reciprocal relationship : renal anemia, diabetes & cvd

Reciprocal Relationship :Renal Anemia, Diabetes &

CVD

Anaemia in diabetic renal disease: an underestimated and unrecognised risk factor?

Diabetes: a worldwide epidemic

Awareness of anaemia in people with diabetes - Europe

Questionnaire based interview with 1054 respondents in six European countries to assess the level of understanding and awareness of anaemia and its impact on quality of life amongst people with diabetes

32% had been given information on anaemia, less than 50% were aware of being tested for anaemia and only 14% attributed anaemia to diabetes

132 (12.5%) known to be anaemic

– one-fifth were not receiving any treatment

– 12 received blood transfusions

– 5 patients were on erythropoietin

– Remainder were given iron and/or vitamin supplements

Perceived state of health in those with anaemia was worse

Stevens et al Curr Med Res Opin 2003; 19: 395-401

Awareness of anaemia in people with diabetes - USA

504 respondents selected from a nationally representative panel of people with diabetes

26% were aware that they were at risk for anaemia

14% were aware that they had been diagnosed with anaemia

Of the 86% of patients not diagnosed with anaemia– 58% indicated they suffer from one or more symptoms often

associated with anaemia• 69% attributed the symptoms to diabetes• 66% attributed the symptoms to ageing

Roper Starch Worldwide 2001

Awareness of anaemia in physicians caring for people with diabetes

Unrecognised anaemia in patients with diabetes1

– cross sectional survey of 820 patients in a diabetic clinic

– 190 (23%) had unrecognised anaemia by WHO definition and 56 (7%) by KDOQI/EBPG definition

– risk of anaemia increased 2-3x in people with diabetes

Prevalence and degree of anaemia in diabetic patients with declining renal function2

– cross sectional survey of 119,730 patients in diabetes clinics and GPs surgeries

– 3507 (2.93%) had creatinine clearance < 90 ml/min

– 39.6% men and 43.9% women had unrecognised anaemia by WHO definition and 17.2% men and 25.8% women by KDOQI/EBPG definition

1. Thomas et al Diabetes Care 2003; 26:1164-11692. 2. Hasslacher et al IDF Paris 2003; poster 946

Awareness of anaemia in physicians caring for people with diabetes

Anaemia in diabetes – under recognised and under treated– prospective survey of all patients unknown to renal services with

serum creatinine >180 µmol/L in men and >135 µmol/L in women over a 2 year period

– 872 people with diabetes and chronic renal failure (median glomerular filtration rate 29.9 ml/min)

– 17.7% of patients had not had Hb levels checked at all

– of the remainder, 65.7% men and 53.6% women had unrecognised anaemia by WHO definition and 21.5% men and 27.8% women had Hb levels < 11 g/dL

John et al IDF Paris, 2003 poster 1315

Increasing awareness of anaemia in diabetic kidney disease

The Individualised Risk-profiling In DIabEtes Mellitus (IRIDIEM) study

An observational study of patients with diabetes and chronic kidney disease aiming to– document current management of diabetic nephropathy

– study the effect of individualised and evidence-based cardio- and reno-protective interventions on cardiovascular and metabolic risk profile and outcomes

IRIDIEM: Study design

Phase l

Pharmaco-epidemiological assessment(~2500 patients with diabetic nephropathy and risk factors)

Phase llEvidence-based educational guidance for individualising reno- and cardio-protective

interventions(~700 patients stage lll or lV CKD and risk factors)

Re-assessment of risk factor status

6 and 12 months after enrolment

Why should we be aware of anaemia in diabetic renal disease?

