ADPKD - Metabolism and Dietary Interventions - Dr. Thomas Weimbs (Santa Barbara, CA)

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Жыл бұрын

Dietary interventions - particularly ketogenic diets - may substantially modify the progression of Autosomal-Dominant Polycystic Kidney Disease (ADPKD). Dr. Weimbs and his laboratory team have investigated the major molecular mechanisms upon which such dietary interventions are based, which has paved the path towards their implementation into clinic.
The interview was recorded on June 7th, 2022. Moderators: Prof. Marcus Säemann (Vienna, Austria), Priv.-Doz. Sarah Seiler (Saarlouis, Germany) and Prof. Dr. Gunnar Heine (Frankfurt / Homburg, Germany).
Articles discussed:
β-hydroxybutyrate and its metabolic effects on age-associated pathology.
Han YM, Ramprasath T, Zou MH.
Exp Mol Med. 2020 doi: 10.1038/s12276-020-0415-z
Glucose promotes secretion-dependent renal cyst growth.
Kraus A, Schley G, Kunzelmann K, Schreiber R, Peters DJ, Stadler R, Eckardt KU, Buchholz B.
J Mol Med (Berl). 2016 doi: 10.1007/s00109-015-1337-4.
Reversal of diabetic nephropathy by a ketogenic diet.
Poplawski MM, Mastaitis JW, Isoda F, Grosjean F, Zheng F, Mobbs CV.
PLoS One. 2011 doi: 10.1371/journal.pone.0018604
Dietary Interventions in Autosomal Dominant Polycystic Kidney Disease.
Pickel L, Iliuta IA, Scholey J, Pei Y, Sung HK.
Adv Nutr. 2021 doi: 10.1093/advances/nmab131
The TSC-mTOR signaling pathway regulates the innate inflammatory response.
Weichhart T, Costantino G, Poglitsch M, Rosner M, Zeyda M, Stuhlmeier KM, Kolbe T, Stulnig TM, Hörl WH, Hengstschläger M, Müller M, Säemann MD.
Immunity 2008 doi: 10.1016/j.immuni.2008.08.012
Short-chain fatty acid, acylation and cardiovascular diseases.
Chen XF, Chen X, Tang X.
Clin Sci (Lond). 2020 doi: 10.1042/CS20200128
A mild reduction of food intake slows disease progression in an orthologous mouse model of polycystic kidney disease. Kipp KR, Rezaei M, Lin L, Dewey EC, Weimbs T.
Am J Physiol Renal Physiol. 2016 doi: 10.1152/ajprenal.00551.2015.
β-Hydroxybutyrate Suppresses Lipid Accumulation in Aged Liver through GPR109A-mediated Signaling.
Lee AK et al.
Aging Dis. 2020 doi: 10.14336/AD.2019.0926
Pain and Obesity in Autosomal Dominant Polycystic Kidney Disease: A Post Hoc Analysis of the Halt Progression of Polycystic Kidney Disease (HALT-PKD) Studies.
Nowak KL et al.
Kidney Med. 2021 doi: 10.1016/j.xkme.2021.03.004
Ketone bodies: from enemy to friend and guardian angel.
Kolb H et al.
BMC Med. 2021 doi: 10.1186/s12916-021-02185-0
Weight loss and cystic disease progression in autosomal dominant polycystic kidney disease.
Hopp K, Catenacci VA, Dwivedi N, Kline TL, Wang W, You Z, Nguyen DT, Bing K, Poudyal B, Johnson GC, Jackman MR, Miller M, Steele CN, Serkova NJ, MacLean PS, Nemenoff RA, Gitomer B, Chonchol M, Nowak KL.
iScience. 2021 doi: 10.1016/j.isci.2021.103697
Ketosis Ameliorates Renal Cyst Growth in Polycystic Kidney Disease.
Torres JA, Kruger SL, Broderick C, Amarlkhagva T, Agrawal S, Dodam JR, Mrug M, Lyons LA, Weimbs T.
Cell Metab. 2019 doi: 10.1016/j.cmet.2019.09.012
Ren.Nu, a Dietary Program for Individuals with Autosomal-Dominant Polycystic Kidney Disease Implementing a Sustainable, Plant-Focused, Kidney-Safe, Ketogenic Approach with Avoidance of Renal Stressors.
Bruen DM, Kingaard JJ, Munits M, Paimanta CS, Torres JA, Saville J, Weimbs T.
Kidney Dial. 2022 doi.org/10.3390/ kidneydial2020020
Ketogenic dietary interventions in autosomal dominant polycystic kidney disease-a retrospective case series study: first insights into feasibility, safety and effects.
Strubl S ..., Weimbs T.
Clin Kidney J. 2021 doi: 10.1093/ckj/sfab162
Overweight and Obesity Are Predictors of Progression in Early Autosomal Dominant Polycystic Kidney Disease.
Nowak KL et al.
J Am Soc Nephrol. 2018 doi: 10.1681/ASN.2017070819
The mTOR pathway is regulated by polycystin-1, and its inhibition reverses renal cystogenesis in polycystic kidney disease.
Shillingford JM, ... , Weimbs T.
Proc Natl Acad Sci U S A. 2006 doi: 10.1073/pnas.0509694103
Sirolimus and kidney growth in autosomal dominant polycystic kidney disease.
Serra AL et al.
N Engl J Med. 2010 doi: 10.1056/NEJMoa0907419
Everolimus in patients with autosomal dominant polycystic kidney disease.
Walz G et al.
N Engl J Med. 2010 doi: 10.1056/NEJMoa1003491
Tolvaptan in patients with autosomal dominant polycystic kidney disease.
Torres VE et al.; TEMPO 3:4 Trial Investigators.
N Engl J Med. 2012 doi: 10.1056/NEJMoa1205511
Polycystic kidney disease.
Bergmann C et al.
Nat Rev Dis Primers. 2018 doi: 10.1038/s41572-018-0047-y
Tolvaptan in Later-Stage Autosomal Dominant Polycystic Kidney Disease.
Torres VE et al.; REPRISE Trial Investigators.
N Engl J Med. 2017 doi: 10.1056/NEJMoa1710030.
Angiotensin blockade in late autosomal dominant polycystic kidney disease.
Torres VE et al. HALT-PKD Trial Investigators.
N Engl J Med. 2014 doi: 10.1056/NEJMoa1402686
Blood pressure in early autosomal dominant polycystic kidney disease.
Schrier RW et al.; HALT-PKD Trial Investigators.
N Engl J Med. 2014 doi: 10.1056/NEJMoa1402685

