Detection, monitoring and referral of chronic kidney disease

1
Detection, monitoring and referral ofchronic
kidney disease

• Canadian Society of Nephrology
• Implementation Committee
• 2007

2
Key messages

• Who to test for chronic kidney disease
• What tests to order
• What to do with the results

3

• Identify patients in your practice at high risk
  for Chronic Kidney Disease
• Patients with hypertension
• Patients with diabetes mellitus
• Patients with atherosclerotic coronary,
• cerebral or peripheral vascular disease

• - Patients with heart failure
• Patients with unexplained anemia
• Patients with a family history of end stage
  renal disease
• First nations peoples

eGFR 30-60
eGFR gt60
eGFR lt30

• Consider reversible factors
• Medication - Volume depletion
• Intercurrent illness - Obstruction
• Repeat tests in 2 - 4 weeks

Individualized follow up and treatment CKD is
diagnosed in this group only if other renal
abnormalities are present (i.e. proteinuria,
hematuria, anatomical)
eGFR lt30
eGFR 30-60
Nephrology referral recommended
Follow eGFR at 3 months then serially Assess for
persistent significant proteinuria Implement risk
reduction
eGFR lt 30 or progressive decline in eGFR or
persistent significant proteinuria or inability
to attain treatment targets
Stable eGFR 30-60 and no significant proteinuria
4
What is Chronic Kidney Disease

• The presence of Kidney Damage or an eGFR lt 60
  ml/min/1.73m2 and
• Present for 3 months and
• Not treated with dialysis or transplant

The diagnosis of CKD is only present in patients
with eGFR 60ml/min if other abnormalities (i.e.
proteinuria, hematuria, anatomical) are also
present.

5
Who should be tested for CKD?

• CSN endorses a case finding approach
• to testing for CKD, which should be
• focused on high-risk groups.
• CSN does not endorse
• mass population screening for CKD
• with either serum creatinine based tests or with
  urine dipstick testing.

6
Who should be tested for CKD?

• Patients with diabetes mellitus
• Patients with hypertension
• Patients with heart failure
• Patients with atherosclerotic coronary,
  cerebrovascular or peripheral vascular disease
• Patients with unexplained anemia
• Patients with a family history of ESRD
• First nations peoples

7
Clinical case

• Joe is a 68 year old welder
• Past Medical History appendectomy age 15,
  hypertension x 4 years, elevated cholesterol x 1
  year, Type 2 DM x 1 year
• Smoker- 1 pack a day since age 21
• Etoh- a case of beer on the weekend
• Allergy- none known
• Family History- father MI age 50, mother HTN age
  48
• Medications- hydrochlorothiazide 25 mg po od,
  amlodipine 5mg po od, metformin 1000 mg po bid
• Weight 75 kg
• BP 149/84 mmHg

8

• Joe should be screened for CKD because he has
  several risk factors.
• Can you name them?

9
Which test would you choose to assess Joes
renal function?

• Serum creatinine
• 24 hour urine collection
• Nuclear medicine scan
• eGFR

10
Joes labs

• Na 138 mmol/L
• K 4.5 mmol/L
• Cl 103 mmol/L
• HCO3 23 mmol/L
• Glucose (R) 6.4 mmol/L
• Urea 10.1 mmol/L
• Creatinine 123 µmol/L

• CBC normal
• HgB A1C 5.6
• Ca 2.46 mmol/L
• PO4 1.10 mmol/L
• Albumin 38 g/L
• TC 7.60 mmol/L
• TG 2.06 mmol/L
• LDL(C) 5.43 mmol/L
• HDL(C) 1.23 mmol/L

11

• Joes serum creatinine is in the normal range,
  doesnt that mean his kidney function is also
  normal?

12
Assessing Joes renal function using eGFR

• 54 ml/min / 1.73m2
• (Stage 3 CKD)
• Clearly, Joes renal function is not normal
• despite a normal serum creatinine

http//www.kidney.org/professionals/kdoqi/gfr_cal
culator.cfm
13
Why use eGFR?

• It gives the health care practitioner
• a different sense as to a patients level of
• renal function that they may not have
• appreciated by using simple serum
• creatinine measurements.

