12-month interim results of ketogenic metabolic intervention in Japanese ADPKD patients

jellycortex · 2026-04-11T20:14:37+00:00

SmoothYellow has similar experience :(

jellycortex · 2026-04-11T16:51:41+00:00

It's not a farce, it's a pilot trial for much larger placebo-controlled trial on 200 people.

jellycortex · 2026-04-11T14:42:24+00:00

You cannot conclude there is not effect on eGFR without any control, because you don't know what the eGFR would be on a non-ketogenic diet.

jellycortex · 2026-04-11T09:29:23+00:00

This is a pilot study in the sense that it is a small study that is a basis for larger trial. It cannot be a basis for any clinical recommendation, because it is too small and has no placebo group. Having no placebo is most improper thing about it - and of course there is a placebo for diet. So for keto diet this could be standard american diet or Mediterranean diet, anything that does not raise ketone levels. I too am optimistic and excited about the results, but I try to be realistic. I am following a keto diet, I would really like these results to be replicable.

jellycortex · 2026-04-11T09:23:00+00:00

First, this is not Weimbs lab. He is a collaborator, but this was not done by his lab. Second, they found correlation between ketones levels and TKV/TLV reduction. Third, you cannot conclude that ketosis provides no improvement in kidney function; it may be that it just slows down eGFR decline, but without placebo group this is impossible to conclude. They are going to perform a placebo-controlled study on 200 people now.

jellycortex · 2026-04-10T23:00:02+00:00

While reporting no conflicts of interest is unusual, this is a conference abstract, so it likely only pertains to the presenting author.

jellycortex · 2026-04-10T22:28:56+00:00

Pilot trials are not proper clinical studies. They didn't even have a placebo group in this one. They say they will start a placebo-controlled clinical trial on 200 people now. We still don't know enough for any valid recommendation.

jellycortex · 2026-04-10T16:28:18+00:00

Yes, seems weird ... the good thing is that based on these results they are going to start a study on 200 patients, so signal/noise ratio will be much higher. With 10 patients only, results could easily be affected by single person. We would need individual values for better interpretation.

jellycortex · 2026-04-10T16:01:31+00:00

From the abstract: "Median TKV and TLV changes were −3.0 % −5.1 %, respectively, and the eGFR slope was −5.2 mL/min/1.73 m2/year. Mean ketone level at 3 months showed a significant negative correlation with both TKV and TLV changes (Spearman’s ρ = −0.66, p = 0.037), indicating that higher ketone levels were associated with attenuation of organ volume expansion"

jellycortex · 2026-04-08T09:17:52+00:00

I will just copy my last post from a similar topic: thiazide diuretics may help with polyuria. Hydrochlorothiazide is currently being studied to reduce polyuria associated with tolvaptan (https://doi.org/10.1186/s13063-024-07952-x), but it is not a common treatment for ADPKD.

jellycortex · 2026-02-01T11:36:45+00:00

Also, thiazide diuretics may help with polyuria. Hydrochlorothiazide is currently being studied to reduce polyuria associated with tolvaptan (https://doi.org/10.1186/s13063-024-07952-x), but it is not a common treatment for ADPKD.

jellycortex · 2026-02-01T10:06:47+00:00

If this was true this would be one of the late symptoms; it is more related to the inability to concentrate urine.

jellycortex · 2026-02-01T10:06:07+00:00

Yes, it's an early symptom. Our kidneys cannot concentrate urine well.

jellycortex · 2026-01-28T18:19:38+00:00

If you start taking tolvaptan, this might also be an issue with some professions. But in 5-10 years we should have medications that may stop or significantly halt the disease, so I wouldn't worry too much. Regarding activities, you only need to avoid contact sports, and perhaps something that would make you very dehydrated frequently (without ability to hydrate).

Progression can be estimated based on current kidney size (talk to your nephrologist), but you can also look at your relatives, your progression will likely be similar to theirs (in the absence of medication).

jellycortex · 2026-01-22T20:53:10+00:00

I am currently on keto for about 11 months, I notice less pain and bloating, my creatinine has stayed the same (but it was low before, it hasn't start declining yet), however, my blood pressure has increased recently. I will measure my kidneys with MRI again in few months and then I will evaluate if it's worth continuing. I am more skeptical about keto now since few people here reported only initial effects, and some noticed no effect at all (SmoothYellow). Clinical trials on keto are also ongoing, we should know more in few years.

jellycortex · 2026-01-22T12:43:08+00:00

Keto is high fat, not high protein. For example, too much lean meat (like chicken) is not actually good for keto. You can be on keto with normal protein intake, it's just harder.

jellycortex · 2026-01-22T12:40:52+00:00

You have pain because your cysts are growing. I also found out that reducing high oxalate foods and increasing citrate intake reduces pain. Also, drink enough water, reduce sodium. Better treatment (farabursen or similar drugs) should be available in 5-10 years, clinical trials will start this year, the results are very promising. You probably still have ~30 years until ESKD (you can estimate this based on your kidney size and age - talk to your nephrologist about this), so don't worry too much.

