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Lead and uric acid

 

Clinical bottom line

Chronic low level lead exposure may inhibit urate excretion. Lead chelation therapy reduces this inhibition. Links between lead exposure and gout remain speculative.


Reference


J-L Lin et al. Environmental lead exposure and urate excretion in the general population. American Journal of Medicine 2002 113: 563-568.


Study

This study was in two parts:

Part 1 was a survey of 111 healthy subjects with normal renal function and no disease or known lead exposure, including 27 with a history of gout. Various tests were made, including blood lead, body lead burden (24-hour urinary lead excretion after intravenous EDTA), and urinary urate excretion.

Part 2 was a randomised trial of lead chelation therapy. Twenty-four subjects with high-normal body lead burden were randomised to a weekly infusion of EDTA for four weeks, or to a placebo infusion of saline and glucose. The study was properly randomised and blinded.

Results

Health subjects and those with gout were demographically similar. Those with gout had a higher body lead burden and serum urate, and a lower urate excretion (Table 1). Blood lead levels were not significantly different.

Table 1: Normal patients and those with gout

Characteristic

Normal

Gout

Number

84

27

Blood lead (micrograms/dL)

3.9

4.2

Body lead burden (micrograms)

45

84

Serum urate (mg/dL)

7.8

10.3

Urate excretion (mL/min/1.7 sq metres)

6.0

3.7

In the randomised trial, the two groups, though small at 12 persons in each, were well matched for a range of demographic and other measurements. About half in each group had a history of gout. After four weeks of chelation therapy patients had a lower serum urate (by 1.7 mg/dL), a higher daily urate excretion (by 108 mg), and a higher urate excretion (by 2 mL/min/1.7 sq metres).

Comment

There has been a literature concerning lead exposure, urate metabolism and gout that goes back a quarter of a century, without reaching any really satisfactory conclusion, especially about the role of lead at low levels and gout.

This paper stakes no claims to proving that exposure to lead causes gout. It does show that persons with gout had higher lead removed by chelation, and in persons with and without gout lowering body lead levels increased urinary urate excretion and reduced serum urate levels by a substantial amount.

But the link between lead and gout remains tenuous. A larger epidemiological study of 777 men (52 with gout) [1] measured blood and bone lead. It found a significant association between gout and body mass index and renal function, but not blood or bone lead levels.

It may be that there is still some interesting work to be done here. In particular, trials of chelation therapy for persons with gout seem to be missing.

  1. Shadick NA, Kim R, Weiss S, Liang MH, Sparrow D, Hu H. Effect of low level lead exposure on hyperuricemia and gout among middle aged and elderly men: the normative aging study. J Rheumatol. 2000 Jul;27(7):1708-12.