BACKGROUND: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors marked a milestone in the breast cancer treatment. Due to the potential impact of adverse effects on treatment decisions and patient outcomes, careful consideration of the varying toxicities of CDK4/6 inhibitors is crucial, as three inhibitors-palbociclib, abemaciclib, and ribociclib-have been approved with differences in adverse event profiles. However, limitations in clinical trials call for urgent real-world safety studies to evaluate and compare the risk of adverse events (AEs) among these CDK4/6 inhibitors. Therefore, this study aimed to analyze AEs of CDK4/6 inhibitors and provide insights for clinical drug selection, using real world database.
METHODS: The AEs of CDK4/6 inhibitors in the FDA Adverse Event Reporting System (2015-2022) were analyzed. Four disproportionality methods were used to detect safety signals: reporting odds ratio (ROR), proportional reporting ratio, Bayesian Confidence Neural Network Propagation, and Multi-Item Gamma Poisson Shrinker. Venn analysis was used to compare and select common and specific AEs.
RESULTS: This study included 73,042 patients treated with palbociclib, 25,142 with ribociclib, and 7563 with abemaciclib. All three inhibitors had 27 common AEs. Palbociclib exhibited the highest ROR for hematologic toxicities, while ribociclib showed the highest ROR for macrocytosis, nail disorders, and hepatic lesions. Abemaciclib displayed the highest ROR for mucosal toxicity. Common signals for both palbociclib and ribociclib included hematologic toxicities, decreased immune responsiveness, and aphthous ulcers. Myelosuppression, oral pain, and pseudocirrhosis were common signals for palbociclib and abemaciclib. Anemia, hepatotoxicity, and pneumonitis were observed as common signals for ribociclib and abemaciclib. Furthermore, specific AEs associated with palbociclib included fatigue, alopecia, and stomatitis. For ribociclib, specific AEs included electrocardiogram QT prolongation, thrombocytopenia, and decreased hemoglobin. Abemaciclib was specifically linked to diarrhea, vomiting, and interstitial lung disease.
CONCLUSIONS: Our analysis revealed that palbociclib showed a higher risk of hematologic toxicity. Ribociclib showed higher risks of hepatotoxicity, nephrotoxicity, and QT prolongation. Abemaciclib showed higher risks of hepatotoxicity, gastrointestinal effects, interstitial lung disease, and thrombosis. These findings provide valuable insights for CDK4/6 inhibitor selection.

Cisplatin, a chemotherapy agent widely used since its FDA approval in 1978 for testicular cancer, is associated with nephrotoxicity and hypomagnesemia. Magnesium supplementation is not only a treatment for hypomagnesemia but also a well-established agent in preventing cisplatin-induced nephrotoxicity (CIN). Considering the challenges associated with intravenous magnesium use and even with the supplementation of oral forms, there is a need for drugs that effectively reduce urinary magnesium excretion. Amiloride and sodium-glucose cotransporter 2 inhibitors (SGLT2 inhibitors) have emerged as potential candidates. Amiloride is a well-known potassium-sparing diuretic that also has a hypomagnesemia effect seen in preclinical data. SGLT2 inhibitors are a drug class initially used in diabetes that was also observed to have positive effects on cardiovascular mortality, diabetic kidney disease, and hypomagnesemia. SGLT2 inhibitors were found to reduce hypomagnesemia in a meta-analysis study of 18 trials. However, these trials were not specifically designed for the evaluation of hypomagnesemia, and their current use in hypomagnesemia is considered off-label.

BACKGROUND: Paracetamol is a widely used analgesic and antipyretic. Paracetamol-induced hepatotoxicity is well known, but nephrotoxicity without hepatotoxicity is rarely seen.
METHODS: We present a case of acute kidney injury without hepatotoxicity in paracetamol overdose. A 15-year-old girl was admitted 48 h after she had taken 10 g of paracetamol. She was complaining of abdominal pain and vomiting. Her blood level of creatinine was 1.20 mg/dL on admission, with a peak at 3.67 mg/dL 3 days later. The liver blood tests and blood paracetamol level were negative. She did not receive N-acetyl cysteine and was treated with intravenous fluid (crystalloid). The ultrasonography of the kidneys was normal. Her renal function returned almost to baseline 7 days after admission. It was concluded that the diagnosis was an acute kidney injury caused by acute tubular necrosis due to paracetamol overdose.
CONCLUSIONS: This case shows that nephrotoxicity can occur without hepatotoxicity in paracetamol overdose.

