Restriction of Dietary Protein and Long-term Outcomes in Patients With CKD

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To the Editor:

The posttrial analysis by Dr Menon and colleagues¹ concluded that assignment of a very low-protein diet (VLPD) increases the risk of death in patients with chronic kidney disease.

However, a satisfying biological or scientific hypothesis for the relation between time-limited exposure to a VLPD and long-term outcomes is not provided. In addition, the long period without dietary treatment (dilution effect) and the many confounders (lack of information for transplantation, starting dialysis criteria, dialysis type, vascular access, and so on) preclude a conclusive judgment about the safety of a VLPD. Furthermore, about two-thirds of VLPD survivors were evaluated and did not show nutritional impairment; thus, development of malnutrition because of the VLPD, given as an explanation for the greater death rate, can be excluded. Finally, the hypothesis of a toxic effect related to the increase in indoxyl-sulfate, a metabolite of tryptophan contained in dietary supplements, is not substantiated. Indoxyl-sulfate is a uremic toxin shown to accelerate the progression of chronic renal failure²; nonetheless, dietary protein restriction can reduce the level of this toxin.³ Hence, a VLPD plus tryptophan should decrease rather than increase the level of indoxyl-sulfate. Significantly, increased levels of indoxyl-sulfate during a VLPD have not been shown, and no link with mortality has been provided.

In conclusion, it seems most likely that there is only a spurious relation between a VLPD and death. At this time, randomized controlled trials of the relationship between a VLPD and outcomes in the general chronic kidney disease population are still needed.

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Acknowledgements 

Financial Disclosure: None.

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References 

1. Menon V, Kopple JD, Wang X, et al. Effect of a very low-protein diet on outcomes: Long-term follow-up of the Modification of Diet in Renal Disease (MDRD) Study. Am J Kidney Disease. 2009;53:208–217
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2. Niwa T, Ise M. Indoxyl-sulfate, a circulating uremic toxin, stimulates the progression of glomerular sclerosis. J Lab Clin Med. 1994;124:96–104
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3. Niwa T, Tsukushi S, Ise M, et al. Indoxyl-sulfate and progression of renal failure: Effects of a low-protein diet and oral sorbent on indoxyl-sulfate production in uremic rats and undialyzed uremic patients. Miner Electrolyte Metab. 1997;23:179–184
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