Effect of Cilnidipine on Normal to Marginally Elevated Urine Albumin-Creatinine Ratio in Asymptomatic Non-Diabetic Hypertensive Patients

Nakatsu, Takaaki; Toyonaga, Shinji; Mashima, Keiichi; Yuki, Yoko; Nishitani, Aya; Ogawa, Hiroyasu; Miyoshi, Toru; Hirohata, Satoshi; Izumi, Reishi; Kusachi, Shozo

doi:10.2165/11538510-000000000-00000

Cited by 2 publications

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“…In addition to studies on microalbuminuria reduction, however, studies focusing on the reduction of normal to high-normal UACR values using drugs are also important. Our recent study clearly demonstrated that cilnidipine, an L-and N-type calcium channel blocker, reduced not only microalbuminuria but also normal to high-normal levels of UACR (45). Further studies on high-normal UACR reduction using various series of drugs are essential.…”

Section: Discussionmentioning

confidence: 85%

Distribution Pattern of Urine Albumin Creatinine Ratio and the Prevalence of High-Normal Levels in Untreated Asymptomatic Non-Diabetic Hypertensive Patients

et al. 2011

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Background Even high-normal albuminuria is reportedly associated with cardiovascular events. Objective We determined the urine albumin creatinine ratio (UACR) in spot urine samples and analyzed the UACR distribution and the prevalence of high-normal levels. Patients and MethodsThe UACR was determined using immunoturbidimetry in 332 untreated asymptomatic non-diabetic Japanese patients with hypertension and in 69 control subjects. The microalbuminuria and macroalbuminuria levels were defined as a UCAR !30 and <300 μg/mg creatinine and a UCAR !300 μg/ mg creatinine, respectively. Results The distribution patterns showed a highly skewed distribution for the lower levels, and a common logarithmic transformation produced a close fit to a Gaussian distribution with median, 25th and 75th percentile values of 22.6, 13.5 and 48.2 μg/mg creatinine, respectively. When a high-normal UACR was set at >20 to <30 μg/mg creatinine, 19.9% (66/332) of the hypertensive patients exhibited a high-normal UACR. Microalbuminuria and macroalbuminuria were observed in 36.1% (120/336) and 2.1% (7/332) of the patients, respectively. UACR was significantly correlated with the systolic and diastolic blood pressures and the pulse pressure. A stepwise multivariate analysis revealed that these pressures as well as age were independent factors that increased UACR. Conclusion The UACR distribution exhibited a highly skewed pattern, with approximately 60% of untreated, non-diabetic hypertensive patients exhibiting a high-normal or larger UACR. Both hypertension and age are independent risk factors that increase the UACR. The present study indicated that a considerable percentage of patients require anti-hypertensive drugs with antiproteinuric effects at the start of treatment.

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Section: Discussionmentioning

confidence: 85%

Distribution Pattern of Urine Albumin Creatinine Ratio and the Prevalence of High-Normal Levels in Untreated Asymptomatic Non-Diabetic Hypertensive Patients

et al. 2011

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Inhibition of dynamin‐related protein 1‐filamin interaction improves systemic glucose metabolism

Kato,

Ariyoshi,

Nohara

et al. 2024

British J Pharmacology

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Background and purposeMaintaining mitochondrial quality is attracting attention as a new strategy to treat diabetes and diabetic complications. We previously reported that mitochondrial hyperfission by forming a protein complex between dynamin‐related protein (Drp) 1 and filamin, mediates chronic heart failure and cilnidipine, initially developed as an L/N‐type Ca2+ channel blocker, improves heart failure by inhibiting Drp1‐filamin protein complex. We investigated whether cilnidipine improves hyperglycaemia of various diabetic mice models.Experimental ApproachRetrospective analysis focusing on haemoglobin A1c (HbA1c) was performed in hypertensive and hyperglycaemic patients taking cilnidipine and amlodipine. After developing diabetic mice by streptozotocin (STZ) treatment, an osmotic pump including drug was implanted intraperitoneally, followed by weekly measurements of blood glucose levels. Mitochondrial morphology was analysed by electron microscopy. A Ca2+ channel‐insensitive cilnidipine derivative (1,4‐dihydropyridine [DHP]) was synthesized and its pharmacological effect was evaluated using obese (ob/ob) mice fed with high‐fat diet (HFD).Key ResultsIn patients, cilnidipine was superior to amlodipine in HbA1c lowering effect. Cilnidipine treatment improved systemic hyperglycaemia and mitochondrial morphological abnormalities in STZ‐exposed mice, without lowering blood pressure. Cilnidipine failed to improve hyperglycaemia of ob/ob mice, with suppressing insulin secretion. 1,4‐DHP improved hyperglycaemia and mitochondria abnormality in ob/ob mice fed HFD. 1,4‐DHP and cilnidipine improved basal oxygen consumption rate of HepG2 cells cultured under 25 mM glucose.Conclusion and implicationsInhibition of Drp1‐filamin protein complex formation becomes a new strategy for type 2 diabetes treatment.

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Effect of Cilnidipine on Normal to Marginally Elevated Urine Albumin-Creatinine Ratio in Asymptomatic Non-Diabetic Hypertensive Patients

Abstract: The present study demonstrated that cilnidipine reduced UACR in hypertensive patients with normal to marginally elevated UACR independent of its BP-lowering effect.

Cited by 2 publications

References 38 publications

Distribution Pattern of Urine Albumin Creatinine Ratio and the Prevalence of High-Normal Levels in Untreated Asymptomatic Non-Diabetic Hypertensive Patients

Distribution Pattern of Urine Albumin Creatinine Ratio and the Prevalence of High-Normal Levels in Untreated Asymptomatic Non-Diabetic Hypertensive Patients

Inhibition of dynamin‐related protein 1‐filamin interaction improves systemic glucose metabolism

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