Early kidney injury occurs in the absence of detectable perirenal adipose tissue remodelling in the Munich Wistar Frömter rat model of chronic kidney disease

Adipose tissue surrounding the kidney, known as perirenal adipose tissue (PRAT), is a metabolically active depot that may influence renal function through inflammatory and fibrotic mediators. In the Munich Wistar Frömter (MWF) rat, a genetic model of spontaneous chronic kidney disease (CKD), PRAT dysfunction has been described at 22 weeks but whether it is present at earlier stages related to the initiation of renal injury remains unclear. This study aimed to assess the temporal relationship between PRAT phenotype and renal injury in MWF rats. Male MWF and control Wistar rats were evaluated at 10 and 16 weeks. Renal injury was assessed by measuring proteinuria, tubular damage markers (Kim-1, Ngal), and using contrast-free magnetic resonance imaging (T1/T2 mapping, arterial spin labelling). PRAT was characterized for adipogenic, inflammatory, fibrotic and calcification-related markers. MWF rats exhibited significant proteinuria and elevated Kim-1 and Ngal expression at 10 weeks compared to age-matched Wistar rats. By 16 weeks, MWF kidneys showed progressive microstructural alterations (increased T1 and T2 relaxation times) and significantly reduced cortical blood flow, together with Tnf-α, Mcp-1 and Tgf-β upregulation compared to controls. In contrast, PRAT showed no significant age- or strain-related changes in major adipogenic, inflammatory, fibrotic and calcifying mediators. These findings suggest that the measured PRAT markers do not support overt PRAT remodelling before or during the early phase of renal injury. KEY POINTS: Perirenal adipose tissue (PRAT) is a metabolically active depot proposed to influence renal injury, but its temporal role in chronic kidney disease (CKD) initiation remains unclear. Using the Munich Wistar Frömter (MWF) rat model of spontaneous CKD, we assessed renal injury and PRAT status longitudinally at early ages. Renal damage was evident at 10 weeks in MWF rats, with increased proteinuria and tubular injury markers, and progressed by 16 weeks with microstructural magnetic resonance imaging alterations and reduced cortical perfusion. In contrast, PRAT showed no major adipogenic, inflammatory, fibrotic or calcifying remodelling at either age. These findings indicate that early renal injury occurs in the absence of detectable PRAT remodelling, suggesting that the measured PRAT markers do not support overt PRAT remodelling before or during the early phase of renal injury.