The risk of coronary heart disease in people with diabetes is 2-4x higher than the general population and the risk of cerebrovascular disease up to 5x higher

Anaemia develops early in chronic kidney disease The risks of cardiovascular disease develop early in the

course of chronic kidney disease and are increased by diabetes

Combination of anaemia and chronic kidney disease substantially increases stroke risks

Anaemia predicts left ventricular mass, left ventricular dilation, heart failure and death

Anaemia develops early in chronic kidney disease

Canadian multicenter cohort study WHO criteria

Levin et al, Am J Kidney Dis 1999; 34: 125-134

Prevalence (%)

Creatinine clearance (ml/min)

100

40

0

>50 35-49 25-34 <25

25

4451

87

20

60

80

Anaemia develops early in CKD

NHANES III– 15,419 non-institutionalised adults over the age of 20

– Prevalence of anaemia (KDOQI) increased from 1% at glomerular filtration rate of 60 ml/min to 9% at 30 ml/min and 33% at 15 ml/min

Astor et al, Arch Int Med 2002; 162: 1401-1408

Hb

(g/d

L)

Glomerular filtration rate (ml/min)

5

10

15

20

60 30 15

Hb (men)Hb (women)

Prevalence of anaemia in early renal insufficiency – PAERI study

1716 subjects, mean age 68 Mean serum creatinine 2.2 mg/dL (194 µmol/L) Mean Hb 12 g/dL Odds ratio of Hb < 12 g/dL or < 10 g/dL 1.8x in diabetes

vs. no diabetes

McClellan et al, ASN 2001

Cardiovascular disease in early chronic kidney disease

HDFP study1

– subjects with serum creatinine >150 µmol/L vs. < 150 µmol/L OR for death after 8 years 2.2

Framingham study2

– increased incidence of cardiovascular disease in those with renal insufficiency

Canadian multicenter cohort3

– incidence of cardiovascular disease already 35.2% in those with glomerular filtration rate >50 ml/min and rose to 45.3% in those with glomerular filtration rate <25 ml/min

1. Shulman et al Hypertension 1989; 13(5):I80-932. Culleton et al Kidney Int 1999; 56: 2214-22193. Levin et al, Am J Kidney Dis 1999; 34: 125

Framingham study, N = 6223

0

5

10

15

20

25

ECG LVH CHD CHF CVD

Culleton et al Kidney Int 1999; 56: 2214-2219

8% mild CRF (males serum creatinine 136-265, females 120-265 µmol/L)

Percentage (%)

No renal insufficiencyChronic renal insufficiency

ECG LVH=echocardiogram left ventricular hypertrophyCHD=coronary heart diseaseCHF=congestive heart failureCVD=cardiovascular disease

Canadian multicenter cohort study of chronic kidney disease

•Prevalence of any cardiovascular disease and left ventricular hypertrophy by creatinine clearance

Per

cen

tag

e (%

)

Levin et al, Am J Kidney Dis 1999; 34: 125-134

Creatinine clearance (ml/min)

60

50

40

30

20

10

0>50 35-49 25-34 <25

Cardiovascular diseaseLeft ventricular hypertrophy

SOLVD study1 – increase relative risk of mortality of 1.44 and relative risk of

pump failure of 1.68 in subjects with glomerular filtration rate <60 ml/min compared with > 60 ml/min

HOPE study2 – cardiovascular disease mortality, myocardial infarction or stroke

22.2% in subjects with serum creatinine 124-200 µmol/L vs. 15.1% in those with serum creatinine < 124 µmol/L

Cardiovascular Health Study3 – OR 2.34 for cardiovascular disease in subjects with serum

creatinine > 132 µmol/L in males and > 114 µmol/L in females

Cardiovascular disease in early chronic kidney disease

1. Dries et al, J Am Coll Cardiol, 2000; 35 :681-6892. Mann et al, Ann Int Med, 2001;134:629-363. Manjunath et al, Kidney Int, 2003; 63: 1121-1129

Prevalence of cardiovascular abnormalities is higher among diabetic patients with CKDNewfoundland/Montreal study

18

24

38

32

48 50

0

10

20

30

40

50

60

Non-diabetic

Diabetic

p=0.003 p<0.00001 p=0.04Prevalence at dialysis start (%)

Foley et al Diabetologia 1997; 40: 1307-1312

CLVHIHD CF

IHD=ischaemic heart diseaseCF=cardiac failure CLVH = concentric left ventricular hypertrophy

