What causes Acute Kidney Injury (AKI) in individuals on a ketogenic diet?

Causes of Acute Kidney Injury in Ketogenic Diet

The primary causes of acute kidney injury (AKI) in individuals on a ketogenic diet include dehydration, electrolyte imbalances, increased acid load, and potential nephrotoxicity from elevated ketone bodies, particularly beta-hydroxybutyrate. 1

Pathophysiological Mechanisms

• Ketogenic diets can lead to significant fluid losses and dehydration due to decreased insulin levels and glycogen depletion, resulting in decreased renal perfusion and prerenal azotemia 2
• The high protein and fat content of ketogenic diets increases dietary acid load and endogenous acid production through fatty acid oxidation, potentially worsening metabolic acidosis 3
• Electrolyte abnormalities, particularly hypokalemia, hypophosphatemia, and hypomagnesemia, are common during ketosis and can contribute to kidney dysfunction 4
• Beta-hydroxybutyrate becomes the predominant ketone body during ketosis, which at high levels may have direct nephrotoxic effects 1

Risk Factors for AKI on Ketogenic Diet

• Pre-existing chronic kidney disease significantly increases the risk of developing AKI while on a ketogenic diet 2
• Age over 65 years is an independent risk factor for AKI development during ketogenic dieting 2
• Diabetes mellitus increases susceptibility to AKI during periods of ketosis 2
• Concurrent use of medications that affect kidney function (ACE inhibitors, ARBs, NSAIDs, diuretics) can exacerbate the risk 2

Diagnostic Findings

• AKI is defined as an increase in serum creatinine ≥0.3 mg/dL within 48 hours or ≥50% increase within 7 days 2
• BUN/creatinine ratio >20:1 often indicates prerenal AKI, which is common in ketogenic diet-related kidney injury 2
• Elevated beta-hydroxybutyrate levels (typically 0.3-4 mmol/L in physiological ketosis) may reach higher levels and contribute to kidney stress 1
• Urine studies may show concentrated urine with positive ketones but standard ketone tests may underestimate total ketone concentration as they don't detect beta-hydroxybutyrate 1

Mechanisms of Kidney Protection and Injury

• While some research suggests ketogenic diets may have protective effects against ischemic kidney injury through antioxidant and anti-inflammatory mechanisms 5, this is counterbalanced by other risks
• Ketogenic diets have been associated with increased risk of kidney stones, particularly in long-term use 3
• The emphasis on animal fats in many ketogenic diets increases saturated fat consumption, potentially increasing cardiovascular risk which can indirectly impact kidney function 3

Prevention and Management

• Adequate hydration is essential to prevent prerenal AKI while following a ketogenic diet 2
• Regular monitoring of kidney function, electrolytes, and acid-base status is crucial, especially during the initial adaptation phase 4
• Suspension of medications that may worsen AKI (ACE inhibitors, ARBs, NSAIDs, diuretics) should be considered when initiating a ketogenic diet 2
• Plant-based versions of ketogenic diets may mitigate some risks associated with animal-based versions 3

Special Considerations

• Individuals with pre-existing kidney disease should approach ketogenic diets with caution due to limited safety data 3
• The metabolic stress of ketosis combined with critical illness can significantly increase the risk of AKI 6
• Long-term adherence to ketogenic diets is generally poor, which may limit chronic kidney effects but increase risk during cycling on and off the diet 3