Association of abnormalities in electrocardiography and ultrasonic echocardiography with the occurrence of cardiovascular disease in patients with advanced chronic kidney disease.

BACKGROUND: In patients with chronic kidney disease (CKD), the incidence of cardiovascular disease (CVD) increases with disease progression. CVD screening tests in those with CKD were researched to determine whether abnormalities observed in electrocardiography (ECG) and ultrasonic echocardiography (UCG) were risk factors associated with the development of CVD. METHODS: This study included 604 patients with CKD G4 and G5, for whom both ECG and UCG were performed. They were divided into four groups: those without ECG- and UCG-indicated abnormalities (group A, n = 333), with only ECG abnormalities (group B, n = 106), with only UCG abnormalities (group C, n = 75), and with both ECG and UCG abnormalities (group D, n = 90). Multivariate analysis using Cox regression analysis of the occurrence of CVD was performed during a follow-up period. RESULTS: During the observation period, 124 patients had clinical events. Among them, 45 patients (13.5%) were in Group A, 25 patients (23.6%) in Group B, 19 patients (25.3%) in Group C, and 35 patients (38.9%) in Group D, respectively. CVD event occurrence was highest in Group D. The results of the multivariate analysis also showed that the CVD event rates were significantly higher in Group C (HR: 2.96, P = < .001) and D (HR: 4.22, P < .001) than in Group A. CONCLUSION: In patients with advanced CKD, there was a significant correlation of ECG and UCG abnormalities with CVD events. Additionally, those having both types of abnormalities may have a higher risk of coronary artery disease than other groups.

Investigation of bone mineral density and the changes by enzyme replacement therapy in patients with Fabry disease.

BACKGROUND: Fabry disease (FD) is an inherited disorder that causes organ dysfunction. However, only a few studies have reported on bone mineral density (BMD) in FD patients, and the relationship between BMD and clinical factors such as globotriaosylsphingosine (lyso-Gb3) remains unclear. Therefore, the current study sought to investigate BMD in FD patients, the relationship between BMD and lyso-Gb3, and the effects of enzyme replacement therapy (ERT) on changes in BMD and lyso-Gb3. METHODS: This single-center, observational study included 15 patients who visited our facility for FD between January 2008 and June 2021. We assessed BMD and clinical characteristics in study patients, including plasma lyso-Gb3 levels, and examined the relationship between BMD and plasma lyso-Gb3 levels, and changes in BMD after starting ERT. RESULTS: Male patients' BMD had reduced, whereas female patients' BMD was preserved. Male patients had significantly higher plasma lyso-Gb3 levels than female patients. Moreover, plasma lyso-Gb3 levels were found to be significantly related to the lumbar spine and femoral BMD. These were strongly linked with plasma lyso-Gb3 levels in male patients, whereas no strong link was observed in female patients. Furthermore, BMD significantly increased only in male patients although plasma lyso-Gb3 levels significantly decreased by ERT in all patients. CONCLUSION: BMD decreased possibly due to Gb3 accumulation, and ERT could increase BMD in male FD patients.

Renal protective effects of astragalus root in rat models of chronic kidney disease.

BACKGROUND: Astragalus root is a commonly used herb in traditional Chinese medicine. Although renoprotective effects have been reported in some clinical and experimental studies, the details remain unknown. METHODS: We used 5/6 nephrectomized rats as chronic kidney disease (CKD) models. At 10 weeks, they were divided into four groups, namely, CKD, low-dose astragalus (AR400), high-dose astragalus (AR800), and sham groups. At 14 weeks, they were sacrificed for the evaluation of blood, urine, mRNA expression in the kidney, and renal histopathology. RESULTS: Kidney dysfunction was significantly improved following astragalus administration (creatinine clearance: sham group; 3.8 ± 0.3 mL/min, CKD group; 1.5 ± 0.1 mL/min, AR400 group; 2.5 ± 0.3 mL/min, AR800 group; 2.7 ± 0.1 mL/min). Blood pressure, urinary albumin, and urinary NGAL levels were significantly lower in the astragalus-treated groups than those in the CKD group. Excretion of urinary 8-OHdG, an oxidative stress marker, and intrarenal oxidative stress were lower in the astragalus-treated groups than those in the CKD group. Furthermore, the mRNA expression of NADPH p22 phox, NADPH p47 phox, Nox4, renin, angiotensin II type 1 receptor, and angiotensinogen in the kidney was lower in the astragalus-treated groups compared with the CKD group. CONCLUSION: This study suggests that astragalus root slowed CKD progression, possibly through the suppression of oxidative stress and the renin-angiotensin system.