14
Measuring renal functionwhats eGFR?
15
GFR

• Glomerular filtration rate (GFR)
• is the volume of fluid filtered from the
• renal glomerular capillaries into the
• Bowmans space per unit time.
• Normal for a 20 year old is 120ml/min

16
Methods to assess GFR

• Serum urea
• Serum creatinine
• Serum cystatin C
• Timed urine collections
• Creatinine clearance
• Inulin clearance
• Calculated GFR calculations
• based on serum creatinine
• many formulas including Cockcroft Gault and MDRD
• Nuclear medicine methods

17
The perfect marker

• Endogenous
• Freely filtered
• Not secreted or reabsorbed
• Inexpensive to measure

doesnt exist !
18
Problems with creatinine
Stevens L et al, NEJM 2006 3542473-2483
19
Problems with timed collections

• Cumbersome
• Prone to error
• No longer recommended in most situations

20
Problems with other methods

• Cystatin
• Inulin
• Nuclear medicine (iothalamate, EDTA etc)
• Complex
• Time-consuming
• Expensive
• Not practical for serial monitoring

21
Creatinine based approximations

• 1) Cockcroft-Gault equation
• CrCl (ml/min) (140-age) x actual weight (kg) x
  1.2 (if male)
  SCreat (µmol/L)
• 2) MDRD (Modification of Diet in Renal Disease)
• 6 variable or abbreviated version
• GFR(ml/min/1.73m2)170 (PCr)-0.999 x
  (Age)-0.176 x (0.762 if female) x (1.21 if
  African American) x (serum urea)-0.170 x
  (Albumin)0.318

Weight probably not available for lab to calculate
Lab has patient age and gender can do
abbreviated version
22
eGFR equation provisos

• eGFR calculations may be less reliable in
• individuals with near normal GFR (gt60
  ml/min/1.73m2)
• individuals with markedly abnormal body
  composition
• extreme obesity
• cachexia
• paralysis
• amputations
• Controversies exist as to the applicability of
  these formulae to various ethnic groups and the
  very elderly

23
Estimate of Glomerular Filtration Rate (eGFR)

• It is not recommended that clinicians rely on
  serum creatinine measurements alone when
  assessing kidney function.
• CSN calls for the reporting of kidney function as
  an estimate of glomerular function rate (eGFR)
  using equations and standardized creatinine
  measurements
• If neither eGFR reporting, nor calculators are
  available to a physician, tables based on serum
  creatinine and other variables are available to
  provide approximations of eGFR.

24
Developed by the BC Medical Services Commission,
Guidelines and Protocols group
25
Developed by the BC Medical Services Commission,
Guidelines and Protocols group
26
Is it just about GFR?

• Should also assess urine protein losses
• 24 hour urines are no longer recommended
• For same reasons as with GFR
• Urine dipsticks are affected by hydration status
• Quantify protein excretion with random urine for
• Urine albumin to creatinine ratio or
• Urine protein to creatinine ratio

27
What do those values mean?
Microalbuminuria (ie in diabetics)
Alarm values to refer
28
Who should be tested for CKD?

• Patients with diabetes mellitus
• Patients with hypertension
• Patients with heart failure
• Patients with atherosclerotic coronary,
  cerebrovascular or peripheral vascular disease
• Patients with unexplained anemia
• Patients with a family history of ESRD
• First nations peoples

29
What tests to order?

• Assess kidney function with
• eGFR
• As reported by lab
• As calculated using equations (and PDA!)
• As estimated by tables
• Quantification of protein with random urine
  samples
• Urine albumin to creatinine or
• Urine protein to creatinine

30
What to do with the results

• Now that I know Joes GFR is not normal what
  should I do?

31
What to do with the results

• Is one eGFR measurement enough?
• Consider reversible factors
• Assess risk of progressive renal disease
• who needs referral to Nephrology

32
Natural history of elevated creatinine levels
Marcotte and Godwin, Canadian Family Physician
2006521264-1265,e1-5

• 1434 patients in a family medicine practice
• 57 patients had an elevated initial serum Cr
  levels (gt130umol/L) and subsequent Cr levels
  within 4-5 years of follow-up

33
Is one eGFR measurement enough?

• Decisions about investigation, treatment or
  referral should not be made based on a single
  isolated test of kidney function
• In a primary care setting, many patients will
  show improvement or normalization of kidney
  function upon repeat testing.
• The diagnosis of CKD is based on serial
  measurements of kidney function and it is not
  possible to diagnose CKD on the basis of a single
  serum creatinine concentration transformed
  through equations.

