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Impaired Renal Autoregulation after Ischemia‐Reperfusion Results from Loss of Dynamic Stability Normally Conferred by Tubuloglomerular Feedback
Author(s) -
Thomson Scott C,
Pham Hai,
Bourgette Ryan,
Singh Prabhleen
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.739.15
Subject(s) - tubuloglomerular feedback , autoregulation , ischemia , renal blood flow , medicine , kidney , renal ischemia , hemodynamics , cardiology , blood flow , renal function , cerebral autoregulation , renal circulation , chemistry , endocrinology , blood pressure , reperfusion injury
Background Autoregulation of renal blood flow ( Q ) results from combined actions of myogenic (Myo) and tubuloglomerular feedback (TGF) systems. Surprisingly little is known about intra‐renal hemodynamics or autoregulation after acute kidney injury. Method We subjected rats (n=13) to renal ischemia‐reperfusion (IR, bilateral pedicle clamp × 1h) or sham ischemia. After 4 or 24 hrs, rats were re‐anesthetized (inactin) and 2‐hr recordings made of spontaneous left renal blood flow ( Q ) and arterial pressure ( BP ) while measuring 2‐kidney inulin clearance ( GFR ). We examined the dynamic relationship between Q and BP by two methods: First, we generated admittance spectra from short‐term Fourier transforms. This is a proven method for detecting TGF and Myo systems, which give respective resonance peaks at 0.03 and 0.15 Hz. Second, we generated autoregulatory step responses by applying the projection theorem to approximate Q as a linear sum of past BP and expressed the result as the fractional compensation following an idealized unit step in BP . The step response out‐performs spectral methods for quantifying the efficiency of autoregulation. Results Data from 4 and 24h were similar and are pooled. GFR was depressed after IR (0.5± 0.3 vs 2.1±0.3 ml/min, P<0.002) but Q was not (14.8±1.9 vs 13.6±2.0 ml/min, P=0.7). Spectral analysis detected Myo activity in both Sham and IR but detected TGF activity only in Sham. Step responses diverged during the 10–20s window where TGF normally contributes most. For BP disturbances lasting longer than 15s, fractional compensation was less by ~50% in IR vs Sham. Interpretation Q is rapidly restored after IR, while GFR remains low enough that BP fluctuations cannot produce a TGF signal, which derives from flow in the tubule. Without a contribution from TGF, overall autoregulatory efficiency is diminished and Q is susceptible to changes in BP . This has implications for how to manage patients recovering from acute kidney injury. Support or Funding Information Veterans Administration Research Service and UCSD‐UAB O'Brien Center for Acute Kidney Injury (P30‐DK‐79337).