1 1 1 1

3.2

1.2

2.32.6

0

0.5

1

1.5

2

2.5

3

3.5

IHD CCF Death CV Death

Non-diabetic

DiabeticRel

ativ

e r

isk

p=0.0003 p=ns p<0.0001 p<0.0001

CV = cardiovascularIHD = ischaemic heart disease CCF = chronic cardiac failure

Foley et al Diabetologia 1997; 40: 1307-1312

Prevalence of cardiovascular abnormalities is higher among diabetic patients with CKDNewfoundland/Montreal study

Anaemia, chronic kidney disease and risk of stroke – the ARIC study, n = 13,716

Community based cohort, 9 yr follow up

– mean age 54.1 ± 5.7, mean Hb 13.9, 10.6% diabetic

– 15 percent Cr Cl < 60 ml/min, mean blood pressure 120/71

– 85 percent Cr Cl ≥ 60 ml/min, mean blood pressure 121/74

– Use of anti-hypertensives 24.6% & 23.5%

Lower Cr Cl associated with higher crude stroke rate

– Cr Cl < 60 ml/min, stroke rate 3.7

– Cr Cl ≥ 60 ml/min, stroke rate 2.06

Abramson et al, Kidney Int 2003; 64: 610-615

ARIC study – influence of anaemia (WHO)

Str

oke

rat

e

Abramson et al, Kidney Int 2003; 64: 610-615

0

2

4

6

8

10

12

Total sample Anaemic group Nonanaemic group

Cr Cl ≥ 60 ml/minCr Cl < 60 ml/min

2.06

3.7

1.52

10.53

2.122.85

Effect of 1g/dL fall in Hb

1.6

1.4

1.2

1.0

0.8

0.6

0.4

0.2

0CLVH LV Dil SDF CCF IHD Death

1

1.491.55

1.24

1

1.25

Foley et al Am J Kidney Dis 1996; 28: 53-61 .

Re

lativ

e r

isk

CLVH = concentric left ventricular hypertrophyLV Dil = left ventricular dilatation SDF = systolic dysfunctionCCF = chronic cardiac failureIHD = ischaemic heart disease

Cause specific death rates for prevalent dialysis patients aged 20

USRDS 1997-1999

0

10

20

30

40

50

60

70

Acute MI Cardiac arrest Cardiac other

Deaths per 1000 patient

years

Diabetes mellitus

No diabetes mellitus

Mortality and haematocrit level: First year follow up, all dialysis patients

USRDS prevalent patients 1994-1997

Haematocrit

0

50

100

150

200

250

300

350

400

<30 30 - <33 33 - <36 36+

Deaths per 1000 patient

years

Diabetes mellitus

No diabetes mellitus

Conclusions

Anaemia is prevalent in people with diabetic kidney disease and is largely unrecognised and untreated

Anaemia occurs earlier in diabetic kidney disease than is commonly recognised

The association between chronic kidney disease and all forms of cardiovascular disease begins early in the evolution of chronic kidney disease, anaemia significantly amplifies this association

Cardiovascular events and mortality in chronic kidney disease are increased in patients with diabetic kidney disease and are closely related to anaemia

Aetiology of anaemia and

benefits of early treatment

in patients with diabetes

Diabetes and renal disease

WHO & IDF estimates suggest that in Europe there are already 32 million adults age 20-79 with diabetes

Diabetes is the commonest cause of end stage renal failure worldwide and up to 1 in 4 people with diabetes will develop diabetic kidney disease over the course of 20 years

Studies such as the RENAAL1 and UKPDS2 clearly demonstrate that the risk of mortality in diabetic kidney disease clearly outweighs the risk of progression to end stage renal disease

1. Keane et al Kidney Int 2003 63:1499-507 2. Adler et al Kidney Int 2003 63:225-32

Cardiovascular risk factors in chronic kidney disease

Traditional– older age– male gender– BP & LVH– LDL-C HDL-C– diabetes– smoking– inactivity– menopause

CKD related– RAS activity– ECFV overload

– Ca/PO4 abnormalities

– anaemia– MIA syndrome– oxidative stress– Homocysteine– thrombogenic factors– GFR

