The Determinant Clinical Parameters for Shifting Prescriptions among Nifedipine+Quercetin; Atorvastatin, and Captopril+Quercetin in Treating the Hypertension of Chronic Kidney Disease

Clinically three categories of antihypertensive drugs are often prescribed for the indication of hypertension in chronic kidney disease (CKD), namely, the calcium channel blockers (CCBs, ex. Nifedipine, N), the hydroxylmethyl glutaryl CoA reducatse inhibitors (HMGRi, ex. Atorvastatin, S), and the angiotensin converting enzymes inhibitors (ACEi, ex. Captopril, C). Each has shown different side effects. Quercetin, the most abundant of the flavonoids, has a wide range of biological effects such as lowering of blood pressure and protecting renal injuries. Our study also showed that quercetin is superior to naringenin, catechin, and rutin in cotreating CKD. The outcomes of the quercetin combined therapy with these three antihypertensives have not been cited. Previously, quercetin has been shown to have improved the side effects of each individual antihypertensive using chronic kidney disease (CKD) animal model (Preliminary studies: supported by NSC-99–2320-B-038–011-MY3): We created doxorubicin (DR) CKD rats model, and treated with three categories of anti-hypertensives including N, S, and C, either alone or in combinaion with quercetin (Q) for a period of 3 months. The parameters examined involved the serum levels of albumin, cholesterol, HMGR, and triglyceride; and creatinine in serum and renal tissues, the collagen deposition in the renal tissues, the blood counts, the serum BUN and urinary BUN, uric acid, and protein. In addition, Western blot of PPAα, Bcl-2 and Bax and TUNEL assay were carried out to compare the action mechanisms between the N, S, and C when used alone and in combined therapy separately with quercetin. We showed the combined DR+Q+N to be more feasible than DR+N, DR+Q+C to be more concrete and beneficial than DR+C; and amazingly, DR+S alone to be more beneficial than its DR+Q+S. In this present research project, based on these preliminary findings as mentioned in the above, we suppose that the better treatments should be administered for a longer period when they are to be used clinically. Considering that the prognosis of all medication may induce more or less some unwanted side effects, the increase of quercetin dosage must be reevaluated and the shifting hour from one prescription to the other must be strictly controlled, regarding to the specific warning parameter changes. Using the better formula obtained previously, DR+N+Q, DR+C+Q, and DR+S, a six month or longer treatment period will be set for treatment of the hypertension in CKD, and the warning signal parameters will be carefully examined.