Introduction

Stages of Chronic Kidney Disease:By NKF’s Kidney Disease Outcomes Quality Initiative (KDOQI) kidney, 2002

Stage DescriptionGFR,

mL/min/1.73 m2

US

Prevalence,

1000s

US

Prevalence*,

%

1Kidney damage with

normal or increased GFR≥90 5900 3.3

2Kidney damage with

mildly decreased GFR60–89 5300 3.0*

3Moderately decreased

GFR30–59 7600 4.3

4 Severely decreased GFR 15–29 400 0.2

5 Kidney failure <15 or dialysis 300 0.1

Stages of CKD: ? Rising prevalence

Stage Description GFR

(ml/min/1.732)

US Prevalence

in Millions

1 Kidney damage and

normal or GFR

90 3.6*

2 Kidney damage and

Mild GFR

60-89 6.5*

3 Moderate GFR 30-59 15.5*

4 Severe GFR 15-29 0.7*

5 Kidney Failure usually

need dialysis

<15 0.5+

*Extrapolation in adults using NHANES 1999-2004, JAMA 16:180-8, 2007+US Renal Data System 2008 Annual Data Report

?

Poor CKD outcomes

PoorCKD outcomes

Poor CKD outcomes

USRDS 2011 Atlas of CKD & ESRD

Abstract

27 998 patients with GFR of < 90 mL/min/1.73 m2 on 2 separate measurements followed up patients from the index date (1996) of the first GFR < 90 mL/ until RRT, death, or June 30, 2001.

over the 5-year observation period:

.

Conclusion: Our data suggest that efforts to reduce mortality in this population should be focused on treatment and prevention of coronary artery disease, congestive heart failure, diabetes mellitus, and anemia.

Many Studies..

Poor CKD outcomes

CKD 3 CKD 4 CKD 5

RRT 1.3% 1.3% 19.9%

Mortality 19.5% 24.3% 45.7%.

1,120,295 adults followed up in 1996-2000, In those with an eGFR <60: 25,621 deaths, only 3171 began dialysis.

Cardiovascular Events according to the Estimated GFR among 1,120,295 Ambulatory Adults

Go, A, et al. NEJM 351: 1296

All cause mortality in CKD pre-dialysis patients from 39 studies with HR OF 0.94 to 5.0

Dr. Nasrulla AbutalebConsultant NephrologistKing Fahad Specialist HospitalP.O. Box 15215, Dammam 31444Kingdom of Saudi ArabiaE-mail: abutaleb_k@hotmail.com

Another Cry! Early preparation & initiation of other RRT

Cut all the hands on reaching CKD3-4 to construct aVF’s !

e.g:“ It is incumbent on us to identify patients who can have fistulas placed at stage 3 & 4 CKD” XXX, MD

The main original source of this lecture is the writings of Richard J. Glassock

Stages of CKD:26 million Americans have CKD (NKF): Where is the defect?

Stage Description GFR

(ml/min/1.732)

US Prevalence

in Millions

1 Kidney damage and

normal or GFR

90 3.6*

2 Kidney damage and

Mild GFR

60-89 6.5*

3 Moderate GFR 30-59 15.5*

4 Severe GFR 15-29 0.7*

5 Kidney Failure usually

need dialysis

<15 0.5+

*Extrapolation in adults using NHANES 1999-2004, JAMA 16:180-8, 2007+US Renal Data System 2008 Annual Data Report

suddenly increased and suddenly decreased

NDT Plus (2010) 3: 213–312 224

Where is the defect ?

Crack 1:

The irrational CKD3 inflation

Why/How?

• CKD3: 58% of CKD (USA: 15.5/26 Million)

(43% with cystatin C-based GFR)

• 85% of CKD3 are in CKD3a!

In fact.. Most of the CKD3 have GFR > 5o ml/min..

