Chronic kidney disease

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Chronic kidney disease

• Dr John Stoves
• Consultant Nephrologist
• Bradford Renal Unit

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• Why? - new classification of renal impairment
• Why? easier to identify patients with renal
  impairment
• Why? - improve cardiovascular outcomes for the
  many, facilitate timely nephrological review for
  the few
• Why? - many do not have progressive renal
  impairment, those that do will benefit from a
  planned start to renal replacement therapy

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But

• Nothing is perfect!
• the eGFR formula
• managing elderly patients
• workload implications
• ethical implications

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Contents

• Renal NSF
• Renal QOF
• Classification of CKD
• GFR and serum creatinine
• Why the new approach to assessing renal function?
• 4-variable MDRD formula
• CKD and CVD
• Screening for CKD
• Referral of CKD patients to secondary care
• Guidance for CKD management
• Learning set in Bradford/Airedale (primary and
  secondary care)
• Challenges and queries

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NSF Part 1

• Published January 2004
• By 2014 the NHS will need to deliver these 5
  standards
• 1) Patient-centred service
• Informed decisions
• Agreed care plan

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NSF Part 1

• 2) Preparation and choice
• Multi-skilled team
• CKD (4/5) management
• 3) Elective dialysis access surgery
• 4) Dialysis
• 5) Transplantation

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NSF Part 2

• Published February 2005
• Quality requirements rather than standards
• 1) Prevention and early detection of CKD
• 2) Minimising the progression and consequences of
  CKD
• 3) Acute renal failure
• 4) End of life care

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NSF Part 2 (CKD elements)

• Integrated care pathways
• Early identification of CKD targeted screening
  in primary care
• Appropriate assessment of kidney function
  urinalysis, eGFR
• Appropriate referral for nephrological review

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Classification of CKD

• CKD1 eGFR gt 90 mL/min/1.73m2 and other evidence
  of renal disease
• CKD2 eGFR 60-89 mL/min/1.73m2 and other
  evidence of renal disease
• CKD3 eGFR 30-59 mL/min/1.73m2
• CKD4 eGFR 15-29 mL/min/1.73m2
• CKD5 eGFR lt15 mL/min/1.73m2
• 5 of adults have CKD stages 3 to 5
• ¼ of these are diabetic, ¾ are hypertensive
• Progression is not inevitable

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Glomerular filtration rate

• The volume of plasma from which a given substance
  is completely cleared by glomerular filtration
  per unit time
• Better correlation with symptoms of CKD than
  serum creatinine

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Hierarchy of renal function measurement

• Isotopic or other measurement of GFR
  time consuming, laborious and expensive
• Serum creatinine-based estimation of GFR (eGFR)
• Creatinine clearance (UV/P)
• Serum creatinine alone
• (? cystatin C)

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Creatinine and eGFR

• Creatinine analytical interferences,
  standardization, muscle mass, low sensitivity for
  CKD (e.g. half of stage 3 disease)
• Creatinine clearance timed urine collection,
  tubular secretion, high CV, overestimation of
  GFR
• Creatinine-based eGFR Cockcroft and Gault,
  MDRD-eGFR (no anthropometric data)

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Why the new approach to assessing renal function
(eGFR)?

• Limitations of serum creatinine
• eGFR is basis of CKD classification, endorsed by
  Renal NSF
• CKD is common and is associated with increased
  cardiovascular risk
• Easier to identify those patients who would
  benefit from nephrological review (crash
  landers)

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eGFR examples

• 30-yr old Caucasian male, creatinine 150
• eGFR
• 70-yr old Caucasian female, creatinine 150
• eGFR
• 30-yr old Caucasian male, creatinine 225
• eGFR

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eGFR examples

• 30-yr old Caucasian male, creatinine 150
• eGFR 51 (36-66) ml/min/1.73m2
• 70-yr old Caucasian female, creatinine 150
• eGFR
• 30-yr old Caucasian male, creatinine 225
• eGFR

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eGFR examples

• 30-yr old Caucasian male, creatinine 150
• eGFR 51 (36-66) ml/min/1.73m2
• 70-yr old Caucasian female, creatinine 150
• eGFR 32 (22-42) ml/min/1.73m2
• 30-yr old Caucasian male, creatinine 225
• eGFR