Clinical value of serum cholinesterase levels in Nephrotic syndrome: an observational study.

BACKGROUND: Nephrotic syndrome (NS) results in massive proteinuria and hypoalbuminemia, which are responsible for a compensatory increase in protein synthesis in the liver. Serum cholinesterase (ChE) also increases in NS. However, its clinical value is not fully elucidated. METHODS: In this study, 184 patients with NS who underwent kidney biopsy were included. The patients were divided into two groups according to serum ChE levels, as follows: hypercholinesterasemia (HC) and non-hypercholinesterasemia (NHC) groups. The clinical factors were compared between the two groups. RESULTS: The HC group had significantly more severe proteinuria and higher prevalence of high selective proteinuria than the NHC group. Furthermore, the prevalence of minimal change nephrotic syndrome (MCNS) was significantly higher in the HC group than that in the NHC group. Multivariate analysis revealed that the severity of proteinuria and MCNS were significantly associated with HC. CONCLUSION: In this study, HC in NS was associated with the severity of proteinuria and MCNS, and could help clinicians predict the histological diagnosis of NS.

Comparison of two protocols for steroid pulse therapy in patients with IgA nephropathy: a retrospective observational study.

BACKGROUND: Steroid pulse (SP) therapy is one of the immunosuppressive therapies for immunoglobulin A nephropathy (IgAN). Although there are various protocols of SP therapy in IgAN, the intermittent SP (ISP) and consecutive SP (CSP) protocols are prevalently performed in clinical settings. However, there is a lack of evidence of comparisons of the effects on IgAN between these two protocols. METHODS: A total of 189 patients with IgAN who had received SP therapy were included in this study. They were divided into two groups according to the SP protocols into the intermittent SP (ISP) or consecutive SP (CSP) group as follows: ISP; three-times SP therapy in alternate months, CSP; three-times SP therapy in three consecutive weeks. Kidney function, remission of urinary findings, and side effects of SP therapy were compared between the two groups. The observational period was 12 months after the initiation of SP therapy. RESULTS: There was no significant difference in kidney function between the two groups during the observational period. The remission rate of proteinuria and hematuria at 12 months also did not significantly differ between the two groups. Furthermore, even after the adjustment of clinical characteristics using propensity score matching, the remission rate of proteinuria and hematuria at 12 months was similar between the two groups. At 2 months, the remission rate of proteinuria was significantly higher in the CSP group than in the ISP group. There were no critical side effects in both groups. CONCLUSION: The effects of SP therapy on IgAN were similar between the ISP and CSP group at 12 months although CSP therapy could remit proteinuria faster than ISP therapy.

Relationship between parathyroid hormone and renin-angiotensin-aldosterone system in hemodialysis patients with secondary hyperparathyroidism.

INTRODUCTION: Hyperparathyroidism (HPT) is associated with mortality and cardiovascular disease (CVD) in dialysis patients. However, its mechanism is still unclear. It is suspected that parathyroid hormone (PTH) is associated with the renin-angiotensin-aldosterone system (RAAS) as a possible mechanism. Thus, we examined their hormonal interaction in hemodialysis patients with secondary HPT. MATERIALS AND METHODS: Seventeen hemodialysis patients with HPT were included. All patients underwent total parathyroidectomy (PTx). Serum intact PTH (iPTH), calcium and phosphate levels, plasma renin activity (PRA), and plasma aldosterone levels (ALD) were measured pre- and post-PTx. RESULTS: Pre-serum iPTH tended to be correlated with pre-PRA and were significantly correlated with pre-ALD (pre-PRA: r = 0.44, p = 0.07, pre-ALD: r = 0.49, p < 0.05). With the reduction in serum iPTH after PTx, PRA and ALD significantly decreased after PTx. Additionally, the change in serum iPTH tended to be correlated with the changes in PRA and ALD (PRA; r = 0.46, p = 0.05, ALD; r = 0.45, p = 0.06). CONCLUSION: Our results suggest that PTH could be interrelated with RAAS in hemodialysis patients with secondary HPT.

