Debate: The expanding definition of CKD is unnecessarily labelling

many people as diseased

Pro: Andy SteinCon: Dan Ford

Chair: Prof. Higgins

Tuesday, 5th November 2013, 1-2pmCSB Room 00067

The expanding definition of CKD is unnecessarily labelling many people as diseased: Summary

1. eGFR declines with age and is therefore “normal”2. Early identification does not prevent ERF3. Labelling people with “CKD” is a burden to the patient4. Labelling people with “CKD” is a burden to the nephrologist

and GP 5. Chronic Kidney Disease is not really a Disease

1. eGFR declines with age and is therefore “normal”

1. eGFR declines with age and is therefore “normal”

• Longitudinal studies of kidney function.– 33-41% of patients showed no decline

• It may be statistically “normal”• It is no more physiologically normal than coronary

atherosclerosis

Baltimore longitudinal study of ageing. Lindeman J Am Geriat Soc 1985;33(4):278-85Progression of kidney dysfunction in the community-dwelling elderly. Hemmelgarn KI 2006;69:2155-61

The expanding definition of CKD is unnecessarily labelling many people as diseased: Summary

1. eGFR declines with age and is therefore “normal”2. Early identification does not prevent ERF3. Labelling people with “CKD” is a burden to the patient4. Labelling people with “CKD” is a burden to the GP and

nephrologist5. Chronic Kidney Disease is not really a Disease

2. Early identification does not prevent ERF

• Early identification– Allows management of complications of CKD– Prevents progression of CKD– Reduces late presentation

• Higher mortality, morbidity, hospital stay, cost (£30,000/year)

• Due to poorer clinical state at presentation, lack of vascular access

• No possibility of pre-emptive transplantation

• Poor psychological preparation

The expanding definition of CKD is unnecessarily labelling many people as diseased: Summary

1. eGFR declines with age and is therefore “normal”2. Early identification does not prevent ERF

– CKD is not just about preventing ERF– Clear association between CKD education (KDOQI, NICE, eGFR, QoF)

and reduction in late presentation (~700 patients/year)

The expanding definition of CKD is unnecessarily labelling many people as diseased: Summary

1. eGFR declines with age and is therefore “normal”2. Early identification does not prevent ERF3. Labelling people with “CKD” is a burden to the patient4. Labelling people with “CKD” is a burden to the GP and

nephrologist5. Chronic Kidney Disease is not really a Disease

3. Labelling people with “CKD” is a burden to the patient

3. Labelling people with “CKD” is a burden to the patient

38: Samal et al. Routine dipstick screening27: Crinson et al. Qualitative exploration of GP perspectives

3. Labelling people with “CKD” is a burden to the patient

38: Samal et al. Routine dipstick screening27: Crinson et al. Qualitative exploration of GP perspectives24: Spence: a bit of a rant in the BMJ

The expanding definition of CKD is unnecessarily labelling many people as diseased: Summary

1. eGFR declines with age and is therefore “normal”2. Early identification does not prevent ERF3. Labelling people with “CKD” is a burden to the patient

– Evidence presented is poor– Population at minimal risk of progression or complications of CKD (i.e.

>70 years with stable eGFR 45-59) has already been addressed by NICE in 2008

?

The expanding definition of CKD is unnecessarily labelling many people as diseased: Summary

1. eGFR declines with age and is therefore “normal”2. Early identification does not prevent ERF3. Labelling people with “CKD” is a burden to the patient4. Labelling people with “CKD” is a burden to the nephrologist

and GP5. Chronic Kidney Disease is not really a Disease

4. Labelling people with “CKD” is a burden to the GP and nephrologist

Nephrologist

4. Labelling people with “CKD” is a burden to the GP and nephrologist

GP– QOF

• Register of patients with CKD• BP monitoring & control• Monitoring of uACR

– Most with CKD 3:• IHD, DM, HTN, vascular disease• Already in “cardio-vascular” registers/clinics/QoFs

The expanding definition of CKD is unnecessarily labelling many people as diseased: Summary

1. eGFR declines with age and is therefore “normal”2. Early identification does not prevent ERF3. Labelling people with “CKD” is a burden to the patient4. Labelling people with “CKD” is a burden to the nephrologist

and GP

?