34
For patients with a new finding of an eGFR
between 30-60ml/min/1.73m2 CSN recommends that
clinicians determine the stability of the
patients eGFR Repeat test within 2-4 weeks,
and then in 3-6 months
35
Consider reversible factors

• Intercurrent illness
• Volume depletion
• Medications
• NSAIDs, aminoglycosides, IV contrast dye
• Obstruction
• An abdominal ultrasound may be indicated at eGFRs
  lt60ml/min/1.73m2

36
Back to Joe

• You measure Joes eGFR in 2 weeks and then again
  in 3 months and it is unchanged
• You order an ultrasound and it is normal
• His urinalysis is normal

37
Conclusions about Joe

• Given the stability of these we can conclude that
  he has stable CKD.
• It is important to continue to serially follow
  his renal function.
• Serial measurement is a cornerstone of chronic
  kidney disease management.

38
CSN recommends that most patients with
non-progressive CKD can be managed by
non-nephrologists without referral. The
recognition that many patients with an eGFR
between 30 and 60 ml/min/1.73m2 do not have a
high risk of progressive kidney disease is
important.
39
CKD is common
40
Estimated prevalence of CKD in Canadians 20
years old

• Stage 1 CKD gt 90 ml/min 792,000
• Stage 2 CKD 60 89 ml/min 720,000
• Stage 3 CKD 30 59ml/min 1,032,000
• Stage 4 CKD 15 29 ml/min 48,000
• Stage 5 CKD lt 15 ml/min 24,000

Numbers are estimates based on an extrapolation
of US data
Stigant, C, et al. CMAJ 20031681553-60.
41
Other common conditions also managed by primary
care physicians
CKD is a common general health problem
42
Estimated prevalence of CKD in Canadians 20
years old

• Stage 1 CKD gt 90 ml/min 792,000
• Stage 2 CKD 60 89 ml/min 720,000
• Stage 3 CKD 30 59ml/min 1,032,000
• Stage 4 CKD 15 29 ml/min 48,000
• Stage 5 CKD lt 15 ml/min 24,000

ESRD is not common
Stigant, C, et al. CMAJ 20031681553-60.
43

• If many patients with CKD do not progress to end
  stage renal failure why then as a primary care
  physician should I even be looking for them using
  eGFR?

44
ESRD is not the problem

• Patients with CKD have high rates of
  cardiovascular disease
• and many patients die before progressing to end
  stage renal failure thus it is important to
  screen for CKD.

45
Go,A et al. NEJM 20043511291-1305
46
Quick Tips on Management of CKD

• Implement measures to slow rate of CKD
  progression
• Treat to target BP lt130/80 most will need 3 or
  more meds, diuretics and salt restriction are
  very useful
• Target urine ACR lt40 or PCR lt60. ACEI and/or ARB
  are first line therapies for albuminuria or
  proteinuria
• Control blood sugar in diabetes, target HbA1C lt7
• Implement measures to modify CV risk factors
• Follow guidelines as per groups at highest risk
  for CV disease
• Minimize further kidney injury
• If possible, avoid nephrotoxins such as NSAIDs,
  aminoglycosides, IV and intra-arterial contrast
  etc
• If contrast is necessary, consider prophylactic
  measures (if eGFR lt60)
• Remember to adjust dosages of renally excreted
  medications

47
Joe three years later

• You have continued to follow his eGFR and notice
  that it is now 42 ml/min/1.73m2
• All clinical targets (BP, HBA1C, cholesterol) are
  stable
• No intercurrent illnesses
• His CKD is no longer stable

Refer to Nephrology
48
Who should be referred to a Nephrologist?

• Patients with acute renal failure
• Patients with eGFR lt30ml/min/1.73m2
• Patients with progressive loss of renal function
• Persistent significant proteinuria (present on 2
  out of 3 samples)
• on dipstick or
• quantified PCR gt100mg/mmol or
• quantified ACR gt60 mg/mmol.
• Inability to achieve treatment targets or other
  difficulties in the management of the CKD patient

49
Violet

• 78 year old female
• longstanding patient of a colleagues followed
  for her hypertension and mild renal failure
• You are on call and see her because she is c/o
  nausea and lethargy

50
Using an eGFR approach
51
This womans renal disease may have been
underdiagnosed
Using eGFR may have given a more accurate measure
of her renal function
Serial measurement of eGFR is a powerful tool
for the clinician
Nephrology referral is recommended for this
patient
52
Linda

• 54 yo female comes for routine annual physical
• no problems identified
• normal physical examination
• family history of ESRD
• All her labs are normal serum creatinine is 90
  µmol/l
• Lab automatically reports an eGFR of 60
  ml/min/1.73m2
• What do you do with this eGFR value?
• Should she be referred to a Nephrologist?

