Renal Failure Without Hemodialysis Is a Risk Factor for Postoperative Complications in Colorectal Cancer Surgery.

Background/Aim: Surgical outcomes of colorectal cancer (CRC) in patients with renal failure (RF) remain to be clarified. The objective of this research was to investigate how RF impacts the surgical outcomes in patients with CRC. Patients and Methods: A retrospective analysis was performed on clinical data from 633 patients who underwent colorectal resection for CRC between January 2017 and December 2021. Outcomes of the patients with and without RF were compared. RF was defined as estimated Glomerular Filtration Rate less than 30. Results: Forty-five (7%) patients with RF were identified. RF was a significant risk factor for postoperative complications after colorectal cancer surgery (odds ratio=2.19, 95% confidence interval=1.08-4.42, p=0.0284). The patients with RF had significantly more comorbidity (p=0.016), and higher American Society of Anesthesiologists physical status (p<0.01). Hemoglobin level (p<0.01) and PNI (p<0.01) were significantly lower in those with RF. Postoperative complications were significantly higher (p=0.016), and the postoperative hospital stay was significantly longer (p<0.01) among patients with RF compared to those without RF. Patients with RF, excluding those undergoing hemodialysis, had significantly more complications compared to those without RF (p=0.004). Conclusion: Careful attention should be paid to perioperative management in RF colorectal cancer patients.

Calcimimetics treatment strategy for serum calcium and phosphate management in patients with secondary hyperparathyroidism undergoing dialysis: A systematic review and meta-analysis of randomized studies.

INTRODUCTION: Several calcimimetics, other than cinacalcet, are commercially available; however, their effects on calcium and phosphate levels have not yet been fully studied. We conducted a systematic review and meta-analysis of randomized controlled trials to evaluate the impact of calcimimetics on the management of serum calcium and phosphate levels in patients with secondary hyperparathyroidism undergoing dialysis. METHODS: A systematic literature search through October 2023 and a meta-analysis were conducted on the effects of upacicalcet, etelcalcetide, evocalcet, and cinacalcet on serum calcium and phosphate levels in patients with secondary hyperparathyroidism undergoing dialysis; we searched PubMed, Ovid MEDLINE, and the Cochrane Central Register of Controlled Trials, and 21 studies comprising 6371 patients undergoing dialysis were included. RESULTS: Participants treated with calcimimetics had lower serum calcium and phosphate levels than placebo. CONCLUSION: Calcimimetics significantly reduced serum calcium and phosphate levels compared to placebo in patients with secondary hyperparathyroidism undergoing dialysis, independent of therapeutic strategy or concomitant vitamin D treatment.

Prevalence of hyponatremia and associated factors in patients with chronic kidney disease: the Fukuoka Kidney Disease Registry (FKR) study.

BACKGROUND: Hyponatremia is a common and important electrolyte disorder. However, the prevalence and factors associated with hyponatremia in patients with chronic kidney disease (CKD) are unknown. METHODS: We studied the factors associated with hyponatremia (< 135 mEq/L) in CKD patients registered in the Fukuoka Kidney Disease Registry (FKR) study using a logistic regression model variable selected using the variable reduction method. RESULTS: We analyzed the baseline characteristics of 4367 participants with CKD (age, 64 ± 16 years; male, 56.1%). Hyponatremia was detected in 2.0% of the patients at baseline, and multivariate logistic analysis showed that the independent factors for hyponatremia were body mass index (odds ratio [OR] 0.91; 95% confidence interval [CI] 0.85-0.97), prescription of benzodiazepine (OR 2.31; 95% CI 1.39-3.86), blood hemoglobin level (OR 0.76; 95% CI 0.65-0.88), and serum C-reactive protein level (OR 1.27; 95% CI 1.04-1.54). CONCLUSION: The cross-sectional analysis using baseline data from the FKR study revealed independent factors associated with hyponatremia in patients with decreased kidney function. Longitudinal analyses of the FKR cohort are needed to evaluate the effects of these factors on the prognosis of hyponatremia in patients with CKD.

Angiotensin II receptor blockers and bone fracture in chronic kidney disease patients: the Fukuoka kidney disease Registry Study.

