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Review
. 2023 Nov 7;17(1):sfad273.
doi: 10.1093/ckj/sfad273. eCollection 2024 Jan.

Ketogenic metabolic therapy for chronic kidney disease - the pro part

Affiliations
Review

Ketogenic metabolic therapy for chronic kidney disease - the pro part

Thomas Weimbs et al. Clin Kidney J. .

Abstract

Ketogenic metabolic therapy (KMT) is a medical nutrition therapy to address certain health and disease conditions. It is increasingly used for many non-communicable diseases that are rooted in abnormal metabolic health. Since chronic kidney disease (CKD) is commonly caused by overnutrition leading to hyperglycemia, insulin resistance and diabetes mellitus, the carbohydrate restriction inherent in KMT may offer a therapeutic option. Numerous studies have found that various forms of KMT are safe for individuals with CKD and may lead to improvement of renal function. This is in contrast to the current standard pharmacological approach to CKD that only slows the relentless progression towards renal failure. Kidney care providers, including physicians and dietitians, are usually not aware of non-standard dietary interventions, including KMT, and often criticize KMT due to common misconceptions and uncertainty about the underlying science, including the common misconception that KMT must involve high protein or meat consumption. This review article discusses the rationales for using KMT, including plant-dominant KMT, for treatment of CKD, clarifies common misconceptions, summarizes the results of clinical studies and discusses why KMT is emerging as an effective medical nutrition therapy (MNT) to consider for patients with kidney disease. KMT, including its plant-dominant versions, can expand a practitioner's kidney health toolbox and will likely become a first-line therapy for CKD in certain CKD-associated conditions such as obesity, metabolic syndrome and polycystic kidney disease.

Keywords: diabetic kidney disease; ketosis; nutrition; obesity; polycystic kidney disease.

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Conflict of interest statement

T.W. is an inventor on issued and pending patents filed by UCSB, is a shareholder and president of Santa Barbara Nutrients, served on the scientific advisory board of Chinook Therapeutics and has received research funding from Chinook Therapeutics unrelated to the scope of this article. J.S. is the owner of Kidney Nutrition Institute and is a shareholder and serves on the advisory board of Santa Barbara Nutrients. K.K.-Z. has received commercial honoraria and/or support from ACI Clinical (Cara Therapeutics), Akebia, Alexion, Ardelyx, AstraZeneca, Chugai, Daiichi, DaVita, Fresenius, GlaxoSmithKline, Haymarket Media, Kabi, Novartis, Novo Nordisk, Pfizer, Resverlogix, Sanofi, Vifor and UpToDate.

Figures

Figure 1:
Figure 1:
Long-term, persistent hyperglycemia due to the standard American diet (SAD) high in sugar, carbohydrates, calories and highly processed foods leads to chronic hyperinsulinemia, insulin-resistance, hypertension, chronic inflammation, and renal tissue damage. In the presence of insulin, excess carbohydrates are converted to triglycerides and stored in adipose tissues leading to obesity. All of these factors lead to type-2 diabetes and diabetic nephropathy. In contrast, ketogenic metabolic therapy (KMT) reverses these underlying factors. The restriction of carbohydrate intake in KMT leads to normoglycemia and prevents glucose spikes, lowers insulin levels and reverses insulin-resistance and hypertension. The lowering of insulin permits lipolysis by the adipose tissues to release fatty acids which are partially converted to the ketone BHB by the liver that releases BHB into circulation. BHB is the preferred energy substrate of most cells and tissues. In addition to serving as an energy source, BHB is also a signaling molecule that impacts multiple cellular pathways including its strong inhibition of the NLRP3 inflammasome leading to its potent anti-inflammatory properties.

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