Effects of Initial Ischemia/Reperfusion Injury on the Transplanted Kidney1

Tilney, Nicholas L.; Guttmann, Ronald D.

doi:10.1097/00007890-199710150-00001

Cited by 225 publications

(131 citation statements)

References 18 publications

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“…This result could be anticipated taking into consideration that DGF is associated with an increased recruitment of inflammatory cells and an increased risk for the development of acute rejection (32,33). Even in rejection-free patients, DGF is an independent risk factor for late graft failure owing to CAN (34).…”

Section: Progression Of Chronic Allograft Nephropathymentioning

confidence: 96%

Serial Protocol Biopsies to Quantify the Progression of Chronic Transplant Nephropathy in Stable Renal Allografts

Moreso

López

Vallejos

et al. 2001

American Journal of Transplantation

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Aim: To evaluate the utility of intimal thickness and interstitial width as a primary efficacy variable in the design of clinical trials aimed to modify the natural history of chronic allograft nephropathy. Methods: A donor and a 4-month protocol biopsy were evaluated in 40 stable grafts according to the Banff schema. In 27 patients, a second protocol biopsy was done at 1 yr. Arterial intimal volume fraction (Vvintima/ artery) and cortical interstitial volume fraction (Vvinterstitium/cortex) were estimated with a point counting technique. Results: Chronic Banff scores increased during followup, while acute scores reached its peak at 4 months. Vvintima/artery and Vvinterstitium/cortex significantly increased at 4 months, but not at 1 yr. Vvintima/artery at 4 months correlated with donor Vvintima/artery (r Ω0.57, p ∞0.001), histocompatibility (r Ω0.38, p Ω 0.01) and serum cholesterol (r Ω0.31, p Ω0.047). Vvinterstitium/cortex at 4 months correlated with recipient body surface area (r Ω0.44, p Ω0.004) and delayed graft function (p Ω0.016). Power calculations showed that Vvintima/artery and Vvinterstitium/cortex allow an important reduction in minimum sample size of a hypothetical trial aimed to prevent chronic allograft nephropathy. Conclusions: Intimal thickening and interstitial widening progresses rapidly during the first 4 months after transplantation and slowly thereafter. These parameters can be considered as a primary efficacy variable in trials aimed to prevent chronic allograft nephropathy.

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Section: Progression Of Chronic Allograft Nephropathymentioning

confidence: 96%

Serial Protocol Biopsies to Quantify the Progression of Chronic Transplant Nephropathy in Stable Renal Allografts

Moreso

López

Vallejos

et al. 2001

American Journal of Transplantation

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“…13,14 Production of oxygen free radicals and chemokines and upregulated expression of adhesion and MHC molecules during reperfusion synergize to direct the recruitment of leukocytes, principally polymorphonuclear cells (PMNs), into the graft within hours after reperfusion. [15][16][17] In addition to infiltration of ischemic tissues, chemokines stimulate PMN degranulation, causing parenchymal tissue damage.…”

mentioning

confidence: 99%

Inhibition of Polymorphonuclear Leukocyte–Mediated Graft Damage Synergizes With Short-Term Costimulatory Blockade to Prevent Cardiac Allograft Rejection

et al. 2005

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Background-The early inflammatory response during reperfusion of cardiac allografts is initiated by the infiltration of polymorphonuclear leukocytes (PMNs) into the graft. The impact of early PMN infiltration on allograft rejection compared with long-term graft survival remains poorly understood. Methods and Results-We tested the role of CXCR2, the receptor for 2 PMN attractant chemokines, KC/CXCL1 and MIP-2/CXCL2, on intragraft inflammation and vascularized cardiac allograft rejection in a murine model. Compared with allografts retrieved from control recipients, both PMN infiltration and intragraft proinflammatory cytokine expression were significantly attenuated in allografts from CXCR2-antisera-treated wild-type or from CXCR2

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“…1,2 It is known that multifactorial events are involved in the pathogenesis of TA, both immunologic and nonimmunologic factors such as ischemia/reperfusion injury. 3 Hence, neointima is formed through diverse events occurring in transplants, and proliferation of SMCs is considered a key event for TA development. 2 Conventionally, the medial vascular SMCs in grafts (donor-derived) have been thought to proliferate and migrate into the intima during the process of TA.…”

mentioning

confidence: 99%

Stromal Cell–Derived Factor-1 and CXCR4 Interaction Is Critical for Development of Transplant Arteriosclerosis

et al. 2004

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Background-Posttransplant chronic allograft deterioration associated with development of transplant arteriosclerosis (TA) remains an unresolved problem. Recent studies suggest that the smooth muscle cells (SMCs) constituting the neointima are derived from recipient hematopoietic stem cells (HSCs). However, the underlying mechanisms of the process are not yet fully elucidated. Methods and Results-We examined the genes expressed in allografts at different stages of TA development using a mice aortic transplantation model. Genes were analyzed by a differential mRNA display technique. We show that stromal cell-derived factor-1␣ (SDF-1␣) is a critical molecular target for the treatment of TA. During the course of TA, intragraft SDF-1␣ expression was upregulated with time, and the circulating HSCs expressing its counterreceptor CXCR4 increased in the recipients receiving allografts. CXCR4-positive HSCs, derived from transplant recipients, migrated into allografts via microvessels in the adventitia and then toward the luminal side. The HSCs differentiated into SMC-like cells, contributing to the in situ formation of the neointima. In support of a functional role for these molecules, in vivo neutralization of SDF-1␣ inhibited HSC mobilization and significantly attenuated neointimal formation. Conclusions-Interaction between SDF-1␣ and CXCR4 plays a key role in TA development. Blockade of SDF-1␣ may become a new therapeutic modality for TA.

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Effects of Initial Ischemia/Reperfusion Injury on the Transplanted Kidney1

Cited by 225 publications

References 18 publications

Serial Protocol Biopsies to Quantify the Progression of Chronic Transplant Nephropathy in Stable Renal Allografts

Serial Protocol Biopsies to Quantify the Progression of Chronic Transplant Nephropathy in Stable Renal Allografts

Inhibition of Polymorphonuclear Leukocyte–Mediated Graft Damage Synergizes With Short-Term Costimulatory Blockade to Prevent Cardiac Allograft Rejection

Stromal Cell–Derived Factor-1 and CXCR4 Interaction Is Critical for Development of Transplant Arteriosclerosis

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