Renal Parenchymal Hypertension Research Articles

Comparison of structural and functional vascular disorders in patients with comorbidity of non-alcoholic fatty liver disease and two types of arterial hypertension

Background: The aim was to conduct a comparative assessment of structural and functional vascular disorders in patiets with comorbidity of non-alcoholic fatty liver disease (NAFLD) and two types of arterial hypertension (HTN). Material and methods: The study included 329 patients 18–66 years old. All patients were divided into five groups: patients with comorbidity of NAFLD and primary HTN (121 subjects), patients with comorbidity of NAFLD and renal parenchymal HTN (88 subjects), patients with NAFLD (60 subjects), patients with primary HTN (30 subjects), patients with renal parenchymal HTN (30 people). The control group consisted of 20 healthy individuals of similar age and gender categories. Results: In the comparative analysis of the structural and functional ultrasonographic parameters of vessels, no significant differences between two comorbidity groups NAFLD + primary HTN and NAFLD + renal parenchymal HTN were found. The influence of AH and degree of liver steatosis on ultrasound indicators of arteries in examined patients with comorbidity was evaluated by MANOVA analysis. The influence of the HTN factor and the influence of the liver steatosis factor were evaluated separately, after which the influence of the comorbidity factor, i.e., the combined influence of these factors and one or another indicator, was evaluated. The additive effect of the factors of AH and liver steatosis was identified according to the parameters: intima media thickness, pulse wave velocity in the carotid artery, pulse wave velocity in the abdominal aorta and endothelial-related vasodilation, which indicates an important comorbid effect of NAFLD and primary/renal parenchymal HTN on the structural and functional state of arteries. Conclusions: There are no differences between the structural and functional indicators of arteries in patients with comorbidity of NAFLD + primary HTN and NAFLD + renal parenchymal HTN. The factor of the presence of HTN and the degree of liver steatosis significantly affect structural and functional indicators of the studied arteries.

Disorders Causing Secondary Hypertension in Patients Less Than 45 Years of Age

Objective: To determine the frequency of disorders causing secondary hypertension in patients less than 45 years of age.
 Study Design: Cross-sectional study.
 Place and Duration of Study: Department of Pathology and Medicine, Combined Military Hospital (CMH), Risalpur, Pakistan, along with Armed Forces Institute of Pathology (AFIP)and Pak Emirates Military Hospital (PEMH) Rawalpindi, Pakistan from Apr 2017 to Apr 2019.
 Methodology: A total of 50 patients, less than 45 years of age, newly diagnosed with hypertension (systolic blood pres-sure>140 mm Hg or diastolic BP>90 mm Hg) and reported to CMH Risalpur for the workup of HTN were included. Analysis of serum cholesterol, triglycerides, urea, creatinine, sodium, potassium, calcium, thyroid stimulating hormone, plasma glucose random, urine analysis and renal ultrasonography were carried out. In addition, serum cortisol, 24 hours urinary free cortisol, dexamethasone suppression test, growth hormone level, insulin-like growth factor-1,24 hours urinary vanillylmandelic acid, serum aldosterone and renin levels, Doppler renal ultrasonography, renal arteriogram, CT abdomen, MRI pituitary and MR/CT angiography were carried out.
 Results: A total of 50 patients comprised of 82% males and 18% females with a mean age of 36.1±6.2years. Primary hypertension was in observed in 31(62%) cases. Secondary causes of HTN in 19(38%) cases, were obstructive sleep apnea (4, 8%), primary hyperaldosteronism (3,6%), renal parenchymal hypertension (3,6%), renal artery stenosis (1,2%), Cushing's syndrome (2,4%), hyperthyroidism (2,4%), hypothyroidism (2,4%), pheochromocytoma (1,2%) and coarctation of aorta (1,2%) cases.
 Conclusion: Obstructive sleep apnea primary hyper-aldosteronism and renal parenchymal diseases were the commonest.........

SHOULD ALL SECONDARY CAUSES OF HYPERTENSION BE SCREENED IN PATIENTS WITH RESISTANT ARTERIAL HYPERTENSION?