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eGFR examples

• 30-yr old Caucasian male, creatinine 150
• eGFR 51 (36-66) ml/min/1.73m2
• 70-yr old Caucasian female, creatinine 150
• eGFR 32 (22-42) ml/min/1.73m2
• 30-yr old Caucasian male, creatinine 225
• eGFR 32 (22-42) ml/min/1.73m2

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MDRD-eGFR (1)

• Age, gender, ethnicity, serum creatinine
• Automated laboratory reporting
• Validated in a CKD population
• Standard formula
• 186 x (serum creatinine/88.4)1.154 x
  (age-0.203) x 0.742 if female x 1.212 if
  Afro-Caribbean

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MDRD-eGFR (2)

• ID-MS standardization of creatinine measurements
  (myriad of lab assays)
• MDRD-eGFR less biased, more precise and accurate
  compared to other formulae
• Performs better at lower GFRs
• Use of GFR in identification of CKD/ monitoring
  of CKD/ prediction of RRT requirement
• Valid in patients at extremes of age and body
  habitus, oedematous states, amputees, pregnancy?

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Bias plot for MDRD-GFR vs 99mTc DTPA-GFR (both
patient groups)
Stoves, J. et al. Nephrol. Dial. Transplant. 2002
172036-2037
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CVD mortality in dialysis patients compared to
the general population
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Levey et al 2003
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Decreased GFR as a risk factor for CVD ARIC
Study
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CKD as risk factor for CVD other evidence

• Go et al 2004
• Prospective study of 1.1 million individuals in
  US
• Hazard ratio for CVD 1.4 (eGFR 45 59)/ 2.0
  (eGFR 30 44), 2.8 (eGFR 15 29)
• VALIANT
• CHARM

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Guidance

• Renal Association website
• http//www.renal.org/
• Department of Health
• http//www.dh.gov.uk/PolicyAndGuidance/HealthAndS
  ocialCareTopics/Renal/fs/en
• Royal College of General Practitioners
• Introducing eGFR. Promoting good
• CKD management
• PACE local guidance

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Who to screen for CKD?

• Hypertension
• Diabetes mellitus
• Congestive cardiac failure
• Ischaemic heart disease
• Peripheral vascular disease
• Cerebrovascular disease
• Multisystem disease
• Polycystic kidney disease
• Reflux nephropathy/ recurrent UTIs

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Who to screen for CKD?

• Chronic glomerulonephritis
• Bladder outflow obstruction
• Neurogenic bladder
• Urinary diversion surgery
• Renal stone disease
• Familial CKD (where evidence of increased
  incidence within individual families)
• Any other CKD
• Patients taking ACE inhibitor, angiotension
  receptor antagonist and/ or diuretic medication

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Screening for CKD in primary care and when to
refer to secondary care

• Disease codes (not all conditions have a code)
• CKD database
• Recall systems
• Thresholds (absolute values and rate of change)

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Starting point in Bradford/ Airedale

• All patients with established renal failure
• are to have timely and appropriate surgery
• for permanent vascular or peritoneal
• dialysis access

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How to achieve streamlining of the patient
pathway?

• Screening in general practice laboratory
  reporting of GFR
• Threshold for referral to pre-dialysis clinic
• Timely provision of patient information re choice
• Timely referral to vascular surgeons
• Timely imaging of arm vessels/ central veins
• Timely listing

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Stakeholders

• SHA
• Vascular surgical team
• Radiology team
• Nephrology team
• General practitioners/ primary care teams
• Other specialties
• Clinical biochemists
• Members of Pursuing Perfection teams
• Patients

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Progress to date

• SHA award to support the project
• Preliminary work (process mapping, run charts,
  Institute for Health Improvement) supported by
  members of the Pursuing Perfection team in
  Bradford
• Stakeholder meeting January 2005 (primary and
  secondary care representatives)

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Key learning points

• The pathway is extensive and starts in primary
  care
• There needs to be an improvement in screening and
  referral of patients with chronic kidney disease
• A multidisciplinary team approach is essential
• A supporting audit strategy is required
• Some quick wins are needed to help establish
  momentum

