Preliminary Study for New Markers of Early Tubuloglomerular Injury and Renal Inflammation in Patients with Visceral Leishmaniasis Receiving Liposomal Amphotericin B Treatment

Gabriela Freire Bezerra Pharmacology Postgraduate Program, Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil;

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Gdayllon Cavalcante Meneses Medical Sciences Postgraduate Program, Department of Internal Medicine, School of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil;

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Vittória Nobre Jacinto Medical Sciences Postgraduate Program, Department of Internal Medicine, School of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil;

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Danya Bandeira Lima Clinical and Toxicological Analysis Department, School of Pharmacy, Federal University of Ceará, Fortaleza, Ceará, Brazil;

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Emanuel Paula Magalhães Clinical and Toxicological Analysis Department, School of Pharmacy, Federal University of Ceará, Fortaleza, Ceará, Brazil;

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Lana Andrade Lucena Lima Clinical and Toxicological Analysis Department, School of Pharmacy, Federal University of Ceará, Fortaleza, Ceará, Brazil;

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Thaiany Pereira da Rocha Clinical and Toxicological Analysis Department, School of Pharmacy, Federal University of Ceará, Fortaleza, Ceará, Brazil;

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Isabella Evelyn Prado de Azevedo Clinical and Toxicological Analysis Department, School of Pharmacy, Federal University of Ceará, Fortaleza, Ceará, Brazil;

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Geraldo Bezerra da Silva Jr. Collective Health Graduate Program, School of Medicine, Health Sciences Center, University of Fortaleza, Fortaleza, Ceará, Brazil

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Elizabeth De Francesco Daher Medical Sciences Postgraduate Program, Department of Internal Medicine, School of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil;

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Alice Maria Costa Martins Pharmacology Postgraduate Program, Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil;
Clinical and Toxicological Analysis Department, School of Pharmacy, Federal University of Ceará, Fortaleza, Ceará, Brazil;

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ABSTRACT.

Visceral leishmaniasis is treated with liposomal amphotericin B (L-AMB), which is associated with nephrotoxicity. Thus, we aimed to investigate nephrotoxicity through novel renal biomarkers in patients with visceral leishmaniasis during L-AMB use. Ours was a prospective study with 17 patients with visceral leishmaniasis treated with L-AMB during their hospital stay. Laboratory tests, renal parameters, urinary biomarkers (urinary kidney injury molecule 1, urinary monocyte chemoattractant protein 1 [uMCP-1], sodium–potassium–2 chloride cotransporter [NKCC2], sodium–hydrogen exchanger 3) [NHE3], aquaporin 2 [AQP2], tumor susceptibility gene 101 [TSH 101], and serum inflammatory biomarkers (MCP-1, interferon-γ, and IL-6) were evaluated in two periods: before and during L-AMB use. Glomerular filtration rate, creatinine, proteinuria, and albuminuria were similar before and during L-AMB use. IL-6 levels, AQT2, and NHE3 expression decreased, whereas uMCP-1 and urinary kidney injury molecule 1 levels increased during L-AMB treatment. In patients who developed acute kidney injury, uMCP-1 showed higher levels. L-AMB aggravated tubuloglomerular lesions, inflammation, and renal tubular disorders. Thus, patients treated with L-AMB need to be monitored for inflammatory and electrolyte disturbances to prevent acute kidney injury, longer length of hospital stay, higher public costs, and mortality.

Author Notes

Address correspondence to Alice Maria Costa Martins, Rua Pastor Manuel Munguba, 1210, Fortaleza, Ceará, Brazil. E-mail: martinsalice@gmail.com

Financial support: The Brazilian Coordination for the Improvement of Higher Education Personnel supported this study through scholarships to G. C. M. and D. B. L (88882.306447/2018-01 and 88887.368537/2019-00). The National Council for Scientific and Technological Development supported the acquisition of scientific materials (405963/2016-5).

Authors’ addresses: Gabriela Freire Bezerra, Pharmacology Postgraduate Program, Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil, E-mail: gabrielafreireb@gmail.com. Gdayllon Cavalcante Meneses, Vittória Nobre Jacinto, and Elizabeth De Francesco Daher, Medical Sciences Postgraduate Program, Department of Internal Medicine, School of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil, E-mails: gdayllon@yahoo.com.br, vittoria_nobrej@hotmail.com, and ef.daher@uol.com.br. Danya Bandeira Lima, Emanuel Paula Magalhães, Lana Andrade Lucena Lima, Thaiany Pereira da Rocha, and Isabella Evelyn Prado de Azevedo, Clinical and Toxicological Analysis Department, School of Pharmacy, Federal University of Ceará, Fortaleza, Ceará, Brazil, E-mails: danya.dbl@gmail.com, emanuelpmagalhaes@gmail.com, lanaanluli@gmail.com, thaianyp.rocha@gmail.com, and isabella.evelyn@hotmail.com. Geraldo Bezerra da Silva Jr., Collective Health Graduate Program, School of Medicine, Health Sciences Center, University of Fortaleza, Fortaleza, Ceará, Brazil, E-mail: geraldobezerrajr@unifor.br. Alice Maria Costa Martins, Pharmacology Postgraduate Program, Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil, and Clinical and Toxicological Analysis Department, School of Pharmacy, Federal University of Ceará, Fortaleza, Ceará, Brazil, E-mail: martinsalice@gmail.com.

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