Protecting Kidney Function: The Role of Mitochondria in Chronic Kidney Disease
Chronic kidney disease (CKD) is often discussed as though declining kidney function is inevitably a one-way process. In reality, progression varies considerably. Some people experience relatively rapid deterioration, while others maintain stable kidney function for many years.
The underlying cause of kidney disease is important, as are blood pressure, proteinuria, blood glucose control, diet, medication use, inflammation and cardiovascular health. Increasingly, however, researchers are also examining what happens inside the kidney cell itself.
One emerging area is mitochondrial dysfunction.
A 2023 review published in Frontiers in Pharmacology examined how impaired mitochondrial function may contribute to kidney disease and investigated a range of natural compounds capable of influencing mitochondrial energy production, oxidative stress and cellular repair mechanisms (Huang, Liang & Zhou 2023).
The research is interesting, although much of it remains experimental. What it does provide is a useful biological framework for understanding how diet, physical activity and selected natural medicines may complement the more established approaches used to protect kidney function.
Why mitochondria matter in kidney disease
The kidneys require a remarkable amount of energy.
Every day they filter large volumes of blood and then selectively reabsorb water, electrolytes, glucose, amino acids and other substances. The tubular cells responsible for much of this work contain particularly high concentrations of mitochondria, which generate most cellular energy in the form of ATP.
When mitochondria become dysfunctional, energy production falls while oxidative stress increases. Fatty-acid metabolism can become impaired and damaged mitochondria may accumulate within kidney cells. These changes can contribute to tubular injury, inflammation, cell death and eventually fibrosis.
This creates the potential for a vicious cycle: kidney injury damages mitochondria, while damaged mitochondria may contribute to further kidney injury.
Huang, Liang and Zhou (2023) identified several processes that appear particularly relevant, including mitochondrial energy production, oxidative stress, the removal of damaged mitochondria through mitophagy, and the maintenance of normal mitochondrial structure.
Much of this involves signalling pathways such as AMPK, Sirtuin-1, PGC-1α and Nrf2. Patients do not need to remember these pathways, but they are interesting because they help explain how mitochondrial metabolism, oxidative stress and cellular repair are being investigated as potential targets in kidney disease.
The first priority is reducing ongoing kidney injury
Before thinking about mitochondrial supplements, the more important question is:
What is continuing to damage the kidneys?
Mitochondrial support is unlikely to compensate for persistently uncontrolled hypertension, substantial proteinuria, poorly controlled diabetes, recurrent acute kidney injury or ongoing exposure to nephrotoxic substances.
Proteinuria is particularly important. It is not simply a marker showing that the filtration barrier has been damaged. Excessive filtration and tubular reabsorption of proteins can also contribute to tubular injury, inflammation and fibrotic signalling, potentially accelerating CKD progression (Makhammajanov et al. 2024).
This is why treatments that reduce albuminuria and intraglomerular pressure have become central to CKD management.
ACE inhibitors and angiotensin receptor blockers remain important in many patients with proteinuric kidney disease, while SGLT2 inhibitors have substantially changed renal medicine.
The DAPA-CKD trial found that dapagliflozin reduced the risk of its primary composite outcome — a sustained major loss of kidney function, kidney failure, or death from renal or cardiovascular causes — by approximately 39% (Heerspink et al. 2020).
EMPA-KIDNEY subsequently demonstrated kidney protection with empagliflozin across a broad CKD population, with benefits observed in people both with and without diabetes (EMPA-KIDNEY Collaborative Group 2023).
These medications require individual medical assessment, but the broader principle is important: reducing the physiological stress being placed upon the remaining nephrons can substantially affect the trajectory of kidney disease.
Dietary and natural approaches should generally complement this foundation rather than replace it.
A more plant-focused renal diet
One of the more significant developments in renal nutrition has been a gradual move away from excessively restrictive diets towards appropriately individualised diets containing a greater proportion of minimally processed plant foods.
The 2024 KDIGO guidelines advise people with CKD to consume more plant-based foods relative to animal foods and reduce ultra-processed food intake. For many adults with stage 3–5 CKD who are not receiving dialysis, approximately 0.8 g of protein per kilogram of body weight per day is suggested, while persistently high protein intake should generally be avoided (KDIGO CKD Work Group 2024).
The benefit of plant foods extends beyond reducing animal protein.
Vegetables, fruit, legumes, herbs, spices, nuts and seeds contain flavonoids, polyphenols, carotenoids and other bioactive compounds capable of influencing oxidative stress, inflammation and a range of cellular pathways (Huang, Liang & Zhou 2023).
A 2025 systematic review and meta-analysis involving 121,927 participants found that plant-based dietary patterns were associated with a lower incidence of CKD and slower CKD progression (Dang et al. 2025).
