Diabetic Kidney Disease, There Are Gender Differences!

Diabetic kidney disease (DKD) is a serious complication of diabetes. As the disease progresses, kidney function gradually declines, and may eventually develop into end-stage kidney disease (ESKD). Although DKD is a potential threat to all patients with diabetes, studies have found significant differences in the incidence, rate of progression, and response to treatment between male and female patients.

Click to Cistanche for kidney disease

In March 2024, in a study published in Science Translational Medicine (IF: 17.1), we revealed the gender differences and possible mechanisms of DKD, providing a new perspective for future gender-specific treatment strategies for DKD.

Gender differences in DKD - men progress faster and women have a higher prevalence!

1. DKD progresses faster in men

Studies have found that men with diabetes tend to develop symptoms of DKD more quickly and more severely than women, putting them at a higher risk of developing end-stage renal disease.

This difference may be related to sex hormone levels, as previous research has found that introducing male hormones, such as testosterone, into male kidney cells leads to changes in glucose and glutamine levels, both of which are key factors in kidney metabolism.

2. Women tend to have higher rates of disease

Research shows that while the cumulative incidence of DKD is higher in men than in women (4.1% in men vs. 2.5% in women), women tend to have higher rates of chronic kidney disease (CKD) and DKD, which may be associated with higher rates of chronic kidney disease (CKD) and DKD than women generally. Men live longer, but women have a lower risk of developing ESKD.

The mechanism behind it-"gender differences" in kidney cell metabolism

Studies have found that male proximal tubular epithelial cells (PTECs) display higher mitochondrial respiration, oxidative stress, apoptosis, and damage than female PTECs under hyperglycemic conditions. Male PTECs show increased glucose and glutamyl flux into the TCA cycle, whereas female PTECs show increased pyruvate content.

The study further explored gonadal and chromosomal effects. By using mouse models with different sex chromosome combinations, the researchers found that mice with male gonads (testicles) had increased kidney mitochondrial DNA content and expression of certain metabolic enzymes, regardless of whether the sex chromosomes were XX or XY. . This suggests that male gonads may increase the risk of DKD by affecting mitochondrial function and glycolysis pathways.

In addition, studies have found that dihydrotestosterone (DHT), a powerful male hormone that acts through the androgen receptor (AR), increases glycolysis and oxygen consumption rates in male kidney cells. This effect was not evident in female kidney cells, which may be due to lower expression levels of androgen receptors in female kidney cells. By analyzing gene expression data from healthy human kidneys, the researchers identified genes that were up-regulated in male kidneys and genes that were up-regulated in female kidneys. The differential expression of these genes may be related to sex differences in DKD.

The study also revealed that dihydrotestosterone mediates its effects through the transcription factor HNF4A, which is increased in kidney cells in both men and women. Additionally, the study identified a role for the histone demethylase KDM6A in the metabolic effects of high glucose levels in male kidney cells. Male kidney cells have higher levels of TCA cycle-related metabolites (such as citric acid, aspartic acid, and malic acid) compared with female cells, a finding that has been confirmed in both healthy people and patients with DKD.

These findings suggest that there are differences in the metabolism of male and female kidney cells, and that these differences may be reflected in the levels of metabolites in the blood circulation. For example, female patients without DKD have higher serum pyruvate levels than male patients with DKD or men without DKD. In addition, pyruvate levels were positively associated with glomerular filtration rate and inversely associated with all-cause mortality.

There is a "gender difference" in DKD treatment response - focus on antioxidants and hormone level maintenance

As mentioned above, PTECs from male patients show higher rates of mitochondrial respiration, oxidative stress, and apoptosis under hyperglycemic conditions, which may mean that male patients may respond differently to treatments targeting metabolic pathways than females.

PTECs from female patients showed increased pyruvate content, which may indicate that female patients may have a more positive response to antioxidant therapy or metabolic modulation therapy.

The progression of DKD in male patients may be affected by testosterone and other male hormones, which may affect their sensitivity to certain drugs and treatment outcomes, while female patients may be protected by estrogen, which may slow the progression of DKD and affect their response to treatment.

➤Male patients may require treatment strategies more focused on controlling metabolic disorders and oxidative stress, such as using antioxidants or inhibitors to reduce mitochondrial stress;

➤Female patients may benefit from treatment strategies that maintain hormonal balance and take advantage of the potential protective effects of estrogen.

New thoughts on "Gender-specific treatment of DKD"

This study provides important insights into gender differences in DKD and provides the following implications for future research directions and clinical practice:

1. Gender-specific disease mechanisms: Research highlights the role of gender in the development of DKD, suggesting that future research should further explore how gender affects the biological mechanisms of kidney disease.

