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Approach to an abnormal eGFR in primary care. Hugh Gallagher Consultant Nephrologist SW Thames Renal Unit. Changes in the way we measure kidney function eGFR Total protein-creatinine ratio Chronic kidney disease (CKD), classification, clinical features and consequences

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Approach to an abnormal egfr in primary care

Approach to an abnormal eGFR in primary care

Hugh Gallagher

Consultant Nephrologist

SW Thames Renal Unit


  • Changes in the way we measure kidney function

    • eGFR

    • Total protein-creatinine ratio

  • Chronic kidney disease (CKD), classification, clinical features and consequences

  • Approach to an abnormal eGFR in primary care

  • The management of CKD in primary care


  • Changes in the way we measure kidney function

    • eGFR

    • Total protein-creatinine ratio

  • Chronic kidney disease (CKD), classification, clinical features and consequences

  • Approach to an abnormal eGFR in primary care

  • The management of CKD in primary care


“Local health organisations can work with pathology services and networks to develop protocols for measuring kidney function by serum creatinine concentration together with a formula-based estimation of glomerular filtration rate (eGFR), calculated and reported automatically by all clinical biochemistry laboratories.”

Renal NSF Part 2, Dept of Health, 2004


The problem with creatinine
The problem with creatinine…. services and networks to develop protocols for measuring kidney function by serum creatinine concentration together with a formula-based estimation of glomerular filtration rate (eGFR), calculated and reported automatically by all clinical biochemistry laboratories.”

  • Affected by muscle mass (age/sex/weight) so poor surrogate for GFR

  • Insensitive – can lose 50% of renal function before serum creatinine rises

  • Therefore poor marker of early renal disease


GFR services and networks to develop protocols for measuring kidney function by serum creatinine concentration together with a formula-based estimation of glomerular filtration rate (eGFR), calculated and reported automatically by all clinical biochemistry laboratories.”

= Glomerular filtration rate

“Normal” = 80-120 ml/min

Therefore see as “% renal function”

Calculate

1) Actual – iohexol/EDTA clearance

2) Estimated – using formula


Formulae in use
Formulae in use services and networks to develop protocols for measuring kidney function by serum creatinine concentration together with a formula-based estimation of glomerular filtration rate (eGFR), calculated and reported automatically by all clinical biochemistry laboratories.”

  • *MDRD formula

    • Age

    • Sex

    • Creatinine

    • Ethnicity (black vs. non-black)

  • Cockcroft-Gault formula

    • Age

    • Sex

    • Creatinine

    • Weight


Cockcroft Gault & MDRD Formula services and networks to develop protocols for measuring kidney function by serum creatinine concentration together with a formula-based estimation of glomerular filtration rate (eGFR), calculated and reported automatically by all clinical biochemistry laboratories.”


Age services and networks to develop protocols for measuring kidney function by serum creatinine concentration together with a formula-based estimation of glomerular filtration rate (eGFR), calculated and reported automatically by all clinical biochemistry laboratories.”

Sex

Weight

Serum

Estimated

(kg)

creatinine

GFR

(

mol/L)

(ml/min)

μ

60

M

70

150


Age services and networks to develop protocols for measuring kidney function by serum creatinine concentration together with a formula-based estimation of glomerular filtration rate (eGFR), calculated and reported automatically by all clinical biochemistry laboratories.”

Sex

Weight

Serum

Estimated

(kg)

creatinine

GFR

(

mol/L)

(ml/min)

μ

60

M

70

150

46


Age services and networks to develop protocols for measuring kidney function by serum creatinine concentration together with a formula-based estimation of glomerular filtration rate (eGFR), calculated and reported automatically by all clinical biochemistry laboratories.”

Sex

Weight

Serum

Estimated

(kg)

creatinine

GFR

(

mol/L)

(ml/min)

μ

60

M

70

150

46

80

M

60

170


Age services and networks to develop protocols for measuring kidney function by serum creatinine concentration together with a formula-based estimation of glomerular filtration rate (eGFR), calculated and reported automatically by all clinical biochemistry laboratories.”

Sex

Weight

Serum

Estimated

(kg)

creatinine

GFR

(

mol/L)

(ml/min)

μ

60

M

70

150

46

80

M

60

170

26


Age services and networks to develop protocols for measuring kidney function by serum creatinine concentration together with a formula-based estimation of glomerular filtration rate (eGFR), calculated and reported automatically by all clinical biochemistry laboratories.”