The Japanese SN estimated the prevalence of CKD 3 alone as 10.4% of population, 7.6% within the range of 50–59 mL/min per 1.73 m2

Crack 1, cont’d

• CKD3b constituted only:

- 11.7% of the CKD3 (462 293 adults) in C. P. Wen et al

- 12.3% of the CKD3 in S. L. White et al study

- 18.3% among the 187701 total CKD3 by Go et al

So , again nearly 90% of the CKD3 patients are CKD3a.. Mostly in the GFR segment 59 to 69 ml/min

• How can early CKD3a (10 ml/min segment) patients outnumber the combined CKD 1 & 2 (span over > 60ml/min width) patirnts by 1.5X

National prevalence of chronic kidney disease in adults in Taiwanlancet.com Vol 371 June 28, 2008

Concentrate on CKD stage 3.. What conclusions?

PREVEND: only 4% of CKD3 are 3b

Taiwan study

Crack 2: Erroneous eGFR estimations !

contributed to CKD3 overestimation

Two CKD3 subgroups ? to be excluded:

1. The False CKD3 subgroup:

AusDiab study: 30.1% of CKD3 by MDRD (all in 3a) were reclassified by CKD-EPI to be Non-CKD patients. but 2.2% to be CKD2

ARIC study : 43.5% of CKD3 by MDRD were found to have eGFR > 60 ml/min/1.73 m2

In Chinese study : CKD misclassified as CKD stage 3 by MDRD 7V and 4V in 60.0 & 68.3% (28.8% of pop. are CKD3!) J Am Soc Nephrol 17: 2937–2944, 2006

CKD-EPI: still suboptimal !

• False positive CKD3 by CKD-EPI 36.2%, divided to:

- 26.2% have GFR> 60 ml/min/1.73 m2 and

- 10.0% have GFR < 30 ml/min/1.73 m2.

Andrew S. Levey et al (Ann Intern Med. 2009;150:604-612)

Only limited correction!

USRDS 2011 Atlas of CKD & ESRD

Crack 3:

The low GFR is mostly age related !

Have we exerted any efforts to excludes those with “age

normalized” eGFR

The 2nd CKD3 subgroups to be excluded is:

2. The aged with eGFR

< 60 ml/min but with no

kidney damage:

The false +ve’s for the low specificity of the cut-off value of 60 ml/min with kidney damage ..!!

:

How? Let us go to CKD2 !

- 51.2% in US with eGFR 60-89 ml/min/1.73 m2, only 6.5% of them has also albuminuria (NHANES 1999-2004)

Q: Accepting such isolated GFR reduction into the CKD 51% of the adult US population would be

CKD2

Current 60 ml/min value is still too non-specific.. andso we have too many false +ve’s

CKD3 is mostly an elderly population

• Taiwan study:

Mean ages: CKD 1: 35.3 (SD 12.3), CKD2: 45.3 (SD 14.4), But CKD3: 61.9 (SD 11.4) The lancet 2008; Vol 371: 2173-82

• Norway study: CKD3: Median age 75.0 years (IQR: 67.0–81.2). Kidney International (2006) 69, 375–382

• Tromso study: CKD3: 75.0 years

• USRDS 2009 Annual Report: 68% of the CKD patients> 60 are within CKD3 !! USRDS 2009 Annual Data Report

• CKD3 in 27.7% of adults > 80 in Norway and in 49% of > 85 in USA J Am Geriatr Soc 57:2217– 2223, 2009.

Age & sex distribution of study population 931000vs. CKD 3-5

Females !!

ClinNephron, 2011,117, c213-c222

Age-standardized rates for CKD 3–5 NEOERICA project

Crack 4: CKD3 (or at least CKD3a) is not a

CVD risk factor?

How true is CKD3 a fatal diseas?!

• A. M. O’Hare et al: Aged patients (>65) with eGFR of 50-59 ml/min/1.73m2 did not have an increased adjusted risk for death. J Am Soc Nephrol 18: 2758–2765, 2007.

