Impaired hemodynamic renal reserve response following recovery from established acute kidney injury and improvement by hydrodynamic isotonic fluid delivery

Abstract

Renal reserve capacity may be compromised following recovery from AKI and could be used to identify impaired renal function in the face of restored GFR or plasma creatinine. To investigate the loss of hemodynamic renal reserve responses following recovery in a model of AKI, rats were subjected to left unilateral renal ischemia reperfusion (I/R) injury and contralateral nephrectomy and allowed to recover for 5 weeks. Some rats were treated 24 hours post I/R, by hydrodynamic isotonic fluid delivery (AKI-HIFD) of saline through the renal vein, previously shown to improve recovery and inflammation relative to control rats receiving saline through the vena cava (AKI-VC). At 5 weeks post-surgery, plasma creatinine and GFR recovered to levels observed in uninephrectomized sham-controls. Baseline renal blood flow (RBF) was not different between AKI or sham groups, but infusion of L-arginine (7.5 mg/kg/min) significantly increased RBF in sham controls, while the RBF response to L-Arg was significantly reduced in AKI-VC rats relative to sham (22.6 ± 2.2% vs 13.8±1.8%; p<0.05). RBF responses were partially protected in AKI-HIFD rats relative to AKI-VC rats (17.0 ±2.2%) and were not significantly different from sham. Capillary rarefaction observed in AKI-VC rats was significantly protected in AKI-HIFD rats. There was also a significant increase in Th17 cell infiltration and interstitial fibrosis in AKI-VC rats vs sham, which was not present in AKI-HIFD rats. These data suggest that recovery from AKI results in impaired hemodynamic reserve and that associated CKD progression may be mitigated by HIFD in the early post AKI period.