Rapidly progressive renal failure associated with successful pharmacotherapy for obesity.

Reply Sir, We thank Drs Calo and Davis for highlighting their interesting studies. We were, in fact, aware of these studies and have used them as background in grant applications in the broader context. Our paper was not intended to be a review of the literature, since this area, we believe, is still evolving. It is always a subjective decision which references to include or not in any given publication. We felt it unnecessary to include the works cited by Drs Calo and Davis, for obvious reasons. It should be apparent that our emphasis was on the modulatory role of transforming growth factor-b (TGF-b) on renal tissue gene expression in the setting of tacrolimus-induced nephrotoxicity, in an experimental rodent model of renal transplantation. In contrast, the studies by Calo and Davis evaluated the modulation by angiotensin converting enzyme (ACE) inhibitor treatment on Cyclosporin and tacrolimus-induced hypertension in human renal transplant models but in peripheral monocytes. In this case, the emphasis for their studies was on non-renal tissue. Due to this and the emphasis on nitric oxide in the setting of hypertension, it is clear that the focus was on the potential interaction of inflammatory cells and endothelial/vascular disease. Since we did not evaluate these issues, we could not credibly comment on them. Our studies were clearly addressing issues of immunosuppression-induced nephro-toxicity as evidenced by renal dysfunction and histological changes. These indices were not end-points of the studies by Calo et al. Calo specifically indicated in their paper that patients had normal kidney function. To illustrate this difference in focus, no published papers by Calo and colleagues could be found using various criteria of literature search on PubMED Õ (e.g. tacrolimus, nephrotoxicity, transforming growth factor; NADPH oxidase, tacrolimus, kidney; NADPH oxidase, tacrolimus). So, it is clear that we are talking about two different facets of calcineurin inhibitor-induced side-effects. We would also like to reiterate the comments explained in our 'Discussion', that our findings of absence of gp 91phox expression (i.e. phagocytic cells) together with the up-regulation of NOX-1 (i.e. a non-phagocytic NADPH oxidase) clearly distinguishes our findings from those of hypertension-induced oxidative stress. It should be noted that Calo et al. dealt solely with issues of monocyte NAPDH oxidase subunit expression in the context of hypertension. This is clearly a separate issue and we did not specifically analyze gene expression in peripheral monocyte fractions. More significantly, the overall goals of the …