Importantly, not every plant-based diet is necessarily beneficial. The same analysis found that unhealthy plant-based dietary patterns may not provide the same renal protection. A diet dominated by refined grains, sugar and highly processed plant foods is metabolically very different from one built around vegetables, legumes, whole grains, nuts, seeds and appropriate fruit (Dang et al. 2025).
Dietary acid load may also matter
Another increasingly interesting area is dietary acid load.
Western dietary patterns containing large amounts of animal protein and relatively few vegetables and fruit generally produce a greater net acid load. Healthy kidneys can dispose of this efficiently, but this ability progressively declines with CKD.
Importantly, acid retention may begin before serum bicarbonate falls sufficiently to produce overt metabolic acidosis. Research has demonstrated increasing acid retention as kidney function declines even in some people whose serum bicarbonate remains within the normal range (Goraya et al. 2018).
A 2024 five-year randomised controlled trial examined 153 people with primary hypertension and macroalbuminuria who were already receiving pharmacological kidney and cardiovascular protection. Participants received additional fruit and vegetables, sodium bicarbonate or usual care.
Kidney function declined more slowly in both acid-reduction groups than with usual care, while the fruit-and-vegetable group also experienced lower systolic blood pressure and greater improvements in cardiovascular risk indices (Goraya et al. 2024).
This does not mean that every patient with CKD should indiscriminately increase fruit and vegetable intake. Potassium tolerance differs considerably, particularly in advanced CKD.
It does, however, reinforce an important principle in renal nutrition: rather than considering diet purely in terms of restriction, it is worth asking how food can improve the metabolic environment in which the remaining kidney tissue is functioning.
Exercise is also a mitochondrial intervention
Exercise is not usually described as mitochondrial therapy, yet mitochondrial adaptation is one of its biological effects.
Physical activity can improve insulin sensitivity, vascular function, blood pressure, skeletal muscle health and cardiovascular fitness. These are particularly important considerations in CKD, where cardiovascular disease, reduced exercise capacity and loss of muscle mass are major concerns (KDIGO CKD Work Group 2024).
There is also evidence that exercise influences mitochondrial signalling in CKD, although the response may differ from that seen in people without kidney disease.
In one study of people with stage 3b–5 non-dialysis CKD, 12 weeks of exercise increased skeletal-muscle PGC-1α expression but did not restore the reductions in mitochondrial mass seen in the CKD participants. This highlights both the potential for exercise to influence mitochondrial signalling and the complexity of mitochondrial dysfunction in established kidney disease (Watson et al. 2020).
KDIGO recommends approximately 150 minutes of moderate physical activity each week, or a level compatible with a person's cardiovascular health, physical capacity and tolerance (KDIGO CKD Work Group 2024).
For many patients, something as straightforward as regular walking combined with appropriate resistance exercise may therefore improve several metabolic and cardiovascular factors relevant to long-term kidney health.
What about natural compounds that support mitochondrial function?
The Frontiers review examined numerous natural compounds capable of affecting mitochondrial metabolism, oxidative stress, mitophagy and antioxidant defence. These included curcumin, resveratrol, quercetin, berberine, green-tea catechins, sulforaphane, Astragalus-derived compounds and thymoquinone (Huang, Liang & Zhou 2023).
This does not mean that all of these compounds have been demonstrated to slow CKD in humans.
For many, most of the renal evidence still comes from cell and animal studies. Biological plausibility is useful, but it is not the same as demonstrating a clinically meaningful effect in patients.
A few interventions, however, have begun to accumulate human evidence.
Curcumin
Curcumin, derived from turmeric, has been studied for its antioxidant and anti-inflammatory effects and its influence on cellular pathways involved in oxidative stress and mitochondrial function (Huang, Liang & Zhou 2023).
Small controlled trials have reported reductions in albuminuria or proteinuria in people with diabetic kidney disease. For example, a 16-week randomised trial involving 46 people with type 2 diabetes and overt albuminuria found a significant reduction in albuminuria with curcumin compared with placebo (Vanaie et al. 2019).
However, the broader clinical evidence remains inconsistent.
A subsequent systematic review and meta-analysis of five randomised controlled trials involving 290 participants found a modest improvement in serum creatinine but did not demonstrate a significant overall effect on proteinuria (Zhao et al. 2021).
Curcumin is therefore better considered a potentially useful adjunct than an established renal therapy.
Astragalus
Astragalus is particularly interesting because it combines a long history of traditional use with an expanding body of experimental and clinical research.
The Frontiers review discusses astragaloside IV, one of the constituents of Astragalus membranaceus, which has demonstrated effects on oxidative stress, mitochondrial dynamics and Nrf2-related signalling in experimental kidney models (Huang, Liang & Zhou 2023).
More importantly, some human evidence is emerging.