Пікірлер: 8

@kimcollard4001 Жыл бұрын

Thank you Thank you all Truely... Please don't give up.. those of us with PKD have all our fingers and toes crossed that you will find some Hope for our children

@CaptainSteve777 Жыл бұрын

Great discussion. Dr. Weimbs is right! I know. My cysts are shrinking with a very-low-carb, clean, whole-food, low-oxalate, low-purine, minimally processed, anti-inflammatory, clean keto diet (75% fat, 10% carb, and 15% protein), lots of water, and KetoCitra to improve ketosis and keep a proper pH to make sure microcrystal can't form in the tubules in my kidneys. I also do IF and water fasting. With all that, my GFR decline reversed and all my nasty symptoms are gone. Now, at age 66, my eGFR is 84, and per my last MRI my largest cyst shrank in volume by 55%.

@Anna-ww4pv Ай бұрын

I did keto 6 years straight… fell off during COVID. Back into keto now. I feel 10 x better in keto. I can tell my abdomen is smaller. I do 70 fat, 15 carb, 15 protein. Keto flu…drink more water and potassium n magnesium.. I exercise and my cholesterol levels are stellar. I have ADPKD nd lost one kidney at 6weeks ( multi-cystic). Keto people trust the diet. A few drs understand unless they do it or use it on there children for seizures. Food is medicine…when in ketosis, the carb craving goes way.I hope drs are more open to keto ( true keto) as people do this a will nit tell their Dr of, they think they are negative about it. For me, I have will power an keto. I would never be an ozempic person when keto works so good. I’m healthy.

@Rene-uz3eb 5 ай бұрын

Vasopressin. When you cut out angiotensin, all the body has left to regulate bp is vasopressin. If your bp is high, it's probably because of stiffening arteries due to damage, and calcification. Magnesium loss leads to calcification. So cut out all the magnesium losing drugs too (calcineurin etc) and ensure proper kidney perfusion by dropping bp meds as low kidney blood flow leaks magnesium (as seen eg under strenuous exercise), and replenish magnesium. Also, blood glucose levels correlate to low magnesium. This makes sense, because shuffling along excessive glucose by the kidney is hugely energy intensive (cotransporter hijacking sodium potassium pump), so you get the low residual energy magnesium leakage. Note sodium potassium gradient always takes precedence.

@btudrus Ай бұрын

"Vasopressin. When you cut out angiotensin, all the body has left to regulate bp is vasopressin" yes " If your bp is high, it's probably because of stiffening arteries due to damage, and calcification" Probably not. It is due to high insulin in the first.

@Rene-uz3eb Ай бұрын

I'm not sure that's the case. Insulin resistance correlates with stiffness and hypertension, but obesity directly causes high bp, and most type 2 Americans are obese. Also, "Although IR is associated with increased arterial stiffness, traditional cardiovascular risk factors, especially obesity and BP, are the major determinants of arterial stiffness in healthy young people." Insulin resistance and arterial stiffness in healthy adolescents and young adults, 2011 Also, there would be a problem with everyone taking insulin. So first, due to obesity

@btudrus Жыл бұрын

As to the question what happens in the kidney due to a ketosis, one important element is that a low insulin means less sodium reabsorbtion. In the case of prolonged fasting this effect is known as the "natriuriesis of fasting". This is likely also the reason why ketosis / starvation can lead to a very significant drop in BP. Insulin is known to directly affect several sodium transporters in the kidney. See e.g. PMID: 25723632 or 7028550.