In our letter of January 1997, we reported the association of chromium picolinate ingestion with the development of renal failure. We carefully considered other possible causes. Our patient was receiving only three other medications at the time: terazosin and hydrochlorothiazide (since 1994) and verapamil (since 1995). Of these, only thiazides have been associated with the rare development of allergic interstitial nephritis. Many of these cases are poorly documented, and some were associated with underlying glomerular conditions that could have mediated tubulointerstitial damage [1]. Most of the patients presented with one or more signs of hypersensitivity (fever, rash, eosinophilia) within several weeks of initiating thiazide therapy and had acute interstitial nephritis on biopsy. In contrast, our patient had been receiving hydrochlorothiazide for 3 years without an overt hypersensitivity reaction and developed chronic interstitial nephritis, a pattern not previously associated with thiazides. Evidence against hypertensive nephrosclerosis as the primary process included the relatively rapid progression to renal failure, the fact that the hypertension was well controlled, and the severe diffuse tubulointerstitial damage in the face of only mild arteriolosclerosis. Thus, by exclusion, we strongly considered nephrotoxicity due to chromium picolinate. Indeed, heavy metals are well-established nephrotoxins and many, including lead, mercury, cadmium, and chromium, have been associated with the development of chronic interstitial nephritis in animals and humans.

Chromium picolinate provides an excellent source of trivalent chromium that is readily absorbed and achieves high blood concentrations [2]. Hexavalent chromium itself is converted intracellularly to the trivalent form, so why should we assume that the trivalent form is necessarily renal sparing? [3] As McCarty himself points out, even trivalent chromium administered parenterally to animals is nephrotoxic [4]. The possibility that nephrotoxicity is enhanced by use of thiazides or other antihypertensive agents has not been addressed. The lack of other reported cases of potential nephrotoxicity to date can be explained by the drug's very recent introduction on a large scale and the absence of published controlled clinical trials. The first study described by Michenfelder is an ongoing study of only 11 patients, and the second exists in abstract form only. Although McCarty alludes to "controlled clinical studies," he fails to cite a single published article. Indeed, our review of the literature uncovered no published controlled trials documenting the safety and efficacy of chromium picolinate in humans. The medication is not regulated as a pharmaceutical by the U.S. Food and Drug Administration (FDA) and is being distributed in an unregulated fashion as a "diet pill" and "body builder" in health food stores. Because of the alarming increase in casual use of this drug by a weight-conscious public, we believe that it is only a matter of time before other cases of nephrotoxicity are recognized. It is in the public interest that chromium picolinate's safety be proven in controlled clinical trials and that the FDA promulgate guidelines for its use.