Dr. Jacob Torres
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The science

How ketones act across the body in PKD

A ketogenic diet and the ketone β-hydroxybutyrate (BHB) work in several places at once to slow polycystic kidney disease. Tap a region of the body to see what the research shows.

Interactive anatomical torso An anatomical torso with four clickable regions: liver, circulation, kidneys, and gut.

Kidney

Starving cyst growth

In PKD, the cells lining kidney cysts become metabolically inflexible — they lean on glucose and glycolysis (a Warburg-like state) and over-activate the growth signal mTOR. Inducing ketosis — and the ketone β-hydroxybutyrate (BHB) on its own — removes that fuel and dampens mTOR signaling, proliferation, and fibrosis. In rat, mouse, and even cat models, ketosis prevents and partially reverses cyst growth. An earlier discovery: microcrystal injury in the tubules is an early trigger that accelerates cyst formation.

Research

For education, not medical advice. For PKD-specific diet guidance, see the Ren-Nu program.

Our model

How injury drives PKD — and how BHB + citrate intervene

"Genes load the gun, but lifestyle pulls the trigger." A PKD mutation sets the stage, but it takes a kidney injury to drive cysts. Step through the model — or let it play.

Renal injury model of PKD A kidney tubule lined with cells moves from a quiet PKD mutation, to microcrystal injury, tubule dilation, runaway cyst growth, and treatment with BHB and citrate. Kidney tubule uninjured tubule a microcrystal lodges & injures the tubule dilates to flush it cyst grows injury drives a cyst to form slowed BHB citrate BHB + citrate = KetoCitra
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    Genes load the gun

    A PKD mutation alone stays largely silent — in animals, deleting the PKD gene barely causes disease for a long time.

    Trigger Warning — Nutrients, 2024 ↗

The story so far

Key discoveries, 2013 → today

Press play to trace how the model came together — the line extends, each date lights up, and its finding appears.

▶ Press play to trace the timeline

2013

BHB is more than fuel

β-hydroxybutyrate is a signaling molecule — an HDAC inhibitor that switches on the body's own protective genes.

Shimazu et al., Science ↗
2019

Ketosis halts cyst growth

Inducing ketosis — or simply giving BHB — stops and partially reverses cyst growth in PKD animals. Cyst cells are “metabolically inflexible.”

Torres et al., Cell Metabolism ↗
2019

Injury is the trigger

Microcrystals lodging in tubules set off a dilation-and-repair response that, in PKD, accelerates cysts — and low urinary citrate tracks worse disease.

Torres et al., J Clin Invest ↗
2021

Into the real world

A case series of 131 ADPKD patients on ketogenic diets finds the approach feasible and safe, with reported gains in health, weight, and blood pressure.

Strubl et al., Clinical Kidney Journal ↗
2022

From bench to program

The science becomes a therapy: KetoCitra — a medical food combining BHB and citrate — and the dietitian-led Ren-Nu program.

Bruen et al., Kidney & Dialysis ↗
2023

The first randomized trial

KETO-ADPKD shows a ketogenic diet is feasible in patients and points to improved kidney function — the first randomized controlled trial of its kind.

Cukoski et al., Cell Reports Medicine ↗
2024

BHB + citrate, proven together

In rats, BHB and citrate act synergistically and partially reverse established disease — the rationale behind KetoCitra, confirmed.

Torres et al., Am J Physiol-Renal ↗
2026 · Today

Real-world outcomes

200+ people have now completed the Ren-Nu program with KetoCitra; a real-world evaluation reports feasibility, safety, and benefit — and the research continues.

Muensterman et al., Frontiers in Nutrition ↗

The molecule

What β-hydroxybutyrate does in the body

BHB is more than a backup fuel — it's a signaling molecule that acts on energy, inflammation, and even gene expression.

An efficient fuel

Cells burn BHB more efficiently than fat, feeding energy straight into the mitochondria — valuable when glucose is scarce.

Nature Medicine, 2015 ↗

Calms inflammation

BHB blocks the NLRP3 inflammasome, lowering inflammatory signals such as IL-1β and IL-18 throughout the body.

Nature Medicine, 2015 ↗

Guards against oxidative stress

BHB is a natural HDAC inhibitor that switches on stress-defense genes like FOXO3, protecting cells from oxidative damage.

Science, 2013 ↗

A signaling molecule

BHB binds the receptor GPR109A (HCAR2), helping regulate metabolism and lipid handling — beyond simply providing energy.

Biomed. & Pharmacother., 2023 ↗

The molecule, in depth

The deeper biology of BHB

Why one small molecule can slow a genetic kidney disease — from cell metabolism to the epigenome, drawn from the primary literature.

