Evaluation of hypoxia-inducible factor-1α and urine non-transferrin-bound iron concentrations in cats with chronic kidney disease.

Abstract

INTRODUCTION: Hypoxia-inducible factors (HIF) regulate gene transcription, which aids hypoxia adaptation while promoting renal fibrosis. Non-transferrin-bound iron (NTBI) is a catalytic form of iron that can lead to oxidative damage. However, NTBI in cat biofluids has rarely been evaluated. AIMS: We assessed cat plasma and urine HIF-1&#x3b1; (pHIF-1&#x3b1;/uHIF-1&#x3b1;) concentrations and urine NTBI (uNTBI) concentrations to investigate their relationship with chronic kidney disease (CKD) severity. METHODS: pHIF-1&#x3b1; and uHIF-1&#x3b1; concentrations were measured using commercial ELISA kits, while uNTBI concentrations were detected by inductively coupled plasma mass spectrometry. RESULTS: Healthy cats (&#x202f;=&#x202f;35) and cats with CKD (&#x202f;=&#x202f;84) formed the study cohorts. pHIF-1&#x3b1; concentrations increased from 9.48&#x202f;pg./mL (median) in the healthy cohort to 11.42&#x202f;pg./mL in early-stage CKD cats but decreased to 8.50&#x202f;pg./mL in late-stage CKD cats. uHIF-1&#x3b1; concentrations gradually decreased with a significant difference between the control group (44.61&#x202f;pg./mL) and the late-stage CKD group (36.79&#x202f;pg./mL,&#x202f;<&#x202f;0.001). Cats with proteinuria had significantly higher uNTBI concentrations (35.61&#x202f;ppb) than non-proteinuric cats (25.13&#x202f;ppb,&#x202f;=&#x202f;0.019). Finally, the concentrations of pHIF-1&#x3b1; and uHIF-1&#x3b1; were positively correlated independent of renal function. CONCLUSION AND CLINICAL IMPORTANCE: Overall, pHIF-1&#x3b1; and uHIF-1&#x3b1; concentrations are lower in advanced CKD cats, while uNTBI concentrations are significantly higher in proteinuric cats.