• PREVEND: prognosis not affected by eGFR in 30-59 ml/min regardless of the presence or absence of albuminuria. Nephrol Dial Transplant (2008) 23: 3851–3858

Lancet, 2008; 371: 2173- 82

HR for all-cause mortality of such CKD 3awith no MAU was found 1.3 compared to2.1 and 4.0 for the CKD3a patients withmicro or macroalbuminuria (not dissectedto age; aged less likely affected by CKD)

Crack 5: CKD3 is not a CVD risk factor?

How true CKD3 is a fatal diseas?!

•Go et: The HR with eGFR < 60 ml/min/1.73 m2 in the

subgroup (172,144 subjects) that had regular follow-up

was 1.0 for death and hospitalization and just 1.2 for

CVD events (HR’s not dissected according to

albuminuria; not adjusted for smoking, race or activity

leve)•.

PREVEND: prognosis not affected by eGFR in 30-59 ml/min regardless of the presence or absence of albuminuria.Nephrol Dial Transplant (2008) 23: 3851–3858

age- and sex-adjusted survival of CVD with CKD3 subdivided according to albumin excretion.

PREVEND study

How com!CKD3 has the best CVD among all the CKD patients !That is because true CKD3 patient group is a minority within currently defined CKD3 !

J Am Soc Nephrol 18: 1959–1965, 2007

Age- and sex-adjusted survival of CVD according to the stages of CKD.

PREVEND study

It is MAU (as a marker not a cause ! of CVD) not eGFR.. Losing GFR down to 30 ml/min had no effect on occurrence of CVD

Non-CKD aged >66 adjusted mortality 15% > unadjusted rates. CKD adjusted 42–51% < adjusted

53.8 75.2 66.0 62.1 104.5

USRDS Report 2011

i.e The 15.0 million out of the 15.5 million in CKD3 (US) who could n’treach CKD4 would have had the same fate whether they had CKD or not.. Same aged pop. with any other medical problem could have hgher higher mortality rate!

USRDS Report 2011

eGFR decline during 6 year of follow-up PREVEND study:

- -2.3 ml/min in the control group

- -0.2 ml/min in the renal failure (adjusted)

- -2.6 ml in the erythrocyturia

- -7.2 ml/min in the macroalbuminuria

J Am Soc Nephrol 17: 2582–2590, 2006.

Stable eGFR over years

Incidence of ESRD according to GFR and dipstick proteinuria test in a 17-yr follow-up of a cohort of 95,252 pts. Dipstick positivity is defined as 1 proteinuria.J Am Soc Nephrol 20: 465–468, 2009

(1/1000)Low even for CKD4

Again.. ESRD is a remote possibility due to pure age related eGFR decline

Stages of CKD:

Where is the defect?

Stage Description GFR

(ml/min/1.732)

US Prevalence

in Millions

1 Kidney damage and

normal or GFR

90 3.6*

2 Kidney damage and

Mild GFR

60-89 6.5*

3 Moderate GFR 30-59 15.5*

4 Severe GFR 15-29 0.7*

5 Kidney Failure usually

need dialysis

<15 0.5+

*Extrapolation in adults using NHANES 1999-2004, JAMA 16:180-8, 2007+US Renal Data System 2008 Annual Data Report

suddenly increased and suddenly decreased

• Diluting CKD3 with 'non-CKD’

better prognosis than stages 1 & 2 !

& irrational inflation of CKD3 group

NB: This dilution happened by the inclusion of the two

previously discussed CKD 3 subgroups (Cracks 2 & 3)

• Slow GFR decline in the ‘healthy’ majority of CKD3 patients + shortened life expectancy of this aged CKD3 majority

Most CKD3 will die within early CKD 3 without progressing to even CKD3b

Let us look through the confluence of these 5 cracks ! Cont’d

• In Norway study:

CKD3 data: 10 yr mortality 51%, Renal failure 4%, eGFR decline 1.03ml/min/1.73m2/yr and RRT in only 0.1% (i.e.only 4 out of 3047 patients); even RRT lower among female and the aged.

