Pharmacological Potential of Cafestol, a Bioactive Substance in Coffee, in Preventing Ischemia-Reperfusion-Induced Acute Kidney Injury

Renal ischemia-reperfusion (I/R) is the leading cause of acute kidney injury (AKI) and is a relevant complication of kidney transplantation. This work evaluated whether a single dose of cafestol (CAF) prevents I/R-induced AKI. We randomly divided male Wistar rats (180-220 g) into sham-operated groups (CTRL) or I/R surgery groups (I/R), which received either CAF 50 mg/kg or 75 mg/kg orally 2 h before the I/R procedure. During 24 h of reperfusion, rats were placed in metabolic cages for urine collection. The rats were euthanized, blood and urine were stored for renal function analyses, and the kidneys were collected for biochemical and histological studies. The I/R rats developed AKI, as evidenced by kidney damage (space between tubules, glomerular segmentation, and marked collagen accumulation throughout the renal tissue) and a decline in function and Na⁺ handling: proteinuria (120% increase), elevated plasma urea nitrogen (40%) and plasma creatinine (66%), and reduced fractional Na⁺ excretion (39%). These observations were associated with a 52% reduction in HIF-1α protein content and a 357% increase in matrix metalloproteinase (MMP)-9 activity. CAF decreased the urine volume and glomerulus area but increased MMP-9 protein content in CTRL. The treatment with CAF (75 mg/kg) prevented the impairment of renal function, alteration of cortical Na⁺ transporters, and the fibrotic changes caused by the I/R process. In conclusion, while the data revealed potential side effects associated with the treatment, CAF proved effective in mitigating the alterations induced by the I/R process.