Objective: Secondary hypertension often presents as treatment-resistant hypertension. Patients with resistant hypertension therefore undergo an extensive workup to identify a potential secondary cause. We aimed to analyze whether it is necessary to screen all patients presenting with resistant arterial hypertension for all secondary causes of hypertension. Design and method: We retrospectively analysed the hospital records of patients with resistant arterial hypertension, who underwent complete laboratory and imaging examinations to exclude the secondary etiology of arterial hypertension. Standard descriptive statistics were used for statistical evaluation. Results: Among the 432 patients with resistant hypertension, secondary etiology of hypertension was found in 135 (31.1%). The most frequent cause was primary aldosteronism in 85 cases (63% relatively), followed by renovascular hypertension (15.6%), renal parenchymal hypertension (14.8%) and hyperreninism (3.7%). Obstructive sleep apnoea has been found in 14.7% patients. Less common causes were hypercortisolism (1.5%), pheochromocytoma (0.7%) and adrenogenital syndrome (0.7%). All patients with the last three rare causes presented with specific clinical symptoms (i.e. patient with pheochromocytoma was admitted for paroxysmal hypertension, adrenogenital syndrome was diagnosed in female patient with secondary male sex characteristics, patients with hypercortisolism had typical cushingoid signs). Conclusions: Secondary etiology was much more frequent (31%) in our group of patients with resistant hypertension than in non-selected hypertensive population (5–15%). We suggest that first line testing only for primary hyperaldosteronism and renovascular hypertension would be sufficient for patients with resistant hypertension without clinical clues suggestive of another particular secondary cause of hypertension.

Urinary tract infection in children presenting with diarrhea

Background: Urinary tract infection (UTI) are the 3rd most common bacterial infection in infants and young children in developing countries after those of respiratory and gastrointestinal tract infection. Because of nonspecific signs and vague symptoms in very young children, they may remain unrecognized. Rapid evaluation and treatment of UTI is important to prevent renal parenchymal damage and renal scarring that can cause hypertension and progressive renal damage. Since gastroenteritis is rampant in developing countries demonstration of an association between UTI and diarrhea will be of clinical significance. The objective of this study was to estimate the prevalence of UTI in children presenting with diarrhea and to identify the clinical co-relates which may guide to identify children with UTI.Methods: This was a descriptive observational study done in 120 children meeting the inclusion and exclusion criteria, who were admitted in the paediatric ward in father Muller medical college hospital for a period of 1 and a half years. After obtaining an informed consent, a detailed clinical examination was performed on children meeting the inclusion criteria and the data was entered to the preformatted sheet. Urine samples were obtained from all the patients by clean catch mid-stream urine sample, following which urine culture was done for all the children.Results: In the present study, out of 120 children presenting with Diarrhea 17% had UTI. E. coli (15 cases) was the most common organism isolated in urine culture followed by Enterococcus. Out of 20 UTI cases, 15 were in the age group of 6 months to 1 year followed by 4 cases among 1-3-year age group.18 out of 20 UTI cases were females. Male:female ratio of UTI patients was 1:9.Conclusions: UTI in young children can present with diarrhea and other nonspecific symptoms. Children presenting with diarrhea need to have a urine analysis and urine culture for the confirmation of UTI, so that long term complications like renal parenchymal damage and hypertension can be prevented.