BACKGROUND: Angiotensin II receptor blockers (ARBs) reportedly reduce the risk of developing bone fractures; however, this association remains unclear among patients with chronic kidney disease (CKD). METHODS: This was a cross-sectional study of 3380 CKD patients enrolled in the Fukuoka Kidney disease Registry Study, a multicenter prospective observational cohort study of non-dialysis-dependent CKD patients. The patients were divided into two groups, those taking ARBs and those who were not. Logistic regression models were used to examine the association between ARBs and bone fracture. RESULTS: Approximately 67.0% of the participants were on ARBs, and 6.3% had a history of bone fracture. The history of bone fracture was significantly lower in patients with prescribed ARB and remained significant even after multivariable adjustment (odds ratio, 0.68; 95% confidence interval, 0.51-0.93). Other antihypertensive drugs, such as thiazide diuretics, which were reportedly helpful in preventing fractures, did not alter the bone fracture history and did not change among ARB users and non-users. CONCLUSIONS: The present study showed that administering ARB was significantly associated with a lower frequency of bone fracture history.

The impact of home electrocardiograph measurement rate on the detection of atrial fibrillation recurrence after ablation: A prospective multicenter observational study.

Background: This multicenter prospective observational study examined the impact of additionally using a home electrocardiograph (ECG) to detect atrial fibrillation (AF) recurrence after ablation. Methods: Between May 2019 and December 2020, 128 patients undergoing ablation were enrolled in the study. After performing ablation, they were instructed to measure their ECGs at home using Complete (ECG paired with a blood pressure monitor; Omron Healthcare, Japan) every day and to visit the hospital every 3 months until after 12 months for 24-hour Holter ECG and 12-lead ECG as usual care (UC). Results: After ablation, 94 patients were followed up, and AF recurrence at 12 months was detected more commonly in adjudicators-interpreted Complete (31 [33 %]) than in UC (18 [9 %]) (hazard ratio 1.95, 95 % confidence interval [95 %CI] 1.35-2.81, P < 0.001). In patients with recurrent AF found via both modalities (n = 16), the time to first AF detection by Complete was 40.9 ± 73.9 days faster than that in UC (P = 0.04). Notably, when the adherence to Complete measurement was divided by 80 %, the add-on effect of Complete on the detection of recurrent AF in UC indicated the hazard ratio (HR) of 1.71 (95 %CI 0.92-3.18, P = 0.09) for the low adherence (<80 %) group, but it was significant for the high adherence (≥80 %) group, with HR of 2.19 (95 %CI 1.43-3.36, P < 0.001). Conclusions: Despite a shorter measurement time, Complete detected recurrent AF more frequently and faster compared with UC after AF ablation. A significant adherence-dependent difference of Complete was found in detecting AF recurrence.

Statin Use Influence on the Occurrence of Acute Kidney Injury in Patients with Peripheral Arterial Disease.

AIM: Acute kidney injury (AKI) is an important clinical issue in the diagnosis and treatment of cardiovascular diseases. The association between pretreatment by statins and the occurrence of AKI in patients with peripheral arterial diseases (PAD) remains unclear. Therefore, we examined the association between statin therapy and the occurrence of AKI in patients with PAD. METHODS: We retrospectively analyzed data from the endovascular treatment (EVT) database in our hospital. A total of 295 patients who underwent angiography and/or intervention for PAD between October 2011 and March 2016 were enrolled and divided into two groups: those without statins (control group; N=157) and those with statins (statin group; N=138) for at least 1 month before admission. We examined the occurrence of AKI and its related factors in these patients. RESULTS: The serum creatinine levels, dose of contrast medium, use of a renin-angiotensin system inhibitor, smoking habit, and blood pressure were similar in both groups. The statin group had more diabetes patients, had patients who were significantly younger, had patients with a higher body mass index (BMI), and had patients with lower low-density lipoprotein cholesterol than the control group. With regard to the occurrence of AKI, there was a significantly lower incidence in the statin group compared with the control group (5% vs. 16%, p＜0.05). The result of the multivariate analysis indicated that statin therapy was significantly correlated with lower occurrence rates of AKI (p＜0.05). CONCLUSIONS: Our study suggests that statin therapy might prevent the occurrence of AKI after angiography and/or intervention for PAD.