BACKGROUND: Early identification of high-risk individuals with cisplatin-induced nephrotoxicity (CIN) is crucial for avoiding CIN and improving prognosis. In this study, we developed and validated a CIN prediction model based on general clinical data, laboratory indications, and genetic features of lung cancer patients before chemotherapy.
METHODS: We retrospectively included 696 lung cancer patients using platinum chemotherapy regimens from June 2019 to June 2021 as the traing set to construct a predictive model using Absolute shrinkage and selection operator (LASSO) regression, cross validation, and Akaike\'s information criterion (AIC) to select important variables. We prospectively selected 283 independent lung cancer patients from July 2021 to December 2022 as the test set to evaluate the model\'s performance.
RESULTS: The prediction model showed good discrimination and calibration, with AUCs of 0.9217 and 0.8288, sensitivity of 79.89% and 45.07%, specificity of 94.48% and 94.81%, in the training and test sets respectively. Clinical decision curve analysis suggested that the model has value for clinical use when the risk threshold ranges between 0.1 and 0.9. Precision-Recall (PR) curve shown in recall interval from 0.5 to 0.75: precision gradually declines with increasing Recall, up to 0.9.
CONCLUSIONS: Predictive models based on laboratory and demographic variables can serve as a beneficial complementary tool for identifying high-risk populations with CIN.

We aimed to describe a case of acute kidney injury (AKI) with an uncommon case. We described a previously health 24 years old male that presented acute kidney injury associated with neurological and respiratory symptoms. He was initially admitted at the hospital with nausea, vomiting, blurred vision, and reduced urine output. The patient\'s condition got worse approximately in one week. Laboratory tests revealed high levels of nitrogenous waste, hyponatremia, metabolic acidosis with an increased anion gap, and the presence of proteinuria and hematuria. The patient experienced paresthesia, seizures, respiratory alterations, and altered consciousness. The initial diagnostic hypothesis of rapidly progressive glomerulonephritis was not confirmed. A deeper investigation of the case exposed that it could have occurred an intentional exogenous poisoning with diethylene glycol (DEG). Renal biopsy unveil findings suggestive of poison-induced nephrotoxicity, which corroborated the suspicion. Despite therapeutic efforts, the patient died due to pulmonary complications. This case report shows the need to consider DEG poisoning as a etiology of AKI, especially in patients with neurological symptoms. Laboratory and histopathological analysis were crucial for the diagnosis.

Colistin is an effective antibiotic utilized for the treatment of Gram-negative bacterial infections with coverage against a broad spectrum of bacteria. Despite the broad antibacterial coverage, this antibiotic can have serious complications such as acute kidney injury. Colistin also can have a toxic effect on the loop of Henle, causing tubulopathy, electrolyte imbalances, and the occurrence of Bartter-like syndrome (BLS) which is characterized by magnesium and calcium disturbances, polyuria, and metabolic alkalosis. We here report a 32-year-old male with a history of multiple trauma due to an accident that received colistin therapy for Pseudomonas isolation from wound culture on the 5th day of hospitalization. Polyuria, hypokalemic metabolic alkalosis, hypomagnesemia, and hypocalcemia were developed on the first week of colistin administration. The patient received colistin until the 21st day of hospitalization. Serum calcium and magnesium levels became normal 1 day after stopping colistin, while urine volume and metabolic alkalosis resolved 6 days after colistin discontinuing. Therefore, it is crucial to adjust the dose of colistin to minimize its toxicity.

UNASSIGNED: Teucrium polium is one of the aromatic plants that grows in the Mediterranean region, and had been used as an herbal treatment for diabetes due to its hypoglycaemia effect. Although this plant is being studied now for its therapeutic role, its side effects are not taken enough into consideration, so this unique case can shed the light on serious toxic effects of this plant.
UNASSIGNED: A 68-year-old woman presented to the hospital with generalized fatigue, malaise, nausea, vomiting, abdominal pain, polydipsia, polyuria, breathlessness, and no defecation for 2 days after drinking big amounts of teucrium polium. The diagnosis was diabetic ketoacidosis (DKA), complete heart block, acute liver and kidney damage, and urinary tract infection (UTI). The patient was admitted to the ICU and treated for the DKA with an insulin pump, an antibiotic treatment for UTI, in addition to a dopamine pump and atropine, and then a temporary pacemaker was placed. The patient\'s DKA, liver and kidney damage were improved on day 9, heart rate returned normal and she was discharged to insert a permanent pacemaker. However, the patient passed away at the end.
UNASSIGNED: Most studies made on this plant focused on the hypoglycaemia effect, with no attention to its toxic effects, so only few studies showed that teucrium polium can cause hepatic, renal toxicity and hyperglycaemia and most of them were studied in animals. While cardiac toxicity has never been noticed before.
UNASSIGNED: For this reason, herbal treatment should be used with caution to avoid catastrophic side effects.

