11.4 sallsten
TRANSCRIPT
Elimination and half-time of cadmium
in kidney
Magnus Akerstrom1, Thomas Lundh2, Lars Barregard1, Gerd Sallsten1
1Occupational and Environmental Medicine, Sahlgrenska Academy, University of Gothenburg2Occupational and Environmental Medicine, Lund University, Sweden
Background• The general population is exposed to cadmium (Cd) from diet and
smoking, approximately 50% of the total Cd body burden is
accumulated in the kidney
• Evidence of tubular damage and bone effects at low levels of Cd
exposure in the general population
• U-Cd is widely used as measure for long-term
Cd exposure or body burden
• No previous study of the relationships between Cd in kidney, blood
and urine for living subjects with valid analytical methods
1. Study design
•109 living kidney donors
•Questionnaire(work history, diet, smoking…)
•Biological samples
• 24h urine (UCd/24h)
• Overnight urine (UON)
• Blood
• Kidney cortex biopsy
•Samples analyzed for:
• U-Cd / B-Cd / K-Cd (ICP-MS)
All Men Women
Subjects 109 49 60
Age: median (range)
51 (24-70)
52 (32-70)
50 (24-64)
Never smokers 41 19 22
Pack-years: median(range)
13(0.4-51)
12 (0.4-51)
13(2-36)
OvernightU-Cd (µg/gC):
Mean(Range)
0.29 (0.04-1.1)
0.23(0.04-0.80)
0.34(0.08-1.1)
Research questions
Biological half-time of Cd in the kidney?
Determinants for UCd/24 h?
Relationship between Cd in kidney and
urine (UON) (and blood)?
Relationship between Cd in kidney and urine
Cd in kidney (μg)
0 2000 4000 6000 8000 10000 12000 14000
Cd
in u
rine
per 2
4h (μ
g)
0.0
0.2
0.4
0.6
0.8
1.0
1.2Regression line with intercept
U-Cd/24h=0.07+0.000062×K-Cdtot
The fraction of K-Cdtot
excreted in urine per 24h
was 0.006%
Akerstrom et al. 2013 TAAP
k = calculated elimination constant
Cd in kidney (μg)
0 2000 4000 6000 8000 10000 12000 14000
Cd
in u
rine
per 2
4h (μ
g)
0.0
0.2
0.4
0.6
0.8
1.0
1.2
1.4Regression line all dataRegression line K-Cdconc < 15 μg/gRegression line K-Cdconc >=15 μg/g
A nonlinear relationship between Cd in kidney
and urine
U-Cd/24h=0.00011×K-Cdtot
p<0.001 fordifference
U-Cd/24h=0.000071×K-Cdtot
Akerstrom et al. 2013 TAAP
A nonlinear relationship between Cd in kidney
and urine
Akerstrom et al. 2013 TAAP
Cd in kidney (μg)
0 2000 4000 6000 8000 10000 12000 14000
Cd
in u
rine
per 2
4h (μ
g)
0.0
0.2
0.4
0.6
0.8
1.0
1.2 Regression line all data
U-Cd/24h=0.11×10-3×K-Cdtot – 5.8×10-9 × K-Cdtot2
T1/2= 21.2
T1/2=28.5
T1/2=43.5
Biological half-time of Cd in kidney
• Linear model with intercept• T1/2=30.4 years (95% CI; 24.3-40.5)
• Linear model without intercept• T1/2=21.0 years (95% CI; 18.9-23.6)
• Linear model without intercept • K-Cdconc<15 µg/g : T1/2=17.9 years (95% CI; 15.7-20.8)
• K-Cdconc≥15 µg/g: T1/2=26.7 years (95% CI; 23.4-31.1)
• In a nonlinear model, half-time is 21 – 44 years dependingon the amount of Cd in the kidney
T1/2 = ln(2) / k
Akerstrom et al. 2013 TAAP
Akerstrom et al TAAP 2013
Albumin in urine was also a determinant for U-Cd/24h
Kidney cortex cadmium concentration (μg/g)
0 10 20 30 40 50Ove
rnig
ht u
rinar
y ca
dmiu
m c
once
ntra
tion
adju
sted
for s
peci
fic g
ravi
ty (μ
g/L
0.0
0.2
0.4
0.6
0.8
1.0
1.2UON-CdSG = 0.11 + 0.010 x K-CdconcR2 = 0.28
Kidney cortex cadmium concentration (μg/g)
0 10 20 30 40 50
Blo
od c
adm
ium
con
cent
ratio
n (μ
g/L)
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5B-Cd = 0.16 + 0.023 x K-CdconcR2 = 0.19
Kidney cortex cadmium concentration (μg/g)
0 10 20 30 40 50Ove
rnig
ht u
rinar
y ca
dmiu
m c
once
ntra
tion
adju
sted
for c
reat
inin
e (μ
g/gC
)
0.0
0.2
0.4
0.6
0.8
1.0
1.2
UON-CdCrea = 0.071 + 0.014 x K-CdconcR2 = 0.44
Relationship between Cd in kidney and urine
U-Cd/K-Cd ratio
• Previous: about 1:20
• This study: about 1:60
Conclusions
• A strong but nonlinear relationship between U-Cd and K-
Cd with slower elimination of Cd at high kidney Cd
• Previous U-Cd/K-Cd ratio may underestimate K-Cd at low
U-Cd
• The half-time for Cd in the kidney is
18 – 44 years, depending on model used
Akerstrom et al. 2013 EHP
Association between
U-Cd and U-proteins
for one study
participant
Akerstrom et al. 2013 EHP
Association between U-Cd and U-Proteins for all study
participants
Akerstrom et al. 2013 EHP
Association
between U-Cd
and U-Proteins for
all study
participants