Preservation of peritubular capillary endothelial integrity and increasing pericytes may be critical to recovery from postischemic acute kidney injury

Decreased renal blood flow following an ischemic insult contributes to a reduction in glomerular filtration. However, little is known about the underlying cellular or subcellular mechanisms mediating reduced renal blood flow in human ischemic acute kidney injury (AKI) or acute renal failure (ARF). To examine renal vascular injury following ischemia, intraoperative graft biopsies were performed after reperfusion in 21 cadaveric renal allografts. Confocal fluorescence microscopy was utilized to examine vascular smooth muscle and endothelial cell integrity as well as peritubular interstitial pericytes in the biopsies. The reperfused, transplanted kidneys exhibited postischemic injury to the renal vasculature, as demonstrated by disorganization/disarray of the actin cytoskeleton in vascular smooth muscle cells and disappearance of von Willebrand factor from vascular endothelial cells. Damage to peritubular capillary endothelial cells was more severe in subjects destined to have sustained ARF than in those with rapid recovery of their graft function. In addition, peritubular pericytes/myofibroblasts were more pronounced in recipients destined to recover than those with sustained ARF. Taken together, these data suggest damage to the renal vasculature occurs after ischemia-reperfusion in human kidneys. Preservation of peritubular capillary endothelial integrity and increasing pericytes may be critical to recovery from postischemic AKI.

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Faculty Opinions recommendation of Preservation of peritubular capillary endothelial integrity and increasing pericytes may be critical to recovery from postischemic acute kidney injury.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1122905.580002 ◽

2008 ◽

Author(s):

Seymour Rosen

Keyword(s):

Acute Kidney Injury ◽

Kidney Injury ◽

Peritubular Capillary ◽

Endothelial Integrity

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P0544INHIBITION OF 15-HYDROXYPROSTAGLANDIN DEHYDROGENASE (15-PGDH) PROTECTS MICE AGAINST CONTRAST-INDUCED ACUTE KIDNEY INJURY

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p0544 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Byeong Woo KIm ◽

Sun hee Kim ◽

Ki beom Bae

Keyword(s):

Acute Kidney Injury ◽

Blood Flow ◽

Protective Effect ◽

Renal Blood Flow ◽

Smooth Muscle Actin ◽

Kidney Injury ◽

Plasma Creatinine ◽

Histological Evaluation ◽

Vehicle Group ◽

Before And After

Abstract Background and Aims Although the mechanism of contrast-induced acute kidney injury (CI-AKI) is not fully known, the imbalance of vasoconstrictive and vasodilative mediators plays a major role. Prostaglandin E2 (PGE2) is one of the vasodilators involved in this process. Inhibition of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) causes elevation of PGE2 level in tissue by delaying the rapid degradation of PGE2 by the enzyme. We tested the hypothesis that the 15-PGE2 inhibitor would protect against CI-AKI in a mouse model and attempted to elucidate the mechanism involved. Method 10-week aged male C57/BL6 Mice were injected with 10gI/kg of iodixanol by tail vein. Renal blood flow measurement, right nephrectomy, and blood sampling were taken at 48 hours after iodixanol injection. The 15-PGDH inhibitor was injected before and after iodixanol administration. Plasma creatinine, NGAL, KIM-1 were measured as biomarkers for renal function. Histological evaluation was analyzed by the necrosis scoring system and TUNEL assay. Arteriolar area of outer medulla was analyzed by α-smooth muscle actin stain. Renal blood flow was measured by the non-invasive laser doppler. Results Plasma creatinine (1.94±0.75 vs 1.11±0.44 mg/dL, p=0.005), NGAL (299.7±115.87 vs 140.4±76.56 ng/mL, p=0.004), and KIM-1 (2.09±2.34 vs 0.43±0.89 ng/mL, p=0.024) levels were significantly lower when the 15-PGDH inhibitor was injected before and after iodixanol administration than the vehicle group. But no significant renal protective effect was shown when the 15-PGDH inhibitor was injected before or after iodixanol administration. The 15-PGDH inhibitor administration before and after iodixanol injection showed a significantly wider renal arteriolar area (683.63±248.46 vs 1132.97±357.46 μm2, p=0.039) and larger renal blood flow (360.0±49.72 vs 635.1±27.20, p=0.011) than vehicle administration. Conclusion The 15-PGDH inhibitor has a renal protective effect against CI-AKI in mice by increasing renal blood flow when injected intravenously before and after iodine contrast media administration.

