Moderator's View

Low-protein Diet in Chronic Kidney Disease

Effectiveness, Efficacy and Precision Nutritional Treatments in Nephrology

Carmine Zoccali; Francesca Mallamaci


Nephrol Dial Transplant. 2018;33(3):387-391. 

In This Article

The Issues At Stake

On reading the position papers of the two contenders it is clear that they agree on the relevance of controlling key dietary components in CKD patients. Both, Kopple and Woodrow repeatedly emphasize that control of salt intake is a centrepiece of the treatment of CKD and correction of acidosis and hyperphosphataemia in patients with Stages G4–5 CKD may be beneficial for retarding CKD progression and for mitigating secondary hyperparathyroidism in these patients. The controversial issue is whether a low-protein diet (≤0.6–0.7 g protein/kg/day) per se can retard CKD progression and whether the same diet can safely be applied in the long term in the CKD population.

The PRO contender discusses two meta-analyses performed in the late 1990s,[7,8] and a more recent one by Fouque in 2009.[9] The first[7] and the third[9] meta-analyses—both showing a renal survival benefit of low-protein diet—were based on the composite endpoint death and/or starting regular dialysis, while the second,[8] which negated a protective effect of clinical relevance, was based on the annual decline of the glomerular filtration rate (GFR). Kopple interprets the discrepant results of these meta-analyses as deriving from the fact that low-protein diet mitigates the symptoms of uraemic toxicity and therefore allows postponement of the start of dialysis treatment because uraemia is better tolerated rather than by slowing the rate of GFR loss. He makes the point that failure by the MDRD trial to document a benefit of low-protein diet on CKD progression might depend on poor adherence to this regimen in the same study. One important point in the PRO contender reasoning is the concept that current treatments of CKD, including renin–angiotensin–aldosterone system inhibitors, phosphate binders, bicarbonate supplements and careful antihypertensive treatment, may overshadow the benefits of dietary interventions on the progression of CKD.

The CON contender remarks that the funnel plots in the meta-analyses by Kasiske et al.[8] and Fouque and Laville[9] show a clear publication bias that—due to the exclusion of negative studies—may generate the false impression that low-protein diet is superior to the control diet. He quotes various studies showing unsatisfactory compliance to low-protein diet and emphasizes that the largest and most rigorous study performed so far, the MDRD study, which was based on gold standard measurements of GFR by 125I-iothalamate clearance, was inconclusive.[10] Creatinine-based measurements of GFR are inherently inadequate for testing long-term interventions reducing protein intake.[11] Like Kopple, Woodrow holds that today's portofolio of treatments applied in CKD dwarfs any effect of low-protein diet for retarding the rate of renal function loss in CKD patients.