Reno protective role of amlodipine in patients with hypertensive chronic kidney disease

Table 1 Classification of chronic kidney disease Stages 1-5[8]

Stage	Description	GFR, mL/min/1.73 m2
-	At increased risk	≥ 60
1	Kidney damage with normal or increased GFR	≥ 90
2	Kidney damage with mild decreased GFR	60-89
3	Moderately decreased GFR	30-59
4	Severely decreased GFR	15-29
5	Kidney Failure	< 15 (or dialysis)

GFR: Glomerular filtration rate.

Table 2 Association of hypertension phenotype with all-cause mortality[18]

BP phenotype	Description1	All-cause mortality hazard ratio (95%CI)
Normotension	Normal clinic BP, normal 24-h ABPM	Reference
White-coat hypertension	High clinic BP, normal 24-h ABPM	1.79 (1.38–2.32)
Sustained hypertension	High clinic BP, high 24-h ABPM	1.80 (1.41–2.31)
Masked hypertension	Normal clinic BP, high 24-h ABPM	2.83 (2.12–3.79)

¹Normal clinic BP defined as < 140/90 mmHg, Normal 24-h BP defined as < 130/80 mmHg. Values represent patients on treatment and without chronic kidney disease. ABPM: Ambulatory blood pressure monitoring; BP: Blood pressure; CI: Confidence interval.

Table 3 Summarized data from various trials demonstrating the role of amlodipine in reducing hypertension

Trial	Objective	Design/primary endpoints	Drug/procedures used	Main outcomes	Benefits on renal parameters
ALLHAT	To determine whether treatment with a CCB or an ACE inhibitor lowers the incidence of CHD or other CVD events vs treatment with a diuretic	A total of 33357 participants aged 55 yr or older with HTN and at least 1 other CHD risk factor from 623 North American centers were enrolled. Primary Endpoints: Combined fatal CHD or nonfatal MI analyzed by intent-to-treat	Participants were randomly assigned to receive chlorthalidone, 12.5 to 25 mg/d (n = 15 255); ALM, 2.5 to 10 mg/d (n = 9048); or lisinopril, 10 to 40 mg/d (n = 9054) for planned follow-up of approximately 4 to 8 yr	In patients with HTN, chlorthalidone, ALM, and lisinopril performed similarly in regard to fatal CAD and nonfatal MI	Post hoc analysis of the trial revealed that in hypertensive patients with reduced GFR, both ALM and lisinopril performed similarly in reducing the rate of development of ESRD
ACCOMPLISH	To evaluate the effect of ALM vs hydrochlorothiazide in patients with HTN who are at high risk CVD	Multi-centered, double-blind, randomized, controlled trial with 548 centers in the US and Europe. 11506 subjects were enrolled who received Benazepril/ALM (n = 5744) or Benazepril/HCTZ (n = 5762). Primary Endpoint: CV mortality, nonfatal MI, nonfatal CVA, UA, resuscitation after cardiac arrest, or coronary revascularization	Subjects received benazepril/ALM 20 mg/5 mg or benazepril/HCTZ 20 mg/12.5 mg daily. Benazepril component was increased to 40 mg after 1 mo.Increase of ALM to 10 mg or HCTZ to 25 mg to reach target BP < 140/90 or < 130/80	Among patients with HTN at high risk for CV complications, benazepril/ALM decreases the rate of CV events as compared to benazepril/HCTZ	Initial antihypertensive treatment with benazepril and ALM demonstrates a superior ability in reducing the progression of nephropathy
SAKURA	To clarify whether the L-/N-type CCB cilnidipine is more renoprotective than the L-type CCB ALM in patients with early-stage diabetic nephropathy	Prospective, multicenter, open-labeled, randomized trial in 77 clinics and hospitals in Japan, to probe the anti-albuminuric effects of cilnidipine and ALM in 367 RAAS inhibitor-treated patients with HTN (BP: 130-180/80-110 mmHg), type 2 diabetes, and microalbuminuria (UACR: 30-300 mg/g). Primary Endpoint: Change in the urinary albumin/Cr ratio after a 1-yr treatment	Study subjects were randomly allocated in two groups and treated with cilnidipine (started at 10 mg/d, then adjusted to 5-20 mg/d) or ALM (started at 5 mg/d, then adjusted to 2.5-10 mg/d). The target BP was < 130/80 mm Hg	Cilnidipine did not offer greater renoprotection than ALM in RAS inhibitor treated HTN patients with type 2 diabetes and microalbuminuria	In hypertensive patients with proteinuria, L/N- and L/T-type CCBs as add-on therapy to an ACEI or an ARB reduce albuminuria and proteinuria and improve kidney function compared with the use of an ACEI or ARB alone or in combination with other antihypertensive agents
ASCOT-BPLA	To evaluate whether treatment with a newer anti-hypertensive regimen of CCB with or without an ACE inhibitor is more effective than an older regimen of β-blocker with or without a diuretic, and whether it reduces CHD events in hypertensive patients with relatively low cholesterol levels	A total of 19257 patients with SBP ≥ 160 mm Hg and/or DBP ≥ 100 mm Hg (untreated) or SBP ≥ 140 mm Hg and/or DBP ≥ 90 mm Hg (treated); total cholesterol ≤ 6.5 mmol/L (250 mg/dL) and triglycerides ≤ 4.5 mmol/L (400 mg/dL); age 40-79 yr; ≥ 3 CVD risk factors; and no history of CHD were enrolled Primary Endpoints: Nonfatal MI and fatal CHD	Patients were randomized open-label to one of the two anti-hypertensive treatments: ALM 5 mg (n = 9639) or atenolol 50 mg (n = 9618). In order to achieve target BP goals of < 140/90 mm Hg, study drug doses were increased, and second-line drugs were added (perindopril 4 mg for the ALM group and bendroflumethiazide 1.25 mg for the atenolol group)	ALM-based regimen is superior to an atenolol-based regimen in regard to demonstrating a greater reduction in BP variability and prevention of major CV events in patients with HTN	ALM based arm demonstrated a significant reduction in new onset diabetes mellitus, development of peripheral arterial disease and renal impairment

ACEI: Ace inhibitor; ALM: Amlodipine; ARB: Angiotensin receptor blockers; BP: Blood pressure; CAD: Coronary artery disease; CCB: Calcium channel blocker; CHD: Chronic heart disease; CVD: Cardiovascular disease; DBP: Diastolic blood pressure; GFR: Glomerular filtration rate; HCTZ: Hydrochlorothiazide; HTN: Hypertension; MI: Myocardial infarction; SBP: Systolic blood pressure; RAAS: Renin–angiotensin–aldosterone system; UACR: Urine albumin-to-creatinine ratio.