Essentials of CKD

Comorbidities and outcomes in CKD

Anaemia is Prevalent in CKD and its Severity Increases with Worsening Kidney Function

Anaemia is prevalent in the CKD population (e.g. 47.7% of a population of 5,222 CKD patients)1

Prevalence of anaemia increases with declining renal function1,2

p<0.05 between all categoriesLVM=left ventricular mass

Hb <12–11 g/dL

Hb <11–10 g/dL

<10 g/dL

Hb 13–12 g/dL

0

5

10

15

20

25

Creatinine clearance (mL/min)

Pati

en

ts (

%)

25%

>50

44%

35–49

51%

25–34

87%

<25

30

1. McClellan W et al. Curr Med Res Opin 2004;20:1501–1510; 2. USRDS 2008 Annual Data Report, Atlas of CKD. Am J Kidney Dis 2009;53(suppl 1):S23–S36

3. Levin A et al. Am J Kidney Dis 1999;34:125–134

Canadian multicentre prospective cohort study3

N= 446 renal insufficiency patients

Anaemia is Defined by a Reduction in Haemoglobin Levels

There are numerous groups that have defined anaemia in patients with CKD1

EBPG 2004 KDOQITM 2006/2007 ERBP 2008

Hb <11.5 g/dL (F)Hb <13.5 g/dL (M ≤70 years)Hb <12 g/dL (M >70 years)

Hb <12 g/dL (F)Hb <13.5 g/dL (M)

Hb <12 g/dL (F)Hb <13.5 g/dL (M)

1. Locatelli F et al. Nephrol Dial Transplant 2009;24:348–354

EBPG=European Best Practice Guidelines; KDOQI™=Kidney Disease Outcomes Quality Initiative; ERBP=European Renal Best Practice; Hb=haemoglobin; F=female; M=male

Anaemia can be Caused by Numerous Factors Related to CKD

EPO deficiency/resistance1

Shortened red cell life span (‘uraemic milieu’)1

Iron deficiency1

Blood loss – dialysis and GI bleeding1

Hyperparathyroidism1

Nutritional deficiencies1

Inflammation1

Drugs (e.g., ACE inhibitors, aspirin, ARBs)1

1. Kazory A & Ross EA. J Am Coll Cardiol 2009;53:639–647EPO, erythropoietin; GI, gastrointestinal; ACE, angiotensin-converting enzyme; ARB, angiotensin II receptor blocker

Falling Hb Levels are Related to Increased Hazard Ratio for ESRD and All-cause Mortality

853 pre-dialysis patients, CKD Stage 3–5

Male US veterans referred to a single nephrology clinic between January 1990 and December 2004

Kovesdy CP et al. Kidney Int 2006;69:560–564ESRD, end-stage renal disease

ESRD All-cause mortality

<11.0

Hazard

rati

o

1

11.1–12.0 12.1–13.0 >13.00

5

10

15

17

Time-averaged Hb (g/dL)

<11.0

Hazard

rati

o

1

11.1–12.0 12.1–13.0 >13.00

2

3

5

7

Time-averaged Hb (g/dL)

4

6

Unadjusted Adjusted Unadjusted Adjusted

Low Hb Levels are Associated with Reduced Rate of Survival

Retrospective, longitudinal study of 44,550 HD patients from FMCNA database

Ofsthun N et al. Kidney Int 2003;63:1908–1914

Days follow-up

80

Su

rviv

al (%

)

1800 30 60 90 120 150

100

90

Hb ranges (g/dL)

Hb ≥13.012.0 ≤ Hb <13.0 11.0 ≤ Hb <12.010.0 ≤ Hb <11.09.0 ≤ Hb <10.0Hb <9.0

HD=haemodialysis; FMCNA=Fresenius Medical Care North America

Unadjusted

Case-mix

Case-mix & MICS

Hb 12–13 g/dL is Associated with a Greater Chance of Survival in HD Patients

Regidor DL et al. J Am Soc Nephrol 2006;17:1181–1191

Prospectively collected data of a 2-year historical cohort of all HD patients in the national database of DaVita Inc

<9

All

cau

se m

ort

ality

hazard

rati

o

0.8

3

1

5

2

Hb (g/dL)

9.0–9.4

9.5–9.9

2000

4000

6000

8000

10000

12000

0

10.0–10.4

10.5–10.9

11.0–11.4

11.5–11.9

12.0–12.4

12.5–12.9

13.0–13.4

13.5–13.9

≥14

Unadjusted

Case-mix

Case-mix & MICS

Fre

qu

en

cy

All-cause death in all patients(Incident and prevalent)

n=58,058

All-cause death in all patients(Incident and prevalent)

n=58,058

Hb (g/dL)

