Besides Penicillin, This Common Clinical Drug Can Also Cause Acute Kidney Injury
Feb 08, 2023
Clinically, we will encounter acute kidney injury (acute kidney injury, AKI) caused by penicillin. Today we use a case to understand AKI caused by another common clinical drug.
Case review
The patient, a male, 52 years old, was admitted to the hospital due to vomiting and black stool. He was diagnosed with upper gastrointestinal bleeding on admission and was given omeprazole 40mg bid. After taking it for 10 days, the patient no longer vomited, and there was no occult blood in the stool routine examination, and his condition improved. However, rash and itching appeared in the patient's abdomen, and the blood creatinine was 211umol/L (the serum creatinine was 98umol/L when the patient was admitted).
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Considering the use of proton pump inhibitors (proton pump inhibitors, PPIs) in patients with renal injury, the drug should be discontinued, and changes in serum creatinine levels should be closely monitored. The blood creatinine was re-examined at 150umol/L 3 days later and 110umol/L after 5 days. The patient improved and was discharged.
PPIs are mainly used to treat various gastric acid-related diseases, such as gastroesophageal reflux, duodenal ulcer, gastric ulcer, gastrointestinal bleeding, etc. Currently, commonly used PPIs include omeprazole, pantoprazole, cancel Larazole and Rabeprazole.
Mechanism of action of PPIs
PPIs are mostly weakly basic benzimidazole derivatives, which are quickly transported to the parietal cells of the gastric mucosa after being absorbed in the intestinal tract. PPIs combine with H+ in the acidic environment of the secretory tubules and vesicles, and after protonation, they have a positive charge, which cannot diffuse back into the cell membrane and accumulate locally, and finally form active products of sulfenic acid and sulfenamide.
Sulphenamide can form a covalently bonded disulfide bond with the sulfhydryl group on the cysteine residue in the α subunit of H+, K+-ATPase (proton pump) to irreversibly inactivate H+, K+-ATPase, thereby Inhibit gastric acid secretion until new proton pumps are produced, and the parietal cells resume acid secretion.
PPIs can inhibit central or peripheral gastric acid secretion and can produce effective inhibitory effects on both basal gastric acid secretion and various forms of stress gastric acid secretion.
It has been reported in the literature that PPIs can cause renal injury, and PPIs can mainly cause AKI, and the pathological manifestation is acute interstitial nephritis (AIN), that is, PPIs-associated acute interstitial nephritis (PPIs-AIN). PPIs can cause PPIs-AIN to transform into chronic interstitial nephritis and then evolve into chronic kidney disease (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 combine with normal components of the renal tubular basement membrane as haptens, inducing the antigen-specific reaction. immune response, resulting in damage to the renal tubules and interstitium.
In addition, activated macrophages in the interstitium can damage the tubular basement membrane by releasing proteolytic enzymes, reactive oxygen species, reactive nitrogen species, and inducible nitric oxide synthase, which can aggravate the disease. Some adhesion molecules and cytokines can directly participate in the injury of the renal interstitium, or aggravate the injury of renal interstitium through cellular and humoral immunity, and play an important role in the occurrence and evolution of the disease. Whether this response is gene-specific or if there are other mechanisms involved is unclear.
Clinical Manifestations of PPIs-AIN
After the patient was admitted to the hospital, only omeprazole was used in combination with hemostatic drugs, and the hemostatic drugs were stopped on the fifth day of admission, but the patient’s serum creatinine increased after the omeprazole injection, which was considered to be closely related to omeprazole. After stopping the omeprazole injection, the patient's serum creatinine improved significantly. Based on the patient's outcome, it can be speculated that the patient's omeprazole injection may cause an increase in serum creatinine.
The clinical manifestations of PPIs-AIN are not typical. Drug-related renal injury is a kind of hypersensitivity reaction, which usually occurs 10-14 days after taking the drug. The clinical manifestations include rash, fever, hematuria, azotemia, and eosinophilia.
Clinically, penicillin is the most classic drug that causes AIN. Different from this classic drug-related AIN, PPIs-AIN has obvious individual differences in the time interval from taking PPIs to AIN. However, most PPIs-AIN is not accompanied by systemic allergic manifestations such as fever and rash, but only non-specific symptoms such as fatigue, fatigue, nausea, and loss of appetite, and there are no obvious specific manifestations in laboratory tests, and some of them only show serum creatinine levels Gradually rise. The patient in this case also had no specific manifestations, only a re-examination of serum creatinine found a significant increase.
Treatment of PPIs-AIN
At present, there is no relevant guideline recommendation for the treatment of PPIs-AIN, and it is the same as other drug-related AIN. Once PPIs-AIN is suspected, PPIs should be stopped immediately, symptomatic and supportive treatment should be given, and changes in creatinine should be closely monitored.
The principles of treatment for drug-induced AKI are rapid identification and timely drug withdrawal; maintaining water and electrolyte balance, maintaining a stable internal environment, and facilitating the recovery of renal function. At the same time, nutritional support and its symptomatic treatment are also important. Generally, after the drug is stopped in time, most of the renal functions can be restored.
How can drug-induced kidney injury be prevented?
First of all, you must ask about the history of drug allergy before using the drug, and you should strictly control the indications of various drugs to avoid abuse. Pay attention to the dose and course of treatment in the drug application, and closely monitor the urine enzyme, urine protein, urine sediment, and renal function during the medication.
For those with impaired renal function, try to choose drugs with less nephrotoxicity. For some patients, drugs are more likely to cause renal damage, 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. Renal function should be evaluated before the above-mentioned patients are administered, and the dosage and interval of administration should be adjusted according to the creatinine clearance rate.
In addition, some drugs are inherently nephrotoxic, while others cause renal damage in a dose-dependent or time-dependent manner. The combined use of multiple nephrotoxic drugs can lead to synergistic effects and increase the risk of renal injury. When several drugs are used together, attention should be paid to the influence of each other, and the simultaneous application of more than two toxic drugs is prohibited.
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