November 3, 2021

Kidney Stone Incidence and Characteristics in Patients Following a Ketogenic Diet

Results from a systematic review and meta-analysis
A ketogenic diet, which consists of adequate protein and high fat, can dramatically increase the incidence of kidney stones.

Reference

Acharya P, Acharya C, Thongprayoon C, et al. Incidence and characteristics of kidney stones in patients on ketogenic diet: a systematic review and meta-analysis. Diseases. 2021;9: 39-42.

Study Objective

The objective of this meta-analysis was to calculate an estimated pooled incidence of kidney stones in patients who follow a ketogenic diet and to determine the most prevalent type of kidney stone as well.

Design

A systematic review and meta-analysis of 36 published clinical trials and observational studies (cohort, case-control, or cross-sectional) that reported the incidence of kidney stones in those on a ketogenic-type diet.

Participants

The literature retrieval, review, and selection process ultimately resulted in the inclusion of 36 studies encompassing 2,795 pooled participants.

The investigators queried the following databases: MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews.

Publication retrieval primarily used the search strategy: (‘ketogenic diet’ OR ‘keto diet’ OR ‘atkins diet’ OR ‘low carb diet’ OR ‘low carbohydrate diet’) AND (nephrolithiasis OR ‘kidney stone’ OR ‘kidney stones’). The initial search resulted in 221 relevant studies. Two independent investigators reviewed these articles, and a third investigator resolved discrepancies.

Study Parameters Assessed

The parameters assessed included number of patients, mean age, gender, time to diagnosis of the kidney stone after ketogenic diet consumption, type of kidney stone, incidence of kidney stones, and duration of follow-up.

Primary Outcome Measures

The primary outcome measures included the incidence and type of kidney stones.

Key Findings

Incidence: The key finding in this study was that the estimated pooled incidence of kidney stones was 5.9% in patients on a ketogenic diet at the mean follow-up time of 3.7 ± 2.9 years.

Because age was not a limitation, the investigators were able to perform a subgroup analysis that demonstrated that the estimated pooled incidence of kidney stones in children was 5.8% as compared to adults, which was 7.9%.

Type: Within reported studies, 48.7% of kidney stones were uric-acid stones, 36.5% were calcium-based stones, and 27.8% were mixed uric-acid and calcium-based stones.

Practice Implications

When you consider that the incidence of nephrolithiasis in the general population is reported at 0.3% per year in men and 0.25% per year in women,1 it becomes clear based on the results of this analysis that following a ketogenic diet may enhance the incidence of kidney stone formation. As such, practitioners prescribing ketogenic diets must evaluate whether the ketogenic-diet benefits outweigh risks. Patients and clients will also need to be informed of increased risk of kidney stone formation and strategies to mitigate their formation.

Practitioners prescribing ketogenic diets must evaluate whether the ketogenic-diet benefits outweigh risks.

While the exact mechanism of nephrolithiasis is still uncertain, it may likely be related to the chronic acid-loaded physiological state that often results from following a high-fat, moderate-protein, low-alkaline diet. If fluid intake is also restricted, kidney stone formation risk increases further.2 Additionally, chronic acidosis leads to bone demineralization, increased calcium excretion,3,4 and even uric acid crystals.2

Modification of the diet and other medical/nutritional strategies may need to be implemented, especially in those who have a history of kidney stone formation.

As it relates to the diet, some modification possibilities include:

  1. Switching from purine-rich animal protein that has been shown to produce an acidic environment to plant-based proteins resulting in lower uric-acid excretion.
  2. Increasing fluid intake to reduce the risk of kidney stone precipitation.5,6

As it relates to dietary supplementation:

  1. Supplementation with oral potassium citrate, which can alkalize urine pH, may be warranted. Potassium citrate has been shown to result in a reduction of kidney stone formation. In one study, formation of kidney stones was reduced from 6.75% to 0.9% with no adverse effects in participants on ketogenic diet.7
  2. Adequate calcium, magnesium, and vitamin D levels are also an essential aspect to support bone health.8,9

In those with recurrent stone formation, regardless of diet, screening for genetic variants that increase risk of kidney stone formation (ie, renal sodium citrate cotransporter) should be considered as part of a holistic and personalized approach.10,11

Duration of the ketogenic diet may also be a factor in kidney stone formation. In those following a ketogenic diet for weight loss, the risk for kidney stone development may be mitigated if the diet is followed short term.

Ultimately, the authors note, “these findings may impact the prevention and management of kidney stones in patients treated with ketogenic diets.” Awareness of this risk on the part of the practitioner and the patient is an essential piece of information before moving forward with a ketogenic diet.

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References

  1. Curhan GC. Epidemiology of stone disease. Urol Clin N Am. 2007;34:287-293.
  2. Bushinsky DA, Coe FL, Moe OW. Nephrolithiasis. Brenner Rector’s Kidney. 2012;9:1455-1507.
  3. Liu YM, Wang HS. Medium-chain triglyceride ketogenic diet, an effective treatment for drug-resistant epilepsy and a comparison with other ketogenic diets. Biomed J. 2013;36:9-15.
  4. Bach AC, Babayan VK. Medium-chain triglycerides: an update. Am J Clin Nutr. 1982;36:950-962.
  5. Agarwal N, Arkilo D, Farooq O, Gillogly C, Kavak KS, Weinstock A. Ketogenic diet: predictors of seizure control. SAGE Open Med. 2017;5.
  6. Wirrell EC, Darwish HZ, Williams-Dyjur C, Blackman M, Lange V. Is a fast necessary when initiating the ketogenic diet? J Child Neurol. 2002;17:179-182.
  7. McNally MA, Pyzik PL, Rubenstein JE, Hamdy RF, Kossoff EH. Empiric use of potassium citrate reduces kidney-stone incidence with the ketogenic diet. Pediatrics. 2009;124:e300-e304.
  8. Bergqvist AC, Schall JI, Stallings VA. Vitamin D status in children with intractable epilepsy, and impact of the ketogenic diet. Epilepsia. 2007;48:66-71.
  9. Bergqvist AGC, Schall J, Stallings V, Zemel BS. Progressive bone mineral content loss in children with intractable epilepsy treated with the ketogenic diet. Am J Clin Nutr. 2008;88:1678-1684.
  10. Okamoto N, Aruga S, Matsuzaki S, Takahashi S, Matsushita K, Kitamura T. Associations between renal sodium-citrate cotransporter (hNaDC-1) gene polymorphism and urinary citrate excretion in recurrent renal calcium stone formers and normal controls. Int J Urol. 2007;14:344-349.
  11. Nicar MJ, Skurla C, Sakhaee K, Pak CY. Low urinary citrate excretion in nephrolithiasis. Urology. 1983;21:8-14.