Evaluation of aortic calcification using a three-dimensional volume-rendering method in patients with end-stage kidney disease.

INTRODUCTION: Very few studies have been performed to evaluate both the severity and site of aortic calcification (AC) in both end-stage kidney disease (ESKD) and diabetes mellitus (DM). The purpose of our study was to examine the utility of a newly developed three-dimensional (3D) visualization and quantification method compared with other methods to evaluate vascular calcification in ESKD patients with and without DM. MATERIALS AND METHODS: Fifty patients with ESKD before initiating hemodialysis at our hospital were included in the present study. They were divided into the two groups, depending on the presence or absence of DM: Control group (n = 31) and DM group (n = 19). The volume and site of AC were evaluated via computed tomography (CT) scan using a 3D visualization and quantification method. RESULTS: Total calcification volume was significantly greater in the DM group than in the Control group. Calcification volume in the descending and abdominal aortas was greater in the DM group compared to the Control group. There were no significant differences in calcification volume in the aortic root, ascending aorta, and aortic arch. Calcification volume of the whole aorta, the descending aorta, and the abdominal aorta were each significantly correlated with age, diastolic blood pressure and pulse pressure. CONCLUSION: This study using a 3D visualization and quantification method demonstrated that AC was more severe and occurred more frequently in the abdominal aorta in ESKD patients with DM compared to those without DM. This method would enable us to precisely evaluate the volume and distribution of AC.

X-chromosome inactivation patterns in females with Fabry disease examined by both ultra-deep RNA sequencing and methylation-dependent assay.

BACKGROUND: Fabry disease is an X-linked inherited lysosomal storage disorder caused by mutations in the gene encoding α-galactosidase A. Males are usually severely affected, while females have a wide range of disease severity. This variability has been assumed to be derived from organ-dependent skewed X-chromosome inactivation (XCI) patterns in each female patient. Previous studies examined this correlation using the classical methylation-dependent method; however, conflicting results were obtained. This study was established to ascertain the existence of skewed XCI in nine females with heterozygous pathogenic variants in the GLA gene and its relationship to the phenotypes. METHODS: We present five female patients from one family and four individual female patients with Fabry disease. In all cases, heterozygous pathogenic variants in the GLA gene were detected. The X-chromosome inactivation patterns in peripheral blood leukocytes and cells of urine sediment were determined by both classical methylation-dependent HUMARA assay and ultra-deep RNA sequencing. Fabry Stabilization Index was used to determine the clinical severity. RESULTS: Skewed XCI resulting in predominant inactivation of the normal allele was observed only in one individual case with low ⍺-galactosidase A activity. In the remaining cases, no skewing was observed, even in the case with the highest total severity score (99.2%). CONCLUSION: We conclude that skewed XCI could not explain the severity of female Fabry disease and is not the main factor in the onset of various clinical symptoms in females with Fabry disease.

Comparison of the effects of lanthanum carbonate and calcium carbonate on the progression of cardiac valvular calcification after initiation of hemodialysis.

BACKGROUND: Although mineral metabolism disorder influences cardiac valvular calcification (CVC), few previous studies have examined the effects of non-calcium-containing and calcium-containing phosphate binders on CVC in maintenance hemodialysis patients. The aim of the present study was to compare the effects of lanthanum carbonate (LC) with calcium carbonate (CC) on the progression of CVC in patients who initiated maintenance hemodialysis and to investigate clinical factors related to CVC. METHODS: The current study included 50 subjects (mean age 65 years, 72% males) from our previous randomized controlled trial (LC group, N = 24; CC group, N = 26). CVC was evaluated as CVC score (CVCS) using echocardiography at baseline and 18 months after initiation of hemodialysis. We compared CVCS and the changes between the two groups. We also analyzed the associations between CVCS and any other clinical factors including arterial plaque score (PS) and serum phosphorus levels. RESULTS: Baseline characteristics of study participants including CVCS were almost comparable between the two groups. At 18 months, there were no significant differences in mineral metabolic markers or CVCS between the two groups, and CVCS were significantly correlated with PS (r = 0.39, p < 0.01). Furthermore, changes in CVCS were significantly correlated with average phosphorus levels (r = 0.36, p < 0.05), which were significantly higher in high serum phosphorus and high PS group compared to low serum phosphorus and low PS group (p < 0.05). CONCLUSIONS: In the present study, there were no significant differences between LC and CC with regard to progression of CVC. However, serum phosphorus levels and arterial plaque seem to be important for the progression and formation of CVC in hemodialysis patients.

