Takeshi Sugaya

Renal L-type fatty acid-binding protein mediates the bezafibrate reduction of cisplatin-induced acute kidney injury

Fibrates, the PPAR alpha ligand-like compounds increase the expression of proximal tubule liver fatty acid binding protein (L-FABP) and significantly decrease cisplatin-induced acute kidney injury. To study whether the bezafibrate-mediated upregulation of renal L-FABP was involved in this cytoprotective effect we treated transgenic mice of PPAR agonists inducible human L-FABP expression with cisplatin in the presence or absence of bezafibrate. Blood urea nitrogen was unchanged in the first day but increased 3 days after cisplatin. While urinary L-FABP increased over 100-fold 1 day after cisplatin treatment in the transgenic mice it was significantly reduced when these transgenic mice were pretreated with bezafibrate. Cisplatin-induced renal necrosis and apoptosis were significantly reduced in bezafibrate pretreated transgenic mice and this correlated with decreased accumulation of lipid and lipid peroxidation products. Immunohistochemical analysis of kidney tissue of bezafibrate-cisplatin-treated transgenic mice showed preservation of cytoplasmic L-FABP in the proximal tubule, but this was reduced in transgenic mice treated only with cisplatin. L-FABP mRNA and protein levels were significantly increased in bezafibrate-cisplatin-treated transgenic mice when compared to mice not fibrate treated. Our study shows that the bezafibrate-mediated upregulation of proximal tubule L-FABP plays a pivotal role in the reduction of cisplatin-induced acute kidney injury.

Potentiality of Urinary L-FABP Tests to Kala-Azar Disease Management

The diagnostic process of disease detection and disease management is different in every disease. Recently, the diagnostic procedure for visceral leishmaniasis (VL), also known as kala-azar, was simplified from a time-consuming pathological examination into a simple blood test. But the monitoring of disease activity during therapy still relies on clinical findings and classical laboratory data in endemic areas. In this chapter, we introduce and examine the utility of a urinary biomarker, fatty acid-binding protein 1 (FABP1) or alternatively L-type fatty acid-binding protein (L-FABP), for monitoring VL disease activities and drug-induced side effects. A FABP1 analysis developed as an enzyme-linked immunosorbent assay was transformed into a urinary immuno-chromatography dipstick test for point of care use in endemic areas. We expect that a FABP1 dipstick test will serve as a triage marker in disease monitoring of VL. In addition, this chapter introduces the impact of FABP1 on predicting survival in septic acute kidney injury and the clinical interpretation of FABP1 measurements in VL.

Pharmacovigilance on Therapeutic Protocols for Visceral Leishmaniasis

Because the primary goal in visceral leishmaniasis (VL) treatment is a cure of this deadly parasitic disease, post-marketing drug safety surveillance is often overlooked. Because overworked patients will not routinely return to the clinic, chronic sequelae of treated VL are not well understood. For example, high doses of drugs that are renally excreted can potentially induce kidney fibrosis. The team of SATREPS (Science and Technology Research Partnership for Sustainable Development) established a patient registration system for VL cases treated in the Surya Kanta Kala-azar Research Center (SKKRC), monitored those subjects periodically by sending field staff on site, and performed surveillance by using a simple urine biomarker kit to detect kidney injury. Herein, this chapter examines the prevalence of people with high urinary levels of L-FABP (FABP1) after VL treatment, which may indicate decreased kidney function. The risk varied according to the treatment protocols and presumably patients’ treatment histories.