SECONDARY CAUSES OF HYPERTENSION IN PATIENTS WITH RESISTANT ARTERIAL HYPERTENSION

Objective: Resistant hypertension is defined as blood pressure that remains above therapeutic goal despite concurrent use of three antihypertensive agents (at full or maximum tolerated doses) of different classes, one of which is a diuretic. The prevalence of secondary causes of hypertension among patients with resistant hypertension is not exactly known. Design and method: We retrospectively analysed the hospital records of patients with resistant arterial hypertension, who underwent complete laboratory and imaging examinations to exclude the secondary etiology of arterial hypertension. Standard descriptive statistics were used for statistical evaluation. Results: Among the 600 patients with resistant hypertension, secondary etiology of hypertension was found in 160 (27,5%). The most frequent cause was primary aldosteronism in 93 cases (58% relatively), followed by renovascular hypertension (30 cases, 18.8%), renal parenchymal hypertension (25 cases, 15,6%). Less common causes were pheochromocytoma (3,1%), hyperreninism (3.1%), hypercortisolism (0,6%). Obstructive sleep apnoea has been found in 75 (12.5%) patients. Conclusion: Secondary etiology was much more frequent (27,5%) in our group of patients with resistant hypertension than in non-selected hypertensive population (5–15%). Conclusions: This work was supported by IGA_LF_2019_036, IGA_LF_2020_039

PREVALENCE OF SECONDARY HYPERTENSION IN PATIENTS WITH RESISTANT ARTERIAL HYPERTENSION

Objective: Resistant hypertension is defined as blood pressure that remains above therapeutic goal despite concurrent use of three antihypertensive agents (at full or maximum tolerated doses) of different classes, one of which is a diuretic. The prevalence of secondary hypertension among patients with resistant hypertension is not exactly known. Design and method: We retrospectively analysed the hospital records of patients with resistant arterial hypertension, who underwent complete laboratory and imaging examinations to exclude the secondary etiology of arterial hypertension. Standard descriptive statistics, Mann-Whitney U test and Fisher's exact test were used for statistical evaluation. Results: Among the 432 patients with resistant hypertension, secondary etiology of hypertension was found in 135 (31.1%). The most frequent cause was primary aldosteronism in 85 cases (63% relatively), followed by renovascular hypertension (21 cases, 15.6%), renal parenchymal hypertension (20 cases, 14.8%). Less common causes were hyperreninism (3.7%), hypercortisolism (1.5%), pheochromocytoma (0.7%) and adrenogenital syndrome (0.7%). Obstructive sleep apnoea has been found in 63 (14.7%) patients. Patients with secondary hypertension were more frequently male (70.4% vs. 52.2%, p < 0.001), had a higher left ventricular mass index (LVMI 119 vs. 106 g / m2, P = 0.037) and lower estimated glomerular filtration rate (69 vs. 75 ml/min/1.73m2, P = 0.009). Both groups did not differ in age, office blood pressure or albuminuria. Conclusions: Secondary etiology was much more frequent (31%) in our group of patients with resistant hypertension than in non-selected hypertensive population (5–15%). Patients with secondary hypertension had more advanced target organ damage. This work was supported by the grant UP - IGA_LF_2019_036 a IGA_LF_2019_035. This work was supported by the grant IGA_LF_2020_039

Etiology and clinical analysis of 232 hospitalized children with hypertension

Objective To analyze the etiology and clinical characteristics of hypertension in children; to analyze the risk factors for primary hypertension with target organ damage, and to provide evidence for clinical diagnosis of hypertension in children. Methods Two hundred and thirty-two hospitalized children with hypertension at Children′s Hospital Institute of Pediatrics from April 2013 to December 2017 were retrospectively analyzed, including general situation, clinical manifestation, laboratory examination, auxiliary examination and damage assessment of target organs. Results (1)There were totally 232 eligible cases, consisting of 184 males(79.3%) and 48 females(20.7%). Among these children: 38 cases(16.4%), 126 cases(54.3%), and 68 cases(29.3%) were diagnosed as prehypertension, hypertension in stage Ⅰ, and hypertension in stage Ⅱ, respectively.(2)The etiological composition of hypertension: there were 181 cases(78%) diagnosed as primary hypertension and 51 cases(22%) diagnosed as secondary hypertension, respectively; the proportion of the primary hypertension children during the period of preschool, school-age, and adolescent was 1.6%(3 cases), 21.0%(38 cases) and 77.4%(140 cases), respectively.The etiology of secondary hypertension was mostly of the renal parenchymal hypertension and renal vascular hypertension(43.1%). (3) The clinical manifestations of primary hypertension were mostly of asymptomatic or mild symptoms, totally 148 cases(64%), and then dizziness, headache, chest pain, chest tightness, palpitation, blurred vision, and other clinical symptoms.(4) The high risk factors for primary hypertension with target-organ damage included cesarean section, glucose metabolism disturbance and body mass index >24 kg/m2. Conclusions In recent years, the proportion of primary hypertension among hospitalized children has increased.The changes in the etiology of secondary hypertension are not found.Primary hypertension children are often accompanied with target organ damage.It is of great significance to make blood pressure monitoring as a routine physical examination for primary and middle school students, so as to detect hypertension in children earlier, and make active intervention and improve the prognosis of hypertension in children. Key words: Hypertension; Child; Etiology; Clinical characteristics