2. Personalized medicine: Given the differences in the metabolic characteristics and prognosis of DKD between men and women, this may mean that individualized treatment strategies need to be developed and adopted to better meet the needs of patients of different genders.

3. Discovery of biomarkers: The study discovered sex-specific blood metabolites associated with kidney function and mortality. These metabolites may become potential biomarkers for diagnosing DKD and predicting disease progression in the future.

4. Identification of therapeutic targets: Research has revealed the role of molecules such as HNF4A and KDM6A in sex-specific metabolic pathways, which may provide clues for the development of new therapeutic targets.

5. Prevention strategies: By understanding how gender affects the risk and progression of DKD, targeted preventive measures can be designed to reduce the disease burden in gender-specific patients.

6. Clinical trial design: Future clinical trials should consider gender to ensure that treatments are effective in all patient groups and to identify possible sex-differential responses.

7. Long-term impact of gender differences: The results of the study suggest the need for further research on the impact of gender differences on the long-term management of DKD and patients' quality of life.

8. Interdisciplinary cooperation: Given that sex differences in DKD involve complex biological and metabolic processes, interdisciplinary cooperation is required, including the joint efforts of experts in the fields of endocrinology, nephrology, metabolic science, and molecular biology.

Summary of this article

Taken together, these findings highlight the importance of gender in the development and treatment of DKD. Future treatment strategies need to take gender differences into account, and further research in this area will help develop more effective, individualized treatments for men and women, thereby improving the prognosis and quality of life of patients with DKD.

How Does Cistanche Treat Kidney Disease?

Cistanche is a traditional Chinese herbal medicine used for centuries to treat various health conditions, including kidney disease. It is derived from the dried stems of Cistanche deserticola, a plant native to the deserts of China and Mongolia. The main active components of cistanche are phenylethanoid glycosides, echinacoside, and acteoside, which have been found to have beneficial effects on kidney health.

Kidney disease, also known as renal disease, refers to a condition in which the kidneys are not functioning properly. This can result in a buildup of waste products and toxins in the body, leading to various symptoms and complications. Cistanche may help treat kidney disease ase through several mechanisms.

Firstly, cistanche has been found to have diuretic properties, meaning it can increase urine production and help eliminate waste products from the body. This can help relieve the burden on the kidneys and prevent the buildup of toxins. By promoting diuresis, cistanche may also help Reduce high blood pressure, a common complication of kidney disease.

Moreover, cistanche has been shown to have antioxidant effects. Oxidative stress, caused by an imbalance between the production of free radicals and the body's antioxidant defenses, plays a key role in the progression of kidney disease. ies help neutralize free radicals and reduce Oxidative stress, thereby protecting the kidneys from damage. The phenylethanoid glycosides found in cistanche have been particularly effective in scavenging free radicals and inhibiting lipid peroxidation.

Additionally, cistanche has been found to have anti-inflammatory effects. Inflammation is another key factor in the development and progression of kidney disease. Cistanche's anti-inflammatory properties help reduce the production of pro-inflammatory cytokines and inhibit the activation of inflammation mandatory pathways, thus alleviating inflammation in the kidneys.

Furthermore, cistanche has been shown to have immunomodulatory effects. In kidney disease, the immune system can be dysregulated, leading to excessive inflammation and tissue damage. Cistanche helps regulate the immune response by modulating the production and activity of immune cells, such as T cells and macrophages. This immune regulation helps reduce inflammation and prevent further damage to the kidneys.

Moreover, cistanche has been found to improve renal function by promoting the regeneration of renal tubes with cells. Renal tubular epithelial cells play a crucial role in the filtration and reabsorption of waste products and electrolytes. In kidney disease, these cells can be damaged, leading to damaged renal function. Cistanche's ability to promote the regeneration of these cells helps restore proper renal function and improve overall kidney health.

In addition to these direct effects on the kidneys, cistanche has been found to have beneficial effects on other organs and systems in the body. This holistic approach to health is particularly important in kidney disease, as the condition often affects multiple organs and systems. che has been shown to have protective effects on the liver, heart, and blood vessels, which are commonly affected by kidney disease. By promoting the health of these organs, cistanche helps improve overall kidney function and prevent further complications.

In conclusion, cistanche is a traditional Chinese herbal medicine used for centuries to treat kidney disease. Its active components have diuretic, antioxidant, anti-inflammatory, immunomodulatory, and regenerative effects, which help improve renal function and protect the kidneys from further damage. , cistanche has beneficial effects on other organs and systems, making it a holistic approach to treating kidney disease.