Canadian Society of Nephrology - Société Canadienne de Néphrologie - Detection, monitoring and referral of chronic kidney disease Canadian.

Canadian Society of Nephrology - Société Canadienne de Néphrologie - www.csnscn.ca

Detection, monitoring and referral ofchronic kidney disease

Canadian Society of Nephrology Implementation Committee

2007


Key messages

• Who to test for chronic kidney disease

• What tests to order

• What to do with the results


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 eGFR 30-60 eGFR >60

Consider reversible factors:-Medication - Volume depletion-Intercurrent illness - ObstructionRepeat 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 <30 eGFR 30-60

Nephrology referral recommended

Follow eGFR at 3 months then seriallyAssess for persistent significant proteinuriaImplement risk reduction

eGFR < 30or progressive decline in eGFR

or persistent significant proteinuriaor inability to attain treatment targets

Stable eGFR 30-60and

no significant proteinuria


What is Chronic Kidney Disease

• The presence of Kidney Damage or an eGFR < 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.


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.



• 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


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


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


Which test would you choose to assess Joe’s renal function?

• Serum creatinine

• 24 hour urine collection

• Nuclear medicine scan

• eGFR


Joe’s 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


Joe’s serum creatinine is in the normal range, doesn’t that mean his kidney

function is also normal?


Assessing Joe’s renal function using eGFR

54 ml/min / 1.73m2

(Stage 3 CKD)

Clearly, Joe’s renal function is not normal

despite a normal serum creatinine

http://www.kidney.org/professionals/kdoqi/gfr_calculator.cfm


Why use eGFR?

It gives the health care practitioner

a different sense as to a patient’s level of

renal function that they may not have

appreciated by using simple serum

creatinine measurements.


Measuring renal function:what’s eGFR?


GFR

• Glomerular filtration rate (GFR):

is the volume of fluid filtered from the

renal glomerular capillaries into the

Bowman’s space per unit time.

• Normal for a 20 year old is ~ 120ml/min


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


The perfect marker

• Endogenous

• Freely filtered

• Not secreted or reabsorbed

• Inexpensive to measure

doesn’t exist !


Problems with creatinine

Stevens L et al, NEJM 2006; 354:2473-2483


Problems with timed collections

• Cumbersome

• Prone to error

• No longer recommended in most situations


Problems with other methods

• Cystatin• Inulin• Nuclear medicine (iothalamate, EDTA etc)

• Complex• Time-consuming• Expensive• Not practical for serial monitoring


Creatinine based approximations

1) Cockcroft-Gault equationCrCl (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


eGFR equation provisos

• eGFR calculations may be less reliable in:– individuals with near normal GFR (>60 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


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.


Developed by the BC Medical Services Commission, Guidelines and Protocols group


Developed by the BC Medical Services Commission, Guidelines and Protocols group


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


What do those values mean?

ACR(mg/mmol)

PCR(mg/mmol)

24 hour

urine

>3 N/A ~30 mg day(albumin)

<40 <60 ~ 500 mg/day(protein)

>60 >100 ~900 mg/day(protein)

Alarm valuesto refer

Microalbuminuria(ie in diabetics)



• 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


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 creatinineor• Urine protein to creatinine


What to do with the results

Now that I know Joe’s GFR is not normal what should I do?


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


Natural history of elevated creatinine levels

1434 patients in a family medicine practice• 57 patients had an elevated initial serum Cr

levels (>130umol/L) and subsequent Cr levels within 4-5 years of follow-up

Marcotte and Godwin, Canadian Family Physician 2006;52:1264-1265,e1-5

Initial serum Cr

Latest serum creatinine (umol/L)

<130 131-200 201-300 >300

131-200 26 12 5 2

201-300 3 3 1 0

>300 3 2 1 0


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.


For patients with a new finding of an eGFR between 30-60ml/min/1.73m2

CSN recommends that clinicians determine the stability of the patient’s eGFR

Repeat test within 2-4 weeks, and then in 3-6 months


Consider reversible factors

• Intercurrent illness • Volume depletion • Medications

– NSAIDs, aminoglycosides, IV contrast dye

• Obstruction

• An abdominal ultrasound may be indicated at eGFRs <60ml/min/1.73m2


Back to Joe

• You measure Joe’s 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


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.


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.


CKD is common


Estimated prevalence of CKD in Canadians ≥ 20 years old

Stage 1 CKD > 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 < 15 ml/min 24,000

Stigant, C, et al. CMAJ 2003;168:1553-60.

