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Deep Dive: Does low protein intake slow down chronic kidney disease progression?

Very low protein diets seem to slow progression but don't affect mortality, raising the question of whether there's a risk-benefit tradeoff. Higher quality, larger trials could shed more light on this issue.

Study under review: Low protein diets for non-diabetic adults with chronic kidney disease

Introduction

Chronic kidney disease (CKD) has been recognized as a leading global health problem for nearly two decades[1]. However, the global disease burden has been rising ever since. On average, every seventh to eighth person worldwide lives with CKD, according to recent estimates[2]. This increasing prevalence is mainly driven by a global increase in diabetes mellitus, hypertension, obesity, and aging—all risk factors that increase the likelihood of developing CKD. Due to the irreversible and progressive nature of[3] CKD, it typically leads to end-stage kidney disease (ESKD), with renal replacement therapy and kidney transplantation[4] as the last treatment options. Today, an estimated 5–7 million people with ESKD[2] are on dialysis treatment and waiting for kidney transplantation. Effective disease management and treatment[5] is essential to delay the natural progression of CKD toward ESKD.

Dietary protein restriction is a commonly recommended intervention to slow CKD progression. Early animal studies[6] have shown that low protein diets reduce sclerotic glomeruli (hardening of the tiny blood vessels in the kidney that filter the blood) and proteinuria (increased levels of protein in the urine), which are two significant physiological alterations caused by CKD. The mechanism of how high protein intake causes these physiological changes in the kidney are not fully understood yet. One hypothesis is that high protein diets lead to intraglomerular hypertension[7] (an increased pressure in the kidneys’ filtration units), which then results in glomerular injury and proteinuria. However, research has not yet fully elucidated the exact mechanism of protein-induced glomerular hyperfiltration.

Nevertheless, the usefulness of protein restriction as a dietary intervention in CKD was subsequently investigated in more detail using clinical trials. Meta[8]-analyses[9] of these studies showed that some RCTs did find a beneficial effect, while others did not. These contradictory findings created considerable controversy around the topic. Nevertheless, diets with slightly reduced protein intake (less than 0.8 grams per kilogram of bodyweight per day, i.e., a maximum intake of 50–60 daily grams for the average person) are generally recommended by leading institutions[10] to alleviate CKD-related complications. But how effective is this rather harsh restriction for slowing CKD? And what about the risks associated with restricted protein diets, such as the possibility of malnutrition?

The efficacy of reduced-protein diets has been studied for almost three decades now. The good news is most meta-analyses found that dietary protein restriction reduced the risk of some CKD-related outcomes, such as the risk of kidney failure, death, or CKD progression, to a small extent. The bad news is that the observed positive effects of low protein diets differ widely between studies. For example, an early meta-analysis[8] evaluated the risk of kidney failure or death and concluded that dietary protein restriction effectively slows disease progression. In stark contrast, a later and larger meta-analysis[9] evaluated change in glomerular filtration rate (GFR, see the sidebar for more information) and concluded that low protein diets provide minimal benefits. The researchers further report that, due to insufficient sample sizes and short follow-up periods, the weak magnitude of the putative positive effects is difficult to determine accurately and that it remains questionable if the apparent benefits would outweigh the potential risks. Most notably, malnutrition and dietary protein wasting[11] are common side effects of low protein diets and could potentially worsen nutritional status. Taken together, the efficacy of low protein diets to slow CKD progression is still a controversial debate.

What was studied?

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What were the findings?

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The bigger picture

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Frequently asked questions

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What should I know?

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