The benefits and risks of a ketogenic diet for ADPKD from the KETO-ADPKD Study
Studies in animal models of autosomal dominant polycystic kidney disease (ADPKD) showed in 2019 that a ketogenic diet may have positive effects on cystic kidneys. Ketogenic diets are low in carbohydrate and high in fat. In animals fed this diet, cyst growth slowed. Also, their kidney function didn’t decline as fast as usual.
These promising findings attracted a lot of attention among kidney specialists, scientists and patients.1 People rightly wanted to know more, and began to question: Should patients with ADPKD eat a ketogenic diet? And what would that involve?
To answer this question, we need clinical studies to assess whether a ketogenic diet is effective and safe in people with ADPKD. Similar to the approval process for drugs, studies in humans are an essential step before medical recommendations can be made about diets. Such studies were lacking — until now.
The KETO-ADPKD study is the first clinical study to compare a ketogenic diet versus a control (normal) diet in patients with ADPKD. The Translational Nephrology Unit at the University Hospital of Cologne, Germany, led the study and it was recently published in the renowned journal Cell Reports Medicine.2
The study was small (23 patients had a ketogenic diet and 19 had a control diet). It was also only 3 months’ long. This means the results are not reliable enough to make any recommendations about ketogenic diets.
We still don’t know with certainty how the diet affects the kidneys, whether any effects last, and whether the diet does any harm. However, the findings show the diet is well worth exploring further in larger, longer trials.
Below, one of the study authors, Professor Roman-Ulrich Müller (MD), explains the main findings.
What does ‘ketogenic diet’ mean?
Usually, our bodies make most of their energy from the carbohydrates we eat (such as sugar, bread, pasta, and rice). A ketogenic diet is low in carbohydrates and high in fat (such as olive oil and fatty fish). This forces the body to make energy from fat instead. This leads to a metabolic state called ketosis.
In KETO-ADPKD, people on the ketogenic diet ate up to 30 grammes of carbohydrate a day (about half a cup of rice or a bagel) and about 0.8 grammes of protein for every kilogram of bodyweight. The rest of their daily calories came from fat.
Is a ketogenic diet feasible for patients with ADPKD in everyday life?
Dietary changes are not always easy to maintain. So, whether it was feasible for people to follow the diet was an important study question.
Feasibility was measured in two ways: 1) by getting patients’ feedback via questionnaires, and 2) by looking for chemical signs of ketosis in people’s blood and breath. The results show that the diet was feasible, with 95% of patients finding it possible to follow for 3 months.
People with ADPKD tend to be very motivated to manage their disease, which might have helped them to stick to the diet. However, there are some hurdles to overcome in everyday life. For example, eating in a restaurant requires more planning.
Did the ketogenic diet slow kidney growth?
Normally, polycystic kidneys slowly increase in size over the years due to cyst growth. In the KETO ADPKD study, kidneys very slightly increased in size in the normal diet group, but slightly shrank in the ketogenic diet group over 3 months.
Statistical analysis shows this difference might not be meaningful. It could be down to random chance.
For readers wanting more detail:
- Kidney size is measured as millilitres of kidney volume, taking into account a person’s height (written as ml/m).
- In the normal diet group, people’s kidneys grew, on average, from about 838 ml/m at the study start to about 845 ml/m at 3 months. This is equivalent to an increase in kidney size of less than 1%.
- In contrast, the kidneys of people on the ketogenic diet shrank, on average, from about 896 ml/m at the study start to 891 ml/m at 3 months. This is equivalent to a decrease in kidney size of less than 1%.
What did KETO-ADPKD show regarding kidney function?
Usually, kidney function decreases slowly over the years in ADPKD. In this study, kidney function slightly decreased for patients in the normal diet group, as expected. In contrast, it increased for patients on the ketogenic diet. Statistical analysis shows this difference is likely to be ‘real’ (it’s probably not due to chance alone).
