, Stockholm, Sweden, 2008.
NTRODUCTION AND AIMS: Exposure to lead (Pb) has been a global health problem for decades. Renal effects of acute exposure to Pb as well as chronic high-level occupational exposure are well established. Controversy exists as to the role of low-level environmental exposure to Pb on the kidneys. Body-lead burden (BLB), is known to be elevated among renal failure patients and several explanations were proposed for this, though none is fully confirmed or uniformly accepted. These include: inadequate Pb excretion by the failing kidneys; cause-effect relation between Pb-exposure and renal failure of unknown cause; and an association with hypertension/hypertensive nephrosclerosis. A further proposed possibility is that increased bone-turnover due to 2ry hyperparathyroidism, in renal failure, releases Pb from its dormant stores in bone. We tried to test these various hypotheses head-on, for the first time, in this study
METHODS: We included 84 subjects divided to 2 main groups.Group1: 50 with pre-ESRD (CKD2-4) divided into 3 subgroups: 1a:19 with CKD of known cause; 1b:15 with hypertensive nephrosclerosis; 1c:16 with CKD of unknown cause. Group2: 34 matched controls with normal kidney functions including 18 normtensive and 16 with essential hypertension
All subjects were evaluated by inquiry about sources of environmental exposure to Pb, symptoms/signs suggestive of Pb toxicity, assessment of BLB by EDTA lead-mobilisation test, measurement of serum parathormone (PTH), calcium, phosphorus, alkaline phosphatase, urea, creatinine, uric acid.
Those with occupational exposure to Pb, acute renal failure, malignant hypertension or renal replacement therapy were excluded
RESULTS: 34 CKD patients (68%) vs 1 control (2%) had a positive Pb mobilisation test (>600ug).Only 9 recalled a source of exposure to Pb, those had higher BLB (p0.038) and 3 had symptoms suggestive of Pb toxicity
BLB was higher in CKD patients compared to controls (<0.0001), there was no difference in BLB between different subgroups of CKD patients nor between normo- and hyper-tensive controls. PTH was higher among CKD patients than controls (p 0.001) with no differences between CKD subgroups. PTH was higher in hyper- than normo-tensive controls (p 0.012)
In CKD patients, BLB correlated positively with serum PTH (r 0.7, p 0.0001). This was true for all subgroups (1a: r 0.84, p <0.0001; 1b: r 0.56, p 0.04; 1c: r 0.7, p 0.02). Regarding the other studied parameters, BLB only correlated posititively with serum creatinine (r 0.4, p .007).
In controls, BLB did not correlate with any studied parameter
CONCLUSIONS: We conclude that: a)BLB is elevated in CKD irrespective of the cause of renal failure b)BLB in CKD is related to hyperparathyroidism c) Higher serum creatinine was associated with higher BLB (ie more Pb excretion in urine) (probably due to higher PTH) d) absence of symptoms of Pb toxicity or failure to recall exposure to Pb donot exclude elevated BLB in renal patients.
These results support the hypothesis that elevated PTH releases Pb from its bone stores which may explain several manifestations of and modify treatment for hyperparathyroidism and the uremic syndrome