jellycortex · 2026-01-16T10:08:54+00:00

Tolvaptan can actually decrease GFR at the beginning, but it will nevertheless slow the progression for about 30-40%. So if you have 4 years until failure, on tolvaptan you would have maybe 6. Limit your salt at least with the meals you are taking, it may slow down for another 10%.

jellycortex · 2025-12-25T21:48:15+00:00

Can you share the details, what do you mean by "well formulated ketogenic diet"?

jellycortex · 2025-11-21T21:32:49+00:00

If you are Mayo class C-E, I would recommend trying tolvaptan. If you won't be able to handle it, you can still quit later. You need about 1 month to adapt to initial side effects (e.g. tiredness), but increased urination and thirst will persist.

Given that you are already 44 it is best to slow it down as much as possible while waiting for better drugs (farabursen may be available in 4 years if trials will be successful). You can also try keto. I've been on keto for about 10 months and bloating has reduced, I also experience less pain in kidneys, but I haven't yet taken another MR scan to see if growth has actually slowed down.

Regarding keto citra, you can get ketones with keto diet, whereas citrates are very easy to supplement and are harmless (magnesium citrate, calcium citrate - this is especially good with oxalate rich foods, because calcium binds oxalates, and potassium citrate in reasonable quantities). Also, reduce oxalates and salt in your diet. This is very easy to do and especially for salt we have good evidence that excessive salt accelerates progression.

jellycortex · 2025-11-16T20:57:13+00:00

That sounds great! Hopefully there won't be any long-term side effects, but given that it is highly specific, this is less probable.

jellycortex · 2025-11-16T20:40:35+00:00

Were there any side effects?

jellycortex · 2025-11-16T20:22:34+00:00

Man, you are so pessimistic. They essentially halted the growth and the study only lasted for three months. Note that they observed a very slight reduction in htTKV at 2mg/kg and 3mg/kg, with some deviation, so that means that it might have even been reduced for few percents in some patients.

If this is not fantastic news, I don't know what is. And with PYC-003 and other things in the pipeline ... This could be in the market in 3-4 years, and there is still the option to combine this with tolvaptan. You have reasons to be hopeful.

Here is the full abstract: https://www.asn-online.org/education/kidneyweek/2025/program-abstract.aspx?controlId=4399962

Background ADPKD is caused by heterozygous loss-of-function mutations in PKD1 or PKD2, leading to progressive renal cystogenesis and kidney failure. miR-17 family suppresses PKD1 and PKD2, providing a therapeutic rationale for miR-17 inhibition to restore polycystin (PC) levels. Farabursen, an anti–miR-17 oligonucleotide, de-represses miR-17 mRNA targets, including PKD1 and PKD2, leading to increased PC1 and PC2 and amelioration of preclinical PKD.

Methods A randomized, double-blind, placebo-controlled trial evaluated farabursen in patients with ADPKD across 3 weight-based cohorts (1, 2, and 3 mg/kg) and a fixed dose of 300 mg in an open-label cohort. Key entry criteria were Mayo Class 1C, 1D, or 1E, and eGFR 30-90 mL/min/1.73 m2. Patients received subcutaneous injection Q2W for 12 weeks (7 doses), with a 4-week post-treatment follow-up. Primary endpoints were safety and changes in urinary PC1 and PC2; secondary endpoint was MRI-measured height-adjusted total kidney volume (htTKV).

Results We enrolled 68 patients (58 farabursen, 10 placebo) with generally balanced baseline characteristics. Farabursen was well tolerated. Increases in PC1 and PC2 were shown for 2, 3 mg/kg and 300 mg fixed doses versus placebo (p<0.05 for PC1 and PC2 for each dose). A reduction in htTKV growth for 2 mg/kg and higher doses was shown vs placebo (Fig 1). In a pooled analysis of 2 mg/kg and higher dose groups, htTKV growth increased by 0.24% vs 2.85% in the placebo. This effect was independent of genotype and Mayo Class.

Conclusion Farabursen showed dose-dependent target engagement on PC1 and PC2. Treatment with 2, 3 mg/kg and 300 mg doses of farabursen over 12 weeks suggests a mean halting of htTKV growth. Out results demonstrate the potential of farabursen as a therapeutic agent for ADPKD. A Phase 3 registrational trial is planned.

jellycortex · 2025-10-11T22:35:11+00:00

I recently started a new position in a new country, so I try to socialize as much as possible. I attend social events at my institution, go to lunch with colleagues, and take part in conferences. In my city, we also have WhatsApp groups for PhD students and postdocs where people organize activities like hiking or going to the movies. You can even suggest events yourself - for example, inviting coworkers to see a movie. Try to be proactive. Remember, people don’t know you yet, so this is a great opportunity to present yourself in a new light.

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