Conflict of Interest Statement. the Weight Management Programme Was Established with Unrestricted Educational Grants from Roche Reply—orlistat and Renal Failure Letters

Sir, We welcome the interest of MacLaughlin and Macdougall in the use of the gastrointestinal lipase inhibitor orlistat in patients with chronic kidney disease (CKD). We previously reported the rapid, non-recoverable decline of renal function in a patient with diabetic nephropathy, that coincided temporally with the successful use of orlistat for weight reduction [1]. There was histological evidence of extensive intratubular calcium oxalate crystal deposition. The report byMacLaughlin andMacdougall of 33 patients with stage 3 or 4 CKD, who were treated with orlistat for >6 months as part of a weight management programme, provides some reassurance about the safety of this medication in CKD patients. Interestingly, the average weight reduction was 6.6% at 6 months, with no acceleration of CKD progression in the majority of patients. There was, however, a reduction in eGFR exceeding 10ml/min at 6 months in 6/33 (18%). It is reasonable to suggest that the risk of hyperoxaluria will parallel the degree of weight reduction if both are due to malabsorption (our patient had an 11% weight loss after 5 months). It would be useful to determine the percentage weight loss in those patients with a more rapid decline in renal function, if there was an alternative clinical explanation for this, and the outcome of those that exhibited continued decline. The conclusion that in the presence of a normal dietary fat intake the addition of orlistat does not make a significant difference to urinary oxalate levels in rodents is misleading. We reference directly to the results of Ferraz et al. [2] ‘compared to baseline, urinary oxalate increased significantly after [standard] diet þ orlistat in controls’. However, we acknowledge that the extrapolation of the results from rodent models is inherently limited for several reasons, including the dose/kg ratio and differing pathophysiology (for example, calcium oxalate urolithiasis is not a spontaneous phenomenon in rats). The mechanism of action of gastrointestinal lipase inhibitors, the temporal association of accelerated renal function decline with the commencement of orlistat, the high degree of compliance and weight reduction, the pathological findings and the absence of an alternative plausible explanation support our proposition that intrarenal precipitation of calcium oxalate triggered the acute deterioration in kidney function in our patient [1]. The data from MacLaughlin and Macdougall support our conclusion that the majority of patients prescribed a gastrointestinal lipase inhibitor do not develop clinically significant hyperoxaluria and that additional dietary restrictions are unnecessary. Nevertheless, we would advise careful monitoring of renal function in CKD patients prescribed orlistat. The risk of accelerated loss of renal function may be particularly high in compliant patients with the most rapid weight loss.