Numbers are estimates based on an extrapolation of US data


Other common conditions also managed by primary care physicians

CVD 38.7% in diabetic men

30.7 % in diabetic women

Thyroid disease 1/20 (Thyroid Fdn of Canada)

Hypertension 28%

Type 2 DM 8-10 % worldwide

CKD is a common general health problem


Estimated prevalence of CKD in Canadians ≥ 20 years old

Stage 1 CKD > 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 < 15 ml/min 24,000

Stigant, C, et al. CMAJ 2003;168:1553-60.

ESRD is not common


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?


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.


Go,A et al. NEJM 2004;351:1291-1305


Quick Tips on Management of CKD

Implement measures to slow rate of CKD progression• Treat to target BP <130/80; most will need 3 or more meds, diuretics and salt restriction are very useful

• Target urine ACR <40 or PCR <60. ACEI and/or ARB are first line therapies for albuminuria or proteinuria

• Control blood sugar in diabetes, target HbA1C <7%

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 <60)

Remember to adjust dosages of renally excreted medications


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


Who should be referred to a Nephrologist?

• Patients with acute renal failure

• Patients with eGFR <30ml/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 >100mg/mmol or – quantified ACR >60 mg/mmol.

• Inability to achieve treatment targets or other difficulties in the management of the CKD patient


Violet

• 78 year old female• longstanding patient of a colleague’s – followed

for her hypertension and “mild” renal failure• You are on call and see her because she is c/o

nausea and lethargy

Date today 1 yr ago 2 yrs ago 5 yrs ago

Serum Creat (µmol/l)

184 168 156 138


Using an “eGFR approach”

Date today 1 yr ago 2 yrs ago 5 yrs ago

Serum Cr(µmol/L)

184 168 156 138

eGFR(ml/min/1.73m2)

24 27 30 35


This woman’s renal disease may have been underdiagnosed

Using eGFR may have given a moreaccurate measure of her renal function

Serial measurement of eGFR is a powerful tool for the clinician

Nephrology referral is recommended for this patient


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?


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 eGFR 30-60 eGFR >60

Consider reversible factors:-Medication - Volume depletion-Intercurrent illness - ObstructionRepeat 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 <30 eGFR 30-60

Nephrology referral recommended

Follow eGFR at 3 months then seriallyAssess for persistent significant proteinuriaImplement risk reduction

eGFR < 30or progressive decline in eGFR

or persistent significant proteinuriaor inability to attain treatment targets

Stable eGFR 30-60and

no significant proteinuria


Linda: continued

• Evaluation of her urine shows no significant amount of proteinuria (ACR <40mg/mmol) and no hematuria

• She is followed annually

• Two years later– same eGFR – blood pressure is 146/94 – persistent proteinuria with ACR > 60mg/mmol

• Progressive CKD = referral to Nephrology


Dave

• 81 year old man, new to your practice– ASHD, stent placed 2 years ago– PSA >100 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


Dave

• Old labs from previous MD show Cr 150-180 umol/L over last 3 years

• What would you do?


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


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


Acknowledgements

Financial support for the development and distribution of these educational materials was provided by unrestricted grants from

Amgen Canada and Bristol Meyers Squibb


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 <60 ml/min/1.73m2.• Minimize further kidney injury by avoiding, if possible, nephrotoxins such as NSAID’s, aminoglycoside

antibiotics, IV contrast, etc (if eGFR < 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 < 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 < 30 ml/min/1.73m2

• Target urine protein/creatinine ratio (mg/mmol) is < 60 (< ~ 500 mg/day) or target urine albumin/creatinine ratio (mg/mmol) is < 40. ACEI and/or ARB are first line therapies in patients with albuminuria or proteinuria.

• Control blood sugar in diabetes, target HbA1C < 7%.

• Implement measures to modify CV risk factors (NB: CV risk >> 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 < 30 ml/min/1.73m2. (CKD stage 4 and 5)– progressive decline of eGFR – urine protein/creatinine ratio (PCR) > 100 mg/mmol (~900 mg/24 hours) or urine albumin to creatinine ratio (ACR) > 60 mg/mmol

(~500 mg/24 hr)– inability to achieve treatment targets

• NOTE: detailed CSN CKD management guidelines are under development, these quick tips should be considered as an interim approach.Insert Quick Tips sheet from the CSN CKD document

Canadian Society of Nephrology - Société Canadienne de Néphrologie - Detection, monitoring and referral of chronic kidney disease Canadian.

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