Detection of indoxyl sulfate levels in dogs and cats suffering from naturally occurring kidney diseases

• Plasma concentrations of indoxyl sulfate (IS), a protein-bound uraemic toxin, are correlated with renal disease severity.
• Plasma IS concentrations of dogs and cats were determined by HPLC with a fluorescence detector.
• Both azotaemic dogs and cats had significantly higher plasma IS levels than non-azotaemic controls.
• The plasma IS level was significantly correlated with BUN, serum creatinine and phosphate levels.
• The IS concentration increased gradually as CKD severity increased, with the highest level in IRIS stage 4.

Indoxyl sulfate (IS), a protein-bound uraemic toxin, has been found to accumulate in the serum of people with renal diseases and is associated with free radical induction, nephrotoxicity cardiovascular toxicity, and osteoblast cytotoxicity. Although IS has been studied in humans and in experimental models, the role of IS in dogs and cats with kidney disease has not been investigated. A high performance liquid chromatography system was applied to detect plasma IS concentrations in non-azotaemic animals (63 dogs, 16 cats) and in animals with renal azotaemia (66 dogs, 69 cats).The IS levels of azotaemic animals were significantly higher (P < 0.01) than those of non-azotaemic animals (median [IQR] 20.4 (9.5) mg/L vs. 7.2 (8.8) mg/L for dogs; median [IQR] 21 (18.9) mg/L vs. 14.8 (12.3) mg/L for cats). The IS level was significantly correlated with blood urea nitrogen, serum creatinine and phosphate concentrations. Dogs with acute kidney injury had significantly higher IS levels (P < 0.01) than those with chronic kidney diseases (CKD) (median [IQR] 57.7 (40.8) mg/L vs. 17.7 (25.1) mg/L). When CKD was graded using the International Renal Interest Society (IRIS) staging system, IS levels were correlated with CKD severity in both dogs and cats. The IS concentration is directly related to loss of renal function. Further studies are necessary to determine whether measurement of IS provides any additional diagnostic or prognostic information in dogs and cats with kidney disease.