Effects of lanthanum carbonate on bone markers and bone mineral density in incident hemodialysis patients.

INTRODUCTION: Recent clinical studies demonstrated the favorable effects of calcium-free phosphate binders on mortality and vascular calcification in hemodialysis (HD) patients. The aim of the present study was to investigate the effects of a calcium-free phosphate binder, lanthanum carbonate (LC), on bone metabolic markers and bone mineral density (BMD), compared with those of calcium carbonate (CC), in subjects new to HD. MATERIALS AND METHODS: The present study included 65 subjects from our previous randomized controlled trial (LC group, N = 31; CC group, N = 34). We investigated the effects of LC on serum intact parathyroid hormone (iPTH), osteocalcin (OC), bone-specific alkaline phosphatase (BAP), tartrate-resistant acid phosphatase 5b (TRACP-5b), sclerostin levels, and BMD, compared with those of CC in patients new to HD at baseline and at 12 and 18 months. RESULTS: Serum OC levels at 18 months were significantly higher in the LC group than in the CC group. During the study period, serum BAP and TRACP-5b and iPTH levels tended to be higher in the LC group than in the CC group. At 18 months, the percentage of low bone turnover, based on a serum BAP cutoff value, was significantly lower in the LC group than in the CC group. There were no significant differences in the lumbar and femoral BMD between the two groups. CONCLUSIONS: The results of the present study suggest that LC has potential in preventing low bone turnover, in comparison to CC, in patients new to HD.

A case of membranous nephropathy characterized by atypical distribution of phospholipase A2 receptor
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A 77-year-old man was referred to our hospital with persistent proteinuria and progressive lower leg edema. Past history was unremarkable except for hypertension. Autoimmune diseases, infections, and malignancies were excluded based on clinical and laboratory test results. Renal biopsy specimens showed membranous nephropathy with segmental distribution of spikes and bubbling appearance. Double contour formation in glomerular tufts was also observed. There were no proliferative changes in the glomeruli. Interstitial fibrosis and tubular atrophy were moderate, and no interstitial inflammation was observed. Arteries showed moderate sclerotic changes with hyalinosis. Immunohistochemical analysis revealed no thrombospondin type 1 domain-containing 7A reactivity. Immunofluorescence staining showed segmental granular positivity of IgG on glomerular tufts and focal staining of IgG on the tubular basement membranes. IgG deposits (subclass distribution: IgG1, 2+; IgG2, -; IgG3, 1+; IgG4, 2+) and phospholipase A2 receptor type 1 (PLA2R1) immunoreactivity showed similar distributions in both glomeruli and renal tubular basement membranes. Electron microscopy revealed subendothelial edema in partially collapsed glomerulus. No subepithelial dense deposits were observed in the glomeruli under an electron microscope. This is the first documented case of membranous nephropathy (MN) with segmental distribution of PLA2R1 in the glomeruli and focal PLA2R1 positivity in renal tubular basement membranes. Our findings extend the pathological presentation of PLA2R1-associated MN. Future studies are required to examine the mechanistic insights of these atypical histopathological features.
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Characteristics of coronary artery disease in chronic kidney disease.

Patients with chronic kidney disease (CKD) commonly experience cardiovascular disease (CVD), and a major cause of death in these patients is CVD. Therefore, the prevention of CVD progression is very crucial in patients with CKD. Recently, this relationship between CKD and CVD has increasingly been examined, and a concept termed "cardiorenal syndrome" has been advocated. Coronary artery disease (CAD) and myocardial injury are crucial factors that contribute to the occurrence of CVD. The initial step CAD is endothelial dysfunction that can be detected as a decrease in the coronary flow reserve (CFR). The previous studies have reported that decreased CFR is significantly correlated to coronary events and mortality. Furthermore, CFR reduces with a decline in the kidney function. Another important presentation of CAD is coronary artery calcification. Vascular calcification is a crucial pathophysiological state, particularly in patients with CKD, and it affects the stability of coronary atherosclerotic plaque. In CKD, not only the traditional risk factors but also CKD-related non-traditional risk factors play key roles in CVD progression. Therefore, the mechanisms responsible for CVD progression are very complex; however, their clarification is crucial to improve the prognosis in patients with CKD.

