Kidney international
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Disasters result in a substantial number of renal challenges, either by the creation of crush injury in victims trapped in collapsed buildings or by the destruction of existing dialysis facilities, leaving chronic dialysis patients without access to their dialysis units, medications, or medical care. Over the past two decades, lessons have been learned from the response to a number of major natural disasters that have impacted significantly on crush-related acute kidney injury and chronic dialysis patients. ⋯ The role of the Renal Disaster Relief Task Force in providing emergency disaster relief and the logistical support required is outlined. In addition, the importance of detailed education of chronic dialysis patients and renal unit staff in the advance planning for such disasters and the impact of displacement by disasters of chronic dialysis patients are discussed.
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Kidney international · Apr 2014
Periostin promotes renal cyst growth and interstitial fibrosis in polycystic kidney disease.
In renal cystic diseases, sustained enlargement of fluid-filled cysts is associated with severe interstitial fibrosis and progressive loss of functioning nephrons. Periostin, a matricellular protein, is highly overexpressed in cyst-lining epithelial cells of autosomal-dominant polycystic disease kidneys (ADPKD) compared with normal tubule cells. Periostin accumulates in situ within the matrix subjacent to ADPKD cysts, binds to αVβ3 and αVβ5 integrins, and stimulates the integrin-linked kinase to promote cell proliferation. ⋯ At 20 weeks of age, pcy/pcy:Postn(-/-) mice had a 34% reduction in kidney weight/body weight, a reduction in cyst number and total cystic area, a 69% reduction in phosphorylated S6, a downstream component of the mTOR pathway, and fewer proliferating cells in the kidneys compared with pcy/pcy:Postn(+/+) mice. The pcy/pcy Postin knockout mice also had less interstitial fibrosis with improved renal function at 20 weeks and significantly longer survival (51.4 compared with 38.0 weeks). Thus, periostin adversely modifies the progression of renal cystic disease by promoting cyst epithelial cell proliferation, cyst enlargement, and interstitial fibrosis, all contributing to the decline in renal function and premature death.
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Kidney international · Apr 2014
Preconditioning with recombinant high-mobility group box 1 protein protects the kidney against ischemia-reperfusion injury in mice.
A preconditioning effect occurs when exposure to a nonharmful quantity of a mediator of injury provides protection against injury upon subsequent reexposure. High-mobility group box 1 (HMGB1) protein, an endogenous ligand for Toll-like receptor (TLR) 4, is a TLR4-dependent mediator of kidney ischemia-reperfusion injury. Here we determined whether preconditioning with recombinant HMGB1 can block kidney ischemia-reperfusion injury, whether this effect is TLR4 dependent and, if so, how preconditioning downregulates TLR signaling. ⋯ While TLR4 and TLR2 knockout mice were protected against kidney ischemia-reperfusion injury, HMGB1 preconditioning provided additional protection to TLR2 but not TLR4 knockout mice. The protective effect of rHMGB1 preconditioning involved Siglec-G upregulation, a negative regulator of HMGB1-mediated TLR4 pathway activation. Thus, preconditioning with rHMGB1 affords significant protection from TLR4-dependent kidney ischemia-reperfusion injury, indicating therapeutic potential.