Clinical Practice Guidelines For Acute Kidney Injury In ChinaⅦ

Clinical question 11: How to use anti-shock drugs?

【Recommendations】

1. It is recommended that patients with septic shock maintain MAP at 65~70 mmHg (1B), and patients with previous hypertension maintain MAP at 80~85 mmHg (2B).

2. It is recommended to use norepinephrine (1B) or vasopressin (1B) to treat AKI patients with vasogenic shock.

3. The use of low-dose dopamine to prevent and treat AKI is not recommended (1A).

4. Fenoldopa/atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP)/levosimendan are not recommended for the treatment of AKI (1A).

Click to Cistanche for kidney disease

Hemodynamic management is crucial for patients with shock and a high risk of AKI. A study from 777 patients with septic shock showed that there was no difference in mortality between the two groups of patients whose MAP was maintained at 80-85 mmHg and 65-70 mmHg. Subgroup analysis showed that patients with MAP maintained at 80-85 mmHg had AKI 2 The incidence rate of AKI stage 2 and the proportion of RRT were higher; and among patients with previous hypertension and whose MAP was maintained at 80~85 mmHg, the incidence rate of stage 2 AKI and the proportion of RRT were lower.

When patients with vasogenic shock remain hypotensive (MAP <65 mmHg) despite adequate fluid resuscitation, the use of vasopressors such as norepinephrine and vasopressin should be considered. A large RCT comparing dopamine and norepinephrine as initial vasopressors in patients with shock found no difference in mortality between the two groups, but the need for long-term RRT was lower in the norepinephrine group. In another RCT of 409 patients with early septic shock (VANISH trial), the use of vasopressin reduced the need for RRT compared with norepinephrine. Therefore, it is recommended to use norepinephrine or vasopressin to treat AKI patients with vascular shock.

Dopamine is a non-selective dopamine receptor agonist, and current studies have not shown its renal protective effect. In a meta-analysis that included 61 studies on the role of low-dose dopamine in the prevention and treatment of AKI, no advantage was found in using dopamine in improving patient survival rates, reducing the proportion of dialysis patients, and improving renal function; the results of another RCT study showed that Dopamine can even reduce renal perfusion in patients with AKI, so the use of low-dose dopamine in the treatment of AKI is not recommended.

Fenoldopam is a dopamine A1 receptor agonist with effects on renal hemodynamics similar to those of low-dose dopamine but without systemic alpha or beta-adrenergic stimulation. Although previous studies have suggested that fenoldopa can reduce the need for RRT and mortality in patients with AKI, the results of multicenter RCT studies are contrary to this, and the results of a subsequent meta-analysis also showed that perioperative use of fenoldopa has an impact on RRT. or no effect on in-hospital mortality. Therefore, considering the possible hypotension and corresponding adverse reactions caused by the use of fenoldopa in high-risk postoperative patients and ICU patients, the use of fenoldopa is not recommended for the prevention and treatment of AKI.

ANP has diuretic, natriuretic and vasodilatory effects. Regarding the preventive application of ANP, two RCT studies found that low-dose ANP can reduce the incidence of postoperative AKI. However, a prospective multi-center randomized double-blind placebo-controlled study showed that although ANP increased urine output, it had no effect on serum creatinine, eGFR, RRT and hospitalization time were not affected, and there was no renal protective effect on postoperative AKI. Similarly, in terms of treatment, a multicenter prospective observational study showed that ANP did not reduce the risk of RRT or death in adult patients with severe AKI. The results of another meta-analysis on ANP in the treatment of AKI that included 18 studies showed that low-dose ANP may be effective in preventing or treating AKI, but the current evidence supporting the effectiveness of ANP is still not strong enough. BNP has similar effects to ANP. Most current BNP studies have small sample sizes and have adverse effects of hypotension and arrhythmia. Therefore, BNP is not recommended for the treatment of AKI.

Levosimendan is a calcium sensitizer with vasodilatory, cardioprotective, and anti-inflammatory effects. A meta-analysis of RCT studies in cardiac surgery populations showed that the use of levosimendan reduced the risk of AKI, the need for RRT, and mortality. A meta-analysis of RCT studies of critically ill patients with AKI or at risk for AKI found that levosimendan reduced the risk of AKI and the need for RRT compared with placebo, but when narrowing the study scope to high-quality studies, both groups There was no significant difference in the need for RRT between The study sizes of these two meta-analyses were small, and there was some heterogeneity and result bias. Three subsequent large placebo-controlled RCT studies showed that levosimendan had no benefit on the risk of AKI, need for RRT, and mortality, but was associated with more adverse events. Therefore, the use of levosimendan in the treatment of AKI is not recommended based on current evidence.

Clinical question 12: Precautions in the use of AKI drugs

【Recommendations】

1. It is recommended to avoid the use of nephrotoxic drugs in patients who are at risk of AKI or have already developed AKI (1A).

2. The drug dosage needs to be adjusted according to changes in renal function during AKI (1C).

3. Close monitoring of serum drug concentrations is recommended when using potentially nephrotoxic drugs in patients with AKI (1C).

Nephrotoxic drugs can cause renal vasoconstriction or directly damage renal tubular epithelial cells, thereby damaging renal function, and are one of the main pathogenic factors of AKI. Common nephrotoxic drugs mainly include anti-tumor drugs such as cisplatin, antibiotics such as aminoglycosides, amphotericin B and vancomycin, non-steroidal anti-inflammatory drugs, antiviral drugs, cyclosporine A and tacrolimus, etc. Immunosuppressants and contrast agents. The incidence of AKI caused by nephrotoxic drugs among pediatric inpatients is 16%, and even as high as 66% among elderly patients. A meta-analysis of risk factors for AKI in critically ill patients showed that the probability of developing AKI increased by 53% for each nephrotoxic drug used. Therefore, nephrotoxic drugs should be avoided in patients who are at risk of AKI or have already developed AKI. For common nephrotoxic drugs, you can obtain relevant information by consulting their drug instructions; if you need to obtain more drug information, you can use the following two methods: (1) Query the World Health Organization Uppsala Monitoring Center (UMC) Database VigiBase to learn whether drugs have nephrotoxicity-related reports and data (https://www.vigiaccess.org/). (2) Search databases such as PubMed and China National Knowledge Infrastructure to see if there are any literature reports related to the nephrotoxicity of the drug.

The pharmacokinetics of patients with AKI change, which may lead to the accumulation of some drugs, leading to further deterioration of renal function or other adverse reactions. Failure to adjust drug dose according to renal function (63%) and use of nephrotoxic drugs (28%) were the most common potential adverse drug events. Therefore, AKI patients need to appropriately adjust drug dosage based on correct assessment of renal function to optimize therapeutic effects and minimize drug toxicity.

In the early stages of AKI, monitoring of drug concentrations is recommended for certain drugs, especially antibiotics that require loading doses to achieve target serum concentrations. In a quality improvement study that included 1,749 non-severe hospitalized pediatric patients, patients who received three or more nephrotoxic drugs or aminoglycosides were closely monitored for drug concentrations and renal function. Exposure was reduced by 38%, and the incidence of AKI was reduced by 64%.

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.