Triamterene in lithium-induced nephrogenic diabetes insipidus: a case report.

Lithium-induced nephrogenic diabetes insipidus (NDI) is a rare and difficult-to-treat condition. We describe the case of an 81-year-old woman with bipolar treated with lithium and no previous history of diabetes insipidus. She was hospitalized due to disturbance of consciousness and was diagnosed with, hypercalcemia, hyperparathyroidism, and NDI. Parathyroidectomy was contraindicated and parathyroid hormone level was improved insufficiently after cinacalcet initiation, percutaneous ethanol injection therapy was performed for the enlarged parathyroid gland. After improvement in hypercalcemia and unsuccessful indapamide treatment, triamterene was administrated to control polyuria. Lithium is one of the indispensable maintenance treatment options for bipolar disorder, but it has the side effect of NDI. Lithium enters the collecting duct's principal cells mainly via the epithelial sodium channel (ENaC) located on their apical membranes, ENaC shows high selectivity for both sodium and lithium, is upregulated by aldosterone, and inhibited by triamterene. To our knowledge, this is the first publication on triamterene use in lithium-induced NDI patients.

Conduction gap mapping of linear ablation lesions with high-density mapping.

INTRODUCTION: When performing linear ablation, creating contiguous and transmural lesions are technically challenging due to the difficulty in finding electrical conduction gaps. We hypothesized that high-density mapping could identify the gaps. METHODS AND RESULTS: This study included consecutive patients who underwent conduction gap mapping of de novo lesions (41 patients, 55 lines) and previous lesions (25 patients, 34 lines). We analyzed the utility of bipolar and unipolar conduction gap mapping and retrospectively assessed the voltage and morphology of the bipolar electrograms at the gap sites. Bipolar and unipolar propagation maps were classified into three types: the propagation wavefront traveled through the linear ablation lesions (direct leak), the wavefront jumped to an opposite site across the line and returned to the line (jump and return leak), and others (indefinite leak). In the jump and return leak maps, the site where it returned suggested a conduction gap site. Bipolar propagation maps identified 30 (54.5%) conduction gaps and unipolar maps identified 40 (72.7%) gaps at de novo linear ablation lesions (P = .01), and 32 (94.1%) gaps and 33 (97.1%) gaps, respectively, at previous lesions (P = .56). Bipolar voltage mapping did not add any further efficacy in detecting conduction gaps, and the morphology of the electrograms recorded at the gap sites was not related to the types of propagation maps. CONCLUSION: Conduction gaps of linear ablation lesions can be visualized by high-density mapping with a high probability. Unipolar propagation, when used with bipolar mapping, may help detect conduction gap sites.

Diagnostic Value of Atrial Fibrillation by Built-in Electrocardiogram Technology in a Blood Pressure Monitor.

Background: Hypertension in patients with atrial fibrillation (AF) is a known independent risk factor for stroke. The Complete blood pressure (BP) monitor (Omron Healthcare, Kyoto, Japan) was developed as the first BP monitor with electrocardiogram (ECG) capability in a single device to simultaneously monitor ECG and BP readings. This study investigated whether the Complete can accurately differentiate sinus rhythm (SR) from AF during BP measurement. Methods and Results: Fifty-six consecutive patients with persistent AF admitted for catheter ablation were enrolled in the study (mean age 65.8 years; 83.9% male). In all patients, 12-lead ECGs and simultaneous Complete recordings were acquired before and after ablation. The Complete interpretations were compared with physician-reviewed ECGs, whereas Complete recordings were reviewed by cardiologists in a blinded manner and compared with ECG interpretations. Sensitivity, specificity, and κ coefficient were also determined. In all, 164 Complete and ECG recordings were simultaneously acquired from the 56 patients. After excluding unclassified recordings, the Complete automated algorithm performed well, with 100% sensitivity, 86% specificity, and a κ coefficient of 0.87 compared with physician-interpreted ECGs. Physician-interpreted Complete recordings performed well, with 99% sensitivity, 85% specificity, and a κ coefficient of 0.85 compared with physician-interpreted ECGs. Conclusions: The Complete, which combines BP and ECG monitoring, can accurately differentiate SR from AF during BP measurement.

