Lead - Toxicology of Metals - page 608

However, B-Pb has particular limitations as an index
of exposure when effects on the blood are assessed,
because a reduced volume of red cells will limit the
availability of lead-binding sites in blood. Plasma lead
may then have advantages. Hence, in lead-smelter
workers, there was an inverse relationship between
blood-hemoglobin level and plasma-lead concentra-
tion, which might indicate an effect on heme synthesis
(Bergdahl et al ., 2006).
Furthermore, some data indicate that bone lead lev-
els may be more closely associated with blood effects
than is B-Pb (Hu et al ., 1994; Lee et al ., 2001b; Smith
et al ., 1995b), perhaps through a local effect on the bone
marrow.
The main target by lead in the heme synthesis is
ALAD, the activity of which seems to be inhibited at
B-Pb right down to those in general populations with
low exposure (approximately 0.10

of their disease during 24 months (Lin et al ., 2003).
Moreover, when patients with high lead burdens were
treated with EDTA for 27 months to mobilize lead,
their glomerular fi ltration rate increased, whereas it
decreased in untreated patients with similar lead bur-
dens (Lin et al ., 2003).
There are several reports of increased mortality
from kidney disease in lead workers (Steenland et al .,
1992; Cocco et al ., 1997), but confounding by cadmium
often precludes fi rm conclusions on a causal relation-
ship with lead.
In Australians who had been treated for lead poi-
soning as children, there was increased mortality from
kidney disease (Emmerson, 1973). However, no such
effect was seen in the U.S. (McDonald and Potter,
1996), and no evidence of impaired renal function as
adults (Hu, 1991a; Moel and Sachs, 1992).
At lower lead exposures in the occupational and
general environments, there were associations between
blood- and bone-lead concentrations, on the one hand,
and increased serum levels of urate, as well as urinary
excretion of low molecular weight proteins (in particu-
lar a 1 -microglobulin and retinol binding protein) and
lysosomal enzymes ( N -acetyl- ß -D-glucosaminidase),
on the other (Chia et al ., 1994a, 1994b; 1995; Endo et al .,
1993; Santos et al ., 1994; Shadick et al ., 2000; Weaver
et al ., 2003a; 2005a,b). The effect on serum urate may
be more pronounced at old age (Weaver et al ., 2005b).
It has been proposed that a urate increase may be the
mechanism behind lead-induced tubulointerstitial
changes, although other mechanisms may also operate
(Weaver et al ., 2005b). Slight tubular proteinuria has
also been reported to be associated with lead exposure
in children (Bernard et al ., 1995; Fels et al ., 1998; Osman
et al ., 1999b; Verberk et al ., 1996). The fi ndings indicate
an effect on the proximal tubuli , with defi ciencies in
excretion of urate and reabsorption of proteins, which
have been fi ltered in the glomeruli, and shedding of
tubular cells (although hyperuricemia in itself may also
refl ect oxidative stress; Waring et al ., 2001). The effects
on a 1 -microglobulin and retinol binding protein were
more evident than on ß 2 -microglobulin, which may be
due to the methodological problem of destruction of
the latter at low urinary pH, but may also be a result
of the fact that it has a lower molecular weight, which
might make it less sensitive to ineffi cient reabsorption
in the proximal tubuli. Possible interference by lead
of renal hydroxylation of vitamin D is discussed later
(Section 2.7.5).
In a recent review, tubular effects have been seen in
occupational groups with mean B-Pb of approximately
1.5

mol/L; Table 3;
Skerfving, 2005). This results in increased ALA con-
centrations. It is not known whether such slight effects
have health consequences. It is not known whether
a corresponding inhibition occurs in other tissues at
similarly low exposure. However, considering the cen-
tral position of heme in the energy metabolism (CNS
inclusive), and in handling of organic xenobiotics by
the tissues (e.g., by cytochrome P450), the effect on the
heme metabolism is potentially adverse. Also, it must
be considered that ALA is neurotoxic and induces for-
mation of free radicals.
There is a rare hereditary ALAD defi ciency (for some
reason denoted plumb porphyria by some authors),
which may constitute an inborn error of lead metabo-
lism, making the subject vulnerable, and predispose
to severe toxic effects at relatively low exposure (Doss
et al ., 1984). Also, other acute porphyrias may predis-
pose (Battle et al ., 1987).

µ

2.7.3 Kidneys

Heavy lead exposure may cause renal dysfunction
characterized by glomerular and tubulointerstitial
changes, resulting in hypertension, hyperuricemia and
gout (”saturnine gouty arthritis”), and chronic renal
failure.
There are indications that environmental lead expo-
sure in the general population plays a role in the eti-
ology and/or progression of kidney disease, at least
in populations with high exposure. Hence, among
Taiwanese patients with chronic renal insuffi ciency,
those with gouty arthritis had higher “body lead
stores” (lead excretion after chelation with EDTA) than
the other cases (Lin et al ., 2001). Furthermore, among
patients with chronic renal disease of varying etiology,
those with high lead burdens had a worse progression

mol/L and higher (Table 3; Skerfving, 2005). In a
few studies, changes have been seen in workers with
mean bone lead levels of approximately 40

µ

µ g/g bone