Protecting the Microvasculature

Norman, Jill T.

doi:10.1681/asn.2006070741

Cited by 5 publications

(6 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Histologic analysis of chronically scarred kidneys reveals the loss of microvasculature in the fibrotic bands of collagen and ECM ( Norman, 2006 ). The hypovascularised and hypoperfused regions are formed after the initial ischemia-reperfusion injury.…”

Section: Impact Of Iri On Renal Graft Survival: Hypothesis and Mechanmentioning

confidence: 99%

Ischemia-Reperfusion Injury Reduces Long Term Renal Graft Survival: Mechanism and Beyond

et al. 2018

View full text Add to dashboard Cite

Ischemia-reperfusion injury (IRI) during renal transplantation often initiates non-specific inflammatory responses that can result in the loss of kidney graft viability. However, the long-term consequence of IRI on renal grafts survival is uncertain. Here we review clinical evidence and laboratory studies, and elucidate the association between early IRI and later graft loss. Our critical analysis of previous publications indicates that early IRI does contribute to later graft loss through reduction of renal functional mass, graft vascular injury, and chronic hypoxia, as well as subsequent fibrosis. IRI is also known to induce kidney allograft dysfunction and acute rejection, reducing graft survival. Therefore, attempts have been made to substitute traditional preserving solutions with novel agents, yielding promising results.

show abstract

Section: Impact Of Iri On Renal Graft Survival: Hypothesis and Mechanmentioning

confidence: 99%

Ischemia-Reperfusion Injury Reduces Long Term Renal Graft Survival: Mechanism and Beyond

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Chronic renal damage after I/R injury is characterized by glomerulosclerosis, tubular interstitial fibrosis, and tubular atrophy [ 29 ] associated with loss of microvasculature [ 30 ]. In humans, patients that survived up to 5 years after transplant, a predominant finding on protocol biopsies is interstitial fibrosis/tubular atrophy [ 31 ], a finding that we also observed in I/R-injured chronic mice.…”

Section: Discussionmentioning

confidence: 99%

“…Loss of microvasculature, a typical finding in chronic interstitial renal damage [ 30 ], by causing chronic oxygen deprivation to the tubule-interstitial compartment, is one of the causes of loss of functional mass after renal I/R [ 28 ]. We indeed observed that macroscopically, I/R-injured chronic kidneys had a reduction in size and a shrunken appearance.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of heparanase protects against chronic kidney dysfunction following ischemia/reperfusion injury

et al. 2018

View full text Add to dashboard Cite

Renal ischemia/reperfusion (I/R) injury occurs in patients undergoing renal transplantation and with acute kidney injury and is responsible for the development of chronic allograft dysfunction as characterized by parenchymal alteration and fibrosis. Heparanase (HPSE), an endoglycosidase that regulates EMT and macrophage polarization, is an active player in the biological response triggered by ischemia/reperfusion (I/R) injury.I/R was induced in vivo by clamping left renal artery for 30 min in wt C57BL/6J mice. Animals were daily treated and untreated with Roneparstat (an inhibitor of HPSE) and sacrificed after 8 weeks. HPSE, fibrosis, EMT-markers, inflammation and oxidative stress were evaluated by biomolecular and histological methodologies together with the evaluation of renal histology and measurement of renal function parameters.8 weeks after I/R HPSE was upregulated both in renal parenchyma and plasma and tissue specimens showed clear evidence of renal injury and fibrosis. The inhibition of HPSE with Roneparstat-restored histology and fibrosis level comparable with that of control. I/R-injured mice showed a significant increase of EMT, inflammation and oxidative stress markers but they were significantly reduced by treatment with Roneparstat. Finally, the inhibition of HPSE in vivo almost restored renal function as measured by BUN, plasma creatinine and albuminuria.The present study points out that HPSE is actively involved in the mechanisms that regulate the development of renal fibrosis arising in the transplanted organ as a consequence of ischemia/reperfusion damage. HPSE inhibition would therefore constitute a new pharmacological strategy to reduce acute kidney injury and to prevent the chronic pro-fibrotic damage induced by I/R.

show abstract

“…Medullary blood flow is <10% of total renal blood flow (RBF), and so tight regulation of the medullary microcirculation is essential for the preservation of normal kidney function. An increase in net MBF would result in 'washout' of the cortico-medullary osmotic gradient (Cowley 1997) and impaired urinary concentrating ability, whereas a sustained decrease in MBF would inevitably lead to ischaemia, which, depending on the severity and duration, could result in tissue (papillary) necrosis, scarring and chronic kidney injury (Fine et al 2000, Nangaku 2006, Norman 2006.…”

Section: Physiological Regulation Of Medullary Blood Flowmentioning

confidence: 99%

“…An increase in net MBF would result in ‘washout’ of the cortico‐medullary osmotic gradient (Cowley ) and impaired urinary concentrating ability, whereas a sustained decrease in MBF would inevitably lead to ischaemia, which, depending on the severity and duration, could result in tissue (papillary) necrosis, scarring and chronic kidney injury (Fine et al . , Nangaku , Norman ).…”

Section: Physiological Regulation Of Medullary Blood Flowmentioning

confidence: 99%

Renal pericytes: regulators of medullary blood flow

et al. 2012

View full text Add to dashboard Cite

Regulation of medullary blood flow (MBF) is essential in maintaining normal kidney function. Blood flow to the medulla is supplied by the descending vasa recta (DVR), which arise from the efferent arterioles of juxtamedullary glomeruli. DVR are composed of a continuous endothelium, intercalated with smooth muscle-like cells called pericytes. Pericytes have been shown to alter the diameter of isolated and in situ DVR in response to vasoactive stimuli that are transmitted via a network of autocrine and paracrine signalling pathways. Vasoactive stimuli can be released by neighbouring tubular epithelial, endothelial, red blood cells and neuronal cells in response to changes in NaCl transport and oxygen tension. The experimentally described sensitivity of pericytes to these stimuli strongly suggests their leading role in the phenomenon of MBF autoregulation. Because the debate on autoregulation of MBF fervently continues, we discuss the evidence favouring a physiological role for pericytes in the regulation of MBF and describe their potential role in tubulo-vascular cross-talk in this region of the kidney. Our review also considers current methods used to explore pericyte activity and function in the renal medulla.

show abstract

Protecting the Microvasculature

Cited by 5 publications

References 28 publications

Ischemia-Reperfusion Injury Reduces Long Term Renal Graft Survival: Mechanism and Beyond

Ischemia-Reperfusion Injury Reduces Long Term Renal Graft Survival: Mechanism and Beyond

Inhibition of heparanase protects against chronic kidney dysfunction following ischemia/reperfusion injury

Renal pericytes: regulators of medullary blood flow

Contact Info

Product

Resources

About