Diabetic kidney disease and anaemia

Anaemia is prevalent in people with diabetic kidney disease and is largely unrecognised and untreated

Anaemia occurs earlier in diabetic kidney disease than is commonly recognised

The association between chronic kidney disease and all forms of cardiovascular disease begins early in the evolution of chronic kidney disease; anaemia significantly amplifies this association

Cardiovascular events and mortality in chronic kidney disease are increased in patients with diabetic kidney disease and are closely related to anaemia

Potential causes of anaemia in chronic kidney disease

Decreased erythropoietin production Shortened red blood cell survival Iron deficiency Inhibition of erythropoiesis Malnutrition and other deficiencies Chronic inflammation

Anaemia in diabetic nephropathy Aetiology

Decreased erythropoietin levels resulting from:

Tubulointerstitial damage Autonomic dysfunction Use of ACE inhibitors?

Reviewed in Bilous Acta Diabetol 2002; 39: S15-19

Erythropoietin (EPO)

Produced predominantly by peritubular fibroblasts in the kidneys and released in response to anaemia and hypoxia

Release is modulated through the sympathetic nervous system (ß-adrenergic receptors)

Anaemia associated with EPO deficiency usually occurs at a glomerular filtration rates below 35-40 ml/min but may occur at higher levels in diabetic kidney disease

Anaemia occurs early in diabetic nephropathy and is more severe than non-diabetic patients

Bosman et al Diabetes Care 2001; 24: 495-499

DN anaemic* DN normal GN Non-DN anaemic

Serum creatinine (mmol/l)

110(63–160)

88(64–133)

93(49–180)

68(59–148)

Proteinuria (g/day)

2.5(0.1–5.2)

0.6(0.1–2.9)

1.9(0.3–5.0)

Hb (g/dl)

10.6(8.7–12.0)

13.7(11.8–15.1)

13.7(11.6–16.3)

9.3(6.9–11.6)

Erythro-

poietin (IU/l)8.1

(2.5–19.0)8.5

(2.5–17.5)8.5

(2.5–17.0)57.7

(29.2–195.8)

*Anaemia <11.5 g/dl women, <12.0 g/dl men

DN=diabetic nephropathy; GN=glomerulonephritis

Low serum erythropoietin levels cause anaemia and may predict the severity of diabetic nephropathy

Bosman et al Diabetes Care 2001; 24: 495-499

0

2

4

6

6 8 10 12 14 16

Non-anaemia and microcytic anaemic control subjects, n=32 Diabetic nephropathy, n=26

Hb (g/dl)

ln E

PO

Erythropoietin-deficiency anaemia in diabetic nephropathyUnderlying autonomic neuropathy

15 type 1 diabetic patients with severe complications including autonomic neuropathy and normal (<122 µmol/L) serum creatinine

Compared with 18 controls matched for age and duration of diabetes but not for renal function

Winkler et al Diabetic Med 1999; 16: 813-819

Diabetes + AN

Diabetes

Number of patients

15 18

Duration (y) 22.7 25.2

Hb (g/dl) 11.1 13.7(p<0.01)

Serum creatinine (µmol/L)

86.9 66.4

Proteinuria 3 micro-albuminuria; 12 proteinuria

3 micro-albuminuria

AN = autonomic nephropathy

Erythropoietin-deficiency anaemia in diabetic nephropathy: Underlying autonomic neuropathy

0

2

4

6

6 8 10 12 14 16

Hb (g/dl)

ln E

PO

Iron deficient and normals, n=32 Diabetic nephropathy, n=26

Winkler et al Diabetic Med 1999; 16: 813-819

Iron deficiency and anaemia in chronic kidney disease

Women Men

(g/dL) P (g/dL) P

Fer ≥ 100 ng/mL & TSAT ≥ 20%

reference reference

Fer < 100 ng/mL & TSAT ≥ 20%

- 0.2 0.002 - 0.1 0.30

Fer ≥ 100 ng/mL & TSAT< 20%

- 0.3 0.001 - 0.4 0.004

Fer < 100 ng/mL & TSAT < 20%

- 0.6 <0.0001 - 0.8 <0.0001

Hsu et al, J Am Soc Nephrol 2002;13:2783-86

Fer=ferritinTSAT=transferrin saturation

Iron deficiency and anaemia in diabetes

Unrecognised anaemia in patients with diabetes Cross sectional survey of 820 patients in a diabetic clinic Mean Hb 13.9 g/dL (men) & 12.9 g/dL (women) 190 (23%) had unrecognised anaemia by WHO