Relative hypophosphatemia early after transplantation is a predictor of good kidney graft function.

BACKGROUND: Phosphate level is a potent independent risk factor for cardiovascular disease and mortality in patients with chronic kidney disease. The association between hypophosphatemia and kidney function in kidney transplant patients is uncertain. METHODS: In total, 90 kidney transplant recipients were divided into two groups: one group of patients with hypophosphatemia and the other group without hypophosphatemia. The recipients with hypophosphatemia were identified as having less than or equal to the lowest quartile of serum phosphate levels at 1-, 3-, and 12-month post-transplant. The cumulative kidney survival rates were calculated for each group using the Kaplan-Meier method, and the adjusted hazard ratio (HR) was calculated using the Cox regression model. RESULTS: The mean age of patients was 47 years and the median follow-up period was 58 months. During the follow-up period, the following results were demonstrated in 90 transplant patients: graft loss (n = 6), mortality (n = 3). According to the Kaplan-Meier analysis results, the patients with hypophosphatemia demonstrated a significantly lower risk of 30% decline in eGFR compared to those without hypophosphatemia at 1- and 3-month post-transplant, but not at 12-month post-transplant. After adjusting for confounding factors, hypophosphatemia at 1- and 3-month post-transplant was an independent predictor of good kidney survival (HR 0.31, 95% CI 0.10-0.82 and HR 0.31, 95% CI 0.07-0.92, respectively). CONCLUSIONS: Our findings suggest that hypophosphatemia during the first 3 months after kidney transplantation was associated with better kidney survival.

Open-Label Randomized Trial Comparing Oral Anticoagulation With and Without Single Antiplatelet Therapy in Patients With Atrial Fibrillation and Stable Coronary Artery Disease Beyond 1 Year After Coronary Stent Implantation.

BACKGROUND: Despite recommendations in the guidelines and consensus documents, there has been no randomized controlled trial evaluating oral anticoagulation (OAC) alone without antiplatelet therapy (APT) in patients with atrial fibrillation and stable coronary artery disease beyond 1 year after coronary stenting. METHODS: This study was a prospective, multicenter, open-label, noninferiority trial comparing OAC alone to combined OAC and single APT among patients with atrial fibrillation beyond 1 year after stenting in a 1:1 randomization fashion. The primary end point was a composite of all-cause death, myocardial infarction, stroke, or systemic embolism. The major secondary end point was a composite of the primary end point or major bleeding according to the International Society on Thrombosis and Haemostasis classification. Although the trial was designed to enroll 2000 patients during 12 months, enrollment was prematurely terminated after enrolling 696 patients in 38 months. RESULTS: Mean age was 75.0±7.6 years, and 85.2% of patients were men. OAC was warfarin in 75.2% and direct oral anticoagulants in 24.8% of patients. The mean CHADS2 score was 2.5±1.2. During a median follow-up interval of 2.5 years, the primary end point occurred in 54 patients (15.7%) in the OAC-alone group and in 47 patients (13.6%) in the combined OAC and APT group (hazard ratio, 1.16; 95% CI, 0.79-1.72; P=0.20 for noninferiority, P=0.45 for superiority). The major secondary end point occurred in 67 patients (19.5%) in the OAC-alone group and in 67 patients (19.4%) in the combined OAC and APT group (hazard ratio, 0.99; 95% CI, 0.71-1.39; P=0.016 for noninferiority, P=0.96 for superiority). Myocardial infarction occurred in 8 (2.3%) and 4 (1.2%) patients, whereas stroke or systemic embolism occurred in 13 (3.8%) and 19 (5.5%) patients, respectively. Major bleeding occurred in 27 (7.8%) and 36 (10.4%) patients, respectively. CONCLUSIONS: This randomized trial did not establish noninferiority of OAC alone to combined OAC and APT in patients with atrial fibrillation and stable coronary artery disease beyond 1 year after stenting. Because patient enrollment was prematurely terminated, the study was underpowered and inconclusive. Future larger studies are required to establish the optimal antithrombotic regimen in this population. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01962545.

