#3937 URINARY EXCRETION OF LIVER-TYPE FATTY ACID-BINDING PROTEIN DETECTS KIDNEY HISTOLOGICAL ALTERATIONS DURING PROGRESSIVE RENAL FIBROSIS
Authors: del Valle Mercado Hernández Joana , Martinez Sandra M Sancho , Fuentes-Calvo Isabel , Lopez-Hernandez Francisco J , Salgado Carlos Martinez 
Published: June 2023

Abstract

Background and Aims
Subclinical sequelae of acute kidney injury (AKI) are commonly associated with the development of chronic kidney disease (CKD). Despite extensive investigation on AKI to CKD transition on different experimental models, the underlying mechanisms of this transition remain unclear, and there are no known biomarkers monitoring this transition to CKD. The liver-type fatty acid-binding protein (L-FABP) is expressed in the kidney under normal and pathological conditions, and seems to play an important role on kidney injury and repair. We evaluated the efficacy of urinary L-FABP excretion as a prognostic indicator of the progression of renal damage in our AKI to CKD experimental model.

Method
8 week old male Wistar rats were divided in two experimental groups: “Control” group (n = 8): SHAM-operated rats, which received saline solution i.p; and Cpt-IR2 group (n = 8): 5 mg/kg cisplatin i.p and 2 weeks after renal function normalization, 60 min ischemia-reperfusion on the left kidney. Blood and urine samples were collected at day 0 (basal), day 4 (AKI development), day 8 (normalized renal function), day 24 (1 day after ischemia), and 2 (M2) and 3 (M3) months after first AKI induction. Renal function was estimated analysing by colorimetric methods plasma and urinary creatinine concentrations (pCr and uCr) and creatinine clearance. Animals were sacrificed at days 56 and 90. Tissue samples were stained with haematoxylin-Eeosin, periodic acid Schiff and Masson's Trichrome for histological analysis. Enzyme-linked immunosorbent assay was used to measure urinary L-FABP concentration.

Results
Cpt-IR2 rats showed a reduction in renal filtration with respect to control rats even though this decrease does not indicate a severe decline in renal function. This group also presented multiple histological alterations such as fibrosis, loss of brush border membrane, inflammatory infiltrates, basement membrane thickening, tubular dilatation, cellular debris and hyaline casts that worsen markedly from M2 to M3. uL-FABP was greater in Cpt-IR2 rats (52,299 ± 8,407 ng/g uCr M2 and 23,427 ± 4,778 ng/g uCr M3) than in control rats (16,657 ± 2,322 ng/g uCr M2 and 10,636 ± 1,395 ng/g uCr), but this urinary excretion does not correlate with the histological alterations in the last month of the study.

Conclusion
Urinary L-FABP may be a potential biomarker for the detection of the presence of histological damage although it is not correlated with the extent and degree of the damage in our AKI to CKD transition model. 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). Joana Mercado-Hernández is recipient of a predoctoral fellowship from the Junta de Castilla y Leon (Spain) and the European Social Fund from the European Commission.