Recovery of methotrexate-induced anuric acute kidney injury after glucarpidase therapy

Harms, James C.; Khawaja, Ayaz; Taylor, Maria E.; Han, Xiaosi; Mrug, Michal

doi:10.1177/2050313x17705050

Cited by 8 publications

(9 citation statements)

References 11 publications

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“…Assuming that glucarpidase reduces methotrexate concentrations by 95% in 15 minutes, this represents a t 1/2 of 3 minutes, or several orders of magnitude shorter than observed during a hemodialysis session. This was confirmed in all studies in which both glucarpidase and extracorporeal treatments were given (58,171,210,213,217,224,227,238,245,247). Some reports noted that dialysis clearance is concentration dependent (190,195,238,244), although this is surprising in the absence of saturation of protein binding or membrane adsorption; this may have been caused by detection sensitivity of the assay at low concentration, or redistribution of methotrexate from red blood cells in the outlet, inflating that methotrexate concentration.…”

Section: Systematic Reviewmentioning

confidence: 71%

Extracorporeal Treatment for Methotrexate Poisoning

Ghannoum

Roberts

Goldfarb

et al. 2022

CJASN

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Methotrexate is used in the treatment of many malignancies, rheumatological diseases, and inflammatory bowel disease. Toxicity from use is associated with severe morbidity and mortality. Rescue treatments include intravenous hydration, folinic acid, and, in some centers, glucarpidase. We conducted systematic reviews of the literature following published EXtracorporeal TReatments In Poisoning (EXTRIP) methods to determine the utility of extracorporeal treatments in the management of methotrexate toxicity. The quality of the evidence and the strength of recommendations (either “strong” or “weak/conditional”) were graded according to the GRADE approach. A formal voting process using a modified Delphi method assessed the level of agreement between panelists on the final recommendations. A total of 92 articles met inclusion criteria. Toxicokinetic data were available on 90 patients (89 with impaired kidney function). Methotrexate was considered to be moderately dialyzable by intermittent hemodialysis. Data were available for clinical analysis on 109 patients (high-dose methotrexate [>0.5 g/m2]: 91 patients; low-dose [≤0.5 g/m2]: 18). Overall mortality in these publications was 19.5% and 26.7% in those with high-dose and low-dose methotrexate–related toxicity, respectively. Although one observational study reported lower mortality in patients treated with glucarpidase compared with those treated with hemodialysis, there were important limitations in the study. For patients with severe methotrexate toxicity receiving standard care, the EXTRIP workgroup: (1) suggested against extracorporeal treatments when glucarpidase is not administered; (2) recommended against extracorporeal treatments when glucarpidase is administered; and (3) recommended against extracorporeal treatments instead of administering glucarpidase. The quality of evidence for these recommendations was very low. Rationales for these recommendations included: (1) extracorporeal treatments mainly remove drugs in the intravascular compartment, whereas methotrexate rapidly distributes into cells; (2) extracorporeal treatments remove folinic acid; (3) in rare cases where fast removal of methotrexate is required, glucarpidase will outperform any extracorporeal treatment; and (4) extracorporeal treatments do not appear to reduce the incidence and magnitude of methotrexate toxicity.

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Section: Systematic Reviewmentioning

confidence: 71%

Extracorporeal Treatment for Methotrexate Poisoning

Ghannoum

Roberts

Goldfarb

et al. 2022

CJASN

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“…In this experimentation, MTX also increased the levels of creatinine and urea both indicators of renal toxicity. Harms et al (2017) also carried out a study where plasma creatinine and urea levels were high after treatment with MTX (Harms, Khawaja, Taylor, Han & Mrug, 2017). As can be observed in Figures 8 and 9, the levels of these metabolic wastes were found to be lowered by associating MTX with either of the extracts.…”

Section: Discussionmentioning

confidence: 91%

Comparative Study of the Protective Effect of Cola anomala and Coffea arabica Against Induced Toxicity in Rats

Mbong¹,

Edoun²,

Ngandi³

et al. 2020

JFR

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This work was aimed at evaluating the effects of C. anomala and C. arabica on Methotrexate (MTX) induced metabolic disorders. For this, the aqueous extract (AE) of C. anomala and C. arabica were prepared and their polyphenols, flavonoids and alkaloids contents determined as well as their antiradical and total antioxidant capacity. An animal experimentation using female rats was carried out for 14 days. Rats were divided into 6 groups; a negative control group receiving water; a positive control group receiving 12mg/Kg Bw of MTX; four tests groups receiving 12mg/Kg Bw of MTX and one of the extracts at a dose of 200mg/Kg Bw or 400mg/Kg Bw. At the end of the experiment, plasmas and hemolysates were prepared as well as liver and kidney homogenates for the evaluation of oxidative status (catalase, total protein and malondialdehyde (MDA)), liver toxicity (alanine amino transferase (ALT)) and renal toxicity (creatinine and urea) and lipid profile (triglycerides, total cholesterol and HDL-cholesterol). Weight gain in extract-treated rats was better with the C. anomala. Concerning oxidative status, MDA levels were generally lower in C. anomala-treated groups compared to C. arabica while catalase level was higher in C. anomala-treated rats. As for lipid profile, it is C. arabica that showed more or less better results. Both extracts led to an amelioration of toxicity markers compared to exclusive treatment with MTX. The results of this study suggest that C. anomala and C. arabica may reduce metabolic disorders associated with the intake of MTX during cancer treatment; C. anomala protecting better C. arabica.

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“…Furthermore, pCaSiNP-MTX treatment reversed the arthritis progression even in mice whose entire paws were inflamed and swollen (with a score of 3; Figure S7B). Notably, multiple doses of pCaSiNPs-MTX did not induce significant toxicities in the liver or kidneys, where the most common adverse effects of MTX are observed 6,55 (Figure S8). This confirmed the biosafety of pCaSiNPs-MTX.…”

Section: Resultsmentioning

confidence: 99%

Porous Silicon-Based Nanomedicine for Simultaneous Management of Joint Inflammation and Bone Erosion in Rheumatoid Arthritis

et al. 2022

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The lack of drugs that target both disease progression and tissue preservation makes it difficult to effectively manage rheumatoid arthritis (RA). Here, we report a porous silicon-based nanomedicine that efficiently delivers an antirheumatic drug to inflamed synovium while degrading into bone-remodeling products. Methotrexate (MTX) is loaded into the porous silicon nanoparticles using a calcium silicate based condenser chemistry. The calcium silicate–porous silicon nanoparticle constructs (pCaSiNPs) degrade and release the drug preferentially in an inflammatory environment. The biodegradation products of the pCaSiNP drug carrier are orthosilicic acid and calcium ions, which exhibit immunomodulatory and antiresorptive effects. In a mouse model of collagen-induced arthritis, systemically administered MTX-loaded pCaSiNPs accumulate in the inflamed joints and ameliorate the progression of RA at both early and established stages of the disease. The disease state readouts show that the combination is more effective than the monotherapies.

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Recovery of methotrexate-induced anuric acute kidney injury after glucarpidase therapy

Cited by 8 publications

References 11 publications

Extracorporeal Treatment for Methotrexate Poisoning

Extracorporeal Treatment for Methotrexate Poisoning

Comparative Study of the Protective Effect of Cola anomala and Coffea arabica Against Induced Toxicity in Rats

Porous Silicon-Based Nanomedicine for Simultaneous Management of Joint Inflammation and Bone Erosion in Rheumatoid Arthritis

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