Chapter 3: Management of kidney injury caused by cancer drug therapy, from clinical practice guidelines for the management of kidney injury during anticancer drug therapy 2022.

Cisplatin should be administered with diuretics and Magnesium supplementation under adequate hydration to avoid renal impairment. Patients should be evaluated for eGFR (estimated glomerular filtration rate) during the treatment with pemetrexed, as kidney injury has been reported. Pemetrexed should be administered with caution in patients with a CCr (creatinine clearance) < 45 mL/min. Mesna is used to prevent hemorrhagic cystitis in patients receiving ifosfamide. Febuxostat is effective in avoiding hyperuricemia induced by TLS (tumor lysis syndrome). Preventative rasburicase is recommended in high-risk cases of TLS. Thrombotic microangiopathy could be triggered by anticancer drugs and there is no evidence of efficacy of plasma exchange therapy. When proteinuria occurs during treatment with anti-angiogenic agents or multi-kinase inhibitors, dose reductions or interruptions based on grading should be considered. Grade 3 proteinuria and renal dysfunction require urgent intervention, including drug interruption or withdrawal, and referral to a nephrologist should be considered. The first-line drugs used for blood pressure elevation due to anti-angiogenic agents are ACE (angiotensin-converting enzyme) inhibitors and ARBs (angiotensin receptor blockers). The protein binding of drugs and their pharmacokinetics are considerably altered in patients with hypoalbuminemia. The clearance of rituximab is increased in patients with proteinuria, and the correlation with urinary IgG suggests similar pharmacokinetic changes when using other antibody drugs. AIN (acute interstitial nephritis) is the most common cause of ICI (immune checkpoint inhibitor)-related kidney injury that is often treated with steroids. The need for renal biopsy in patients with kidney injury that occurs during treatment with ICI remains controversial.

A Case Involving Massive Insulin Overdose: Direct and Indirect Conditions Requiring Extended Management of Serum Potassium.

BACKGROUND Insulin lowers not only blood glucose levels but also serum potassium levels by driving potassium into the cells. Hypokalemia can occur during aggressive treatment of hypoglycemia in patients with insulin overdose and is a well-documented clinical phenomenon; however, there are no studies describing delayed hyperkalemia occurring after initial treatment in patients with insulin overdose. CASE REPORT A 23-year-old male with a history of type 2 diabetes mellitus and self-medicating with insulin, attempted suicide by subcutaneously injecting 2100 units of insulin. He was admitted to our emergency department due to recurrent hypoglycemia. Continuous administration of 50% glucose and potassium via a central venous catheter was performed to maintain his glucose levels above 80 mg/dL and serum potassium level between 3.5 and 4.0 mEq/L. Because his serum potassium level exceeded 4.5 mEq/L at day 3 after admission, the dosage was adjusted accordingly. After his serum potassium level declined to 3.0 mEq/L, his potassium level abruptly increased to 6.0 mEq/L at day 5 after admission. The patient was placed on a potassium-restricted diet and administered furosemide. Potassium infusion was also discontinued. After serum potassium levels returned to the normal range without interventional therapies, the patient was discharged to home on day 14. CONCLUSIONS In cases of high-dose insulin overdose, management of hyperkalemia following recovery from hypoglycemia is a critical aspect of patient management. Conservative administration of potassium to correct initial hypokalemia may be considered in patients with high-dose insulin overdose.

Effect of high-dose vitamin C therapy on severe burn patients: a nationwide cohort study.

