Triple combination therapy with telmisartan, amlodipine, and hydrochlorothiazide ameliorates albuminuria in a normotensive rat remnant kidney model

Some types of antihypertensive drugs may have pleiotropic effects in patients with chronic kidney disease (CKD). However, whether triple combination therapy with angiotensin II receptor blockers (ARBs), calcium channel blockers (CCBs), and thiazide diuretics (TZD) confer renoprotective effects in normotensive CKD remains unknown. Thus, we explored this issue using a normotensive rat remnant kidney model. Sprague-Dawley rats were randomly allocated into four groups: sham (n = 10), 5/6 nephrectomy (NTx) (n = 9), NTx treated with telmisartan and amlodipine (dual) (n = 8), and NTx treated with telmisartan, amlodipine, and hydrochlorothiazide (triple) (n = 7), and followed for 4 weeks. Blood pressure (BP), blood chemistry including renal function, urinary albumin excretion (UAE), and renal pathology were evaluated in all groups. There was no significant change in systolic BP among the four groups during the study period. Serum blood urea nitrogen (BUN) was significantly higher, and 24-h creatinine clearance (Ccr) was lower in all NTx groups (p < 0.001). Dual therapy further increased the glomerular diameter in NTx rats (p < 0.001), which was significantly ameliorated by triple therapy (p < 0.001). Triple therapy, but not dual therapy, significantly reduced NTx-induced UAE levels (p < 0.05), whereas BUN, 24-h Ccr, and tubulointerstitial injury scores were comparable among all the NTx groups. Our results suggest that triple combination therapy with telmisartan, amlodipine, and hydrochlorothiazide could ameliorate glomerular hypertrophy and albuminuria in normotensive CKD rats in a BP-lowering independent manner.