Newly Developed Rat Model of Chronic Kidney Disease-Mineral Bone Disorder.

AIM: Chronic kidney disease-mineral bone disorder (CKD-MBD) is associated with all-cause and cardiovascular morbidity and mortality in patients with CKD. Thus, elucidating its pathophysiological mechanisms is essential for improving the prognosis. We evaluated characteristics of CKD-MBD in a newly developed CKD rat model. METHODS: We used male Sprague-Dawley (SD) rats and spontaneously diabetic Torii (SDT) rats, which are used as models for nonobese type 2 diabetes. CKD was induced by 5/6 nephrectomy (Nx). At 10 weeks, the rats were classified into six groups and administered with a vehicle or a low- or high-dose paricalcitol thrice a week. At 20 weeks, the rats were sacrificed; blood and urinary biochemical analyses and histological analysis of the aorta were performed. RESULTS: At 20 weeks, hemoglobin A1c (HbA1c) levels, blood pressure, and renal function were not significantly different among the six groups. Serum calcium and phosphate levels tended to be higher in SDT-Nx rats than in SD-Nx rats. The urinary excretion of calcium and phosphate was significantly greater in SDT-Nx rats than in SD-Nx rats. After administering paricalcitol, serum parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) levels were significantly higher in SDT-Nx rats than in SD-Nx rats. The degree of aortic calcification was significantly more severe and the aortic calcium content was significantly greater in SDT-Nx rats than in SD-Nx rats. CONCLUSIONS: We suggest that our new CKD rat model using SDT rats represents a useful CKD-MBD model, and this model was greatly influenced by paricalcitol administration. Further studies are needed to clarify the detailed mechanisms underlying this model.

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.

Very long-term clinical outcomes after radiofrequency catheter ablation for atrial fibrillation: A large single-center experience.

AIMS: Radiofrequency catheter ablation (RFCA) has become widely used for drug-refractory atrial fibrillation (AF). However, there is a paucity of data on the long-term clinical outcomes after RFCA for AF. The aim of the present study was to investigate the very long-term outcomes after RFCA for AF in a large number of consecutive patients. METHODS AND RESULTS: In this retrospective single-center study, we evaluated very long-term follow-up results in 1206 consecutive patients undergoing first RFCA for AF. The primary outcomes were adverse outcomes at 30-day as a safety outcome measure and event-free rates from recurrent atrial tachyarrhythmias as efficacy outcome measures. Final follow-up rate reached 99.3% with a mean follow-up duration of 5.0±2.5years. The incidence of overall 30-day adverse outcomes was 3.6% without death. The 10-year event-free rates from recurrent atrial tachyarrhythmias after the initial and last procedures were 46.9% and 76.4%, respectively. Arrhythmia recurrence occurred most commonly during the first year and decreased beyond 3-year, although it continued to occur at an annual rate of 2.0% and 1.3%, respectively, throughout the 10-year follow-up period. The cumulative 10-year incidences of stroke and major bleeding were 4.2% and 3.5%, respectively, with annual rates of 0.3%. Discontinuation rate of oral anticoagulation at 1-, 3-, and 10-year was 34.6%, 53.4%, 58.0% and 61.9%. CONCLUSIONS: RFCA for AF provided favorable very long-term arrhythmia-free survival without much safety concerns. The 10-year rates of stroke and major bleeding were low even with discontinuation of oral anticoagulation in a large proportion of patients.

A Case of Fibrillary Glomerulonephritis with Fibril Deposition in the Arteriolar Wall and a Family History of Renal Disease.

Herein, we report a case of fibrillary glomerulonephritis (FGN). FGN usually shows non-amyloidal fibrils in the mesangium and glomerular capillary walls on electron microscopy. Inherited cases of FGN have been reported in only 3 families, and the suspected genetic form was autosomal dominant. In the present case, the deposition of microfibrils in the arteriolar wall as well as the glomerulus is unique. Our patient's father died of nephrotic syndrome, and his elder brother had a biopsy-proven glomerulopathy. The histological findings of the brothers are similar to mesangial proliferative glomerulonephritis and resemble each other. Therefore, our case is presumed to be familial FGN. Additionally, herein, we review the literature and reconsider the histological and clinical characters of FGN.