BACKGROUND: Vitamin C is a well-documented antioxidant that reduces oxidative stress and fluid infusion in high doses; however, the association between high-dose vitamin C and reduced mortality remains unclear. This study evaluates the effect of high-dose vitamin C in severe burn patients under two varying thresholds. METHODS: We enrolled adult patients with severe burns (burn index ≥ 15) who were registered in the Japanese Diagnosis Procedure Combination national inpatient database from 2010 to 2016. Propensity score matching was performed between patients who received high-dose vitamin C within 1 day of admission (vitamin C group) and those who did not (control group). High-dose vitamin C was defined as a dosage in excess of 10 g or 24 g within 2 days of admission. The primary outcome was in-hospital mortality. RESULTS: Eligible patients (n = 2713) were categorized into the vitamin C group (n = 157) or control group (n = 2556). After 1:4 propensity score matching, we compared 157 and 628 patients who were administered high-dose vitamin C (> 10-g threshold) and controls, respectively. Under this particular threshold, high-dose vitamin C therapy was associated with reduced in-hospital mortality (risk ratio, 0.79; 95% confidence interval, 0.66-0.95; p = 0.006). In contrast, in-hospital mortality did not differ between the control and high-dose vitamin C group under the > 24-g threshold (risk ratio, 0.83; 95% confidence interval, 0.68-1.02; p = 0.068). CONCLUSIONS: High-dose vitamin C therapy was associated with reduced mortality in patients with severe burns when used under a minimum threshold of 10 g within the first 2 days of admission. While "high-dose" vitamin C therapy lacks a universal definition, the present study reveals that different "high-dose" regimens may yield improved outcomes.

Successful treatment switch from lenvatinib to sorafenib in a patient with radioactive iodine-refractory differentiated thyroid cancer intolerant to lenvatinib due to severe proteinuria.

Sorafenib and lenvatinib showed efficacy for patients with radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC) in pivotal phase 3 clinical trials. Although the efficacy of lenvatinib in patients who received previous treatment with multi-target kinase inhibitors (m-TKIs), including sorafenib, was reported, the efficacy of sorafenib in patients who previously received lenvatinib remains unknown. A 75-year-old woman diagnosed as RAI-refractory poorly differentiated carcinoma with multiple lung metastases and started treatment with lenvatinib. She continued to receive lenvatinib but with repeated dose interruptions and reductions due to continuous proteinuria. Because of severe and persistent proteinuria as well as newly developed renal impairment, lenvatinib was suspended after two years of treatment. After the 7-month suspension, her proteinuria and renal impairment were partially improved, but her lung metastases progressed. Because she was unable to tolerate previous treatment with lenvatinib, sorafenib was started. At 7 months of treatment with sorafenib, her lung metastases shrank and she could continue sorafenib without exacerbation of proteinuria or renal impairment. This case may suggest that sorafenib does not exacerbate the proteinuria or renal impairment induced by lenvatinib, and may be an effective treatment option for RAI-refractory DTC patients who are unable to tolerate lenvatinib.

Lecithinized superoxide dismutase suppresses free radical substrates during the early phase of burn care in rats.

Severe hypovolemia is caused by an increase in blood vessel permeability in the early phase after an extensive burn; massive fluid volume replacement has been used for the treatment of this condition. The release of oxygen free radicals and chemical mediators, especially from skin tissue, induces the increase in blood vessel permeability. Free radical burst is associated with ischemia-related skin tissue injury. Although various antioxidant therapies have been used to inhibit the consequences of hypovolemia, an effective method has not been established. To elucidate the protective effects of lecithinized superoxide dismutase (PC-SOD) as an antioxidant agent. Each rat sustained a 30% total body surface area burn (n = 20) on the back by the Walker and Mason method were allocated into three groups: (1) no treatment group (n = 6), (2) a low dose of PC-SOD (0.67 mg/kg) group (n = 7), and (3) a high dose of PC-SOD (1.33 mg/kg) group (n = 7). The concentrations of malondialdehyde and SOD in the serum, skin tissue, and lung tissue were measured in each group 1 hour after burning. Both low and high doses of PC-SOD prevented malondialdehyde concentration associated with free radical burst after burning compared with the no treatment group (P < .05); serum (27.7 +/- 6.8, 10.8 +/- 2.7, and 12.1 +/- 2.8 nmol/L), skin tissue (2251.3 +/- 560.5, 802.7 +/- 228.8, and 790.1 +/- 188.3 nmol/wet.g), and lung (157.3 +/- 19.5, 109.1 +/- 23.9, and 81.9 +/- 20.3 nmol/wet.g). These data suggest that PC-SOD may be a protective agent against free radical-induced vasodilatation caused by severe, extensive burns.