Systemic Vasculitis: An Important and Underestimated Cause of Malignant Hypertension

Objectives: Malignant hypertension (MHT) is defined as severe hypertension accompanied by ischemic failure of one or more organs. The aims of this study were to evaluate the current clinical and etiologic profiles of MHT. Methods: As a retrospective study, we selected all patients admitted to our center from January 2013 to December 2016. Seventy patients with MHT were included. Results: The average age of the patients was 40 years, and more than half of the patients were male (78.57%). There were 24 patients with essential hypertension, accounting for 34.29% of the patients, and 46 with secondary hypertension, accounting for 65.71% of the patients. For secondary MHT, systemic vasculitis (25.57%) was the most common cause, followed by severe obstructive sleep apnea syndrome (15.71%), primary renal parenchymal hypertension (11.43%), primary aldosteronism (7.14%), and Cushing syndrome (1.43%) and nutcracker phenomenon (1.43%). Twenty patients with systemic vasculitis were characterized by severe hypertension accompanied by damage to two or more target organs of differing severity. The levels of white blood cells, hypersensitive C-reactive protein, serum creatinine, and 24-hour urinary protein were above their normal range. Conclusion: Systemic vasculitis may be one of the main causes of MHT, and has been underestimated in the past. In future clinical work, clinicians need to pay more attention to patients with systemic vasculitis.

RENAL ARTERIAL HYPERTENSION IN CHILDREN AND ADOLESCENTS: CAUSES, CLASSIFICATION, DIAGNOSIS

Classification of blood pressure in children and adolescents, features of renovascular hypertension and renal parenchymal hypertension in children and adolescents. Mid-aortic syndrome is characterized by the narroving of the abdominal aorta and bilateral renal artery stenosis. In the article are discussed diagnosis renal arterial hypertension and the defeat of target-organs in children and adolescents.

Bilateral nephrectomy for uncontrolled hypertension in hemodialysis patient: A forgotten option?

Resistant arterial hypertension in chronic hemodialysis patients is still a therapeutical challenge despite the development of modern antihypertensive drugs and dialysis procedures. Bilateral nephrectomy seems to be a forgotten option, although it has given good results. We present a case of a 39-year-old female chronic hemodialysis patient, in whom the problem of uncontrolled renal parenchymal hypertension remained despite multiple drug therapy and the ultrafiltration intensification. The problem was solved by bilateral nephrectomy. We discuss the role of bilateral nephrectomy for arterial hypertension control in chronic hemodialysis patients and the surgical and non-surgical options of nephrectomy.

Approach to a case of secondary hypertension

Abstract Secondary hypertension, i.e. where a definite cause for hypertension can be found, is not uncommon in clinical practice and accounts for about 5% cases of hypertension. Common causes of secondary hypertension include renal parenchymal disease, renovascular hypertension, Conn Syndrome and pheochromocytoma. In Asian countries, aortoarteritis is still a common cause of secondary hypertension among young patients, especially females. Early diagnosis and appropriate treatment may significantly alter the natural history of the disease with substantial improvement in prognosis. Whenever a patient is diagnosed with hypertension, every effort should be made to rule out any possible secondary cause for the hypertension. Suspicion of secondary hypertension should be high in early or late onset hypertension, resistant hypertension, accelerated hypertension and in patients with markedly elevated blood pressure with severe target organ damage. Reno-vascular hypertension can be evaluated by non-invasive modalities like Ultrasound Doppler, MR angiography and CT angiography. If primary aldosteronism is suspected, patients should undergo screening with plasma rennin/aldosterone ratio and MRI for the detection of morphological adrenal abnormalities. Patient suspected of pheochromocytoma shows an increase in plasma or urinary catecholamines, but CT and MRI are needed to localize the tumours. Targeted testing should be done in all these patients to rule out any possible cause for secondary hypertension. Careful and thorough clinical evaluation and simple algorithms are needed to avoid unnecessary tests in making the diagnosis of secondary forms of hypertensions more accurately and promptly. Correcting the cause of secondary hypertension can lead to cure, avoiding the need for long-term medical therapy.