Changes in serum and intracardiac fibroblast growth factor 23 during the progression of left ventricular hypertrophy in hypertensive model rats.

BACKGROUND: Recent clinical studies have demonstrated that serum fibroblast growth factor 23 (FGF23) levels have a significant association with left ventricular hypertrophy (LVH). Although LVH is commonly seen in hypertensive patients, the association between FGF23, hypertension, and LVH remains unclear. We aimed to examine the changes in serum and intracardiac FGF23 during the progression of hypertension using spontaneously hypertensive rats (SHR). METHODS: Male SHR comprised the experimental group (HT group) and Wistar Kyoto rats served as controls. At 10 weeks, urinary and blood biochemical analyses and blood pressure measurements were performed for both the groups. At 18 weeks, the rats were sacrificed: urinary and blood biochemical analyses and real-time PCR were performed. RESULTS: At 18 weeks, the relative heart weight and serum N-terminal pro-brain natriuretic peptide and aldosterone levels were significantly greater in the HT group. Serum calcium and phosphate levels were significantly lower, while serum FGF23 levels were significantly higher in the HT group compared to the control group. Further analyses showed that the mRNA expression of FGF23 in the heart was significantly increased in the HT group compared to the control group. Both serum FGF23 levels and intracardiac mRNA expression of FGF23 showed significant correlation with the relative heart weight. CONCLUSIONS: During LVH progression, serum and intracardiac FGF23 increased in hypertension. Although it is unclear whether the change in FGF23 is the cause or result of LVH, the interaction between FGF23 and aldosterone may be associated with the development of LVH in hypertension.

Effects of Lanthanum Carbonate on Coronary Artery Calcification and Cardiac Abnormalities After Initiating Hemodialysis.

It is known that calcium-containing phosphate binders are more closely associated with the progression of vascular calcification than non-calcium-containing phosphate binders. In this study, we investigated the effect of the non-calcium-containing phosphate binder, lanthanum carbonate on the progression of coronary artery calcification and cardiovascular abnormalities compared to that of calcium-containing phosphate binder in chronic kidney disease patients during the early period after initiating hemodialysis. This was a randomized open-label study in which patients were divided into the calcium carbonate or lanthanum carbonate group. We evaluated blood samples, coronary artery calcification using high-resolution computed tomography, and cardiac abnormalities using echocardiography prior to and after initiating hemodialysis. Cardiac dimension and systolic function were significantly improved in the lanthanum carbonate group compared to those in the calcium carbonate group. Although statistically significant differences were not observed in all the patients, only among patients with moderate coronary artery calcification, the changes in coronary artery calcification score at 18 months were significantly smaller in the lanthanum carbonate group than those in the calcium carbonate group. The percent change in coronary artery calcification at 18 months was significantly correlated with the serum fibroblast growth factor 23 levels at 18 months (r = 0.245, P < 0.05). This significant correlation was particularly strong in patients with moderate coronary artery calcification (r = 0.593, P < 0.001). Our study suggests that lanthanum carbonate ameliorates cardiac abnormalities, and may slow coronary artery calcification development in patients with moderate coronary artery calcification, during the early period following hemodialysis initiation.

Influence of Uncertain Anticipation on Brain Responses to Aversive Rectal Distension in Patients With Irritable Bowel Syndrome.