definition and 56 (7%) by KDOQI/EBPG definition Most powerful predictors were transferrin saturation and

glomerular filtration rate accounting for 22% and 10% of the variance in Hb respectively

Thomas et al, Diabetes Care 2003;26:1164-1169

Why do we treat renal anaemia?

Subjective1

– well-being– life satisfaction– happiness– psychological affect

Objective1

– energy level– functional ability– activity level– health status

Others– cardiac status2

– blood transfusions3

– hospitalisation4

– mortality5

1. Evans et al J Am Med Soc. 1990; 263:825-8302. Winearls Nephrol Dial Transplant 1995; 10(suppl10):3-93. Fellner et al Kidney Int; 1993; 44:1309-13154 Churchill et al Clin Nephrol 1995; 43:184-1885. US Renal Data System 1998

What do we hope to achieve by the early treatment of renal anaemia?

Increased exercise capacity, improved quality of life, cognitive function and sexual function

Regression of left ventricular hypertrophy

Reduced mortality and hospitalisation

Reduced transfusion requirements

?Regression of chronic renal failure progression

Epoetin improves quality of life in predialysis patients

83 predialysis patients entered into a parallel-group, open-label clinical trial and randomised to – epoetin

– no treatment

Epoetin treatment significantly improved anaemia and– energy

– physical function

– home management

– social activity

– cognitive function

Revicki et al Am J Kidney Dis 1995; 25: 548-554

QOL following correction of anaemia

Moreno et al, Am J Kidney Dis 1996;27:548-56

Ka

rno

fsky

sca

le s

core

Age <60 years Age >60 years

50

60

70

80

90

Basal 6 months

QOL following correction of anaemia

Moreno et al, Am J Kidney Dis 1996;27:548-56

Age <60 yearsAge >60 years

Sic

knes

s im

pac

t p

rofi

le

sco

re

0

5

10

15

20

25

30

35

Basal 6 months

Correction of anaemia improves left ventricular hypertrophy in dialysis patients

22 dialysis patients studied by echocardiogram before and after correction of their anaemia with epoetin

Hb increased at least 3.0 g/dL over baseline

Correction of anaemia produced:– decrease in left ventricular mass (p = 0.0004)

– decrease in left ventricular end-diastolic volume (p <0.0001)

Adapted from Silverberg et al. Can J Cardiol 1990; 6: 1-4

Adapted from Portolés et al Am J Kidney Dis 1997; 29: 541-548

Partial correction (n=11)

Reduction in LVMI with partial anaemia correction in predialysis patients

LVM

I (g/

m2 )

Baseline Hb = 9.0 g/dl

0

100

140

180

220

260Epoetin

p<0.05

178.2

147.3

6 MonthsHb = 11.7 g/dl

LVMI = left ventricular mass index

Mean value

111.2

p=0.0108

Epoetin

0

20

40

60

80

100

120

140

160

180

200

140.6126.9

Complete correction (n=9)

Baseline Partial Normal Hct = 23.6% Hct = 32.1% Hct = 39.1%

LVM

I (g/

m2 )

Reduction in LVMI with complete anaemia correction in predialysis patients

Adapted from Hayashi et al Am J Kidney Dis 2000; 35: 250-256LVMI = left ventricular mass index

Building the evidence: Mortality & hospitalisation

Lombardy registry1

– all cause mortality and hospitalisation risks reduced with Hct levels >32% compared with <27% (n=5302)

Ma et al2

– RR mortality reduces as Hct rises, 1.51 at Hct < 27% to 0.9 at Hct 33-36% (n=96,369)

Xia et al3

– hospitalisation risks lowest in patients with Hct 33-36% (n=71,717)

