The Pathophysiologic Role of Endothelin in Acute Vascular Rejection After Renal Transplantation

Watschinger, Bruno; Vychytil, Andreas; Schüller, M.; Hartter, Engelbert; Traindl, O; Pohanka, E; Walter, Ulrich; Kovařík, Josef

doi:10.1097/00007890-199110000-00035

Cited by 39 publications

(18 citation statements)

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“…Intravenous infusion of a selective ET-A receptor antagonist (BQ-123) on the day after ischemia improved GFR and preserved tubular function for sodium reabsorption, potassium excretion, and prevented fatal hyperkalemia [56], Similar protective effects of BQ-123 were observed in another rat study in which the antagonist was infused intravenously before renal artery occlusion and during reperfusion [57], On the other hand, a rat study showed that the number or affinity of glomerular ET receptors was not altered during initia tion and maintenance of ARF produced by 60 min renal artery occlusion, raising doubt that enhanced ET activity in glomeruli is responsible for the reduction in GFR in this model [58], There are scarce data in human studies to implicate and define the role of ET in the initiation or maintenance of ARF since only plasma levels have been examined and show conflicting results. In patients with ARF, plasma immunoreactive ET levels were reported to be elevated [59], In patients with renal transplantation complicated by acute tubular necrosis, plasma immunoreactive ET concentrations were normal but were elevated when vas cular rejection occurred [60]. However, another report showed that postrenal transplant acute tubular necrosis was associated with increased plasma immunoreactive ET levels, which also correlated positively with serum cre atinine concentrations [61].…”

Section: Acute Renal Failurementioning

confidence: 99%

Endothelins and Kidney Diseases

Brown¹,

Chou²,

Porush³

1996

Nephron

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Section: Acute Renal Failurementioning

confidence: 99%

Endothelins and Kidney Diseases

Brown¹,

Chou²,

Porush³

1996

Nephron

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“…In a clinical study of renal transplantation, the serum ET-1 concentration decreased after the graft function improved [8]. But when acute rejection occurs, the increase in the ET-1 level accompanied a decline of graft function [17][18][19]. These results suggested that ET-1 works in conjunction with renal function and, especially in renal transplantation, ET-1 may be a marker for rejection of the transplanted kidney.…”

Section: Discussionmentioning

confidence: 99%

Effect of Endothelin Receptor Antagonist (TAK-044) on Autotransplanted Perfused Kidneys in Dogs

Yoshida

Kagebayashi²,

Kitauchi³

et al. 2000

Urol Int

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Background: Endothelin-1 (ET-1) is involved in some diseases, including renal disease. Recently, the role of ET-1 in postrenal transplantation has been demonstrated in experimental and clinical studies. A new endothelin receptor antagonist, TAK-044, blocks both, ETA and ETB receptors, and was useful in treating acute renal failure in rats. In this study, we evaluated the effect of TAK-044 on autotransplanted kidneys with 18 h of perfusion. Materials and Methods: TAK-044 was injected subcutaneously at 15 mg/kg/day for 2 weeks in one group of dogs, and blood analysis and renal function, were evaluated. A control group was given saline in the same manner as that used for the TAK-044 group. Histopathological examination and immunohistochemistry for ET-1 were performed in the two groups. Results: In the control group, 5 of the 7 dogs died of renal failure within 2 weeks after autotransplantation of the kidney. In the TAK-044 group, 5 of the 7 dogs survived and 2 died of renal failure within the same period. Although the histological changes in the tubules in both groups were severe due to the 18 h of perfusion, TAK-044 ameliorated these changes. Immunohistochemical staining for ET-1 was seen in tubules in the control group. Conclusion: These findings suggest that TAK-044 effectively reduces damage in autotransplanted perfused kidneys in dogs, and may be useful in limiting damage to the kidney by acute tubular necrosis after renal transplantation in humans.

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“…It was demonstrated that ET-1 elevates c-fos, c-jun and c-myc expression and extracellular matrix protein synthesis [16, 171. Many of the studies of the role of ET in kidneys have concentrated on ET-1, very few studies of ET-3 have been reported. Circumstantial evidence exists for the potential pathophysiological role of ETin several renal abnormalities such as ischemia-induced acute renal failure, cyclosporine A-(CyA) and FK506 nephrotoxicity, radiocontrast nephrotoxicity, hepatorenal syndrome, and polycystic kidney disease [7,13,24,29,32].…”

Section: Introductionmentioning

confidence: 99%

“…Raised ET-1 blood levels were detected during vascular rejection in association with reduced ET-1 immunostaining in the endothelium [33]. In cellular rejection, where endothelial cells are intact, no significant elevation of plasma ET-1 was observed [32]. However, blood levels do not reflect the true biological significance of ET well since these peptides are rapidly cleared and only very high concentrations are detected.…”

Section: Introductionmentioning

confidence: 99%

Endothelin-1, endothelin-3 and their receptors (endothelin_Aand endothelin_B) in chronic renal transplant rejection in rats

Deng¹,

Jiang²,

García³

et al. 2000

Transplant Int

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Endothelins (ET) are a family of vasoactive peptides that play an important role in several disorders affecting kidneys. In this study we investigated the expressions of ET-1, ET-3, and their receptors, ETA and ET,, in a rat chronic renal transplant rejection model. Renal allografts were performed (F344 ?r Lewis) with bilateral nephrectomy in recipients. For isograft control, lewis + lewis transplantations were performed. All recipients were sacrificed 140 days after transplantation and the grafts were analyzed histologically. ET-1 and ET-3 protein expression in grafts was measured by immunohistochemistry and ELISA. Semiquantitative RT-PCR methods were used for mRNA levels of ET-1, ET-3, ETA and ET,. No evidence of chronical rejection was manifested in isografts. The allografted rats showed proteinuria and increased serum creatinine levels. Histologically, renal allografts showed atrophy and sclerosis of the glomeruli, cortical scarring and vascular intimal thickening. Immunohistochemically, ET-1 and ET-3 were localized in the convoluted tubules, collecting ducts, endothelium and smooth muscle cells of the large blood vessels. Significantly increased staining for ET-1 and ET-3 were found in allografts compared to isografts. Simultaneously, ELISA for ET-1 and ET-3 showed elevated protein concentrations in allografts compared to isografts. Allografts showed significantly increased ET-1-and ET-3 mRNA compared to isografts. On the other hand, a significant down regulation of the ETA mRNA was noted, and the ET, mRNA remained unchanged. The data from the present study suggest that alteration of ET system may be of importance in the pathogenesis of chronic renal transplant rejection.

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The Pathophysiologic Role of Endothelin in Acute Vascular Rejection After Renal Transplantation

Cited by 39 publications

References 0 publications

Endothelins and Kidney Diseases

Endothelins and Kidney Diseases

Effect of Endothelin Receptor Antagonist (TAK-044) on Autotransplanted Perfused Kidneys in Dogs

Endothelin-1, endothelin-3 and their receptors (endothelin_Aand endothelin_B) in chronic renal transplant rejection in rats

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The Pathophysiologic Role of Endothelin in Acute Vascular Rejection After Renal Transplantation

Cited by 39 publications

References 0 publications

Endothelins and Kidney Diseases

Endothelins and Kidney Diseases

Effect of Endothelin Receptor Antagonist (TAK-044) on Autotransplanted Perfused Kidneys in Dogs

Endothelin-1, endothelin-3 and their receptors (endothelinAand endothelinB) in chronic renal transplant rejection in rats

Contact Info

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Endothelin-1, endothelin-3 and their receptors (endothelin_Aand endothelin_B) in chronic renal transplant rejection in rats