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Beyond safety, mechanistic plausibility, preclinical data, and even some RCT studies suggest that carbohydrate-restricted diets may be beneficial in improving moderate kidney dysfunction and in reducing progression of CKD. In contrast, systematic reviews and meta-analyses that assessed pooled effects of RCTs reported beneficial effects of low-carbohydrate diets. In this study, CR-LIPE significantly decreased doubling of serum creatinine (relative risk, 0.53, 95% CI 0.33 to 0.86, p117 However, the CR-LIPE intervention was a multimodal dietary intervention that included carbohydrate restriction (35% of the energy intake) as one of the dietary modifications along with low-iron availability and polyphenol enrichment in the diet. Clinical and observational studies that examined kidney function in response to low-carbohydrate diets ranging from online supplemental table 1. In both models, the mice initially developed albuminuria on chow diet, and after transitioning to the ketogenic diet reversed and normalized urinary albumin/creatinine ratio (UACR) within 8 weeks.112 Furthermore, the expression of several stress-induced genes involved in oxidative stress and toxicity was completely normalized by ketogenic diet in both models, with an observed effect that was more consistently robust in the type 1 mouse model. For most individuals with normal kidney function consuming a ketogenic diet, it should be emphasized to ingest an additional 1–2 g sodium/day (4–5 g sodium/day total), a maintenance of 3–4 g/day potassium, and sufficient fluid intake. The next section briefly discusses the typical renal metabolic response to a ketogenic diet that maintains pH and electrolyte status. SGLT2i decreases reabsorption of excessive glucose, reduces energy production from glucose in the kidney, and increases fatty acid utilization in the kidney.32 Furthermore, the glycosuric effect of SGLT2i also augments the BHB level in the kidney mainly through increased production of ketones rather than reduced kidney clearance.33 The kidney is indeed an avid consumer of ketones.34 BHB serves as an important alternative source of energy for the kidney during metabolic imbalance. Increased lipolysis and ketogenesis are upregulated in response to a low insulin-to-glucagon ratio, which occurs during calorie restriction/fasting, prolonged exercise, consumption of a ketogenic diet, or pathologic insulin deficiency. The human body naturally produces ketones, mostly in the liver, at varying rates that result in circulating ketones that span more than four orders of magnitude (10 mM)20 21 depending primarily on a person’s carbohydrate intake and insulin level. 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