We appreciate the comments of Dr Graves. Indeed, we recognize that controlling protein intake in people with chronic kidney disease (CKD) is a time-consuming process that requires the establishment of a dedicated team in pre-dialysis CKD clinics. We respectfully disagree, however, with Dr Graves' interpretation of the results of the Modification of Diet in Renal Disease (MDRD) study. As discussed in our original article (citation above), a number of caveats have been reported in subsequent analyses, leading to consideration of the MDRD study as being “inconclusive” rather than negative. P values as low as 0.07 in clinical research are considered by many to be indicative of a significantly beneficial intervention that is worthy of being proposed to patients. Many other medications are given to patients without such a level of statistical confidence.
Far from ignoring the MDRD data, we used it in our meta-analysis.1 One of well-accepted strengths of a meta-analysis is to take the 'essence' of clinical trials and correct for insufficient power (of individual trials) by increasing the number of observations. This is just what happened with the MDRD data. Had the MDRD study included 10% more patients or been prolonged by 6 months, the results would have been significant. Secondary analyses clearly confirmed this opinion.2
We fully agree with Dr Graves that CKD patients die from cardiovascular disease. We reported previously that reducing total protein intake induces a reduction in the intake of animal protein relative to vegetable protein; vegetal protein sources, which clearly have anti-atherogenic properties, subsequently predominate.3 So, a reduction in protein intake helps to improve patients' food 'profiles', and has the potential to ameliorate cardiovascular risk, rather than having the opposite effect. A low-protein diet also mimics the effects of angiotensin inhibition, as shown by Gansevoort and colleagues in 1995,4 and could enhance the nephroprotective impact.
Fouque D et al. Low protein diets for chronic kidney disease in non diabetic adults. Cochrane Database of Systematic Reviews 2006, Issue 2. Art. No.: CD001892. DOI: 10.1002/14651858.CD001892.pub2
Levey AS et al. (1996) Effects of dietary protein restriction on the progression of advanced renal disease in the Modification of Diet in Renal Disease Study. Am J Kidney Dis 27: 652–663
Bernard S et al. (1996) Effects of low-protein diet supplemented with ketoacids on plasma lipids in adult chronic renal failure. Miner Electrolyte Metab 22: 143–146
Gansevoort RT et al. (1995) Additive antiproteinuric effect of ACE inhibition and a low-protein diet in human renal disease. Nephrol Dial Transplant 10: 497–504
Drs Fouque and Aparicio have received speakers fees from Fresenius-Kabi.
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Fouque, D., Aparicio, M. Authors' response to “The two best reasons NOT to focus on protein restriction in chronic kidney disease”. Nat Rev Nephrol 3, E2 (2007). https://doi.org/10.1038/ncpneph0634