Risk factors for atherosclerosis in patients with chronic kidney disease: recognition and management

Heart disease is the most common cause of death in patients with chronic kidney disease (CKD), particularly in those receiving dialysis. Atherosclerosic cardiovascular (CV) disease (CVD) accounts for a large number of these deaths. Atherosclerosis is accelerated in patients with CKD due predominantly to the high prevalence of traditional CVD risk factors in the CKD population. CKD aggravates pre-existent traditional risk factors such as hypertension and dyslipidemia due to secondary renal parenchymal hypertension and secondary dyslipidemia. In addition, a variety of non-traditional risk factors that occur commonly in CKD patients contribute to CV risk. Recent studies suggest that CKD itself may be an independent risk factor for CVD, particularly coronary heart disease (CHD). Many therapies aimed at CV risk factor modification that have been successful in reducing CV risk in the general population are less effective or ineffective in favorably modifying CV risk in CKD.

Artist® Tablets (Carvedilol) for Hypertensive Patients in Japan

Background: In Japan, when pharmaceutical companies launch a new drug, they are obligated to conduct a post-marketing survey to evaluate the safety and efficacy of the drug in accordance with Good Post-Marketing Surveillance Practice under Article 14-4 (re-examination) of the Pharmaceutical Affairs Law at contracted medical institutions. We report the results of a long-term special survey that we conducted as a post-marketing survey.Objective: The results of a prospective post-marketing survey that was conducted to assess the safety and efficacy of the b-adrenergic receptor antagonist (β-blocker) Artist® tablets 10 mg, 20mg (carvedilol) in patients with hypertension in Japan, were investigated in order to examine the safety and efficacy of the drug during long-term treatment (18 months).Patients: Patients were carvedilol-naive and had essential hypertension or renal parenchymal hypertension.Methods: We performed this survey as a prospective cohort study (special survey) utilizing a centralized registration method over 3 years (starting from April 1994), for an observation period of 18 months of carvedilol treatment.Results: Sixty-one medical institutions across Japan collected 380 case report forms of patients who received long-term administration of carvedilol, with 363 and 341 cases evaluated for safety and efficacy, respectively. The discontinuation rate was 7.2% and the incidence of adverse drug reactions was 5.23% (19 of 363) in the safety population. There was no significant change in fasting plasma glucose levels from baseline (118.1 ± 46.5mg/dL) to after carvedilol treatment (114.6 ± 43.3 mg/dL) [n = 141; p = 0.310].In 341 evaluable patients in the efficacy population, decreases in both blood pressure and pulse rate were statistically significant at all assessment points in comparison with baseline data (p < 0.001). Similarly, in hypertensive patients with diabetes mellitus, decreases in blood pressure were statistically significant at all assessment points in comparison with baseline data (p < 0.001).Conclusions: The results of this study show that carvedilol exerted stable antihypertensive effects leading to favorable blood pressure control throughout long-term treatment, without showing any safety concerns. It was concluded that there were no clinically significant issues in terms of safety or efficacy with the long-term treatment of carvedilol in patients with hypertension.