Hypertension Induced by Tyrosine-Kinase Inhibitors for the Treatment of Renal Cell Carcinoma in Hemodialysis Patients: A Single-Center Experience and Review of the Literature.

Malignancy is a major cause of mortality in dialysis patients. Although molecular-targeted anticancer drugs, including tyrosine-kinase inhibitors, are used for advanced renal cell carcinoma treatment, there are few reports on their effectiveness and safety in dialysis patients. Renal cell carcinoma dialysis patients treated at our hospital from 2010 to 2013 participated in this study. Thirteen patients were treated with tyrosine-kinase inhibitors and 15 patients with surgery only (control group). During treatment, blood pressure changes and dry weight reduction tended to be greater in the tyrosine-kinase inhibitor group than in controls. More intensive management of hypertension was necessary in the tyrosine-kinase inhibitor group than in the controls. Renal cell carcinoma treatment by tyrosine-kinase inhibitors increased blood pressure in hemodialysis patients. We should prevent and manage hypertension carefully by adjusting antihypertensive drugs and dry weight in renal cell carcinoma 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.

The Effects of Plasma Exchange on Severe Vasculitis with Diffuse Alveolar Hemorrhage.

Antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis is a life-threatening disease characterized by rapidly progressive glomerulonephritis (RPGN) and diffuse alveolar hemorrhage (DAH). Glucocorticoids and immunosuppressants are commonly used to treat this disease but may induce irreversible side effects, particularly in elderly patients. We herein report the case of a 76-year-old woman with RPGN. After methylprednisolone pulse therapy, DAH occurred, and she required ventilatory support. After plasma exchange, her serum creatinine level improved, and she was discharged with home oxygen therapy. Immunosuppressive agents other than glucocorticoids were not required. In conclusion, plasma exchange with glucocorticoid therapy may be effective in treating severe ANCA-associated vasculitis in elderly patients.

Comparison of the effects of novel vitamin D receptor analog VS-105 and paricalcitol on chronic kidney disease-mineral bone disorder in an experimental model of chronic kidney disease.

When using vitamin D, the most important clinical problems are hypercalcemia, hyperphosphatemia, and vascular calcification. VS-105 is a novel vitamin D receptor (VDR) analog. In the present study, we compared the effects of VS-105 and paricalcitol on chronic kidney disease-mineral bone disorder (CKD-MBD) in a CKD rat model. We used male Sprague-Dawley (SD) rats and performed 5/6 nephrectomy at 8-9 weeks. At 10 weeks, the rats were classified into five groups and administered vehicle, low-dose paricalcitol (LP, 0.1µg/kg), high-dose paricalcitol (HP, 0.3µg/kg), low-dose VS-105 (LV, 0.2µg/kg), and high-dose VS-105 (HV, 0.6 µg/kg) three times a week for 10 weeks. There were no significant differences in blood pressure or renal function among the five groups. Alhough serum calcium levels were comparable between the LP and LV groups, they were higher in the HP group than in the HV group. Serum phosphate levels were higher in the paricalcitol-treated groups than in the VS-105-treated groups and paticularly higher in the HP group than in the other groups. The urinary excretion of phosphate was greater in the VS-105-treated groups than in the paricalcitol-treated groups. Serum parathyroid hormone (PTH) levels decreased and serum fibroblast growth factor-23 (FGF23) levels were elevated after administering paricalcitol and VS-105; however, serum FGF23 levels were remarkably elevated in the paricalcitol-treated groups. Further biochemical analyses revealed that the calcium content of the aorta was higher in the paricalcitol-treated groups than in the VS-105-treated group. VDR and Klotho expression in the kidney was significantly higher in the VS-105-treated groups than in the paricalcitol-treated groups although both agents increased these expressions. Our data suggest that VS-105 had a lesser effect on CKD-MBD than paricalcitol except in the case of serum PTH levels. The mechanism appears to be associated with the difference in VDR and Klotho expression.