The Protective Role of Ozone Therapy in Kidney Disease: A Review

Background

Kidney disease is a growing global health burden. Acute and chronic renal injury reduce both the quality and the length of life, and they place heavy costs on health systems and on patients themselves. A recurring feature across many forms of kidney damage - whether triggered by interrupted blood flow, toxic drugs, or long-term disease - is oxidative stress and inflammation, in which reactive molecules overwhelm the kidney's natural defences and drive scarring (fibrosis) and cell death. Researchers have therefore looked for interventions that can strengthen the kidney's own antioxidant systems, and ozone therapy is one approach that has drawn attention.

What this review covers

This narrative review, published in the journal Life in 2023, gathers and interprets the published evidence on ozone (O3) therapy across different models of kidney injury. The authors set out to explain an apparent paradox: ozone is itself a reactive oxygen species that can cause oxidative stress, yet at low, controlled concentrations it appears to prime cells to produce more of their own antioxidants. They note that therapeutic concentrations vary widely, with around 50 µg/mL commonly used in experimental and clinical work, and that higher concentrations risk acting as a germicide or causing damage. The review focuses on how ozone therapy relates to fibrosis, apoptosis (programmed cell death), oxidative stress and inflammation, drawing together findings from injury models caused by ischaemia, xenobiotics (foreign chemicals and drugs), and chronic damage.

Findings

The authors report that, across the studies they reviewed, controlled low-dose ozone was associated with reduced oxidative damage and dampened inflammation in injured kidneys. Mechanistically, the review describes ozone activating the Nrf2 pathway, which increases production of antioxidant enzymes, while ozonated lipid products appear to suppress inflammatory signalling through the NF-κB pathway. These effects were reported when ozone was applied before or after renal insults. The review discusses several categories of injury: ischaemia-reperfusion injury (damage that occurs when blood supply is cut off and then restored), toxicity from drugs and chemicals such as cisplatin, cadmium and acetaminophen, and chronic kidney damage including diabetic nephropathy models. In these settings the reviewed studies generally reported better functional markers and less tissue damage with ozone treatment. Most of this evidence comes from laboratory and animal experiments, with human data appearing mainly as case reports rather than controlled trials.

Shock wave lithotripsy: protecting the kidney during stone treatment

A short further section of the review deals with extracorporeal shock wave lithotripsy, usually shortened to ESWL and more commonly described as shock wave treatment for kidney stones. It is the standard first-line treatment for kidney stones (renal calculi) smaller than about 2.0 cm: focused sound waves are aimed at the stone from outside the body to break it into fragments small enough to pass naturally. The review describes the procedure as highly efficient, while noting that after-effects can occur, haematuria (blood in the urine) among them, because the shock waves also travel through healthy kidney tissue on their way to the stone.

It is that incidental tissue damage, rather than the stone, that the ozone research addresses. The review cites a single experimental study reporting that ozone treatment reduced the morphological and oxidative damage caused by shock wave therapy. That study - Uğuz and colleagues, published in Renal Failure in 2016 - used 24 male Sprague-Dawley rats in three groups (sham, shock wave, and shock wave plus ozone), with ozone given at 1 mg/kg/day intraperitoneally two hours before the procedure and for three days afterwards. The ozone group showed lower oxidative stress markers and lower histopathological injury scores than the shock wave group. The authors of that paper stated plainly that well-designed clinical studies are still needed. The full record is available on PubMed.

An important boundary. None of this evidence suggests that ozone dissolves, shrinks, passes or prevents kidney stones, and we are not aware of any research that does. The stone is broken up by the shock waves. The only question this research asks is whether the surrounding kidney tissue sustains less incidental damage during the procedure, and so far that question has only been asked in rats. Kidney stones are a matter for a urologist.

The same section of the review notes two further applications, both resting on ozone's antimicrobial activity: reduced oxidative damage in kidney infection (pyelonephritis) and in models of septic shock affecting the kidneys. The review does not expand on either, and the underlying evidence is again experimental.

Terms used in this section

• Extracorporeal shock wave lithotripsy (ESWL) - commonly called shock wave treatment, lithotripsy, or simply having stones broken up. Extracorporeal means from outside the body; lithotripsy comes from the Greek for stone-crushing.
• Renal calculi - kidney stones. The condition of having them is called nephrolithiasis.
• Haematuria - blood in the urine.
• Pyelonephritis - infection of the kidney.

What the authors concluded

The authors conclude that ozone therapy shows promise as an auxiliary, or complementary, treatment for kidney injury, principally by reducing the oxidative stress and inflammation that accompany renal disease. They frame ozone's benefit as arising from controlled, low-level toxicity that strengthens the cell's own antioxidant capacity rather than from any direct healing action. They also argue that the accumulated experimental evidence provides a rationale for further study, and they call for standardised dosing and more clinical research before ozone therapy could be adopted more widely in renal care.

Limitations of this study

This is a narrative review rather than a systematic review or meta-analysis, so the studies were selected and interpreted by the authors without a formal, reproducible search and appraisal method. Much of the evidence it draws on is preclinical - largely rat models with induced kidney damage - and results from animal experiments do not always translate to people. The human evidence is limited to case reports and small clinical observations, without the randomised controlled trials needed to establish effectiveness and safety. Dosing and delivery methods varied across the studies, and the authors themselves highlight the lack of standardised protocols. The findings should therefore be read as a summary of an emerging, mechanistically plausible research area rather than as proof that ozone therapy treats kidney disease. Anyone considering ozone therapy for a kidney condition should discuss it with their medical team, as a complement to - not a replacement for - established care.