#4248 COMBINED EFFECT OF DEHYDRATION, HYPERTENSION, AND AGE ON RENAL FRAILTY

Abstract Background and Aims Renal frailty (RF) is a premorbid and, at least partly, modifiable condition arising from diminished renal functional reserve defective adaptive response capacity predisposing to acute kidney injury (AKI). RF ensues subclinical wear or distortion of the haemodynamic tubular homeostatic responses that defend excretory function supervening circumstances (i.e., stressors such as drugs). In this work, we aimed study impact generated by combined effect hydration state, hypertension ageing on nephrotoxicity developed low dose cisplatin in rat. Method Young Wistar rats, young spontaneously hypertensive rats (SHR), aged were used. Rats each group randomly subject four experimental conditions: - Control: with ad libitum water intake, receiving vehicle (0.9% NaCl, i.p). Cisplatin: treated 2.5 mg/kg, i.p. cisplatin. Water deprivation: deprived for 48 h, i.p.). deprivation + cisplatin: h prior mg/kg administration. Tail vein blood 24-hour urine samples collected basal time (B), after (D0), 4 days cisplatin/vehicle administration (D4, day maximum damage). Haematocrit was measured plasma osmolality, creatinine (Jaffe reaction) urea (Jung method) concentrations determined. Urine analysed volume (urinary flow), proteinuria (Bradford method). Body fluid composition bioimpedance spectroscopy an ImpediVETTM VetBIS1 device. Results All showed clear signs dehydration hours weight loss, increases osmolality haematocrit (more pronouncedly SHR than animals), reduced flow highly concentrated elevated osmolality). Bioimpedance analysis revealed parallel loss intracellular extracellular net total body (explaining most loss), no changes liquid distribution between compartments. Dehydration reverted rehydration vehicle-treated alteration observed due deprivation. Administration young, normohydrated minimal not worsened Hypertensive completely normal when administered under normohydration. Interestingly, however, dehydrated did suffer cisplatin-induced AKI (significant creatinine, proteinuria). compromised (as supported concentration), significantly amplified Conclusion This suggests fully competent itself significant risk factor AKI, while combination AKI. Furthermore, poses animals state renders their kidneys unable respond (such cisplatin). Frailty boldly animals. perspective, models reproducing conditions increased vulnerability provide useful tools search biomarkers pre-emptively predicting undesired health outcomes before exposure stressors, developing preventing strategies. Project PI21/01226, funded Instituto de Salud Carlos III (ISCIII) co-funded European Union, grant Consejería Educación, Junta Castilla y León (IES160P20), Spain, FEDER funds. Noelia Diaz-Morales recipient Juan la Cierva-Formación postdoctoral contract (FJC2020-043205-I) MCIN/AEI/10.13039/501100011033 Union “NextGenerationEU/PRTR”.