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 acute kidney injury (AKI) and could be used to identify impaired renal function in the face of restored glomerular filtration rate (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 wk. Some rats were treated 24 h 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 that received saline through the vena cava (AKI-VC). At 5 wk after 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, whereas the RBF response to l-arginine was significantly reduced in AKI-VC rats relative to sham rats (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 rats. Capillary rarefaction observed in AKI-VC rats was significantly protected in AKI-HIFD rats. There was also a significant increase in T helper 17 cell infiltration and interstitial fibrosis in AKI-VC rats versus sham rats, 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. NEW & NOTEWORTHY: Despite the apparent recovery of renal filtration function following acute kidney injury (AKI) in rats, the renal hemodynamic reserve response is significantly attenuated, suggesting that clinical evaluation of this parameter may provide information on the potential development of chronic kidney disease. Treatments such as hydrodynamic isotonic fluid delivery, or other treatments in the early post-AKI period, could minimize chronic inflammation or loss of microvessels with the potential to promote a more favorable outcome on long-term function.