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Renal blood flow and acute kidney injury in septic shock: an arduous conflict that smolders intrarenally?

Kidney International ◽

10.1016/j.kint.2016.03.025 ◽

2016 ◽

Vol 90 (1) ◽

pp. 22-24 ◽

Cited By ~ 8

Author(s):

Patrick M. Honore ◽

Rita Jacobs ◽

Elisabeth De Waele ◽

Marc Diltoer ◽

Herbert D. Spapen

Keyword(s):

Septic Shock ◽

Acute Kidney Injury ◽

Blood Flow ◽

Renal Blood Flow ◽

Kidney Injury

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Acute kidney injury in sepsis: Is renal blood flow more than just an innocent bystander?

Intensive Care Medicine ◽

10.1007/s00134-007-0735-7 ◽

2007 ◽

Vol 33 (9) ◽

pp. 1498-1500 ◽

Cited By ~ 10

Author(s):

Martin Matejovic ◽

Peter Radermacher ◽

Michael Joannidis

Keyword(s):

Acute Kidney Injury ◽

Blood Flow ◽

Renal Blood Flow ◽

Kidney Injury ◽

Innocent Bystander

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Renal Blood Flow Redistribution During Acute Kidney Injury

American Journal of Kidney Diseases ◽

10.1053/j.ajkd.2010.03.035 ◽

2010 ◽

Vol 56 (4) ◽

pp. 785-787 ◽

Cited By ~ 3

Author(s):

Filippo Mangione ◽

Valeria Calcaterra ◽

Ciro Esposito ◽

Antonio Dal Canton

Keyword(s):

Acute Kidney Injury ◽

Blood Flow ◽

Renal Blood Flow ◽

Kidney Injury ◽

Blood Flow Redistribution

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Measuring renal blood flow in acute kidney injury

Critical Care Medicine ◽

10.1097/ccm.0b013e31824c900c ◽

2012 ◽

Vol 40 (6) ◽

pp. 1972-1973

Author(s):

Jean-Sebastien Rachoin

Keyword(s):

Acute Kidney Injury ◽

Blood Flow ◽

Renal Blood Flow ◽

Kidney Injury

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Contrast-induced acute kidney injury

10.1093/med/9780199592548.003.0246 ◽

2015 ◽

Author(s):

Douglas Stewart ◽

Gaurav Shah ◽

Jeremiah R. Brown ◽

Peter A. McCullough

Keyword(s):

Acute Kidney Injury ◽

Blood Flow ◽

Renal Blood Flow ◽

Kidney Injury ◽

Cell Dysfunction ◽

Transient Rise ◽

The Hours ◽

Proximal Tubular ◽

Contrast Exposure ◽

Considerable Damage

Contrast-induced acute kidney injury (CI-AKI) occurs because all forms of intravascular contrast contain iodine and their biochemical structures induce immediate changes in systemic and renal vasoreactivity. In the kidneys, contrast induces a transient decrease in renal blood flow. This is more pronounced in patients with chronic kidney disease and diabetes mellitus. The reduction in blood flow allows slowed transit of contrast and reabsorption by the proximal tubular cells where contrast is directly toxic resulting in tubular cell dysfunction and death. When there is considerable damage, a transient rise in serum creatinine and reduction in urine output will be observed in the hours to days after contrast exposure. Principles to reduce CI-AKI include limiting the amount of contrast used, intravascular volume expansion to maximize renal blood flow and speed transit of contrast, and possibly agents to reduce the oxidative damage caused by the contrast agents themselves.

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