Characterization of Binding of Folates and Antifolates to Brush-Border Membrane Vesicles Isolated from Human Kidney

Damaraju, Vijaya L.; Hamilton, Katherine F.; Seth-Smith, M.L.; Cass, Carol E.; Sawyer, Michael B.

doi:10.1124/mol.104.004978

Cited by 11 publications

(6 citation statements)

References 23 publications

(29 reference statements)

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“…12 Folates and antifolates are reabsorbed at kidney proximal tubules via folate receptors and transported into cells. [13][14][15] We hypothesize that the accumulation of the drug intracellularly and the subsequent inhibition of purine and protein synthesis, result in tubular cytotoxicity and possibly secondary tubulointerstitial inflammation leading to AKI. Our patient did not respond to corticosteroid treatment.…”

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confidence: 99%

Interstitial nephritis and nephrogenic diabetes insipidus in a patient treated with pemetrexed

et al. 2010

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We present a case of interstitial nephritis and nephrogenic diabetes insipidus (NDI) in a patient treated with pemetrexed (500 mg/m 2 ) for non-small cell lung cancer. Renal impairment and diabetes insipidus appeared after the first treatment cycle while he totally received four cycles of chemotherapy. There was not any significant myelosuppression and the patient was on regular supplementation with folic acid and vitamin B 12 . He was not on any other medications and he did not receive any nephrotoxic agents. Kidney biopsy showed acute tubular necrosis together with interstitial inflammatory infiltrate of mononuclear cells and interstitial fibrosis occupying 25% of the cortex. There was not any improvement of renal function after a 2-week trial of oral prednisone. In the present case report, we review the literature for pemetrexed-induced renal toxicity and the possible mechanisms involved.

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confidence: 99%

Interstitial nephritis and nephrogenic diabetes insipidus in a patient treated with pemetrexed

et al. 2010

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“…13,14) It has been found that these carriers are pH-sensitive and are expressed not only in the intestine but also in other organs, including the placenta. [15][16][17] Furthermore, it is possible that intracellular accumulation of folates reflects the operation of outward transport mediated by members of the family of ATP-binding cassette transporters, such as MRPs and breast cancer resistance protein (BCRP/ ABCG2). 18) It is known that the placenta is an organ that develops in a short period of time, and that its functions change with the progress of gestation.…”

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confidence: 99%

Placental Folate Transport during Pregnancy

Yasuda

Hasui

Yamamoto

et al. 2008

Bioscience, Biotechnology, and Biochemistry

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“…Moreover, a proximal tubular damage, even if mild, as demonstrated in an experimental study published in 2005 (7), could increase drug nephrotoxicity, since the proximal tubule is the site where folic acid is reabsorbed through FR-α and RFC carriers. Besides, folate absorption is increased by an acidic environment, and decreased by a high urine flow, meaning that fluid and alkaline solutions administration could augment folate excretion, and as a consequence reduce its protective effects.…”

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confidence: 99%

Pemetrexed-induced acute kidney failure following irreversible renal damage: two case reports and literature review

Zattera¹,

Lotti²,

Trezzi³

et al. 2016

J Nephropathol

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BackgroundPemetrexed (PEM) is a new-generation multitargeted antifolate agent with a demonstrated broad-spectrum activity in several types of human cancers, including non-small cell lung cancer (NSCLC) and mesothelioma. Major side effects include dose-limiting hematologic toxicities. PEM nephrotoxicity is well known; however, its frequency is considered to be low.Case PresentationHere we report two cases of acute kidney injury (AKI) related to PEM administration (500 mg/m2) in patients with NSCLC. The first patient required hemodialysis treatment and was submitted to renal biopsy which showed acute tubular damage and interstitial edema without acute tubular necrosis. No other potential nephrotoxic agents were identified. The second patient developed AKI, not proven by biopsy and did not require renal replacement therapy. Both patients, on regular supplementation with folic acid and vitamin B12, concomitantly developed myelosuppression and even several months after PEM withdrawal, showed only a modest improvement of renal function.ConclusionsPEM is an antifolate antineoplastic agent with a broad-spectrum activity in locally advanced or metastatic NSCLC. It has been shown that PEM allows longer survival. The risk of acute or chronic kidney disease may be one of the prices to be paid for this success.

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Characterization of Binding of Folates and Antifolates to Brush-Border Membrane Vesicles Isolated from Human Kidney

Cited by 11 publications

References 23 publications

Interstitial nephritis and nephrogenic diabetes insipidus in a patient treated with pemetrexed

Interstitial nephritis and nephrogenic diabetes insipidus in a patient treated with pemetrexed

Placental Folate Transport during Pregnancy

Pemetrexed-induced acute kidney failure following irreversible renal damage: two case reports and literature review

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