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Unilateral renal ischaemia in rats induces a rapid secretion of inflammatory markers to renal lymph and increased capillary permeability
Author(s) -
Bivol Liliana Monica,
Iversen Bjarne Magnus,
Hultström Michael,
Wallace Paal William,
Reed Rolf Kåre,
Wiig Helge,
Tenstad Olav
Publication year - 2015
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jp271578
Subject(s) - kidney , lymph , renal ischemia , medicine , renal circulation , ischemia , renal blood flow , renal function , endocrinology , vascular permeability , inflammation , renal artery , pathology , reperfusion injury
Key points Transient reduction in renal blood flow results in inflammation and is a primary cause of acute kidney injury, thereby representing a major clinical problem. It is not known whether the inflammatory reaction is local only or part of a systemic response. We accessed the renal microenvironment through isolation of lymph and were in this way able to investigate whether the inflammatory reaction is local or systemic. Transient ischaemia followed by reperfusion resulted in a rapid production of inflammatory mediators locally in the renal interstitium. We moreover showed that the injury response affected the glomerular as well as the non‐glomerular barrier and resulted in a reduced size and charge selectivity of the glomerular capillaries.Abstract A better understanding of the inflammatory process associated with renal ischaemia–reperfusion (IR) injury may be clinically important. In this study we examined the role of the kidney in production of inflammatory mediators by analysing renal lymph after 30 min unilateral occlusion of renal artery followed by 120 min reperfusion, as well as the effect of IR on size selectivity for proteins in both glomerular and peritubular capillaries. All measured mediators increased dramatically in renal hilar lymph, plasma and renal cortical tissue samples and returned to control levels after 120 min reperfusion. The responses were differentiated; interleukin‐1β, monocyte chemoattractant protein‐1 and leptin were markedly increased in plasma before reperfusion, reflecting an extrarenal response possibly induced by afferent renal nerve activity from the ischaemic kidney. Tumour necrosis factor‐α was the only mediator showing elevated lymph‐to‐plasma ratio following 30 min reperfusion, indicating that most cytokines were released directly into the bloodstream. The IR‐induced rise in cytokine levels was paralleled by a significant increase in high molecular weight plasma proteins in both lymph and urine. The latter was shown as a 14‐ to 166‐fold increase in glomerular sieving coefficient of plasma proteins assessed by a novel proteomic approach, and indicated a temporarily reduced size selectivity of both glomerular and peritubular capillaries. Collectively, our data suggest that cytokines from the ischaemic kidney explain most of the rise in plasma concentration, and that the locally produced substances enter the systemic circulation through transport directly to plasma and not via the interstitium to lymph.