Conversion to Sirolimus Ameliorates Cyclosporine-Induced Nephropathy in the Rat : Focus on Serum, Urine, Gene, and Protein Renal Expression Biomarkers

Abstract EN

Protocols of conversion from cyclosporin A (CsA) to sirolimus (SRL) have been widely used in immunotherapy after transplantation to prevent CsA-induced nephropathy, but the molecular mechanisms underlying these protocols remain nuclear.

This study aimed to identify the molecular pathways and putative biomarkers of CsA-to-SRL conversion in a rat model.

Four animal groups (n=6) were tested during 9 weeks: control, CsA, SRL, and conversion (CsA for 3 weeks followed by SRL for 6 weeks).

Classical and emergent serum, urinary, and kidney tissue (gene and protein expression) markers were assessed.

Renal lesions were analyzed in hematoxylin and eosin, periodic acid-Schiff, and Masson’s trichrome stains.

SRL-treated rats presented proteinuria and NGAL (serum and urinary) as the best markers of renal impairment.

Short CsA treatment presented slight or even absent kidney lesions and TGF-β, NF-κβ, mTOR, PCNA, TP53, KIM-1, and CTGF as relevant gene and protein changes.

Prolonged CsA exposure aggravated renal damage, without clear changes on the traditional markers, but with changes in serums TGF-β and IL-7, TBARs clearance, and kidney TGF-β and mTOR.

Conversion to SRL prevented CsA-induced renal damage evolution (absent/mild grade lesions), while NGAL (serum versus urine) seems to be a feasible biomarker of CsA replacement to SRL.