Table 2.

Preclinical studies to investigate the effects of PHD inhibitors on the progression of various models of CKD

CKD ModelApproach for HIF Activation/InhibitionWhich HIF Was Activated/InhibitedOutcomesHIF Protective or DeleteriousReference
5/6 NephrectomyCobalt for 4 wk, starting 5 wk after the surgeryHIF-1 and HIF-2 activatedTubulointerstitial injury ↓, serum creatinine ↓Protective(87)
Uninephrectomized Thy-1 nephritisCobalt for 3 wk, starting a wk after Thy-1 injectionHIF-1 and HIF-2 activatedTubulointerstitial injury ↓Protective(88)
Glomerular injury was not affected
STZ-induced diabetesCobalt for 4 wk, starting right after the induction of diabetesHIF-1 and HIF-2 activatedTubulointerstitial injury ↓, proteinuria ↓Protective(89)
Adenine-induced nephropathyPHD inhibitors (ICA or roxadustat) for 3 wk, coadministered with adenineHIF-1 and HIF-2 activatedProteinuria ↓, plasma creatinine ↓, tubulointerstitial damage ↓, fibrosis →Protective(90)
5/6 Nephrectomy(1) l-Mimosine from 2 to 12 wk after the surgeryHIF-1 and HIF-2 activated(1) Exacerbated glomerular and tubulointerstitial injuryDepends on timing(95)
(2) l-Mimosine from 4 to 12 wk after the surgery(2) Ameliorated glomerular and tubulointerstitial injury
(3) l-Mimosine from 8 to 12 wk after the surgery(3) No effects
  • PHD, prolyl-hydroxylase domain; HIF, hypoxia-inducible factor; STZ, streptozotocin; ICA, 2-(1-chloro-4-hydroxy isoquinoline-3-carboxamido) acetate.