The expanding definition of CKD is unnecessarily labelling many people as diseased: Summary

1. eGFR declines with age and is therefore “normal”2. Early identification does not prevent ERF3. Labelling people with “CKD” is a burden to the patient4. Labelling people with “CKD” is a burden to the nephrologist

and GP5. Chronic Kidney Disease is not really a Disease

?

5. Chronic Kidney Disease is not really a Disease

1. a disordered or incorrectly functioning organ, part, structure, or system of the body

2. any harmful, depraved, or morbid condition

Is CKD associated with dysfunction or harm?

• Reduced GFR• Albuminuria

– Are both, independently, associated with increased mortality

Nitsch D et al. BMJ 2013;346:bmj.f324

Summary:

Burden of CKD guidelines1. eGFR declines with age and is

therefore “normal”2. Early identification does not

prevent ERF3. Labelling people with “CKD” is a

burden to the patient4. Labelling people with “CKD” is a

burden to the GP and nephrologist

5. Chronic Kidney Disease is not really a Disease

Benefits of CKD guidelines• Reduced progression in small but

significant numbers who progress to ERF

• Reduction in late presentation to dialysis

• Awareness of CKD– CVS risk management– Monitor for progression

?

• CKD is pathological, not statistically normal• CKD is truly prevalent• CKD is manageable• A CKD label is a minimal burden to a patient provided it is

communicated well• ERF is rare but harmful, burdensome and preventable

• CKD guidelines have done considerably more good than harm

The expanding definition of CKD is unnecessarily labelling many people as diseased: No

Thank you

“CKD Controversy: how expanding definitions are unnecessarily labelling many people as diseased” Moynihan R et al, BMJ 2013; 347

Dr Andrew SteinConsultant in Renal and Acute Medicine

Ebers Papyrus (1550 BC)

Why do new ‘diseases’ occur?

• Some are genuinely new, eg – Bugs evolve

– Humans evolve

– Planet changes

• Or, ‘created’ by confusion between causation and association .. and drug and technology industries, fuelling the capitalist dream (taxes, growth etc)

CKD/eGFR a new disease?

• Is it a new disease? No• Is it a disease? No

• What is it?• Is it a good thing even if its all made up?

3 Possible Equations for eGFR

• GG = (140-Age) x weight (in kg)]/72 x Serum creatinine (in mg/dL)*

• MDRD = 32788 x sCr (mmol/L)-1.154 x age-0.203 x [1.212 if black] x [0.742 if female]

• CKD-EPi = 141 x min(sCr/k,1)a x max(sCr/k,1)-1.209 x 0.993age x (1.018 if female) x (1.159 if black)

So, how common is CKD?

Age-specific prevalence of CKD. Prevalence of CKD for each age group by gender in 10,063 participants of the Tehran Lipid and Glucose Study (TLGS). Hosseinpanah et al. BMC Public Health 2009 9:44

Choices

• Is Dan right?• Ie, 60% pop > 70y have kidney

failure• Or not?

Consequences of Adoption of eGFR/CKD concept

• The adoption of this definition has resulted in more than 1 in 8 adults (almost 14%) in the US being labelled as having CKD

• And as many as 1 in 6 adults in Australia

Levey AS, Coresh J. Chronic kidney disease. Lancet 2012;379:165-80Chadban SJ, Briganti EM, Kerr PG, Dunstan DW, Welborn TA, Zimmet PZ, Atkins RC.Prevalence of kidney damage in Australian adults: the AusDiab kidney study. J Am SocNephrol 2003;14(suppl 2):S131-8

100 consecutive UHCW medical take patients (Oct 2012)

AKI/CKD44%

No AKI/CKD56%

What Happens to patients with CKD (not much)

• Norwegian study (2006) surveyed 65,000 members of the general population with a median age of 49

• Less than 1% of people with an eGFR of 45-59 ml/min/1.73 m2 (stage 3A disease) went on to develop end stage renal disease after eight years of follow-up

Hallan SI, Dahl K, Oien CM, Grootendorst DC, Aasberg A, Holmen J, Dekker FW.Screening strategies for chronic kidney disease in the general population: follow-up of cross sectional health survey BMJ 2006;333:1047.

