Pathophysiology of unilateral ischemia-reperfusion injury: importance of renal counterbalance and implications for the AKI-CKD transition.

Unilateral ischemia-reperfusion (UIR) injury leads to progressive renal atrophy and tubulointerstitial fibrosis (TIF) and is commonly used to investigate the pathogenesis of the acute kidney injury-chronic kidney disease transition. Although it is well known that contralateral nephrectomy (CNX), even 2 wk post-UIR injury, can improve recovery, the physiological mechanisms and tubular signaling pathways mediating such improved recovery remain poorly defined. Here, we examined the renal hemodynamic and tubular signaling pathways associated with UIR injury and its reversal by CNX.

Autoregulatory Efficiency Assessment in Kidneys Using Deep Learning.

A convolutional deep neural network is employed to assess renal autoregulation using time series of arterial blood pressure and blood flow rate measurements in conscious rats. The network is trained using representative data samples from rats with intact autoregulation and rats whose autoregulation is impaired by the calcium channel blocker amlodipine. Network performance is evaluated using test data of the types used for training, but also with data from other models for autoregulatory impairment, including different calcium channel blockers and also renal mass reduction.

BP Fluctuations and the Real-Time Dynamics of Renal Blood Flow Responses in Conscious Rats.

Background: Renal autoregulation maintains stable renal function despite BP fluctuations and protects glomerular capillaries from hypertensive injury. However, real-time dynamics of renal autoregulation in conscious animals have not been characterized.

Methods: To develop novel analytic methods for assessing renal autoregulation, we recorded concurrent BP and renal blood flow in conscious rats, comparing animals with renal autoregulation that was intact versus impaired (from 3/4 nephrectomy), before and after additional impairment (from the calcium channel blocker amlodipine).

Glomerulosclerosis in the diet-induced obesity model correlates with sensitivity to nitric oxide inhibition but not glomerular hyperfiltration or hypertrophy.

The diet-induced obesity (DIO) model is frequently used to examine the pathogenesis of obesity-related pathologies; however, only minimal glomerulosclerosis (GS) has been reported after 3 mo. We investigated if GS develops over longer periods of DIO and examined the potential role of hemodynamic mechanisms in its pathogenesis. Eight-week-old male obesity-prone (OP) and obesity-resistant (OR) rats (Charles River) were administered a moderately high-fat diet for 5 mo.

Failed Tubule Recovery, AKI-CKD Transition, and Kidney Disease Progression.

The transition of AKI to CKD has major clinical significance. As reviewed here, recent studies show that a subpopulation of dedifferentiated, proliferating tubules recovering from AKI undergo pathologic growth arrest, fail to redifferentiate, and become atrophic. These abnormal tubules exhibit persistent, unregulated, and progressively increasing profibrotic signaling along multiple pathways.