• PREVEND study

eGFR decline 0.1 vs. 0.5 ml/min/1.73m2/yr among CKD3 without vs. with albuminuria. HR for CVD in 'CKD3 with no MAU’ was 1.0 (adjusted for age) but actual mortality (unadjusted) was 2X that of the rest of non-CKD patients (14 vs. 7.0 events/1000 person-years).

So, The bulk of CKD3 patients die within early CKD3 (GFR> 50 ml/m); mortality at this stage can't be CKD related.

?? 'silent killer’?

Age (Years)

CLD

GFR &CKD

CHDCJD: OACHD

CBD: Dementia

CLuDCLD:CEaD CED

Chronic Organ DysfunctionWhy is it only for nephrologists to creat a chronic disease from age related decline?

.. Isn’t it just generalized melting!! Starting from subclinical dysfunctions

.. We are dying with some dysfunction in every organ system!

CLD: Chronic subclinical liver dysfunctionCLuD: Chronic Lung dysfinctionCBD: Chronic brain dysfinction/atrophyCJD: Chronic Joint dysfinction/attritionCED: Chronic eye diseasesCEaD: Chronic ear diseasesCHD: Chronic cardiac dysfinction

BUT..

Baseline CVD and Incident CKD :

Which causes which? .. Same situation as MAU !

Chonchol et al, 2008Meguid El Nahas

Even with adjustment for risk factors: CKD patients have higher prevalence of not only CVD but also other ageassociated chronic diseases: e.g: AMD.. We can not account for all therisk factors

CKD Increases the Risk of Age-Related Macular Degeneration

A Levin

• Females 70%, 63.2 % and 61.8% (9.4/15.4), 62% of

CKD3 in Norway study, PREVEND, NHANES data and the AusHEART study.

• Nijmegen Biomedical Study:

The 5th percentile values for the males and females at 60-64 years is 59 vs. 50 ml/min/1.73m2.

Also, C. Diez: The eGFR 5th percentile values for the 60 to 64 aged the cardiac patients patients were 45 & 37 ml/min for the male and female, respectively.

The Problem:

Disproportionately higher female non-CKD included among the CKD3-4 population by choosing the same cut-off GFR for both genders??.

Crack 5: Gender discriminationOr

Equality means unfairness with females

Prevalence of stages 3–5 of chronic kidney disease by genderin selected countries.

NDT Plus (2010) 3: 213–312 224

Crack 6b:

Also, Don’t forget ethnicity and the eGFR cut-off values

• NHANES 2003 and 2006:

AA > whites to have low Hb, higher UA & PTH; the metabolic consequences of low eGFR in AA appear earlier (1) ..

ESRD risk 3-4 X compared with Caucasians, but in nondialysisCKD: eGFR <60 ml/min was present in 43.3%, greater prevalence in Caucasian vs. AA (OR 0.51), reversed at GFR< 20 (OR 1.73) (2) ,(1) A Kukla and Hassan N I

(2) The American Society of Nephrolog, 2007.

• Rossini Botev: eGFR of 64 ml/min in a 25-yr-old white woman (SCr of 1.1 mg/dl) or an eGFR drop from 109 to 77 ml/min per 1.73 m2 in a 45-yr-old white man (SCr rise 0.8 to 1.1 mg/dl), both with “normal” SCr and will not be

reported as abnormal eGFR ! Clin J Am Soc Nephrol 3: 1606–1607, 2008.

• Eckardt et al.. A 20 years old pt. with a GFR of 75 ml/minute/1.73m2 (Scr/Q=1.5) has a much worse prognosis than a 75 years aged with a GFR of 55ml/minute/1.73m2

(corresponding to a Scr/Q=1.4). European Nephrology,

2011;5(1):10–4

• How many true CKD with GFR > 60 are being missed ?