Sex

Weight

Serum

Estimated

(kg)

creatinine

GFR

(

mol/L)

(ml/min)

μ

60

M

70

150

46

80

M

60

170

26

80

F

60

170


Age services and networks to develop protocols for measuring kidney function by serum creatinine concentration together with a formula-based estimation of glomerular filtration rate (eGFR), calculated and reported automatically by all clinical biochemistry laboratories.”

Sex

Weight

Serum

Estimated

(kg)

creatinine

GFR

(

mol/L)

(ml/min)

μ

60

M

70

150

46

80

M

60

170

26

80

F

60

170

22


The introduction of eGFR will allow early identification of CKD

and

Will result in increased awareness of advanced CKD previously not recognised as such



Urine total protein creatinine ratio
Urine total protein:creatinine ratio CKD

  • Replaces timed 24 hour urine collections for protein

  • Random spot urine (preferably early morning, but not essential)

  • Result in mg/mmol (mg of protein per mmol of creatinine)

  • Multiply by 10 = total daily protein excretion in mg



Urine total protein creatinine ratio1
Urine total protein:creatinine ratio CKD

Urine protein = 500 mg/l

Urine creatinine = 5 mmol/l

Therefore TPCR = 500/5 = 100 mg/mmol

Therefore daily protein excretion

= 100 x 10

= 1000 mg

= 1 g


Not to be confused with
Not to be confused with…. CKD

Urine albumin:creatinine ratio

NOT for quantifying urine total protein excretion

BUT simply to diagnose the earliest stage of diabetic nephropathy

Raised ACR = treat with ACEI/ARB (even if normotensive) and address CV risk


  • Changes in the way we measure kidney function CKD

    • eGFR

    • Total protein-creatinine ratio

  • Chronic kidney disease (CKD), classification, clinical features and consequences

  • Approach to an abnormal eGFR in primary care

  • The management of CKD in primary care


K doqi classification of ckd
K-DOQI Classification of CKD CKD

Chronic kidney disease is defined as either kidney damage or GFR < 60 ml/min for > 3 months. 1 Kidney damage is defined as pathological abnormalities or markers of damage, including abnormalities in urinalysis or imaging


K doqi classification of ckd1
K-DOQI Classification of CKD CKD

Chronic kidney disease is defined as either kidney damage or GFR < 60 ml/min for > 3 months. 1 Kidney damage is defined as pathological abnormalities or markers of damage, including abnormalities in urinalysis or imaging


In real money
In real money... CKD

  • GP practice 10,000 patients

    • Stage 3 CKD: 500 patients

    • Stage 4 CKD: 20 patients

    • Stage 5 CKD: 20 patients

    • Unreferred stage 4 and 5: 28 patients

  • Renal unit, serving 1.8 million population

    • Unreferred stage 4 and stage 5: 5,100 patients


Functional consequences of ckd
Functional consequences of CKD CKD

  • Hypertension (all stages)

  • Anaemia (stage 4-5, earlier in DM)

  • Disorders of Ca/Pi/PTH metabolism (stage 4-5)

    • renal osteodystrophy

    • vascular calcification



Snapshot of a ckd population in primary care
Snapshot of a CKD population in primary care CKD

  • GFR estimated on patients from 12 practices in Surrey, Kent and Greater Manchester

  • 19% of sample (5% population) stage 3-5 CKD

  • mean age 74 years (control 57 years)

  • 75% stage 3-5 (22% control) co-existing circulatory disease

  • 25% stage 3-5 (men) prostatic disease

  • 15% stage 3-5 anaemic by WHO (4% requiring treatment by European Best Practice guidelines)

  • 3% recorded as having a renal disease



Cardiovascular diseases in CKD CKD

Damage to the heart

(Uraemic cardiomyopathy)

Damage to the arteries

(Uraemic arteriopathy)


Cardiovascular mortality rates are higher among dialysis patients
Cardiovascular Mortality Rates are Higher among Dialysis Patients

100

10

1

Dialysis: male

Dialysis: female

0.1

General

population: male

0.01

General

population: female

0.001

Adapted from Levey AS et al. Am J Kidney Dis 1998; 32: 853-906.


The kaiser permanante experience
The Kaiser Permanante experience Patients

Derangements in renal function are independently associated with a graded increase in (cardiovascular) risk. This effect is seen even with relatively minor impairments in function.

