Key result
Irbesartan combined with cilnidipine or amlodipine equally reduces albuminuria and glomerular injury in diabetic rats.
Why the study?
Calcium channel blockers suppress albuminuria in diabetic nephropathy with variable efficacy, and it was unknown whether adding an angiotensin receptor blocker alters their effects on albuminuria.
Does combination therapy with irbesartan plus amlodipine versus irbesartan plus cilnidipine attenuate albuminuria and improve glomerular microcirculation in rats with streptozotocin-induced diabetic nephropathy?
Does combination therapy with irbesartan plus amlodipine versus irbesartan plus cilnidipine attenuate albuminuria and improve glomerular microcirculation in rats with streptozotocin-induced diabetic nephropathy?
Although cilnidipine monotherapy provides superior renoprotection compared to amlodipine in experimental diabetic nephropathy, combining either CCB with the ARB irbesartan achieves equivalent reductions in albuminuria, glomerular oxidative stress, and endothelial injury.
Supports equivalent renoprotection with either CCB added to irbesartan in diabetic rats; hypothesis-generating and should not yet change practice.
Background: Excessive urinary albumin excretion is associated with hypertension and diabetic nephropathy.Calcium channel blockers (CCBs) used as antihypertensives suppress such albuminuria with variable efficacy.While hypertension benefits from the addition of angiotensin receptor blockers (ARBs), it is unknown if ARBs alter the effects of CCBs on albuminuria.Objective: This study compared the efficacy of combined ARB irbesartan with either CCB amlodipine or CCB cilnidipine on albuminuria associated with experimental diabetic nephropathy.Methods: Male Sprague-Dawley rats with streptozotocin-induced diabetes were treated with a CCB alone (amlodipine 2.0 mg/kg/d or cilnidipine 2.0 mg/kg/d), an ARB alone (irbesartan 20.0 mg/kg/d), or combinations.In the acute protocol, changes in glomerular afferent and efferent arteriole diameters were examined by a charge-coupled device video microscope following single doses.In the chronic protocol, urinary albumin excretion, glomerular reactive oxygen species, and endothelial surface layer (ESL) condition were evaluated after 2 weeks of daily treatment.Results: In the acute protocol, cilnidipine mono therapy caused a greater dilation in glomerular efferent arterioles than amlodipine monotherapy, while combination therapy with irbesartan induced comparable efferent arteriole dilation.In the chronic protocol, cilnidipine mono therapy suppressed albuminuria, reduced glomerular oxidative stress, and protected the glomerular ESL against degeneration to a much greater extent that amlodipine monotherapy.However, addition of irbesartan reduced albumin excretion, oxidative stress, and ESL degeneration to the same extent in both groups.Conclusions: While cilnidipine is more effective alone, the combinations of irbesartan with cilnidipine or amlodipine are equally effective for reducing albuminuria and other pathological sequela of experimental diabetic nephropathy.
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Minoru Satoh Yuko Nishi (2015) studied Streptozotocin-induced diabetic nephropathy in male Sprague-Dawley rats (n=69). Irbesartan combined with cilnidipine or amlodipine vs. Cilnidipine monotherapy (2.0 mg/kg/d), amlodipine monotherapy (2.0 mg/kg/d), irbesartan monotherapy (20.0 mg/kg/d), untreated diabetic control, and non-diabetic control was evaluated on Urinary albumin excretion, glomerular afferent/efferent arteriole diameters, glomerular oxidative stress, and endothelial surface layer (ESL) degeneration (p=<0.05). Combination therapy with irbesartan plus either cilnidipine or amlodipine equally reduced albuminuria, glomerular oxidative stress, and endothelial surface layer degeneration in diabetic rats (p<0.05).
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