Crack 6: Omission of CKD patients with

eGFR>60 ml/min but no proteinuria:

Crack 7: Exaggerated MicroalbuminuriaEstimates in the Aged:

So, also CKD 1 & 2 are exaggerated!

Definitions of Proteinuria

Urine Collection Method Normal MicroalbuminuriaAlbuminuria or

Clinical Proteinuria

Total protein

Spot urine dipstick <30 mg/dL NA ≥ 30 mg/dL

Spot urine protein-to-creatinine ratio(varies with method)

<200 mg/g NA ≥ 200 mg/g

Albumin

Spot urine albumin-specific dipstick

<3 mg/dL >3 mg/dL NA

Spot urine albumin-to-creatinine ratio(varies by sex)

<17 mg/g (men) <25 mg/g (women)

17–250 mg/g (men)25–355 mg/g

(women)

>250 mg/g (men)>355 mg/g (women)

NA = not applicable.

National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Guideline 1. Definition and stages of chronic kidney disease.Available at: http://www.kidney.org/professionals/kdoqi/guidelines_ckd/p4_class_g1.htm. Adapted with permission from the National Kidney Foundation.

Albuminuria & Age: How much real? The role of the low denominator in ACR & PCRlow

MONICANHANESIII

14,622

19% 32.7%15%

Garg et al, 2002Meguid El Nahas

• Common causes of ESRD are almost not existing among CKD3 (e.g. CGN, CPN, ADPKD/ARPKD and CAKUT, SLE..)

• The prevalence of DM and HTN among CKD3 reflect that of population:

- DM (Taiwan study) among CKD3, with a median age of 61.9, was 14.5%.

- HTN among CKD3 was 26.8%; with Taiwanese population (>45 years) prevalence of 27% or 33.2% (men) and 29% or 40.9% (women)

- Note that prevalence of DM and HTN in CKD 1 & 2 is higher than that of population .

Can we equate these two CKD3 cases?

• 35 years old diabetic with DM related CKD3 (eGFR 40 ml/min)

With

• 65 years old with CKD3 (eGFR 40 ml/min)of unknown etiology with no MAU..

The risk of ESRD is hugely different between the two!

Higher rates of ESRD among true CKD groups !

• DIAMETRIC (3,228 with DKD X 2.8 yrs from IDNT &RENAAL): 19.5% ESRD: 2.5 X CV death and 1.5 X all-cause mortality. Am J Kidney Dis. 59(1):75-83

• MDRD (1666 patients): rates for kidney failure were 4X higher than that for death

Kidney International 73, 1310-1315 (June (1) 2008)

• AASK: the rate of ESRD was 1.8 X greater than mortality (Blacks for 11 yrs)

DIAMETRIC StudyAm J Kidney Dis. 59(1):75-83. 2011

Serum sNGAL cut-off level of 435 ng/ml and progression to endpoint (P 0.002, 2X s Cr), with HR 3.37.Clin J Am Soc Nephrol 4: 337–344, 2009

Current renal dysfunction often reflects the sequalae of past insults that are not existing at present.. GFR is likely to remain steady in the absence of disease activity..Current CKD model can not predict prognosis

(Ungal< & > cut-off level 231 ng/ml and progression to endpoint (P 0.0001, 2X Cr) with a HR of 7.45Clin J Am Soc Nephrol 4: 337–344, 2009

J Am Soc Nephrol 18: 2601–2608, 2007

• The kidney donors and recipients with stable GFR

• The reported majority of CKD patients with stable eGFR (The overwhelming majority would never progress

to CKD3b)

• The predialysis elderely who often maintain same low GFR for long periods

J Am Soc Nephrol 18: 2758–2765, 2007.

So, how appropriate is the recommendation to construct AVF on all hands reaching CKD3-4 !

