Post on 26-Mar-2015
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