Hypertension after renal transplantation

Schwenger, Vedat; Zeier, Martin; Ritz, Eberhard

doi:10.1007/s11906-001-0063-1

Cited by 42 publications

(36 citation statements)

References 65 publications

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“…About 70-90% of kidney recipients display high blood pressure (BP) [3,4]. To date, calcineurin inhibitors remain essential in the immunosuppressive treatment after transplantation.…”

Section: Introductionmentioning

confidence: 99%

Renal Sodium Transporters Are Increased in Urinary Exosomes of Cyclosporine-Treated Kidney Transplant Patients

et al. 2014

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Background/Aims: Cyclosporine (CsA) is a calcineurin inhibitor widely used as an immunosuppressant in organ transplantation. Previous studies demonstrated the relationship between CsA and renal sodium transporters such as the Na-K-2Cl cotransporter in the loop of Henle (NKCC2). Experimental models of CsA-induced hypertension have shown an increase in renal NKCC2. Methods: Using immunoblotting of urinary exosomes, we investigated in CsA-treated kidney transplant patients (n = 39) the excretion of NKCC2 and Na-Cl cotransporter (NCC) and its association with blood pressure (BP) level. We included 8 non-CsA-treated kidney transplant patients as a control group. Clinical data, immunosuppression and hypertension treatments, blood and 24-hour urine tests, and 24-hour ambulatory BP monitoring were recorded. Results: CsA-treated patients tended to excrete a higher amount of NKCC2 than non-CsA-treated patients (mean ± SD, 175 ± 98 DU and 90 ± 70.3 DU, respectively; p = 0.05) and showed higher BP values (24-hour systolic BP 138 ± 17 mm Hg and 112 ± 12 mm Hg, p = 0.003; 24-hour diastolic BP, 83.8 ± 9.8 mm Hg and 72.4 ± 5.2 mm Hg, p = 0.015, respectively). Within the CsA-treated group, there was no correlation between either NKCC2 or NCC excretion and BP levels. This was confirmed by a further analysis including potential confounding factors. On the other hand, a significant positive correlation was observed between CsA blood levels and the excretion of NKCC2 and NCC. Conclusion: Overall, these results support the hypothesis that CsA induces an increase in NKCC2 and NCC in urinary exosomes of renal transplant patients. The fact that the increase in sodium transporters in urine did not correlate with the BP level suggests that in kidney transplant patients, other mechanisms could be implicated in CsA-induced hypertension.

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“…About 70-90% of kidney recipients display high blood pressure (BP) [3,4]. To date, calcineurin inhibitors remain essential in the immunosuppressive treatment after transplantation.…”

Section: Introductionmentioning

confidence: 99%

Renal Sodium Transporters Are Increased in Urinary Exosomes of Cyclosporine-Treated Kidney Transplant Patients

et al. 2014

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“…1 Clinical signs such as a murmur in the graft region occur infrequently and are nonspecific. 2 Several diagnostic tests for TRAS have been proposed, such as a renogram with administration of the angiotensin-converting-enzyme inhibitor captopril, color Doppler sonography (CDUS) with spectral analysis, MR angiography (MRA), and digital subtraction arteriography (DSA). 3 DSA is considered the gold standard in the diagnosis of TRAS.…”

Section: Introductionmentioning

confidence: 99%

Duplex Doppler sonography of transplant renal artery stenosis

Morais

Muglia

Mamere

et al. 2003

J of Clinical Ultrasound

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“…Since its introduction in clinical practice, CsA has been linked to a major side effect, arterial hypertension (19,20). Although several mechanisms have been proposed including nephrotoxicity, sympathetic nervous system activation, and endothelin-1 secretion (21), much evidence points to endothelial dysfunction as an essential factor in the pathogen-esis of CsA-induced hypertension.…”

mentioning

confidence: 99%

Cyclosporin A Inhibits Flow-mediated Activation of Endothelial Nitric-oxide Synthase by Altering Cholesterol Content in Caveolae

Lungu¹,

Jin²,

Yamawaki

et al. 2004

Journal of Biological Chemistry

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Fluid shear stress generated by blood flowing over the endothelium is a major determinant of arterial tone, vascular remodeling, and atherogenesis. Nitric oxide (NO) produced by endothelial NO synthase (eNOS) plays an essential role in regulation of vascular function and structure by blood flow. Although cyclosporin A (CsA), an inhibitory ligand of cyclophilin A, is a widely used immunosuppressive drug, it causes arterial hypertension in part by impairing eNOS-dependent vasodilation. Here we show that CsA inhibits fluid shear stress-mediated eNOS activation in endothelial cells via decreasing cholesterol content in caveolae. Exposure of cultured bovine aortic endothelial cells to 1 M CsA for 1 h significantly inhibited NO production and eNOS phosphorylation at Ser-1179 induced by flow (shear stress ‫؍‬ 12 dynes/cm 2 ). The effect of CsA was not related to inhibition of two known eNOS kinases, protein kinase B (Akt) and protein kinase A, because CsA did not affect Akt or protein kinase A activation. In rabbit aorta perfused ex vivo, CsA also significantly inhibited flow-induced eNOS phosphorylation at Ser-1179 but had no effect on Akt measured by phosphorylation at Ser-473. However, CsA treatment decreased cholesterol content in caveolae and displaced eNOS from caveolae, which may be caused by CsA disrupting the association of caveolin-1 and cyclophilin A. The magnitude of the cholesterol depleting effect was similar to that of ␤-cyclodextrin, a cholesterol-binding molecule, and ␤-cyclodextrin had a similar inhibitory effect on flow-mediated eNOS activation. Treating bovine aortic endothelial cells for 24 h with 30 g/ml cholesterol blocked the CsA effect and restored eNOS phosphorylation in response to flow. These data suggest that decreasing cholesterol content in caveolae by CsA is a potentially important pathogenic mechanism for CsA-induced endothelial dysfunction and hypertension.Vascular endothelial cells, which form the inner lining of the blood vessel wall, are exposed to fluid shear stress, the dragging force generated by blood flow. Fluid shear stress modulates endothelial structure and function and is a major determinant of vascular remodeling, arterial tone, and atherogenesis (1, 2). Physiologically, fluid shear stress is the most important stimulus for the continuous formation of nitric oxide (NO) 1 by endothelial nitric-oxide synthase (eNOS) in vessels (3, 4), which plays an essential role in mediating many effects of fluid shear stress including regulation of vascular tone and diameter (5). Although flow-induced NO production appears to be both Ca 2ϩ -dependent and Ca 2ϩ -independent (6, 7), phosphorylation of eNOS by flow has been recognized as a critical regulatory mechanism controlling eNOS activity (6,8). In particular, we and others have showed that increased eNOS phosphorylation in response to flow occurs mainly at serine 1179 (pS1179-eNOS, serine 1177 in the human eNOS sequence) in bovine aortic endothelial cells (BAEC) (9 -11). Protein kinase B (Akt) and cAMP-dependent protein kinase A (PK...

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Hypertension after renal transplantation

Cited by 42 publications

References 65 publications

Renal Sodium Transporters Are Increased in Urinary Exosomes of Cyclosporine-Treated Kidney Transplant Patients

Renal Sodium Transporters Are Increased in Urinary Exosomes of Cyclosporine-Treated Kidney Transplant Patients

Duplex Doppler sonography of transplant renal artery stenosis

Cyclosporin A Inhibits Flow-mediated Activation of Endothelial Nitric-oxide Synthase by Altering Cholesterol Content in Caveolae

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