OBJECTIVE: We investigated whether certainty and uncertainty of impending aversive visceral sensation differently modulate regional brain activity, both during anticipation and visceral sensation in irritable bowel syndrome (IBS) patients compared with healthy controls. METHODS: Twenty-six IBS patients (14 women) and 29 healthy controls (15 women) were enrolled in a functional magnetic resonance imaging study. Participants received rectal distention at an individually titrated severe discomfort level that was preceded by visual cues to induce certain (100% chance of distention), uncertain (50% chance), and safe (0% chance) anticipation. RESULTS: Subjective ratings of anticipatory fear before and discomfort during distention were similar between IBS and control participants under cued certainty and uncertainty (p > .05). Uncertain anticipation compared with certain anticipation induced greater activation of anterior midcingulate cortex, thalamus, and visual processing areas in IBS patients compared with controls. Rectal distention after the uncertain, but not certain, cue induced higher activity in the posterior- and midcingulate cortices and the precuneus in IBS compared with controls. Controls exhibited bilateral insula activation during the nondistention period after the uncertain cue compared with the safe cue. IBS patients failed to produce this response, which was possibly due to elevated bilateral insular responses during nondistention after the safe cue. Brain data were significant at a voxel-level threshold of puncorrected value of less than .005 combined with a cluster-level threshold of pFWE-corrected value of less than .05. CONCLUSIONS: Preceding uncertainty differentially modulates the brain processing of physiologically identical rectal stimulation in IBS patients. Cue-dependent alterations in brain responses may underlie hypervigilance to visceral sensations in IBS patients.

Relationship between cardiac calcification and left ventricular hypertrophy in patients with chronic kidney disease at hemodialysis initiation.

Coronary artery calcification (CAC), cardiac valve calcification (CVC) and left ventricular hypertrophy (LVH) are frequently observed in chronic kidney disease (CKD) patients. These abnormalities significantly affect morbidity and mortality. The aim of this study was to investigate the relationship between CAC, CVC and LVH in CKD patients. This study included 96 patients who were hospitalized and initiated hemodialysis between December 2011 and July 2014 at our five institutions. Multi-detector computed tomography for the quantification of CAC using the Agatston score and transthoracic echocardiography for assessing CVC and LVH were performed for all patients included in the study. We semi-quantitatively evaluated the severity of CVC as a valvular calcification score. We also assessed the presence of LVH in patients with CAC and/or CVC. Among the 96 patients, the prevalence of CAC was 81.3% and CVC was 65.0%. The severity of CAC was closely and significantly associated with that of CVC. The percentage of patients with LVH was the greatest in those with both severe CAC and CVC. CAC was significantly more severe in patients with concentric hypertrophy compared to those with normal geometry. At the initiation of hemodialysis, most CKD patients had CAC, CVC and LVH. In addition, cardiac calcification was significantly associated with LVH in these patients.

Relationship Between Type of Hypertension and Renal Arteriolosclerosis in Chronic Glomerular Disease.

BACKGROUND/AIMS: Hypertension (HT) is a common complication in patients with chronic kidney disease (CKD). However, the relationship between circadian rhythm disorder of blood pressure (BP) and intra-renal damage remains unclear. METHODS: Ninety patients with chronic glomerular disease (CGD) were included in the present study. On the basis of the clinic BP (CBP) and 24 h-ambulatory BP (ABP) measurements, the patients were divided into the following groups; normotension (NT), white coat HT (WHT), masked HT (MHT), and sustained HT (SHT). For renal histopathological assessment, we evaluated each biopsy specimen for sclerotic glomeruli (SG), interstitial fibrosis (IF), intimal thickening of intra-lobular arteries (ILA), and arteriolar hyalinosis (AH). RESULTS: The prevalence of NT, WHT, MHT and SHT was 60.0%, 3.3%, 23.3%, and 13.4%, respectively. Compared with circadian BP pattern, all-day HT was most prevalent in the SHT group, whereas nighttime HT was most prevalent in the MHT group. The results of histological analysis showed that the SHT group had more severe SG and IF and the MHT group had more severe IF compared to the NT group. As for renal arteriolosclerosis, the MHT and SHT groups had more severe AH compared with the NT group, whereas ILA was comparable among all four groups. Furthermore, multivariate analysis revealed that ILA was significantly correlated only with age, whereas AH was significantly correlated with age and HT based on ABP, but not HT based on CBP. CONCLUSIONS: Our findings suggest that renal AH was severe not only in the SHT group, but also in the MHT group. Careful ABP monitoring should be recommended in patients with CGD.

Riser pattern is a predictor of kidney mortality among patients with chronic kidney disease.