Artist® Tablets (Carvedilol) for Hypertensive Patients in Japan

Background: In Japan, when pharmaceutical companies launch a new drug, they are obligated to conduct a post-marketing survey to evaluate the safety and efficacy of the drug in accordance with Good Post-Marketing Surveillance Practice under Article 14.4 (re-examination) of the Pharmaceutical Affairs Law at contracted medical institutions. We report the results of a drug use survey, which we conducted as a post-marketing survey.Objective: This prospective post-marketing drug use survey was conducted to assess the safety and efficacy of the β-adrenergic receptor antagonist (β-blocker) Artist® Tablets (carvedilol) in patients with hypertension in Japan.Patients: Patients were carvedilol-naive and had essential hypertension or renal parenchymal hypertension.Methods: This was a prospective survey conducted over 3 years from October 1993 to September 1996. The standard observation period for the patients was defined as 12 weeks of treatment with carvedilol.Results: We collected data on 4961 patients at 561 medical institutions who had not been previously treated with carvedilol; 4574 patients were included in the safety analysis and 4422 in the efficacy analysis. The incidence of adverse drug reactions (the proportion of patients with adverse drug reactions) was 4.31% (197 of 4574 patients), which is less than that shown in the pre-approval clinical trial of carvedilol (6.85%[68 of 993]). The most common adverse drug reactions were bradycardia, dizziness, hypotension, headache, and feeling light-headed.After 12 weeks’ treatment with carvedilol, systolic/diastolic blood pressure (SBP/DBP) was reduced from 168.2 ± 18.6/95.7 ± 11.3mmHg at baseline to 144.3 ± 17.3/83.4 ± 10.8mmHg. Patients were classified according to which antihypertensive drug they had been using when carvedilol treatment was initiated. Coadministered agents were calcium channel blockers (CCBs), angiotensinconverting enzyme inhibitors (ACEIs), diuretics, and a-adrenergic receptor antagonists (α-blockers). At 12 weeks, the change in SBP/DBP in the monotherapy group was −22.7/−12.2mmHg and that of each combination therapy subgroup, CCB, ACEI, diuretic, and b-blocker, was −26.1/−12.7mmHg, −25.4/−11.9mmHg, −26.3/−13.0mmHg, and −24.4/−11.5mmHg, respectively. The achievement rates for target BP (<140/90mmHg) were 29.5% in the monotherapy group, 34.8% in the CCB group, 31.3% in the ACEI group, 31.8% in the diuretic group, and 32.4% in the β-blocker group. There was no significant difference in the achievement of target BP among the four combination therapy subgroups (p = 0.475). These results indicate that carvedilol exerts reasonable BP reduction regardless of whether it is used as monotherapy or in combination therapy, and that the effect is not influenced by the coadministered drug. Moreover, carvedilol was also effective in reducing BP levels in elderly patients (≥65 years) and in patients with diabetes mellitus or renal diseases.Conclusions: The results of this study reflect the results of clinical trials up to the time of approval and it was confirmed that carvedilol is a highly useful drug in the treatment of hypertension.

腎実質性高血圧症入院患者における Nitrendipine の血圧日内変動に及ぼす影響

腎実質性高血圧症入院患者における Nitrendipine の血圧日内変動に及ぼす影響

Secondary Hypertension

Hypertension is a common disease and a crucial predisposing factor of cardiovascular diseases. Approximately 10% of hypertensive patients are secondary hypertension, a pathogenetic factor of which can be identified. Secondary hypertension consists of endocrine, renal, and other diseases. Primary aldosteronism, Cushing's syndrome, pheochromocytoma, hyperthyroidism, and hypothyroidism result in endocrine hypertension. Renal parenchymal hypertension and renovascular hypertension result in renal hypertension. Other diseases such as obstructive sleep apnea syndrome are also very prevalent in secondary hypertension. It is very crucial to find and treat secondary hypertension at earlier stages since most secondary hypertension is curable or can be dramatically improved by specific treatment. One should keep in mind that screening of secondary hypertension should be done at least once in a daily clinical practice.

