In Addition To Penicillin, This Common Clinical Drug Can Also Cause Acute Kidney Injury

PPIs are mostly weakly alkaline benzimidazole derivatives, which are rapidly transported to the parietal cells of the gastric mucosa after being absorbed in the intestine. PPIs bind to H+ in the acidic environment of the secretory tubules and alveolar cavity and carry a positive charge after protonation. They can no longer diffuse into the cell membrane and aggregate locally, finally forming active products such as sulfenic acid and sulfenamide.

Click to Cistanche for kidney disease

Sulfenamide can form a covalently bound disulfide bond with the sulfhydryl group on the cysteine residue in the α subunit of the H+, K+-ATPase (proton pump), making the H+, K+-ATPase irreversibly inactivated, thereby inhibiting gastric acid secretion until a new proton pump is produced and the parietal cells resume their acid secretion function.

PPIs can inhibit central or peripherally mediated gastric acid secretion, and can effectively inhibit both basal gastric acid secretion and various forms of stress gastric acid secretion, with the characteristics of complete acid suppression, strong inhibition, and long acid suppression time.

PPIs cause renal injury. It has been reported in the literature that PPIs can mainly cause AKI, with pathological manifestations of acute interstitial nephritis (AIN), namely PPIs-related acute interstitial nephritis (PPIs-AIN). Long-term use of PPIs can cause PPIs-AIN to transform into chronic interstitial nephritis, which then evolves into chronic kidney disease (CKD) and renal failure.

Pathogenesis of PPIs-AIN

At present, the specific pathogenesis of PPIs-induced AIN is not clear. It is believed that PPIs and (or) their metabolites are deposited in the renal tubules and renal interstitium, and as haptens, they combine with the normal components of the renal tubular basement membrane to induce an immune response against the antigen, thereby causing damage to the renal tubules and interstitium.

In addition, activated macrophages in the interstitium can damage the renal tubular basement membrane by releasing substances such as proteolytic enzymes, reactive oxygen, reactive nitrogen, and inducible nitric oxide synthase, thereby aggravating the disease. Some adhesion molecules and cytokines can directly participate in the damage of renal interstitium, or aggravate the damage of renal interstitium through cellular and humoral immunity, and play an important role in the occurrence and evolution of the disease. It is not clear whether this reaction is gene-specific or whether there are other mechanisms involved.

Clinical manifestations of PPIs-AIN

After admission, this patient only used omeprazole injection combined with hemostatic drugs. The hemostatic drugs were discontinued on the fifth day of admission, but the patient's blood creatinine increased after the omeprazole injection, which was considered to be closely related to omeprazole. After discontinuing the omeprazole injection, the patient's blood creatinine improved significantly. According to the patient's outcome, it can be inferred that the patient's omeprazole injection is likely to cause an increase in blood creatinine.

The clinical manifestations of PPIs-AIN are mostly atypical. Drug-related renal injury is a hypersensitivity reaction, which usually occurs 10-14 days after taking the drug. Clinical manifestations include rash, fever, hematuria, azotemia, eosinophilia, etc.

Clinically, penicillin is the most classic drug that causes AIN. Unlike this classic drug-related AIN, the time interval from taking PPIs to the onset of AIN in PPIs-AIN varies significantly from person to person. PPIs-AIN is not usually accompanied by systemic allergic manifestations such as fever and rash, but only some non-specific symptoms such as fatigue, weakness, nausea, and loss of appetite. Laboratory tests also show no obvious specific manifestations, and some only show a gradual increase in blood creatinine levels. This patient also had no specific manifestations, and only a reexamination of blood creatinine revealed a significant increase.

Treatment of PPIs-AIN

Currently, there are no relevant guidelines for the treatment of PPIs-AIN, and it is the same as other drug-related AINs. Once PPIs-AIN is suspected, PPIs should be discontinued immediately, symptomatic supportive treatment should be given, and creatinine changes should be closely monitored.

The treatment principle of drug-induced AKI is rapid identification and timely discontinuation of the drug; maintaining water and electrolyte balance, maintaining a stable internal environment, and facilitating the recovery of renal function. At the same time, nutritional support and symptomatic treatment are also very important. Generally, after timely discontinuation of the drug, most renal functions can be restored.

How to prevent drug-induced renal injury?

First of all, the history of drug allergy must be asked before taking the medicine, and the indications of various drugs should be strictly mastered to avoid abuse. Pay attention to the dosage and course of treatment when using the medicine, and closely monitor urine enzymes, urine protein, urine sediment, and renal function during medication.

For those with impaired renal function, try to choose drugs with less nephrotoxicity. Drugs are more likely to cause renal damage in some patients, such as the elderly (age>60 years old), patients with potential renal insufficiency [glomerular filtration rate GFR<60ml/(min·1.73m2)], hypovolemia, combined use of multiple nephrotoxic drugs, diabetes, heart failure, and sepsis. Before taking the medicine for the above patients, the renal function should be evaluated and the dosage and dosing interval should be adjusted according to their creatinine clearance.

In addition, some drugs are nephrotoxic in themselves, while the renal damage caused by other drugs is dose-dependent or time-dependent. The combined use of multiple nephrotoxic drugs can lead to synergistic effects and increase the risk of renal damage. When using several drugs together, attention should be paid to the influence of each other, and it is forbidden to use more than two toxic drugs at the same time.

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 mandatory pathways for inflammation, 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.