53

• Identify patients in your practice at high risk
  for Chronic Kidney Disease
• Patients with hypertension
• Patients with diabetes mellitus
• Patients with atherosclerotic coronary,
• cerebral or peripheral vascular disease

• - Patients with heart failure
• Patients with unexplained anemia
• Patients with a family history of end stage
  renal disease
• First nations peoples

eGFR 30-60
eGFR gt60
eGFR lt30

• Consider reversible factors
• Medication - Volume depletion
• Intercurrent illness - Obstruction
• Repeat tests in 2 - 4 weeks

Individualized follow up and treatment CKD is
diagnosed in this group only if other renal
abnormalities are present (i.e. proteinuria,
hematuria, anatomical)
eGFR lt30
eGFR 30-60
Nephrology referral recommended
Follow eGFR at 3 months then serially Assess for
persistent significant proteinuria Implement risk
reduction
eGFR lt 30 or progressive decline in eGFR or
persistent significant proteinuria or inability
to attain treatment targets
Stable eGFR 30-60 and no significant proteinuria
54
Linda continued

• Evaluation of her urine shows no significant
  amount of proteinuria (ACR lt40mg/mmol) and no
  hematuria
• She is followed annually
• Two years later
• same eGFR
• blood pressure is 146/94
• persistent proteinuria with ACR gt 60mg/mmol
• Progressive CKD referral to Nephrology

55
Dave

• 81 year old man, new to your practice
• ASHD, stent placed 2 years ago
• PSA gt100 led to biopsy and diagnosis of prostate
  cancer, being treated with hormone therapy alone
• On atorvastatin 40 mg, aspirin 81 mg, ramipril 5
  mg
• Bp 144/82, nil else on exam
• Cr 167, eGFR 36, ACR 0.7

56
Dave

• Old labs from previous MD show Cr 150-180 umol/L
  over last 3 years
• What would you do?

57
Summary

• Who should be tested for CKD?
• Patients with diabetes mellitus
• Patients with hypertension
• Patients with heart failure
• Patients with atherosclerotic coronary,
  cerebrovascular or peripheral vascular disease
• Patients with unexplained anemia
• Patients with a family history of ESRD
• First nations peoples

58
Summary

• What tests should be ordered?
• eGFR to assess kidney function
• random urine sample to assess for significant
  persistent proteinuria
• What should be done with the results?
• follow serially
• assess for proteinuria
• implement risk reduction strategies

Monitoring for evidence of progressive disease -
declining eGFR - persistent significant
proteinuria
59
Acknowledgements

• Financial support for the development and
  distribution of these educational materials was
  provided by unrestricted grants from Amgen Canada
  and Bristol Meyers Squibb

60
Quick Tips on Referral and Management of Chronic
Kidney Disease

• Most patients with non-progressive CKD can be
  managed without referral to a nephrologist. The
  goals of therapy are listed below
• Consider reversible factors, such as medications,
  intercurrent illness, volume depletion, or
  obstruction. An abdominal ultrasound may be
  indicated when eGFR lt60 ml/min/1.73m2.
• Minimize further kidney injury by avoiding, if
  possible, nephrotoxins such as NSAIDs,
  aminoglycoside antibiotics, IV contrast, etc (if
  eGFR lt 60 ml/min/1.73m2).
• Remember to adjust dosages of renally excreted
  medications.
• Implement measures to slow the rate of
  progression of CKD
• Target BP is lt 130/80 mmHg. Most patients will
  need 3 or more medications. Diuretics and salt
  restriction are very useful, and if needed,
  consider furosemide BID dosing when eGFR lt 30
  ml/min/1.73m2
• Target urine protein/creatinine ratio (mg/mmol)
  is lt 60 (lt 500 mg/day) or target urine
  albumin/creatinine ratio (mg/mmol) is lt 40. ACEI
  and/or ARB are first line therapies in patients
  with albuminuria or proteinuria.
• Control blood sugar in diabetes, target HbA1C lt
  7.
• Implement measures to modify CV risk factors (NB
  CV risk gtgt ESRD risk).
• Follow the Canadian Hypertension Education
  Program, the Canadian Diabetes Association, and
  the Canadian Cardiovascular Society guidelines as
  per groups at highest risk for CV disease.
• Referral to a nephrologist is recommended for
• acute kidney failure
• eGFR lt 30 ml/min/1.73m2. (CKD stage 4 and 5)
• progressive decline of eGFR
• urine protein/creatinine ratio (PCR) gt 100
  mg/mmol (900 mg/24 hours) or urine albumin to
  creatinine ratio (ACR) gt 60 mg/mmol (500 mg/24
  hr)
• inability to achieve treatment targets