An Open-label, Randomized, Controlled, 4-week Comparative Clinical Trial of Barnidipine Hydrochloride, a Calcium-channel Blocker, and Benazepril, an Angiotensin-converting Enzyme Inhibitor, in Chinese Patients with Renal Parenchymal Hypertension

This study compared barnidipine, a calcium-channel blocker, and benazepril, an angiotensin-converting enzyme inhibitor, in 85 Chinese patients with renal parenchymal hypertension (diastolic blood pressure range 95 - 110 mmHg). Patients were randomly assigned to receive either 10 mg barnidipine or 10 mg benazepril orally daily for 4 weeks. In patients with diastolic blood pressure > 90 mmHg after 2 weeks of treatment, the dose of barnidipine or benazepril was increased by 5 or 10 mg, respectively. Both the barnidipine-treated group (n = 43) and the benazepril-treated group (n = 42) showed significant mean reductions from baseline in sitting systolic and diastolic blood pressures. The decrease in diastolic blood pressure with benazepril was significantly greater than with barnidipine treatment. Sitting heart rate was not changed by either drug. There was no significant difference in adverse events between the two groups. Barnidipine is similar to benazepril for the treatment of renal parenchymal hypertension.

Thromboxane blockade reduces blood pressure and progression of renal failure independent of endothelin-1 in uremic rats

This study was designed to investigate the role of eicosanoids, thromboxane A 2 (TXA 2) and prostacyclin (PGI 2) as well as their relationship with endothelin-1 (ET-1) in the pathogenesis of renal parenchymal hypertension. Uremic rats were prepared by renal mass ablation and compared with sham-operated controls. The stable metabolites of TXA 2 (TXB 2) and PGI 2 (6-keto-PGF 1α) and immunoreactive ET-1 concentrations were measured by specific RIAs in biological fluids and in vascular and renal tissues. To investigate the functional role of TXA 2 in the progression of hypertension and renal failure, a group of uremic rats were treated with ridogrel (25 mg/kg/day), a TXA 2 synthase inhibitor and receptor antagonist. Renal preproET-1 expression was assessed by Northern blot analysis. Systolic blood pressure (SBP), serum creatinine and proteinuria were found to be higher in uremic rats as compared to sham-operated controls ( P<0.01). TXB 2 and ET-1 concentrations were increased in blood vessels, the renal cortex and in urine ( P<0.05). 6-keto-PGF 1 α concentrations were also increased in blood vessels and the renal cortex but decreased in urine ( P<0.05). Ridogrel significantly lowered SBP and proteinuria ( P<0.05) and blunted the increase of serum creatinine. Treatment with ridogrel resulted in a marked fall in vascular, renal and urine TXA 2 concentrations, while ET-1 and 6-keto-PGF 1 α concentrations remained unchanged. The preproET-1 expression was higher in uremic rats than in the controls and was unaffected by ridogrel. These results suggest that TXA 2 is involved in the pathogenesis of hypertension and renal failure progression in rats with subtotal 5/6 nephrectomy and that this effect is independent of the ET-1 system.

Open-label, uncontrolled, clinical trial of barnidipine hydrochloride in Korean patients with renal parenchymal hypertension