Risk Factors not Diseases

• Pre-diabetes• Hypertension• Hypercholesterolaemia• Obesity• CKD?

Two ambiguities:– Causation and association

– Is the carrier of a (possibly genetic) predisposition ill or not?

What is kidney failure?

Why Does Overdiagnosis Occur?

• Screening• Increasingly sensitive tests (D-dimer)• Incidentalomas (things picked up on CT for

another reason)• Widened definitions (‘pre-diabetes’)• Confusion between causation and

association (CKD)

Who developed this concept?

• Kidney Disease Outcomes Quality Initiative under the auspices of the US National Kidney Foundation (2002)

• The guideline that launched the framework was supported by a pharmaceutical company

• “In the face of confusion and criticism of the potential for the framework to lead to overdiagnosis, specialist international meetings were held in 2004, 2006, and 2009 to discuss modifications”

Other Diseases are Overdiagnosed (Hint: some may not exist)

• Asthma — Canadian study suggests 30% of people with diagnosis may not have asthma, and 66% of those may not require medications

• Attention deficit hyperactivity disorder — Widened definitions have led to concerns about overdiagnosis; boys born at the end of the school year have 30% higher chance of diagnosis and 40% higher chance of medication than those born at the beginning of the year

• Breast cancer — Systematic review suggests up to a third of screening detected cancers may be overdiagnosed

• Gestational diabetes — Expanded definition classifies almost 1 in 5 pregnant women • High blood pressure — Systematic review suggests possibility of substantial overdiagnosis• High cholesterol — Estimates that up to 80% of people with near normal cholesterol treated for life

may be overdiagnosed• Lung cancer — 25% or more of screening detected lung cancers may be overdiagnosed• Osteoporosis — Expanded definitions may mean many treated low risk women experience net

harm• Prostate cancer — Risk that a cancer detected by prostate specific antigen testing is

overdiagnosed may be over 60%• Pulmonary embolism — Increased diagnostic sensitivity leads to detection of small emboli. Many

may not require anticoagulant treatment • Thyroid cancer — Much of the observed increase in incidence may be overdiagnosis

Attention deficit hyperactivity disorder

• Diagnoses of children with ADHD have increased++, as have prescriptions for drugs to control it

• Are they badly behaved children whom parents and schools cannot control

• Or, do children behave badly because they have a disease that requires pharmaceutical intervention?

Osteoporosis and Homosexuality – Diseases?

• Osteoporosis, which after being officially recognised as a disease by the WHO in 1994, switched from being an unavoidable part of normal ageing to a pathology

• Homosexuality has travelled in the opposite direction through medical territory, and out the other side

• Redefined during the 19th century as a state rather than an act• In the first half of the 20th it was viewed as an endocrine disturbance

requiring hormonal treatment• Later its pathological identity changed as it was re-categorised as an

organic mental disorder treatable by electroshock and sometimes neurosurgery; and finally in 1974 it was officially de-pathologised, when the American Psychiatric Association removed it from the list of disease states in the Diagnostic and Statistical Manual IV

What would convince me of eGFR/CKD thing?

1. “The incidence of the disease should increase in relation to the duration and intensity (dose) of the suspected factor

2. The distribution of the suspected factor should parallel that of the disease in all relevant aspects

3. A spectrum of illness should be related to exposure to the suspected factor

4. Reduction or removal of the factor should reduce or stop the disease”

Lilenfeld, A. M., On the methodology of investigations of etiologic factors in chronic disease. Some comments. J. Chronic Dis. 10, 41 (1959)

So what is eGFR/CKD thing?

• A new disease? No• A disease? No• A confusion between causation and association? Yes• A concept created with the best of intentions? Yes• Fuelled by the drug and technology industries? Yes• A risk factor? Possibly• A genetic predisposition? Possibly• A ’good thing’? Possibly

If you go looking for Zebras ..

Thankyou!