Treatment of cyclosporine induced hypertension: Results from a long-term observational study using different antihypertensive medications

摘要

Post-transplant hypertension (PTH) is a common complication in cyclosporine immunosuppressed patients; however choosing the right antihypertensive medication is challenging. In a long-term observational study (<= 13y) we examined different antihypertensive medications on graft/patient survival of kidney recipients with pre-existing and PTH. Altogether thirty-three co-variables were analyzed including dose and type of immunosuppressive and antihypertensive medication, co-medications, serum biochemistries and the glomerular filtration rate (GFR). A Cox proportional-hazard multivariable survival model was developed to detect a Hazard Ratio (HR) of 3.0 at the Bonferroni corrected level alpha = 0.0015. Importantly, a significant relationship between immunosuppressive cyclosporine dose/serum concentration, systolic blood pressure (SBP) and GFR (p < 0.001) was observed with post-transplant hypertension being a major risk factor (HR6.1) for graft/patient survival. Although all medications lowered effectively elevated SBP the risk of graft failure/death was significantly increased when hypertension was treated with ACE inhibitors or beta-blockers (HR3.3 and 3.1) but not with angiotensin receptor- and/or Ca-channel blockers. Antihypertensive medication was associated with a decline in GFR but beta-blockers alone or in combination with ARB and/or CCB improved GFR. Neither BMI nor any of the drug combinations used in immunosuppression, i.e. prednisolone, mycophenolic acid, azathioprine and/or sirolimus influenced patient and/or graft survival while decision tree analyses informed on complex dependencies between immunosuppressive medications, dose of anti-hypertensive drug and diuretics in the management of hypertension. In conclusion, our study is suggestive for graft/patient survival to be influenced by the class of antihypertensive medication. A prospective randomized clinical trial is needed to confirm the results.