Card

iovascu

lar

mort

ali

ty h

azard

rati

o

1

0.8

2

3

5

<9

9.0–9.4

9.5–9.9

10.0–10.4

10.5–10.9

11.0–11.4

11.5–11.9

12.0–12.4

12.5–12.9

13.0–13.4

13.5–13.9

≥14

MICS, malnutrition inflammation complex syndrome

No. at risk

Normal haematocritLow haematocrit

1,233 patients on HD for 3 years– 65±12 years (normal group), 64±12 years (low group)

– CHF, ischemic heart disease

39–45 %

27–33 %

Besarab A et al. N Engl J Med 1998;339:584–590

Lower Haematocrit has been Shown to be Associated with Reduced Mortality

0

Pro

bab

ilit

y o

f d

eath

or

myocard

ial in

farc

tion

(%

)

0

10

20

30

40

Normal-haematocrit group

Months after randomisation3 6 9 12 15 18 21 24 27 30

50

60

Low-haematocrit group

618 540 476 415 353 259 186 124 69 26 615 537 485 434 391 292 216 131 80 20

Numerous Comorbidities are Associated with CKD

CV disease, diabetes and hypertension are also common comorbidities observed in patients with CKD1

1. USRDS 2008 Annual Data Report, Atlas of CKD. Am J Kidney Dis 2009;53 (suppl 1):S23–S36

Pre

vale

nce (

%)

eGFR (mL/min/1.73 m2)

0

25

50

75

100

>105 90–105 75–<90 60–<75 45–<60 30–<45 <30

Diabetes1 CV disease1 Hypertension1

CV Morbidity and Mortality Increase with Worsening Kidney Function

CKD progression leads to a requirement for dialysis and/or kidney transplantation1

However, most patients with CKD die prematurely of CVD2

– CV morbidity and mortality increases with decreasing kidney function3–5

1. Zhang Q-L & Rothenbacher D. BMC Public Health 2008;8:117; 2. Besarab A et al. N Engl J Med 1998;339:584–590; 3. Go AS et al. N Engl J Med 2004;351:1296–1305; 4. Shlipak MG et al. JAMA 2005;293:1737–1745; 5. Keith DS et al. Arch Intern Med 2004;164:659–663

KPRR=Kaiser Permanente Renal Registry;HR=hazard ratio

Risk of CV Events and Hospitalization Increases with Declining Kidney Function

Cohort of 1,120,295 pre-dialysis patients from the KPRR studied for 2.84 years1

1. Go AS et al. N Engl J Med 2004;351:1296–1305

Ag

e-s

tan

dard

ised

rate

of

death

fro

m a

ny c

au

se

(per

100

pers

on

years

)

0.76

≥60

1.08

45–59 30–44 15–29 <15

eGFR (mL/min/1.73 m2)

15

10

5

0

Mortality (N=51,424)

Ag

e-s

tan

dard

ised

rate

of

CV

even

ts

(per

100

pers

on

years

)

2.11

≥60

3.65

45–59 30–44 15–29 <15

eGFR (mL/min/1.73 m2)

40

20

0

CV events (N=138,291) Hospitalisation (N=554,651)

Ag

e-s

tan

dard

ised

rate

of

hosp

italisati

on

(p

er

100

pers

on

years

)

13.54

≥60

17.22

45–59 30–44 15–29 <15

eGFR (mL/min/1.73 m2)

150

100

50

0

30

1011.29

21.80

36.60

4.76

11.36

14.14

42.26

86.75

144.61

Anaemia Contributes to the Incidence of CVD in Patients with CKD

CV events1–5 and disease progression?2,4

– Anaemia is a risk factor for CVD in patients with CKD1–4

In the NKF’s KEEP cohort of 37,000 patients, anaemia and GFR were independently associated with CVD and decreased survival3

– Anaemia is a risk factor for worse outcomes in patients with CKD4,5

– Anaemia is a risk factor for progression of CKD?2,4

1. Mix TC et al. Am Heart J 2005;149:408–413; 2. Walker AM et al. J Am Soc Nephrol 2006;17:2293–2298; 3. McCullough PA et al. Arch Intern Med 2007;167:1122–1129; 4. Thorp ML et al. Nephrology 2009;14:240–246;

5. Schmidt RJ & Dalton CL. Osteopath Med Prim Care 2007;1:14

CVD=cardiovascular disease; NKF=National Kidney Foundation; KEEP,=Kidney Early Evaluation Program