Crack 11: Confusing Physiology:

The 60 ml/min GFR zone: an overlapping zone, with significant physiological fluctuation due to factors as: fluctuating intake of protein, fluids, medications (ACEI/ARB) and others (? Recovering AKI)

Studies indicate significant reduction in CKD dx on getting a repeat eGFR reading

LA recent study: sinle s. Cr derived eGFR value increased CKD3-5 from 5.4% to 6.4% and CKD3 proportion from 14.7% to 17.2 % Nephronclin 2011. 117, 213-222

.

These 'normal’s jump every day! directly to CKD3 bypassing earlier CKD stages!!

Crack 12: Macro-albuminuria not just

MAU

• MAU seen in overweight, aged > 65, HTN, DM, drug? with no evidence of kidney disease..

• “Isolated” MA accounts for 30% of CKD in epidemiologic studies in the absence of obvious renal disease? biomarker of widespread vascular injury and atherosclerotic burden.. ? Yes as a risk factor but ? No as disease.. Dr. Glassock

• MAU reflects low creatinine as it reflects the MAU itself

Crack 12: Macro-albuminuria not just MAU

0

1

2

3

4

5

6

<0.5 0.5-0.9 1.0-1.4 1.5-1.9 2.0-2.9 3.0-3.9 4.0-4.9 5.0-5.9 6.0+

Urine Protein Excretion and Progression of CKD AIPRD Study Group

of 11 RCTs of ACEIs Meta-analysis

4685 records with non-diabetic kidney disease

RR

Urine protein excretion (g/day)

Jafar et al, Ann Intern Med 2003;139:244-252

Some suggested Solutions:

• Protect CKD3 as done for 2 !

• Different cut-off values for gender.. Unless new indexing eliminate eGFR differences

• Glassock approach: 5 centile for age and gender to define upper threshold for stage 3 + using overt albuminuria

• Consider SCr/Q approach or accept eGFR< 90 ml/min if age <45 (prev. of CKD<45 is 0.70%)

• Accounting for race & ? age factors ?

• ? Not including isolated MAU as a disease

• Introducing a correction factor for uACR/uPCR

• Introducing etiology into the classification..

Kidney International (2009) 75, 1009–1014 &Kidney Int 2007; 72: 534–536.

The term CKD to be used for a specific, persisting, irreversible pathology of the kidney

Q=0.90mg/dl for the av, male Caucasian, Q=0.70mg/dl for the female Caucasian, Q=1.01mg/dl for the AA male, Q=0.79mg/dl for the AA female.MDRD equation: eGFR=262 (Scr/Q)–1.154 Age–0.256 CKD-EPI equation: eGFR=142 (Scr/Q)–1.234 (0.993)Age

Chronic Kidney Disease Classification – A Simple Proposal: Scr/Q is independent of age, sex and race by Hans Pottel et al

Chronic Kidney Disease Classification – A Simple Proposal: Scr/Q is independent of age, sex and race by Hans Pottel et al

Scr/Q = ratio of serum creatinine to constant Q, which is the Scr concentration for theaverage healthy person from a typical population. Glomerular filtration rate values inml/minute/1.73m2Q=0.90mg/dl for the av, male Caucasian, Q=0.70mg/dl for the female Caucasian, Q=1.01mg/dl for the AA male, Q=0.79mg/dl for the AA female.MDRD equation: eGFR=262 (Scr/Q)–1.154 Age–0.256 CKD-EPI equation: eGFR=142 (Scr/Q)–1.234 (0.993)Age

Chronic Kidney Disease Classification – A Simple Proposal: by Hans Pottel et al

Scr/Q is independent of age, sex and race with the advantage over eGFR of reduced prevalence of CKD in the elderly and increased sensitivity in young adults.

But ! But..!

KDIGO ‐ ?Controversies Conference

We are programmed to decline gradually in all capabilities long before we finally scummb.. This is physiological and not necessarily pathological.. Otherwise, all the aged are variably patients and sick

Why should

we inflate

CKD stage3

by 7-8 X by

non-CKD

who would

die prior to

being

touched by

any CKD

related

pathological

process?

