It is wise to avoid dihydropyridine calcium channel blockers in CKD patients with already increased urinary albumin excretion, particularly if there is not concomitant use of an ACE-I or ARB.132 Drug combinations. Fluid retention, seen particularly with dihydropyridines, can be problematic in patients with CKD, such that avoiding other vasodilators may be sensible. The combination of non-dihydropyridines such as verapamil and diltiazem with beta-blockers can lead to severe bradycardia, particularly in patients with advanced CKD if drugs such as atenolol and bisoprolol, (that accumulate in CKD) are used. Calcium-channel blockers, particularly non-dihydropyri- dines, interfere with the metabolism and excretion of the CNIs, cyclosporine and tacrolimus, as well as the mammalian target of rapamycin (mTOR) inhibitors, sirolimus and (Table 2). This is relevant to the treatment of high BP in kidney-transplant recipients, but also in patients with immune-mediated CKD requiring immunosuppression. When such patients are prescribed non-dihydropyridine calcium-channel blockers, careful monitoring of CNIs and mTOR inhibitors blood levels is required if drugs or dosages are changed. Some clinicians use non-dihydropyridine calcium-channel blockers to increase CNI or mTOR inhibitor blood levels and thus reduce cost, particularly in kidney- transplant patients. Centrally acting alpha-adrenergic agonists Centrally acting alpha-agonists cause vasodilatation by reducing sympathetic outflow from the brain.133,134 The main agents in use are methyldopa, clonidine, and moxonidine. Moxonidine was not widely available in 2004 and thus was not reviewed for the KDOQI Clinical Practice Guidelines on Hypertension and Antihypertensives Agents in Chronic Kidney The use of this drug in essential hypertension was extensively reviewed by Fenton at al. in 2006.133 Dosing of centrally acting alpha-antagonists is limited by side effects, but since they interact minimally with other antihypertensives or immunosuppressants, they are valuable as adjunct therapy for resistant hypertension in CKD patients. Dose considerations in CKD patients. 