1. Lombardy registry Nephrol Dial Transplant 1998;13:1642-442. Ma et al J Am Soc Nephrol 1999;10:610-6193. Xia et al J Am Soc Nephrol 1999;10:1309-1316

Building the evidence: Mortality & hospitalisation

Collins et al1

– Relative risk of death and/or hospitalisation lowest at Hct levels of 36-39%

Fink et al2

– Pre-dialysis epoetin treatment leads to a relative risk of mortality of 0.8 (n=4866, 1107 epoetin)

1. Collins et al J Am Soc Nephrol November 20012. Fink et al Am J Kidney Dis 2001;37:348-355

0

2

4

6

8

10

12

14

16

18

Epoetin therapy correlates with reduced mortality and less hospitalisation

Adapted from Locatelli et al Nephrol Dial Transplant 1998

Hct <27%

Patients with diabetes = 7.6%

Hospitalisation days per patient-year

Adjusted general mortality(n=5302)

Odds

rati

o

Adjusted CVmortality(n=5302)

rh EPO-treated haemodialysis patientsUntreated haemodialysis patients

0.8

0.6

0.4

0.2

0

1

p <0.001 p <0.05

Hct 27–32% Hct >32%

Adapted from Ma et al. J Am Soc Nephrol 1999; 10: 610-619

Mortality adjusted for risk factors [without severity of disease]

Relative risk of mortality according to haematocrit in US patients with end stage renal disease

0.5 1.0 1.5

33-36

30-33

27-30

<27

Hae

mat

ocrit

(%

)

Relative risk

(0.90)

(1.00)

(1.20)

(1.51)

2.0

n = 96,369Diabetes = 50%

Mortality, hospitalisation, and economic associations in HD patients aged 65 years

Incident Medicare HD cohort 1/1/1996 to 30/6/1998 Follow-up period: one year Variables

– age, gender, race, renal diagnosis, comorbidity, number of transfusions, number of access procedures, number of hospital days

Hct groups: <30, 30<33, 33<36, 36<39, 39+ Outcome: risk of death and first hospitalisation

Collins et al, ASN 2001

0.0

0.5

1.0

1.5

2.0

2.5

Relative risks of death and 95% CIRelative risks of death and 95% CI

< 30 30-<33 33-<36 36-<39 39

All-cause

Cardiac

Infection

reference


Haematocrit

Rel

ativ

e ri

sk

Relative risks of hospitalisation & 95% CI

Relative risks of hospitalisation & 95% CI


<30 30-<33 33-<36 36-<39 >=39

All-cause

Cardiac

Infection

reference

Haematocrit

Rel

ativ

e ri

sk

0.0

0.2

0.4

0.6

0.8

1.0

1.2

1.4

1.6

1.8

2.0

Reduced mortality with anaemia treatment pre-dialysis

4,866 patients, median follow up 26.2 months 1,107 treated with epoetin pre-dialysis Relative risk of death for epoetin-treated

pre-dialysis = 0.8 Most significant survival benefit was in those with

the highest haematocrit Concluded that epoetin use pre-dialysis confers

survival benefit

Fink et al, Am J Kid Dis 2001;37:348-355

Reversal of anaemia by epoetin can retard progression of chronic renal failure

Adapted from Kuriyama et al Nephron 1997; 77: 176-185

Cum

ulat

ive

rena

l sur

viva

l rat

e (%

)

20

0

40

60

80

100

0 5 10 15 20 25 30 35 40

p=0.

0024

p=

0.31

11

p=0.