Acquired tubulopathies are frequently underdiagnosed. They can be characterized by the renal loss of specific electrolytes or organic solutes, suggesting the location of dysfunction. These tubulopathies phenotypically can resemble Bartter or Gitelman syndrome). These syndromes are infrequent, they may present salt loss resembling the effect of thiazides (Gitelman) or loop diuretics (Bartter). They are characterized by potentially severe hypokalemia, associated with metabolic alkalosis, secondary hyperaldosteronism, and often hypomagnesemia. Tubular dysfunction has been described as nephrotoxic effects of platinum-based chemotherapy. We present 4 cases with biochemical signs of tubular dysfunction (Bartter-like/Gitelman-like phenotype) related to chemotherapy.

A 52-year-old male with acute onset right-sided weakness, numbness, and buttock pain after consuming 30 tablets of doxylamine antihistamine the night prior. Laboratory tests showed elevated creatinine kinase, blood urea nitrogen, creatinine, troponins, liver transaminases, and phosphate. The patient was admitted to the medical intensive care unit for severe rhabdomyolysis, acute liver failure, and acute kidney injury secondary to doxylamine intoxication. Studies describe symptoms of severe doxylamine intoxication, such as impaired consciousness (coma), grand mal seizures, and cardiopulmonary arrest. Circulating myoglobin causes oxidative injury to the kidney through the formation of F2-isoprostanes leading to renal vasoconstriction. One study explained drug-induced rhabdomyolysis via two mechanisms: direct drug injury to the striated muscle and local muscle compression in seizure, coma, and metabolic abnormality. Treatment involves aggressive hydration with monitoring of serum electrolytes and renal function. Aggressive volume expansion via intravenous fluids remains critical in preventing rhabdomyolysis-associated nephrotoxicity and myoglobin-induced acute renal failure. Alkalinization of urine may prevent renal vasoconstriction resulting in enhanced excretion of the toxic metabolites of doxylamine and myoglobin via renal tubules, thereby reducing peak serum concentration time and preventing direct renal tissue damage.

BACKGROUND: The incidence of tenofovir disoproxil fumarate (TDF)-induced nephrotoxicity ranges from 15.8 to 19.3 percent. Following cessation of TDF, approximately one-half of patients with nephrotoxicity regained full renal functions. This study aimed to determine the incidence and risk factors for nephrotoxicity, as well as the complete recovery of renal function, in human immunodeficiency virus (HIV)-infected patients receiving TDF regimens.
METHODS: This was a retrospective case-control study of HIV-positive patients who received TDF regimens from 2 tertiary hospitals between 2012 and 2018. Signs of TDF-induced renal dysfunction, defined as having estimated glomerular filtration rate (eGFR) decline of greater than 25%, and proximal renal tubulopathy (PRT) were followed for 48 months. After discontinuing TDF due to nephrotoxicity, the renal parameters of patients were monitored for 48 months. Univariate and multivariate regression analyses were used to determine the factors associated with TDF-induced nephrotoxicity and renal function recovery.
RESULTS: Twelve percent of 3,214 TDF-treated patients were diagnosed with renal dysfunction, whereas 303 patients (15.20%) were diagnosed with PRT. TDF-induced renal dysfunction was associated with older age (odds ratio [OR] = 2.851), smoking (OR = 1.972), and TDF use for more than 3 years (OR 1.928). Receiving trimethoprim-sulfamethoxazole (TMP/SMX) or nonsteroidal anti-inflammatory drugs (NSAIDs) and being elderly were associated with PRT (OR = 4.727, 4.313, and 3.357, respectively). Following the discontinuation of TDF, 12.96% of patients regained full renal function. Elderly patients and those taking renin-angiotensin-aldosterone system (RAAS) inhibitors or protease inhibitors (PIs) had a lower likelihood of full recovery (OR = 0.811, 0.793, 0.582, respectively). One-third experienced PRT recovery, whereas RAAS inhibitors use, old age, and receiving PIs decreased the likelihood of PRT recovery (OR = 0.709, 0.504, 0.311, respectively). TDF cessation at an eGFR greater than 60 mL/min/1.73 m² increased the likelihood of renal function recovery and PRT by 4.07 and 2.11 times, respectively.
CONCLUSIONS: Twelve percent and 15 percent of patients receiving TDF developed renal dysfunction and PRT, respectively. Age, TMP/SMX, NSAIDs, and long-term TDF exposure were independent risk factors for TDF-induced nephrotoxicity. Thirteen and thirty-three percent of patients with renal dysfunction and PRT recovered from their conditions, respectively. The discontinuation of TDF at an eGFR greater than 60 mL/min/1.73 m² was advantageous for the recovery of renal function and PRT.