#3950 EFFECT OF DEHYDRATION, HYPERTENSION, RENAL MASS REDUCTION AND AGE ON TRIPLE WHAMMY-ACUTE KIDNEY INJURY
Authors: Alonso Eva María Baranda , Diaz-Morales Noelia , Sidhu-Muñoz Rebeca , Martinez Sandra M Sancho , Fuentes-Calvo Isabel , Lopez-Hernandez Francisco J , Salgado Carlos Martinez 
Published: June 2023

Abstract

Background and Aims
Renin-angiotensin system inhibitors, diuretics and non-steroidal anti-inflammatory drugs (NSAIDs) is known as Triple Whammy (TW), a common combination used in hypertensive patients suffering from pain or inflammation; this combination of drugs can cause in some cases acute kidney injury (AKI). The renal outcome of the TW therapy seems to be influenced by additional factors, as the incidence of TW-induced AKI ranges from &lt;1% to up to 22% depending on the study. The incidence of TW-AKI is higher among older adults, therefore age and other clinical conditions such as dehydration could be associated with TW-AKI. Furthermore, loss of functional nephrons in chronic kidney disease is a risk or predisposing factor for new AKI episodes. Consequently, the aim of our study was to analyse in vivo the influence of dehydration, age, renal mass reduction and hypertension (HTA) in TW therapy-induced AKI.

Method
Five experimental groups were subjected to TW therapy: (1) control group (3 months old Wistar rats); (2) dehydrated rats (3 months old Wistar rats with 60-70% water restriction); (3) aged rats (16 month old Wistar rats); (4) renal mass reduction (RMR) rats (3 months old Wistar rats with a 5/6 reduction of renal mass one month before the experiment); and (5) 3 months old spontaneously hypertensive rats). All rats received antihypertensive double therapy with Trandolapril in water and Furosemide i.p. for 4 days, and then a triple therapy for 2 days with Trandolapril and Ibuprofen in drinking water and Furosemide i.p. Blood and urine samples were collected at baseline (B), after 4 days of double therapy (day 4) and two days after triple therapy (day 6). Renal outcomes of the TW therapy were analysed by plasma creatinine, creatinine clearance, plasma urea and proteinuria.

Results
Risk factors such as dehydration or the loss of nephrons significantly increase plasma creatinine and urea and reduce creatinine clearance at day 6 compared to 3 months old Wistar rats without risk factors. Creatinine clearance is significantly reduced at day 4 in RMR and dehydration groups. Also, the RMR group shows at baseline and day 4 decreased creatinine clearance and increased plasma creatinine and urea than 3 months old Wistar rats. Proteinuria values are within normal ranges (&lt; 10mg/day) in all experimental groups.

Conclusion
Renal mass reduction and dehydration are important risk factors in the development of AKI after TW therapy, while hypertension and age do not seem to influence renal outcomes. The knowledge of the specific conditions and the different factors that increase the risk of developing AKI in patients undergoing TW therapy will help us to stratify these patients based on their individual risk and to apply in each case the appropriate individualized treatment.
This research was funded by grants from Instituto de Salud Carlos III (ISCIII) PI21/00548 and PI21/01226 co-funded by the European Union and Red de Investigación Renal RICORS2040 (Kidney Disease), RD21/0005/0004 co-funded by the European Union – NextGenerationEU, Mecanismo para la Recuperación y la Resiliencia (MRR). Eva M. Baranda-Alonso is recipient of a predoctoral fellowship from the Junta de Castilla y Leon (Spain) and the European Social Fund from the European Commission.Noelia Diaz-Morales is recipient of a Juan de la Cierva-Formación postdoctoral contract (FJC2020-043205-I) funded by MCIN/AEI/10.13039/501100011033 and European Union “NextGenerationEU/PRTR”.