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Browsing by Subject "Renal reserve"

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    Impaired hemodynamic renal reserve response following recovery from established acute kidney injury and improvement by hydrodynamic isotonic fluid delivery
    (American Physiological Society, 2024) Ullah, Md Mahbub; Collett, Jason A.; Bacallao, Robert L.; Basile, David P.; Anatomy, Cell Biology and Physiology, School of Medicine
    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.
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    Quantifying Glomerular Filtration Rates in Acute Kidney Injury: A Requirement for Translational Success
    (Elsevier, 2016-01) Molitoris, Bruce A.; Reilly, Erinn; Department of Medicine, IU School of Medicine
    Acute kidney injury (AKI) remains a vexing clinical problem that results in unacceptably high patient mortality, development of chronic kidney disease, and accelerated progression to end-stage kidney disease. Although clinical risks factors for developing AKI have been identified, there is no reasonable surveillance technique to definitively and rapidly diagnose and determine the extent of severity of AKI in any patient. Because patient outcomes correlate with the extent of injury, and effective therapy likely requires early intervention, the ability to rapidly diagnose and stratify patients by their level of kidney injury is paramount for translational progress. Many groups are developing and characterizing optical measurement techniques using novel minimally invasive or noninvasive techniques that can quantify kidney function independent of serum or urinary measurements. The use of both one- and two-compartment models, as well as continuous monitoring, are being developed. This review documents the need for glomerular filtration rate measurement in AKI patients and discusses the approaches being taken to deliver this overdue technique that is necessary to help propel nephrology to individualization of care and therapeutic success.
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    Rethinking CKD Evaluation: Should We Be Quantifying Basal or Stimulated GFR to Maximize Precision and Sensitivity?
    (Elsevier, 2017-05) Molitoris, Bruce A.; Medicine, School of Medicine
    Chronic kidney disease (CKD) is an increasing clinical problem. Although clinical risk factors and biomarkers for the development and progression of CKD have been identified, there is no commercial surveillance technology to definitively diagnose and quantify the severity and progressive loss of glomerular filtration rate (GFR) in CKD. This has limited the study of potential therapies to late stages of CKD when FDA-registerable events are more likely. Because patient outcomes, including the rate of CKD progression, correlate with disease severity and effective therapy may require early intervention, being able to diagnose and stratify patients by their level of decreased kidney function early on is key for translational progress. In addition, renal reserve, defined as the increase in GFR following stimulation, may improve the quantification of GFR based solely on basal levels. Various groups are developing and characterizing optical measurement techniques using new minimally invasive or noninvasive approaches for quantifying basal and stimulated kidney function. This development has the potential to allow widespread individualization of therapy at an earlier disease stage. Therefore, the purposes of this review are to suggest why quantifying stimulated GFR, by activating renal reserve, may be advantageous in patients and to review fluorescent technologies to deliver patient-specific GFR.
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