A 2024 multicentre randomised controlled trial studied 118 patients with type 2 diabetes, stage 2–3 CKD and macroalbuminuria. Participants received standard medical care either alone or with oral Astragalus granules for 48 weeks.
The estimated difference in the annual rate of eGFR decline was 4.6 mL/min/1.73 m² slower in the Astragalus group. Urinary albumin-to-creatinine ratio, however, was not significantly different between groups (Chan et al. 2024).
This is a clinically interesting result, particularly because Astragalus was used alongside rather than instead of standard renal treatment.
It remains one trial, however. Larger independent studies examining longer-term renal outcomes would substantially strengthen the evidence.
Resveratrol and other phytochemicals
Resveratrol has attracted considerable interest because it can influence cellular pathways involved in energy metabolism, oxidative stress and mitochondrial function, including Sirtuin-1, AMPK and PGC-1α (Huang, Liang & Zhou 2023).
A 2025 systematic review and dose-response meta-analysis of 31 randomised trials involving 2,299 participants found a modest reduction in blood urea nitrogen with resveratrol supplementation. Some subgroup analyses also found improvements in creatinine and GFR, although the studies were heterogeneous and were not confined to people with progressive CKD (Hajhashemy et al. 2025).
These results are interesting, but they are not evidence that resveratrol supplementation prevents kidney failure or reliably slows CKD progression.
Green-tea catechins and sulforaphane from cruciferous vegetables have also demonstrated potentially beneficial effects on oxidative and mitochondrial pathways in experimental research, including effects involving Nrf2 signalling (Huang, Liang & Zhou 2023).
At present, however, the evidence provides a stronger argument for consuming a broad diversity of phytochemical-rich foods than for assuming that concentrated extracts will necessarily preserve kidney function.
Avoiding preventable kidney injury
Supporting mitochondrial function makes little sense if avoidable kidney injury continues at the same time.
Depending on the individual, this can include addressing:
uncontrolled blood pressure
diabetes and insulin resistance
high levels of albuminuria or proteinuria
smoking
excessive sodium intake
unnecessarily high protein intake
recurrent dehydration or acute kidney injury
frequent or inappropriate NSAID use
obesity and metabolic dysfunction
potentially nephrotoxic herbs, supplements or medications.
People with CKD should also be cautious about complex supplement combinations bought online. Declining kidney clearance can alter exposure to certain compounds, while contamination, adulteration and inappropriate dosing may themselves create renal risks.
What does this mean if you have kidney disease?
The mitochondrial research adds another useful layer to our understanding of CKD, but it should not encourage patients to search for a single mitochondrial supplement.
A more effective approach is to systematically identify the factors driving kidney damage and address as many of them as possible.
That generally means understanding the cause of the kidney disease, monitoring both eGFR and urinary albumin or protein, controlling blood pressure, addressing metabolic and cardiovascular risk, avoiding nephrotoxic exposures and adopting a renal diet appropriate to the individual's stage and type of kidney disease.
From there, nutrition and natural medicines can be used more selectively.
For many patients this may involve shifting towards a predominantly whole-food, plant-rich diet, moderating excessive protein intake, reducing sodium and ultra-processed foods, improving dietary acid load, increasing phytochemical diversity and maintaining regular physical activity. Specific nutritional or herbal interventions can then be considered where the evidence and individual clinical picture justify them.
Importantly, kidney disease is not one disease. Diabetic kidney disease, IgA nephropathy, polycystic kidney disease, hypertensive nephropathy and advanced stage 5 CKD are very different clinical situations.
Protein, potassium, phosphate and fluid requirements can also change substantially as kidney function declines and again once dialysis begins.
The bigger picture
The most interesting message from the emerging mitochondrial research is not that researchers have discovered a supplement capable of repairing damaged kidneys.
They have not.
Instead, it helps explain why kidney disease may continue to progress at the cellular level. Mitochondrial energy failure, oxidative stress, impaired fatty-acid metabolism and defective cellular quality control all appear capable of contributing to kidney injury and fibrosis.
Natural compounds including curcumin, resveratrol, green-tea catechins, sulforaphane and Astragalus constituents can influence some of these pathways experimentally, and limited human evidence is beginning to emerge for several of them.
At the same time, some of the most accessible ways of improving the metabolic environment remain remarkably familiar: eating an appropriate renal diet, reducing excessive sodium and protein, consuming more minimally processed plant foods where tolerated, exercising, controlling blood pressure and metabolic disease, and removing ongoing sources of kidney injury.
For someone living with CKD, the aim is rarely to find one treatment that will fix the kidneys. It is to identify the modifiable factors contributing to progression and gradually shift the physiological environment towards preserving as much remaining kidney function as possible.
That is where nutrition, lifestyle, appropriately selected natural medicines and conventional renal care can potentially work together.
References
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