Evaluation of Urinary Big Endothelin-1 in Feline Spontaneous CKD

SIMPLE SUMMARY: Chronic kidney disease is a common and progressive disease of elderly cats. It is a cause of pet suffering and owner expense. Biologic biomarkers for early diagnosis and for noninvasive evaluation of kidney damage are certainly useful in both research and clinical practice. In this study, we evaluated the biomarker big endotelin-1 in the urine of cats affected with chronic kidney disease. Big endothelin-1 is molecule linked to inflammation and pressure regulation, and it was not previously evaluated in nephropathic cats. We found that urinary big endothelin was increased in patients at late stage of the disease and in patients with proteinuria (a marker of kidney damage). Despite that, big endothelin 1 seemed not to be a useful biomarker for disease progression. According to results of this preliminary study, we suggest this biomarker for future research on feline kidney disease. ABSTRACT: The endothelin-1 (ET-1) system has been implicated in the development and progression of chronic kidney disease (CKD). No information on big ET-1 in feline urine is available. The purpose of this study was to evaluate if urinary big endothelin-1 (bigET-1) is associated with feline CKD. Sixty urine samples were prospectively collected from 13 healthy cats at risk of developing CKD and 22 cats with CKD of different International Renal Interest Society (IRIS) stages (1–4). Urinary bigET-1 was measured using a commercially available ELISA. BigET-1 normalized to urine creatinine (bigET-1:UC) was compared amongst stages and substages, as proposed by IRIS, and correlated with serum creatinine concentration, proteinuria and blood pressure. BigET-1:UC at the time of inclusion was compared between cats that remained stable and cats that progressed after 12 months. BigET-1:UC was significantly higher (p = 0.002) in cats at IRIS stages 3–4 (median: 21.9; range: 1.88–55.6), compared to all other stages, and in proteinuric (n = 8, median: 11.0; range: 0.00–46.4) compared with nonproteinuric cats (n = 38 median: 0.33; range: 0.00–55.6) (p = 0.029). BigET-1:UC was not associated with CKD progression. Urinary bigET-1 increased in advanced stages of CKD and in proteinuric patients, suggesting that ET-1 may be indicative of the severity of feline CKD.