0003

Months of follow-up

Hct <30%, treated with epoetinHct >30%, untreatedHct <30%, untreated

n=108

Building the evidence: delaying progression of chronic renal failure

• 63 patients (serum creatinine > 300 μmol/L, creatinine clearance < 15 mL/min/1.73 m2)

• 20 with Hb < 10 g/dL = study group (epoetin+) 43 with Hb > 10 g/dL= control group

• Significant reduction in rate of progression of chronic renal failure in study group, no change in control group

Jungers et al Nephron Dial Transplant 2001; 16: 307-312

Trials in treatment of CKD anaemia

CREATE trial (Cardiovascular risk Reduction by Early Anaemia Treatment with Epoetin beta)

CHOIR trial (Correction of Haemoglobin and Outcomes In Renal Insufficiency)

ACORD (Anaemia CORrection in Diabetes)

Aims of the studies : to establish whether early intervention– prevents development of left ventricular hypertrophy– reduces cardiovascular mortality and morbidity– delays progression of chronic renal failure– reduces stroke and heart failure related hospitalisations

Time or creatinine

CREATE trial (Cardiovascular risk Reduction by Early Anaemia Treatment with Epoetin beta)

Hb

(g

/dl)

15

12.5

10

Group 1(Hb 13-15 g/dl)

Group 2(Hb 10.5-11.5 g/dl)

•600 subjects glomerular filtration rate 15-35 ml/min randomised to 2 groups, early intervention and standard practise

Time or creatinine

CHOIR trial (Correction of Haemoglobin and Outcomes In Renal Insufficiency)

Hb

(g/

dl)

15

12.5

10

Group 1(Hb 13-13.5 g/dl)

Group 2(Hb 10.5-11.0 g/dl)

•2000 subjects GFR 15-50 ml/min randomised to 2 groups

The Anaemia CORrection in Diabetes (ACORD) study

The ACORD study is investigating the effects of anaemia correction with subcutaneous epoetin beta on – cardiac structure

– cardiac function In patients with early diabetic nephropathy Primary endpoint

– effect of early anaemia treatment on left ventricular hypertrophy as a cardiovascular risk marker

Hb (g/dl)

16

14

12

10

8

6

16

14

12

10

8

6

Early intervention

Target Hb: 13–15 g/dl

Standard treatment

Target Hb: 10.5–11.5 g/dl

Inclusion:Hb 10.5–13.0 g/dlCreatinine clearance ≥30 ml/min

m

f

Time

n = 160

Randomisation

ACORD: Study design

European recommendations for optimising treatment of renal anaemia

Indication for start of epoetin therapy:– repeated Hb measurements <11g/dL

– after exclusion of non-renal causes of anaemia (bleeding, nutritional deficiencies, hypothyroidism, iron deficiency, haemolysis)

Target haemoglobin: – general: Hb >11 g/dL (no upper limit)

– in CHD: Hb 11-12 g/dL Administration of epoetin:

– SC dosing preferred; IV dosing also an option in HD patients

– the goal is to increase Hb levels by 1–2 g/dL per month

van Ypersele de Strihou Nephrol Dial Transplant 1999; 14 (suppl 2): 37-45

Iron stores

Target– serum ferritin > 100 g/l (aim for 200-500)

– hypochromic red blood cell count < 10%, TSAT > 20% (aim for < 2.5% & 30-40%)

Level B Treatment strategies

– predialysis and CAPD oral intravenous

– HD will need intravenous

Level B

How should epoetin be administered to predialysis patients with diabetes and

anaemia?

EBPG & KDOQI recommend epoetin treatment for anaemia due to CKD when Hb < 11 g/dL

Hb correction should be gradual to avoid:– exacerbation of hypertension– increased viscosity with adverse haemodynamics

Guidelines recommend an increase of Hb 0.5 g/dL every 2 weeks

Common practice suggest a target Hb of 11–12 g/dL (or ?12-13 g/dL)

Conclusions

Anaemia is prevalent in diabetic kidney disease and occurs earlier than is commonly recognised

Proven benefits of treatment of anaemia with epoetin (± intravenous iron) include– improved quality of life and performance status– regression of left ventricular hypertrophy– reduced transfusion requirements

Potential benefits of early anaemia treatment include– reduced cardiovascular mortality and morbidity– delayed progression of chronic renal failure– reduced stroke and heart failure related hospitalisations

reciprocal relationship : renal anemia, diabetes & cvd

Documents

attributed anaemia

diabetesunrecognised

degree of anaemia

diabetic patients

diabetes cvdanaemia

diabetes prevalence

diabetes clinics

diabetes care