Effect of cyclosporine on blood pressure

Robert, Nadège; Wong, Gavin WK; Wright, James M

doi:10.1002/14651858.cd007893.pub2

Cited by 82 publications

(54 citation statements)

References 64 publications

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“…To date, calcineurin inhibitors remain essential in the immunosuppressive treatment after transplantation. These drugs, which include cyclosporine (CsA) and tacrolimus, are highly effective in preventing graft rejection; however, this is achieved at the cost of various adverse effects, such as CsA-induced hypertension [5]. CsA-induced hypertension could be responsible for sodium retention, which might be triggered via apical sodium transporters [6,7].…”

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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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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“…One of the main reasons for restricting the usage of CsA in certain situations is nephrotoxicity and hypertension in approximately 30% of patients. However, the mechanism of this action remains unknown (9).…”

Section: Introductionmentioning

confidence: 99%

“…High blood pressure persisting for long periods of time may lead to organ complications, atherogenesis, renal failure, heart failure or stroke. Decisions regarding the treatment of hypertension should be based on clinical investigations that include classification of hypertension, presence of organ complication, additional risk factors (intercurrent diseases) and age (9). Due to the similar effectiveness of drugs from five basic groups, the European Society of Hypertension, European Society of Cardiology and Polish Society of Hypertension do not recommend a specific class of hypertension drugs.…”

Section: Introductionmentioning

confidence: 99%

Calcium blockers inhibit cyclosporine A-induced hyperreactivity of vascular smooth muscle cells

et al. 2012

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Abstract. Cyclosporine belongs to the group of the most commonly used immunosuppressants. Hypertension occurs in approximately 30% of patients treated with this drug. However, the pathogenesis of this occurrence has not been explained to date. The purpose of our study was to clarify the mechanisms leading to the evolution of hypertension induced by cyclosporine A (CsA). We examined the changes in transmission within receptors and around the receptors. We also aimed to elucidate the mechanisms responsible for averting arterial hyperresponsiveness induced by the drug. Experiments were performed on isolated and perfused tail arteries of Wistar rats. Tissues surrounding the artery were removed and the proximal segment (length of 2-3 cm) was used for cannulation. Cannulated arteries were placed in a 20-ml glass chamber (vertical position). The contraction force in our model was measured by an increased degree of perfusion pressure with a constant flow rate (approximately 1 ml/min). The results showed that in the presence of CsA, the concentration-response curves/phenylephrine (PHE) curve shifted to the left. Cyclosporine increased the reactivity of the arteries to PHE. This effect was directly linked to the increase in the receptor reserve. The analysis of the reactivity of vascular smooth muscle showed that CsA increased the influx of calcium ions from the extracellular to the intracellular area. No difference was found between the contraction triggered by Bay-K8644 in the presence of CsA and the control probe. The increase in perfusion pressure induced by CsA was blocked by L-type calcium channel blockers (nifidipine and diltiazem). The results from our experiments show that CsA increases the reactivity of vessels to the effect of catecholamines. CsA also enhances signal transmission between G-protein coupled receptors (GPCRs) and calcium channels. The activation of protein kinase C also plays a significant role in this process. Our results suggest that the best choice for the pharmacotherapy of hypertension induced by CsA would be calcium channel antagonists.

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“…17 Similarly, an increase in blood pressure levels secondary to the use of lefl unomide and cyclosporine can occur in patients with RA. [18][19][20] Factors inherent to the disease, such as the systemic infl ammation of RA, might also contribute to the appearance of SAH in those patients. During its course, RA shows an increased expression of tumor necrosis factor alpha (TNF-α), interleukins (IL) 1 and 6, adhesion molecules, angiotensin II type 1 receptor, and endothelin, and a lower expression of nitric oxide; that unbalance might contribute to SAH.…”

Section: Systemic Arterial Hypertensionmentioning

confidence: 99%

Consenso 2012 da Sociedade Brasileira de Reumatologia sobre o manejo de comorbidades em pacientes com artrite reumatoide

Pereira¹,

Mota²,

Cruz³

et al. 2012

Rev. Bras. Reumatol.

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Objective: To elaborate recommendations of the Rheumatoid Arthritis Committee of the Brazilian Society of Rheumatology (SBR) to manage comorbidities in rheumatoid arthritis (RA). Methods: To review the literature and the opinions of the SBR RA Committee experts. Results and conclusions: Recommendations: 1) Early diagnosis and proper treatment of comorbidities are recommended; 2) The specifi c treatment of RA should be adapted to the presence of comorbidities; 3) Angiotensin-converting-enzyme inhibitors or angiotensin II receptor blockers are preferred to treat systemic arterial hypertension; 4) In patients diagnosed with rheumatoid arthritis and diabetes mellitus, the continuous use of a high cumulative dose of corticoids should be avoided; 5) Statins should be used to maintain LDL cholesterol levels under 100 mg/dL and the atherosclerotic index lower than 3.5 in patients with RA who have other comorbidities; 6) Metabolic syndrome should be treated; 7) Performing non-invasive tests to investigate subclinical atherosclerosis is recommended; 8) Greater surveillance for the early diagnosis of occult malignancy is recommended; 9) Preventive measures of venous thrombosis are suggested; 10) Bone densitometry is recommended in RA patients over the age of 50 years and in younger patients on corticoid therapy at a dose greater than 7.5 mg for over three months; 11) Patients with RA and osteoporosis should be instructed to avoid falls, to increase their dietary calcium intake and sun exposure, and to exercise; 12) Calcium and vitamin D supplementation is suggested. Bisphosphonates are suggested for patients with T score < -2.5 on bone densitometry; 13) A multidisciplinary team, with the active participation of a rheumatologist, is recommended to treat comorbidities.

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Effect of cyclosporine on blood pressure

Cited by 82 publications

References 64 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

Calcium blockers inhibit cyclosporine A-induced hyperreactivity of vascular smooth muscle cells

Consenso 2012 da Sociedade Brasileira de Reumatologia sobre o manejo de comorbidades em pacientes com artrite reumatoide

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