BACKGROUND: Hypertension is a crucial risk factor for cardiovascular death and loss of residual kidney function. Absence of the nocturnal decline in blood pressure (BP) predicts cardiovascular events and poor prognosis. However, characteristics of hypertension in moderate-to-severe chronic kidney disease (CKD) have not been fully evaluated. We aimed to assess the circadian variation of BP and kidney survival in CKD patients. METHODS: Patients who were examined by 24-h ambulatory BP monitoring (ABPM) and estimated glomerular filtration rate (eGFR), <45 ml/min/1.73 m(2), were enrolled in the study. The impacts of BP circadian rhythm and brain natriuretic peptide (BNP) on kidney survival were evaluated. RESULTS: A total of 124 patients were enrolled. The average age was 64 ± 14 years, 57% were male, and 43% had diabetes. Forty-five percent of patients had a non-dipper pattern, 35% had a riser pattern, 19% had a dipper pattern, and 1% had an extreme-dipper pattern. The prevalence of diabetes and plasma BNP levels was higher and eGFR was lower in the riser-pattern group than in the non-riser-pattern group. Kidney survival rates were significantly worse in the riser-pattern group than in the non-riser-pattern group (p < 0.05). Moreover, among riser and non-riser pattern groups divided by BNP levels, the riser group with higher BNP level showed the worst kidney survival (p < 0.05). CONCLUSION: The riser pattern is frequently associated with several conditions at higher risk for kidney survival. Patients with a rising pattern and higher BNP levels have a worse kidney prognosis.

The Vitamin D Receptor Activator Maxacalcitol Provides Cardioprotective Effects in Diabetes Mellitus.

PURPOSE: Recent reports showed a significant association between vitamin D levels and cardiovascular disease events and mortality. In the current study, we investigated the effect of the vitamin D receptor activator maxacalcitol (OCT) on cardiac damage in a rat model of type 2 diabetes. METHODS: At 20 weeks of age, the rats were divided into three groups: vehicle-treated (DM), insulin-treated (INS) and OCT-treated (OCT). At 30 weeks, the rats were sacrificed and urinary and blood biochemical analyses and cardiac histological and immunohistochemical analyses were performed. To evaluate the effect of OCT on the renin-angiotensin system, we performed a further study using aliskiren (ALS). At 20 weeks, the diabetic rats were divided into two groups: the ALS-treated group (ALS) and the ALS plus OCT-treated group (ALS + OCT), and we evaluated the renin-angiotensin system (RAS) and cardiac lesions at 30 weeks. RESULTS: At 30 weeks, despite comparable blood pressure and renal function, heart volume, intracardiac oxidative stress by immunohistological analysis, cardiac and perivascular fibrosis and urinary excretion of 8-hydroxydeoxyguanosine and serum N-terminal pro-brain natriuretic peptide levels were significantly decreased in the OCT group compared to the DM group. mRNA expressions of dihydronicotinamide adenine dinucleotide phosphate (NADPH) p47 subunit and cardiac injury-related markers in the heart were also significantly decreased in the OCT group compared to the DM group. The cardioprotective effect of OCT was preserved even in the context of RAS inhibition. CONCLUSION: Our results suggest that OCT prevents the development of cardiac damage in DM, independent of RAS inhibition.

Anti-oxidative effect of the ß-blocker carvedilol on diabetic nephropathy in non-obese type 2 diabetic rats.

Oxidative stress plays an important role in the pathogenesis of diabetic nephropathy. The ß-blocker carvedilol has been proven to have an anti-oxidant property. The aim of the present study was to elucidate the effects of carvedilol on diabetic nephropathy. At 20 weeks of age, male Spontaneously Diabetic Torii (SDT) rats were divided into three groups based on treatment: (i) an INS group (administered insulin); (ii) a CAR group (administered 10 mg/kg per day, p.o., carvedilol); and (iii) a diabetic (DM) group (administered vehicle). Rats were treated for a period of 10 weeks and were killed at 30 weeks of age. Urinary albumin excretion, renal histomorphology, and oxidative stress were evaluated. Urinary albumin excretion was significantly lower in the CAR than DM group (42.82 ± 3.94 vs 76.62 ± 13.74 mg/day respectively; P < 0.05). The mesangial index was lower in the CAR group than in the DM group. Urinary excretion of 8-hydroxydeoxyguanosine (8-OHdG), the number of 8-OHdG-positive cells in glomeruli, and the mRNA expression of NADPH oxidase p22phox and p47phox were also lower in the CAR than DM group. However, haemoglobin A1c (HbA1c) and blood pressure levels were comparable between the two groups. The results suggest that carvedilol could prevent the progression of diabetic nephropathy by suppressing oxidative stress.