Background: Barnidipine hydrochloride is a calcium channel blocker that is administered in a single daily dose. It has been shown to be effective in lowering blood pressure in Japanese patients with essential hypertension, renal parenchymal hypertension, and renovascular hypertension. Objective: The purpose of this study was to assess the antihypertensive efficacy and tolerability of barnidipine hydrochloride in Korean patients with renal parenchymal hypertension. Methods: This open-label, uncontrolled study used a dose-escalation design, with 5 to 15 mg barnidipine administered once daily for 4 to 8 weeks. Korean patients with renal parenchymal hypertension were enrolled. Results: Of the 31 patients enrolled, 30 (15 men and 15 women; mean age, 45.1 ± 10.4 years; mean body weight, 62.5 ± 10.4 kg; mean sitting systolic blood pressure [SBP], 158.0 ± 13.2 mm Hg; mean diastolic blood pressure [DBP], 101.8 ± 7.1 mm Hg) completed the entire schedule of drug administration. One patient discontinued hospital visits at 2 weeks. In 3 patients treated with barnidipine 5 mg/d for 4 weeks, mean SBP and DBP were 131.7 ± 16.1 mm Hg and 85.0 ± 5.0 mm Hg, respectively, after 4 weeks of treatment compared with 160.0 ± 34.6 mm Hg and 105.0 ± 13.2 mm Hg at baseline. In 15 patients treated with barnidipine 5 mg/d for 2 weeks and 10 mg/d for 4 weeks, mean SBP and DBP were 138.3 ± 7.9 mm Hg and 84.3 ± 8.0 mm Hg, respectively, 6 weeks after treatment compared with 160.7 ± 13.7 mm Hg and 102.7 ± 9.0 mm Hg at baseline ( P < 0.05). In 12 patients treated with barnidipine 5 mg/d for 2 weeks, 10 mg/d for 2 weeks, and 15 mg/d for 4 weeks, mean SBP and DBP were 139.6 ± 8.7 mm Hg and 85.8 ± 8.7 mm Hg, respectively, 8 weeks after treatment compared with 158.3 ± 13.7 mm Hg and 100.8 ± 6.0 mm Hg at baseline ( P < 0.05). Mean sitting SBP after 4 to 8 weeks of treatment with barnidipine was 139.9 ± 8.5 mm Hg (mean reduction, 18.1 mm Hg [11.4%]) and mean sitting DBP was 85.5 ± 7.5 mm Hg (mean reduction, 16.3 mm Hg [16%]). Sitting heart rate did not change after treatment with barnidipine. Barnidipine was well tolerated; mild adverse events occurred in 5 of 30 patients (17%) and included facial flushing (13%), tachycardia (13%), and headache (7%). Conclusions: The results suggest that barnidipine is effective in reducing systemic hypertension and is well tolerated in this sample of Korean patients with renal parenchymal hypertension.

Antihypertensive efficacy and tolerability of barnidipine hydrochloride in patients with renal parenchymal hypertension

ObjectiveThe goal of this study was to assess the therapeutic efficacy and tolerability of barnidipine hydrochloride in patients with renal parenchymal hypertension. MethodsThe study consisted of 2 phases: a 2-week observation period and a 6- to 8-week treatment period. During the observation period, 1 placebo capsule was administered orally once daily for 2 weeks. One capsule of barnidipine 5 mg was given orally once daily during the initial 2 weeks of the treatment period. If the target hypotensive effect (ie, a decrease in systolic blood pressure [SBP]>20 mm Hg or in diastolic blood pressure [DBP]>10 mm Hg) was not achieved during the initial treatment period, the daily dose of barnidipine could be increased in 5-mg increments at 2-week intervals up to a maximum daily dose of 15 mg. Patients were instructed to discontinue all medications that could affect blood pressure. ResultsThirty-seven patients with renal parenchymal hypertension were enrolled. Of these, 31 completed the study. Six patients dropped out: 2 voluntarily discontinued treatment during the observation period; 2 stopped hospital visits at 4 and 6 weeks, respectively; and 2 discontinued because of adverse events. At the end of the 2-week observation period, the median values for baseline SBP and DBP were 170 mm Hg (range, 140ȁ200 mm Hg) and 110 mm Hg (range, 95ȁ130 mm Hg), respectively. After the initial 2 weeks of treatment, the respective values were 150 mm Hg (range, 120ȁ185 mm Hg) and 100 mm Hg (range, 80ȁ130 mm Hg). After 4 weeks of treatment, median SBP was 145 mm Hg (range, 120ȁ180 mm Hg) and median DBP was 90 mm Hg (range, 80ȁ130 mm Hg). At the end of treatment, the respective SBP and DBP values were 140 mm Hg (range, 120ȁ180 mm Hg) and 90 mm Hg (range, 70ȁ130 mm Hg). All of these reductions were significant compared with baseline values (P < 0.01). Blood pressure was considered to be reduced in 25 patients (80.6%), slightly reduced in 1 (3.2%), unchanged in 4 (12.9%), and slightly elevated in 1 (3.2%). Heart rate was not significantly affected. No significant adverse events were observed during or after treatment with barnidipine. ConclusionResults of this study suggest that barnidipine may be helpful in treating patients with renal parenchymal hypertension.