MAJOR SOCIO-ECONOMIC,
MEDICAL AND SCIENTIFIC
CHALLENGE
R Vanholder
University Hospital, Gent
MECHANISMS KIDNEY
FAILURE
• Healthy kidneys purify the blood from waste
products by excreting them in the urine
• Normally, 120 mL of blood are purified per
minute (GFR)
• In kidney failure this blood purifying process
is blunted: waste products are accumulated
in the body
• This induces a progressive process of
intoxication, which affects all organ systems,
leading to an accelerated death, even if
dialysis is performed (worse than cancer)
K/DOQI stages of renal failure (1)
1 Normal or > 90
increased GFR
1.4 Pre-dialysis
1.2 * * Dialysis
*
1.0 ** **
** ** **
CA-IMT, mm
#
0.8 **
0.6
0.4
0.2
60 26 71 123 30 125 80 27 97 39 27 52 302 110 345
0
40-49 50-59 60-69 70-79 Total
Age, years
• 85 studies (1986-2003)
– 552,258 patients
– 71 with correction for “traditional” risk factors
• Sharpest threshold
• Screa: 0,90 mg/dL
• GFR: 90 mL/min
RELATIEF RISICO
15
RR_mortality (fold increase)
10
y = -0.1262 x + 10.77
r = 0.645; p< 0.001
5
y = -0.0180 x + 2.727
r = 0.574; p < 0.004
0
0 25 50 75 100 125 150
GFR (ml/minute)
0.85
0.80 15 ≤ GFR ≤59, mL/min/1.73 m²
0.75
60 ≤ GFR ≤89, mL/min/1.73 m²
0.70
0.65
0.60 90 ≤ GFR ≤130, mL/min/1.73 m²
0.55
Log-rank P value < 0.001
0.50
0 500 1000 1500 2000
Time since baseline, days
•Coresh et al, AJKD, 41, 1-12, 2003; Chadban et al,JASN, 14, S131-S138, 2003
POPULATIONS AT RISK
• Worldwide in dialysis or transplanted: ±
2,000,000 persons
• Worldwide with GFR < 60 mL/min:
– 6,000,000,000 x 0.05 = 300,000,000
• This problem has similar epidemic
proportions as diabetes mellitus, but is
unfortunately strongly underestimated
Cost of HD
80000 COSTDIAL
MEDRIZ
HOSPRIZ
6719
TECHRIZ
6557
4407
60000 4660
10382
Type:
6506
0 = PD
1 = HD
2 = TX
Period: 40000
Mean
0 = 1th hospital
1 = Year 1
2 = Year X
53432 51929
20000 4218
10869
2676
3590
0
.00 1.00 2.00
PERIOD
Rise of cost
200
180
Patients
+8%
160
140
Economies
120 +2%
100
1 2 3 4 5 6 7 8 9 10
FUTURE AIMS
• Correct and timely estimation kidney
function, especially in risk groups: diabetes,
hypertension, familial renal failure, > 60j,
nephrotoxic medication, proteinuria
• If GFR < 60 mL/min Æ secundary prevention:
life style, smoking stop, correction tension,
treatment diabetes, angiotensin blockers,
correction lipid disturbances,
hypercoagulability blood, inflammation
• Prevention of both the early complications
and the progression towards dialysis
MORTALITY
Age CO HD HD/CO
25-34 0.008 3 375.0
35-44 0.03 4.5 150.0
45-54 0.1 6 60.0
55-64 0.3 8 26.7
65-74 0.9 10 11.1
75-84 3 15 5.0
90
90
80
80
70
70
60
60
% Intensity
% Intensity
50 50
40 40
30 30
20 20
10
10
0 0
0 0 0 14 28 42 56 70
0 14 28 42 56 70
Retention Time (Min)
Retention Time (Min)
mass/charge(KD/z
7 kD
Protein display, DC, F10 Protein display, DC, F70
6 kD
5 kD
4 kD
3 kD
2 kD
1 kD
Atherosclerosis Inflammation
Malnutrition
Stenvinkel et al. Nephrol Dial Transplant 2000; 15: 953–60
DEAD VS ALIVE AT 34 MTHS
DEAD (41) ALIVE (50)
CRP (µg/mL) 10.1 3.4**
Alb (g/dL) 3.7 3.8*
BUN (mg/dL) 53±15 64±18*
Crea (mg/dL) 9.0±3.0 11.1±3.2*
PCRn (g/kg.d) 0.93±0.19 1.06±.21*
Adherence Adherence
and
Endothelial Leukocyte Endothelial Leukocyte Smooth-muscle
Foam-cellT-cell aggregationand
of entry
permeabilitypermeabilityadhesion adhesion migration formation
activation
platelets of leukocyte