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Progress to date (secondary care)

• Development of proformas to speed up the referral
  process for vascular access and Doppler
  assessment of failing access
• Development of databases to record clinical
  activity

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Progress to date (primary)

• Stakeholder meeting April 2005
• Representatives from primary care, diabetes
  services, chemical pathology and PACE
• Learning set - Dr Mike Bosomworth, Dr John
  Connolly, Dr Helen Dewhirst, Kate Farrar, Dr
  Brian Karet, Dr Javed Rehman, Claire Seymour,
  Erica Warren

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Progress to date (primary)

• Identifying high risk patients (screening using
  eGFR), guidelines for referring patients with CKD
  to renal services
• 3 practice pilot from January 2006
• PACE team to facilitate guideline development

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Challenges ahead (1)

• Roll out
• QOF, UKCKD and PACE guidelines
• Meeting with primary care and diabetes teams
• The possibility of a bolus of secondary care
  referrals as CKD screening becomes established
  shared care, virtual clinics

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Challenges ahead (2)

• Elderly patients
• Validation of MDRD-GFR formula in other subgroups

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Changes to CKD management guidance in the future?

• Trend in eGFR as well as absolute values (built
  in to local guidance)
• CKD stages in the elderly need for a sliding
  scale of stage thresholds (e.g. CKD3 25 45)?
• Proteinuria as well as eGFR?

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Levey et al 2003
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PREVEND
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Albuminuria and CVD risk other evidence

• HOPE
• MA associated with adjusted relative risk of 1.83
  for major cardiovascular events, 3.23 for CCF
  hospital admissions
• LIFE
• Risk of CV death/MI/stroke increased with
  increasing UAE
• NHANES II, EPIC-Norfolk
• PREVEND-IT
• No significant benefit on CVD outcomes
  (fosinopril)

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CKD queries

• PACE 2006

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Active disease

• 40 year old man, feverishness and lower back pain
• Initial review creatinine 185 umol/l
• Recalled a fortnight later creatinine 650
  umol/l
• Urgent admission haematoproteinuria

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Active disease

• Biopsy - crescentic IgA nephropathy
• High dose steroid therapy
• Creatinine improved to 180 umol/l
• Repeat biopsy showed diffuse scarring
• Earlier intervention may have led to a better
  outcome
• Systemic symptoms
• Urinalysis

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Elderly patients to refer or not to refer?

• eGFR 30
• age 85
• congestive cardiac failure, unable to manage
  stairs
• no proteinuria

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Elderly patients to refer or not to refer?

• Age per se is not the key issue
• There is an age-related decline in renal function
  ( approx 1mL/ min/ year)

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Elderly patients to refer or not to refer?

• This patient is likely to have a cardiorenal
  syndrome
• Evidence of progression?
• if not, conservative management as per guidance
• if so, is there any prospect of reversibility (in
  this case probably not) or would the patient
  tolerate/ benefit from renal replacement therapy
  (in this case probably not)
• Palliative care pathway in evolution

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Ultrasound scan KUB?

• Often not necessary in patients with CKD
• Urinary tract symptoms
• Haematuria
• Refractory hypertension (Doppler)

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To continue with ACE inhibitor?

• Serum creatinine 150 to 165, K 5.9
• Likelihood of renal vascular disease?
• Other drugs?
• Losalt?
• Diet
• Diuretic

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Effect of antihypertensive drugs on systemic and
glomerular pressure
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Treat anaemia?

• Hb gt 11 g/dL
• Iron deficiency?
• oral vs iv replacement
• Other factors (B12, folate, drugs)
• NICE guidance

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Haemoglobin and eGFR NHANES III
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Haemoglobin and eGFR Canadian Multicentre
Longitudinal Cohort Study
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Treat hyperparathyroidism?

• Monitoring frequency as per guidance
• Keep within 2-3x upper limit of normal range
• Alfacalcidol (calcium, phosphate)

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PTH vs creatinine clearance Martinez et al 1997
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Dietitian

• Na
• K
• Protein 1g/kg/day
• Calories
• Phosphate
• Calcium
• Cholesterol