For readers wanting more information:
- Kidney function is measured as estimated glomerular filtration rate (eGFR), which is an estimate of how much blood (in millilitres) the kidneys can filter in 1 minute (adjusted by bodyweight – per 1.73 m2). This is written as ml/min/1.73 m2.
- In the normal diet group, eGFR dropped from an average of about 82 at the start to about 81 ml/min/1.73 m2 after 3 months. This is equivalent to a drop in kidney function of less than 2%.
- In the ketogenic diet group, eGFR increased from an average of about 86 at the start to about 90 ml/min/1.73 m2 at 3 months. This is equivalent to an increase in kidney function of over 5%.
This increase in eGFR with the ketogenic diet could signal an improvement in kidney health. However, it could also be a sign that the kidneys are working unusually hard. This is called ‘hyperfiltration’ and can be caused by a few things, including eating more protein.
More research is needed to find out whether the increase in eGFR seen with a ketogenic diet is a good or bad thing, and whether the effect lasts.
Were there any side effects of the ketogenic diet?
The study was too short to see if a ketogenic diet has any long-term risks for people with ADPKD.
It does show some possible short-term side effects:
- 10 of the 23 people on the ketogenic diet got ‘keto flu’. This is a well-known side effect some people get in the first few days of starting a ketogenic diet. Symptoms are similar to an infection, such as headaches or tiredness. Keto flu passes after a few days.
- 4 people on the ketogenic diet (versus 0 on the normal diet) developed increased cholesterol levels. Cholesterol is a fat found in the blood. This could be important as increases in certain cholesterols can increase the risk of cardiovascular disease.
- 1 patient in the ketogenic diet group (versus 0 on the normal diet) got a kidney stone causing symptoms. The researchers don’t know whether this stone had formed before the person started the diet. However, kidney stones do occur in some people who don’t have ADPKD who are following a ketogenic diet.
- 4 people on the ketogenic diet (versus 1 on the normal diet) had higher than normal levels of uric acid. High levels of this chemical may be a risk factor for kidney stones.
- 4 people on the ketogenic diet (versus 0 on the normal diet) sometimes felt lightheaded when they got up, which is a sign of low blood pressure. This could be a good thing, as people with ADPKD often have high blood pressure, but might mean their blood pressure medications need altering.
A longer, larger study could help to spot any additional side effects, including rare yet important ones.
Should patients with ADPKD follow a ketogenic diet?
Neither the PKD Charity nor the KETO-ADPKD researchers recommend that people with ADPKD follow a ketogenic diet based on the study results. While some of the results are promising, a larger and longer study (for example following at least 200–300 people for 2–3 years) in multiple locations is needed so we can be confident about the diet’s risks and benefits.
The study did not include any patients who were underweight, obese, or who had more advanced ADPKD. Benefits and risks might differ in these groups.
The findings of the KETO-ADPKD study can help doctors to give patients who are curious about the diet some advice on potential effects, both good and bad.
Further sources of information from the researchers:
References
1. Torres, J. A., Kruger, S. L., Broderick, C., Amarlkhagva, T., Agrawal, S., Dodam, J. R., Mrug, M., Lyons, L. A. & Weimbs, T. Ketosis Ameliorates Renal Cyst Growth in Polycystic Kidney Disease. Cell Metab. (2019). doi:10.1016/j.cmet.2019.09.012
2. Cukoski, S., Lindemann, C. H., Arjune, S., Todorova, P., Brecht, T., Kühn, A., Oehm, S., Strubl, S., Becker, I., Kämmerer, U., Torres, J. A., Meyer, F., Schömig, T., Hokamp, N. G., Siedek, F., Gottschalk, I., Benzing, T., Schmidt, J., Antczak, P., Weimbs, T., Grundmann, F. & Müller, R.-U. Feasibility and impact of ketogenic dietary interventions in polycystic kidney disease: KETO-ADPKD—a randomized controlled trial. CR Med 0, (2023).
To find out more about other diet and lifestyle changes, see our fact sheet Diet and lifestyle in ADPKD.
ADPKD, Research, Grants awarded, PKD, Diet, keto
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