Nephrotoxicity biomarkers able to identify oncological patients at risk of developing kidney damage
Abstract Cisplatin and carboplatin are very used drugs for the treatment of solid tumours. However, their efficacy is limited by their nephrotoxicity. It is known that 25-30% of the patients that have been exposed to these treatments will end up developing acute kidney injury (AKI). Nowadays, for the clinical diagnosis of AKI some biomarkers are used, such as plasma creatinine and urea, which are not very sensitive and specific. The aim of this work is focused on searching some urinary biomarkers able to predict the occurrence of a possible kidney damage even before starting the treatment, being able to classify the patients according to their severity, to predict the evolution of kidney function and to carry out a more adapted treatment for every patient.A clinical study was carried out with voluntary patients from the Oncology Service of the University Hospital of Salamanca. The studied biomarkers were proteinuria, N-acetil-?-glucosamidinase (NAG), neutrophil gelatinase-associated lipocalin (NGAL) and albumin. The quantification of these proteins in urine was performed by colorimetric methods and ELISA.It was evidenced that the levels of the biomarkers in the basal time and in the one before the maximum kidney damage are practically the same, what indicates that these levels do not vary during the chemotherapy cycle. Moreover, they could indicate, before starting the treatment, that kidney damage is going to happen. These biomarkers would be a great advantage in determining, before undergoing the first chemotherapy cycle, whether a patient will suffer kidney complications.
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Espinosa-Sevilla A, Amezcua-Macías AI, Ruiz-Palacios PC, Rodríguez-Weber F, Díaz-Greene E. Nuevos marcadores de lesión renal aguda en el enfermo grave. Med Interna México. 2013; 29(5):513-17.
Launay-Vacher V, Rey J-B, Isnard-Bagnis C, Deray G, Daouphars M. Prevention of cisplatin nephrotoxicity: state of the art and recommendations from the European Society of Clinical Pharmacy Special Interest Group on Cancer Care. Cancer Chemother Pharmacol. 2008; 61(6):903-9. - https://doi.org/10.1007/s00280-008-0711-0
Lombi F, Muryan A, Canzonieri R, Trimarchi H. Biomarcadores en la lesión renal aguda: ¿paradigma o evidencia?. Nefrología. 2016; 36(4):339-46. - https://doi.org/10.1016/j.nefro.2016.01.012
Manjón-Rodríguez MD. Estudio de N-acetil-B2-glucosaminidasa y otros marcadores de daño renal en nefroangioesclerosis hipertensiva. Editorial de la Universidad de Granada; 2010.
Montañés Bermúdez R, Gracia García S, Pérez Surribas D, Martínez Castelao A, Bover Sanjuán J. Documento de Consenso. Recomendaciones sobre la valoración de la proteinuria en el diagnóstico y seguimiento de la enfermedad renal crónica. Nefrol Madr. 2011; 31(3):331-45.
Perazella MA. Onco-Nephrology: Renal Toxicities of Chemotherapeutic Agents. Clin J Am Soc Nephrol. 2012;7(10):1713-21. - https://doi.org/10.2215/CJN.02780312
Prada, M, Gastelbondo, R, Garcés, S. Nefrotoxicidad por Quimioterapia. Nefrol Pediátrica. 2011; 11(3):136-44.
Rabik CA, Dolan ME. Molecular mechanisms of resistance and toxicity associated with platinating agents. Cancer Treat Rev. 2007; 33(1):9-23. - https://doi.org/10.1016/j.ctrv.2006.09.006
Salabarría, J. Laboratorio clínico y función renal. 2015; 1-30.
Segarra-Medrano A, Carnicer-Cáceres C, Arbós-Via MA, Quiles-Pérez MT, Agraz-Pamplona I, Ostos-Roldán E. Biomarcadores en el síndrome nefrótico: algunos pasos más en el largo camino. Nefrol Madr. 2012; 32(5):558-72.
Seijas M, Baccino C, Nin N, Lorente JA. Definition and biomarkers of acute renal damage: New perspectives. Med Intensiva Engl Ed. 2014; 38(6):376-85. - https://doi.org/10.1016/j.medin.2013.09.001
Vicente-Vicente L, Sánchez-Juanes F, García-Sánchez O, Blanco-Gozalo V, Pescador M, Sevilla MA et al. Sub-nephrotoxic cisplatin sensitizes rats to acute renal failure and increases urinary excretion of fumarylacetoacetase. Toxicol Lett. 2015; 234(2):99-109. - https://doi.org/10.1016/j.toxlet.2014.11.033
Vilander LM, Kaunisto MA, Pettilä V. Genetic predisposition to acute kidney injury - a systematic review. BMC Nephrol. 2015; 16(1):197. - https://doi.org/10.1186/s12882-015-0190-6
Pérez-Sánchez, L., Casanova, A. G., & Morales, A. I. (2019). Nephrotoxicity biomarkers able to identify oncological patients at risk of developing kidney damage. FarmaJournal, 4(2), 41–50. https://doi.org/10.14201/fj2019424150
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