SGLT2 Inhibitors Can Effectively Improve Anemia in Patients With Chronic Kidney Disease

Patients with chronic kidney disease (CKD) treated with erythropoietins (ESAs) often receive iron supplements. However, ESAs increase the risk of major cardiovascular events, and hypoxia-inducible factor prolyl hydroxylase (HIF-PHD) inhibitors pose cardiovascular risks that are comparable to or greater than those of ESAs.

Click to Cistanche for kidney disease

In contrast, in patients with CKD, sodium-glucose cotransporter 2 (SGLT2) inhibitors increase hemoglobin and hematocrit and correct anemia while also reducing the risk of cardiovascular death and heart failure hospitalization.

Recently, researchers evaluated the red blood cell effects of SGLT2 inhibitors in subjects with CKD in 5,060 subjects with anemia in four large-scale long-term trials. Two of the trials were in participants with chronic heart failure (about half of whom had CKD), and two trials were in participants with CKD (with or without diabetes).

In these 4 trials, SGLT2 inhibitors increased hemoglobin (approximately 0.7 g/L) and hematocrit (2.0% to 2.5%) compared with placebo, and these changes occurred after 4 to 12 weeks in the trial. , and persisted during the follow-up period of 1 to 3 years. During long-term treatment, subjects who received an SGLT2 inhibitor were more than twice as likely to have their anemia corrected as those who received a placebo. Hemoglobin and hematocrit levels reached the non-anemic range in 50% to 70% of treated subjects. Anemia-correcting effects of SGLT2 inhibitors were observed despite approximately 10% of subjects receiving iron supplements or other anemia treatments.

Importantly, in the CREDENCE trial, after adjustment for placebo, the increase in hemoglobin was greater in participants with baseline hemoglobin levels of <10.0 g/dl, 10.0 to 12.0 g/dl, and 12.0 to 13.0 g/dl. They are 0.74 g/dl, 0.68 g/dl and 0.70 g/dl respectively. Additionally, participants treated with SGLT2 inhibitors were less likely to develop anemia requiring iron supplementation (hazard ratio, 0.64; 95% CI, 0.52 to 0.80) or ESA (hazard ratio, 0.65; 95% CI, 0.46 to 0.91). , although utilization of these treatments is low.

Similar results have been observed in other large-scale trials. It follows that SGLT2 inhibitors induce red blood cell effects of similar magnitude to those seen with low-dose HIF-PHD inhibitors (often used with iron supplements). Among subjects who were not anemic at baseline, SGLT2 inhibitor treatment reduced the risk of new-onset anemia by approximately 50% during long-term follow-up.

Initially, SGLT2 inhibitors were not recommended to patients for the treatment of cardiovascular disease. Because CKD damages the patient's glucose metabolism function, thus affecting its function, SGLT2 inhibitors have shown good results in CKD patients. Four large clinical trials involving more than 5,000 subjects have confirmed that SGLT2 inhibitors can stimulate the production of endogenous erythropoietin, thereby correcting anemia caused by moderate to severe CKD (excluding iron supplements). However, these trials did not include patients with an estimated glomerular filtration rate <20 mL/(min·1.73 m2) or patients receiving renal replacement therapy. If SGLT2 inhibitors can improve anemia symptoms in patients with renal failure, they will provide a more effective clinical alternative to erythropoietin and HIF-PHD inhibitors. At present, the mechanism by which SGLT2 inhibitors stimulate erythropoietin has not yet been fully elucidated. There are many hypotheses in the academic community. With the deepening of research, clear conclusions may be drawn in the future.

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.