate, bicarbonate, albumin, glucose, lipid profile, haemoglobin and haematinics results of a recent USS (within 6 months) if relevant. 22 THRESHOLD for referral Refer to nephrology if: PCR 100mg/mol (or ACR 70mg/mmol) The following information should accompany the referral letter: full medical history including relevant renal history current (and recently changed) medications examination including blood pressures (previous and current), oedema etc urinalysis results including PCR (or ACR) a list of the dates and results of previous measurements of serum creatinine / egfr (particularly if not undertaken in Southampton lab) recent biochemical and haematological profile to include (if relevant) calcium, phosphate, bicarbonate, albumin, glucose, lipid profile, haemoglobin and haematinics results of a recent USS (within 6 months) if relevant. 24 Consider Choose & Book Advice and Guidance Many patients with positive urinalysis and egfr >60ml/min/1.73m 2 can be managed via Choose and Book advice in the first instance. Local administrative info: Renal Medicine / Nephrology Inpatient and admin enquiries: Tel: 023 8079 6257 Outpatient queries: Tel: 023 8079 4188 Fax: 023 8079 5203 Choose and Book services available: General nephrology Page 10 of 13

Difficult hypertension Systemic vasculitis CKD Consultants: Dr Kirsty Armstrong, MBBS PhD MRCP Specialty: Nephrology Contact: 023 8079 4188 Dr Armstrong is fully trained in all areas of nephrology and has a special interest in cardiovascular risk factor modification in patients with chronic kidney disease or renal transplant Dr Mary Rogerson, FRCP Specialty: Renal and general medicine Contact: 023 8079 6257 Dr Rogerson is the lead clinician for renal medicine at SUHT. Southampton Area 24-May-2011 28 Consider Choose & Book Advice and Guidance Many patients with positive urinalysis and egfr >60ml/min/1.73m 2 can be managed via Choose and Book advice in the first instance. Local administrative info: Renal Medicine / Nephrology Inpatient and admin enquiries: Tel: 023 8079 6257 Outpatient queries: Tel: 023 8079 4188 Fax: 023 8079 5203 Choose and Book services available: General nephrology Difficult hypertension Systemic vasculitis CKD Consultants: Dr Kirsty Armstrong, MBBS PhD MRCP Specialty: Nephrology Contact: 023 8079 4188 Dr Armstrong is fully trained in all areas of nephrology and has a special interest in cardiovascular risk factor modification in patients with chronic kidney disease or renal transplant Dr Mary Rogerson, FRCP Specialty: Renal and general medicine Contact: 023 8079 6257 Dr Rogerson is the lead clinician for renal medicine at SUHT. Southampton Area 24-May-2011 29 Discharged to primary care Patients who are discharged back to primary care after a preliminary assessment should be managed according to the CKD management in the community pathway. Page 11 of 13

31 Management by nephrology Patients with progressive CKD and risk factors for progression, e.g. significant proteinuria, hypertension, diabetes or inherited kidney disease, are likely to remain under long term nephrological review. 32 Discharged to primary care Patients with stable CKD are likely to be discharged to primary care after a preliminary assessment or a period of monitoring. For advice on ongoing management, see CKD management in the community pathway. Page 12 of 13

Key Dates Published: 19-May-2011, by Southampton Area Valid until: 31-Jan-2013 Evidence summary for Chronic kidney disease (CKD) (Southampton pathway) This pathway has been developed according to the Map of Medicine editorial methodology (http://mapofmedicine.com/whatisthemap/editorialmethodology). The content of this pathway is based on high-quality guidelines [1,2,4-8,10] and critically appraised meta-analyses and systematic reviews [9]. Practice-based knowledge has been added by contributors with front-line clinical experience [3]. References This is a list of all the references that have passed critical appraisal for use in the care map Chronic kidney disease ID Reference 1 National Institute for Health and Clinical Evidence (NICE). Early identification and management of chronic kidney disease in adults in primary and secondary care. Clinical guideline 73. Clinical guideline 73. London: NICE; 2008. http://www.nice.org.uk/nicemedia/pdf/cg073niceguideline.pdf 2 Department of Health (DH). National service framework for renal services. Part two: chronic kidney disease, acute renal failure and end of life care. London: DH; 2005. http://www.dh.gov.uk/prod_consum_dh/groups/dh_digitalassets/@dh/@en/documents/digitalasset/ dh_4102680.pdf 3 Contributors representing the Royal College of Physicians. 2009. 4 Renal Association (RA). Chronic kidney disease in adults: UK guidelines for identification, management and referral. London: RA; 2005. http://www.renal.org/ckdguide/full/ukckdfull.pdf 5 Joint Speciality Committee on Renal Medicine of the Royal College of Physicians of London (RCP) and the Renal Association (RA). Identification, management and referral of adults with chronic kidney disease. Guidelines for General Physicians and General Practitioners 5. London: RCP; 2006. http://www.rcplondon.ac.uk/pubs/contents/57f485dc-4730-4b2d-be90-fa6937cc15af.pdf 6 Scottish Intercollegiate Guidelines Network (SIGN). Diagnosis and management of chronic kidney disease. A national clinical guideline. SIGN publication no. 103. Edinburgh: SIGN; 2008. http://www.sign.ac.uk/pdf/sign103.pdf 7 American College of Radiology (ACR). ACR Appropriateness Criteria. Renal Failure. Reston, VA: ACR; 2008. http://www.acr.org/secondarymainmenucategories/quality_safety/app_criteria/pdf/expertpanelonuro logicimaging/renalfailuredoc15.aspx 8 National Collaborating Centre for Chronic Conditions (NCC-CC). Chronic kidney disease: national clinical guideline for early identification and management in adults in primary and secondary care. London: Royal College of Physicians; 2008. http://www.guideline.gov/content.aspx?id=14330&search=end+stage+renal+disease 9 Schroth RJ, Hitchon CA, Uhanova J et al. Hepatitis B vaccination for patients with chronic renal failure. Cochrane Database Syst Rev 2004; CD003775. http://www.ncbi.nlm.nih.gov/pubmed/15266500 10 Bolton WK. Renal physicians association clinical practice guideline: appropriate patient preparation for renal replacement therapy: guideline number 3. J Am Soc Nephrol 2003; 14: 1406-1410. http://jasn.asnjournals.org/cgi/reprint/14/5/1406 Page 13 of 13