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. Doses of methyl- dopa or clonidine are not generally reduced in patients with impaired kidney function. Moxonidine is extensively excreted by the kidney and accordingly it has been recommended that the dosage (usually 200 to 400 mg daily) should be reduced in the presence of a low GFR.134 On the other hand, an RCT of moxonidine, 300 mg daily, or the calcium-channel blocker nitrendipine, 20 mg daily, added to an ACE-I or ARB plus loop diuretic in 177 hypertensive CKD patients (GFR by the ) indicated that adverse events occurred in similar proportions of patients treated with moxonidine (50 of 89 [56.2%]) and nitrendipine (46 of 82, [56.1%]), as did those adverse events possibly due to the study drug (moxonidine 28%, nitrendi- pine 32%), suggesting that although side effects are common, moxonidine can be used in advanced CKD.135 Common Table 2 | Selected calcium-channel blockers Class Accumulate in renal failure Increase CNI levels Increase sirolimus levels Amlodipine D N Y Diltiazem B N Y Y Felodipine D N Isradipine D N Lercanidipine D N Nicardipine D Y Y Y Nifedipine D N N Nimodipine Y Nisoldipine D N Verapamil P N Y Y B, non-dihydropyridine benzothiazepine; CNI, calcineurin inhibitor; D, Dihydropyri- dine; N, No; P, phenylalkylamine; Y, Yes; , no data. severe adverse events associated with moxonidine in this RCT were gastrointestinal symptoms, dizziness, headache and tiredness; all of which occurred in between 10 to 15% of the patients receiving moxonidine. Indications for centrally acting alpha-agonists. 