Cysts are metabolically inflexible

PKD cyst cells run on glucose in a Warburg-like state and can barely burn ketones — so a shift into ketosis starves the cysts while healthy cells adapt.

Cell Metabolism, 2019 ↗

It quiets mTOR

mTOR is the overactive growth switch driving cyst proliferation and fibrosis. Ketosis — or BHB alone — dampens mTOR signaling and shrinks cystic burden, without the toxicity that sank mTOR-inhibitor drugs.

Cell Metabolism, 2019 ↗

A direct epigenetic mark

Beyond inhibiting HDACs, BHB physically tags histones — β-hydroxybutyrylation, a mark written by p300 and erased by HDAC1/2 — switching on its own protective gene programs.

Science Advances, 2021 ↗

It reprograms the kidney

Through that mark, BHB turns up fat-burning genes (HMGCS2) and turns down mTORC1 in kidney cells — a newly described, direct route to renal protection.

Hypertension, 2025 ↗

BHB is the active ingredient

Oral BHB on its own recapitulates the benefits of the full ketogenic therapy in PKD — pinpointing the ketone itself, not just the diet, as the driver.

iScience, 2024 ↗

Borne out in patients

In 521 people with ADPKD, every doubling of blood BHB was associated with a slower yearly decline in kidney function — the first human signal matching the animal data.

Nephrol Dial Transplant, 2024 ↗

The disease

PKD is more than kidney cysts

Polycystic kidney disease is a systemic condition — fluid-filled cysts enlarge the kidneys over decades, but the effects reach well beyond them.

Kidneys

Cysts grow over decades, enlarging the kidneys and slowly eroding function. About 75% of people with ADPKD need dialysis or a transplant by age 70.

Cell Reports Medicine, 2023 ↗

Gut

As disease advances, the intestinal barrier grows leakier and more inflamed — a gut–kidney link now under active study.

Am J Physiol-Renal, 2025 ↗

What pulls the trigger

Triggers that can accelerate PKD

From Trigger Warning — the dietary, lifestyle, and environmental factors that injure the kidney and can speed the disease.

Carbohydrate overload

Chronic high-carb, ultra-processed eating drives hyperglycemia, insulin resistance, and inflammation that injure the kidney.

Dehydration

Too little fluid concentrates the urine and raises the risk of crystals forming in the tubules.

Microcrystals

Oxalate, phosphate, and uric-acid crystals lodge in tubules and set off the injury response.

Nephrotoxins

Exposure to toxins and nephrotoxic medications is a direct form of renal injury.

Gut dysbiosis

An imbalanced, leaky gut fuels systemic inflammation along the gut–kidney axis.

High uric acid

Hyperuricemia — often from sugar and purines — promotes crystals and faster progression.

The protective flip side: a plant-focused ketogenic diet that avoids oxalate, phosphate, and purines, paired with citrate — the basis of the Ren-Nu program. Trigger Warning — Nutrients, 2024 ↗

From the lab to the clinic

What the human trials show

The mechanism is now being tested in people with ADPKD — the early results are promising, and reported honestly.

The first randomized trial

KETO-ADPKD randomized 66 patients to a ketogenic diet, water fasting, or usual care. Both diets reliably induced ketosis, and most found them feasible — 95% on the ketogenic diet.

Cell Reports Medicine, 2023 ↗

Early signals of benefit

The ketogenic-diet group lost body fat and liver volume and showed improved kidney function (eGFR), while the control group declined — as is typical in ADPKD.

Cell Reports Medicine, 2023 ↗

Depth of ketosis matters

The ketogenic diet improved kidney function, but repeated water fasting — which causes only mild ketosis — did not, pointing to deep ketosis rather than calorie-cutting as the driver.

Cell Reports Medicine, 2023 ↗

Real-world experience

In a case series of 131 people on a ketogenic or time-restricted diet for ~6 months, 86% reported better overall health, 90% lost weight, and 64% of those with hypertension saw blood-pressure improvement.

Clinical Kidney Journal, 2021 ↗

Cysts held steady for years

In four ADPKD patients on long-term ketogenic therapy with KetoCitra (6 months to ~4 years), total kidney volume stabilized or shrank — a reversal of the relentless growth that defines the disease — with kidney function preserved and one patient’s imaging class improving.

Frontiers in Nutrition, 2026 ↗

An honest caveat: these are early, mostly short-term findings — not a treatment recommendation. Larger, longer trials are needed to confirm benefit and watch for risks such as higher cholesterol or kidney stones. Cukoski et al., 2023 ↗