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

Sakuya Ito,Kensei Taguchi,Yusuke Kaida,Yosuke Nakayama,Kanji Ota,Goh Kodama,Sho-Ichi Yamagishi,Kei Fukami

doi:10.1186/s41100-021-00333-z

Sakuya Ito, Kensei Taguchi + Show 6 more

Open Access

https://doi.org/10.1186/s41100-021-00333-z

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Abstract

BackgroundSome 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.MethodsSprague-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.ResultsThere 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.ConclusionsOur 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.

Highlights

Chronic kidney disease (CKD) is a major contributor to the increased risk of morbidity and mortality worldwide [1]
The Kidney Disease Improving Global Outcome Clinical Practice Guideline for the Management of Blood Pressure in chronic kidney disease (CKD) has announced that renin-angiotensin system inhibitors (RAS-i) are the first-line therapy for decreasing blood pressure (BP) and preventing the progression of renal dysfunction in CKD patients with albuminuria and diabetes [2, 3]
We examined the effects of combination therapy involving Angiotensin II type-1 receptor blocker (ARB) and Calcium channel blocker (CCB) with or without HCTZ on renal involvement in a normotensive subtotal nephrectomy (NTx) rat model

Summary

Introduction

Chronic kidney disease (CKD) is a major contributor to the increased risk of morbidity and mortality worldwide [1]. Combination therapy with RAS-i and CCB has been proven to decrease all-cause and cardiovascular mortality as well as major cardiovascular events, especially in high-risk patients such as CKD patients [5, 6] Whether these combinations could contribute to the amelioration of renal injury independent of BP is unknown. 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. We explored this issue using a normotensive rat remnant kidney model

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