Go, A. S. et al. N Engl J Med 2004;351:1296-1305



Esrd is the tip of an iceberg
ESRD is the tip of an iceberg Patients

DIALYSIS DEPENDENT 0.04%

PROGRESSIVE STAGE 4 CKD 0.05%

STABLE STAGE 4 CKD 0.15%

STAGE 3 CKD 4%


3 key messages
3 Key Messages Patients

  • Most patients with CKD are elderly

  • The majority have stable disease and die of CV causes well before they reach ESRD

  • Their management is therefore that of their CV risk


  • Changes in the way we measure kidney function Patients

    • eGFR

    • Total protein-creatinine ratio

  • Chronic kidney disease (CKD), classification, clinical features and consequences

  • Approach to an abnormal eGFR in primary care

  • The management of CKD in primary care


Questions to ask with a newly detected abnormal egfr 60 ml min
Questions to ask with a newly detected abnormal eGFR (< 60 ml/min)

  • Is this acute renal failure?

    • Historical records

    • Repeat within 1/52

  • Is it in the context of intercurrent illness?

    • Repeat after illness treated

  • Is there suspicion of obstruction?

    • Renal tract US (not otherwise)

  • Are there abnormalities on urinalysis?

    • Dipstick urine, send simultaneous MSU/TPCR

  • Should the patient be referred?


Urinanalysis and the patient with a newly detected abnormal egfr 60 ml min
Urinanalysis and the patient with a newly detected abnormal eGFR (< 60 ml/min)

  • Nephrology referral is indicated in the presence of persistent microscopic haematuria (if age > 45 then urological malignancy should be excluded first)

  • Nephrology referral is also indicated (in the presence or absence of microscopic haematuria) if total protein-creatinine ratio > 100 mg/mmol (1 g proteinuria)

  • Nephrology referral is not required (in the absence of microscopic haematuria) for lower levels of proteinuria, although these patients should be labelled as Stage 3 CKD and entered into appropriate care pathway


Should the patient with newly detected egfr 60 ml min be referred
Should the patient with newly detected eGFR < 60 ml/min be referred?

  • Not in the majority of cases

  • ARF

  • Obstruction (urology)

  • Abnormalities on urinalysis

  • For those patients with previously abnormal creatinine/eGFR, treat as CKD


What about referral indication in patients with egfr 60 ml min
What about referral indication in patients with eGFR > 60 ml/min?

  • Proteinuria > 1g/day (TPCR > 100 mg/mmol)

  • Proteinuria > TPCR 45 mg/mmol plus microscopic haematuria

  • Multisystem disease with evidence of kidney damage

  • Accelerated hypertension with evidence of kidney damage

  • Suspicion of renal artery stenosis

  • New diagnosis of APKD


  • Changes in the way we measure kidney function ml/min?

    • eGFR

    • Total protein-creatinine ratio

  • Chronic kidney disease (CKD), classification, clinical features and consequences

  • Approach to an abnormal eGFR in primary care

  • The management of CKD in primary care


General management of ckd
General management of CKD ml/min?

  • Blood pressure

    • Home meter

    • 140/90 threshold

    • 130/80 target (125/75 if TPCR > 100 mg/mmol)

    • ACEI/ARB if MA/proteinuria/heart failure

    • Refer if >150/90 despite 3 complementary drugs

  • Lipid management

    • JBS guidelines

  • Other

    • Aspirin if 10 year CV risk > 20%

    • Influenza/pneumococcal vaccination

    • Smoking/weight

    • Medication review



Specific management of stage 3 ckd
Specific management of Stage 3 CKD ml/min?

  • Renal US only if:

    • Refractory hypertension

    • Lower tract symptoms

  • 50% dose reduction metformin if eGFR < 45 ml/min

  • Refer if:

    • Progressive (fall in eGFR > 10 % over 1 year)

    • Functional haematological/biochemical consequences:

      • Hb < 11

      • K > 6

      • Ca < 2.1, Pi > 1.5, PTH > 7 pmol/l

    • Poorly controlled hypertension


Specific management of stage 4 ckd
Specific management of Stage 4 CKD ml/min?

  • Discuss with nephrology

  • Renal US

  • Stop metformin

  • Refer if:

    • Diabetic

    • Progressive (fall in eGFR > 15 % over 1 year)

    • eGFR < 20 ml/min

    • Functional haematological/biochemical consequences:

      • Hb < 11

      • K > 6

      • Ca < 2.1, Pi > 1.5, PTH > 11 pmol/l

    • Poorly controlled hypertension



Take home messages
Take home messages ml/min?

  • eGFR as a “% kidney function”

  • 0.5-1%/year lost from 40+

  • Most CKD patients are stable and management is that of CV risk

  • CKD patients that should be referred are those:

    • With progressive disease

    • With advanced disease (Stage 5 +/- Stage 4)

    • With functional consequences of disease




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