Am J Kidney Dis. 59(1):75-83. 2011

Paola S. Timira,s in Physiological Basis of Aging and Geriatrics

Reference values of eGFR for non-diseased Caucasianmales and females:Median values and 5, 25, 75, and 95 percentiles

Kidney International (2007) 72, 632–637

All-cause mortality ratesby age, 2004

ESRD: prevalent

ESRD patients, 2004.

General Medicare:

non-ESRD patients

with at least one

month of Medicare

eligibility in 2004.

Adjusted for gender

& race. Medicare

patients, 2004, used

as reference cohort.

USRDS 2006

Poor CKD outcomes

Summary of categorical meta-analysis (adjusted relative risk (RR)) for general population cohorts with albumin-to-creatinine ratio (ACR)

CKD Outcomes Are WorseLongitudinal Follow-up and Outcomes Among a Population With Chronic Kidney Disease in a Large Managed Care Organizat

Keith DS, et al. Arch Int Med 164:659-663, 2004

ControlGFR 60 - 89Absent

proteinurian = 14,20253.9 months f/u

Stage 3n = 1,74149.8 months f/u

Stage 4n = 11,27851.1 months f/u

Stage 5n = 77737.6 months f/u

Blue DeathYELLOW Dialysis

or Kidney Transplantation

Death, Control, 10.2

Death19.5

CKD3

Death24.3

CKD4

Death45.7

CKD5

ESRD, Control, 0.07

ESRD1.1

ESRD1.3

ESRD19.9

De

ath

an

d E

SR

D, %

Many Studies..

KI 2007;72:632-637

It is just 10 years earlier or 20P difference !

In a study of over 1,000,000 individuals in the Medicare in the US, outcomes per 100 patient-years at two year follow-up for those CKD-Non DM and those with both CKD and diabetes were :

• RRT were 1.6 and 3.4

• Death rates 17.7 and 19.9

• Atherosclerotic VD 35.7 and 49.1

• Heart failure rates 30.7 and 52.3.

CKD with GFR < 60 ml/min are a CHD risk equivalent .uptodate 15.1

Medicare: death in CKD without DM is >10 X risk for ESRD

Age based ckd distribution

Females! Unexpected?

1.8%

Changing Risk factors into Diseases and Inventing Population Epeidemics !

• So, my earlier published suggestion about offering renal transplantation to reduce the high CKD mortality looks like offering knee replacement at an early osteoarthritis stage to reduce the high mortality in those osteoarthritic elderly population..

• Balancing..This not to say that advanced age

related CKD is not a disease! GFR < 30- 45 ml/min/1.73 m2 Excessive brain cell is a disease..

Prevalence CKD according to age, (the AusHEART study):Nephrol Dial Transplant (2012) 27: 1396–1402

A representative, cluster stratified, cross-sectionalsurvey among 322 GPs for patients >55

CKD 3

D. Banerjee et al documented the well known finding of presence of a very high prevalence of cardiovascular risk factors among their CKD population. Int Urol Nephrol (2009) 41:443–451

BUT..

The False CKD3 subgroup

• Botev RC et al (J Am Soc Nephrol 16: 508A, 2005):

CG and MDRD formulas misclassified overall 39.8 and 44.0% of the entire population, respectively.

Hazard ratios for all-cause mortality by stages of chronic kidney disease in cohort participants

Taiwan study, The lancet 2008; Vol 371: 2173-82

CKD1 worse: Not only in PREVEND??

Risk of all-cause mortality according to eGFR (CKD-EPI), adjusted for age, sex, and comorbidities.

RR of death with higher eGFR was more in older than younger individuals (e.g. HR of eGFR>105 ml/min was 5.3 for people aged> 60 and 1.1 for aged <40 years).

Kidney International (2011) 80, 1306–1314