Plasma ANGPTL8 Levels and Risk for Secondary Cardiovascular Events in Japanese Patients With Stable Coronary Artery Disease Receiving Statin Therapy.

BACKGROUND: The ability to predict secondary cardiovascular events could improve health of patients undergoing statin treatment. Circulating ANGPTL8 (angiopoietin-like protein 8) levels, which positively correlate with proatherosclerotic lipid profiles, activate the pivotal proatherosclerotic factor ANGPTL3. Here, we assessed potential association between circulating ANGPTL8 levels and risk of secondary cardiovascular events in statin-treated patients. METHODS: We conducted a biomarker study with a case-cohort design, using samples from a 2018 randomized control trial known as randomized evaluation of high-dose (4 mg/day) or low-dose (1 mg/day) lipid-lowering therapy with pitavastatin in coronary artery disease (REAL-CAD [Randomized Evaluation of Aggressive or Moderate Lipid-Lowering Therapy With Pitavastatin in Coronary Artery Disease])." From that study's full analysis set (n=12 413), we selected 2250 patients with stable coronary artery disease (582 with the primary outcome, 1745 randomly chosen, and 77 overlapping subjects). A composite end point including cardiovascular-related death, nonfatal myocardial infarction, nonfatal ischemic stroke, or unstable angina requiring emergent admission was set as a primary end point. Circulating ANGPTL8 levels were measured at baseline and 6 months after randomization. RESULTS: Over a 6-month period, ANGPTL8 level changes significantly decreased in the high-dose pitavastatin group, which showed 19% risk reduction of secondary cardiovascular events compared with the low-dose group in the REAL-CAD [Randomized Evaluation of Aggressive or Moderate Lipid-Lowering Therapy With Pitavastatin in Coronary Artery Disease] study. In the highest quartiles, relative increases in ANGPTL8 levels were significantly associated with increased risk for secondary cardiovascular events, after adjustment for several cardiovascular disease risk factors and pitavastatin treatment (hazard ratio in Q4, 1.67 [95% CI, 1.17-2.39). Subgroup analyses showed relatively strong relationships between relative ANGPTL8 increases and secondary cardiovascular events in the high-dose pitavastatin group (hazard ratio in Q4, 2.07 [95% CI, 1.21-3.55]) and in the low ANGPTL8 group at baseline (166

Increased numbers of pre-operative circulating monocytes predict risk of developing cardiac surgery-associated acute kidney injury in conditions requiring cardio pulmonary bypass.

BACKGROUND: Evaluating patients' risk for acute kidney injury (AKI) is crucial for positive outcomes following cardiac surgery. Our aims were first to select candidate risk factors from pre- or intra-operative real-world parameters collected from routine medical care and then evaluate potential associations between those parameters and risk of onset of post-operative cardiac surgery-associated AKI (CSA-AKI). METHOD: We conducted two cohort studies in Japan. The first was a single-center prospective cohort study (n = 145) to assess potential association between 115 clinical parameters collected from routine medical care and CSA-AKI (≥ Stage1) risk in the population of patients undergoing cardiac surgery involving cardiopulmonary bypass (CPB). To select candidate risk factors, we employed random forest analysis and applied survival analyses to evaluate association strength. In a second retrospective cohort study, we targeted patients undergoing cardiac surgery with CPB (n = 619) and evaluated potential positive associations between CSA-AKI incidence and risk factors suggested by the first cohort study. RESULTS: Variable selection analysis revealed that parameters in clinical categories such as circulating inflammatory cells, CPB-related parameters, ventilation, or aging were potential CSA-AKI risk factors. Survival analyses revealed that increased counts of pre-operative circulating monocytes and neutrophils were associated with CSA-AKI incidence. Finally, in the second cohort study, we found that increased pre-operative circulating monocyte counts were associated with increased CSA-AKI incidence. CONCLUSIONS: Circulating monocyte counts in the pre-operative state are associated with increased risk of CSA-AKI development. This finding may be useful in stratifying patients for risk of developing CSA-AKI in routine clinical practice.

Circulating angiopoietin-like protein 2 levels and mortality risk in patients receiving maintenance hemodialysis: a prospective cohort study.

BACKGROUND: Patients undergoing hemodialysis treatment have a poor prognosis, as many develop premature aging. Systemic inflammatory conditions often underlie premature aging phenotypes in uremic patients. We investigated whether angiopoietin-like protein 2 (ANGPTL 2), a factor that accelerates the progression of aging-related and noninfectious inflammatory diseases, was associated with increased mortality risk in hemodialysis patients. METHODS: We conducted a multicenter prospective cohort study of 412 patients receiving maintenance hemodialysis and evaluated the relationship between circulating ANGPTL2 levels and the risk for all-cause mortality. Circulating ANGPTL2 levels were log-transformed to correct for skewed distribution and analyzed as a continuous variable. RESULTS: Of 412 patients, 395 were included for statistical analysis. Time-to-event data analysis showed high circulating ANGPTL2 levels were associated with an increased risk for all-cause mortality after adjustment for age, sex, hemodialysis vintage, nutritional status, metabolic parameters and circulating high-sensitivity C-reactive protein levels {hazard ratio [HR] 2.04 [95% confidence interval (CI) 1.10-3.77]}. High circulating ANGPTL2 levels were also strongly associated with an increased mortality risk, particularly in patients with a relatively benign prognostic profile [HR 3.06 (95% CI 1.86-5.03)]. Furthermore, the relationship between circulating ANGPTL2 levels and mortality risk was particularly strong in patients showing few aging-related phenotypes, such as younger patients [HR 7.99 (95% CI 3.55-18.01)], patients with a short hemodialysis vintage [HR 3.99 (95% CI 2.85-5.58)] and nondiabetic patients [HR 5.15 (95% CI 3.19-8.32)]. CONCLUSION: We conclude that circulating ANGPTL2 levels are positively associated with mortality risk in patients receiving maintenance hemodialysis and that ANGPTL2 could be a unique marker for the progression of premature aging and subsequent mortality risk in uremic patients, except those with significant aging-related phenotypes.

The predictive role of serum calprotectin on mortality in hemodialysis patients with high phosphoremia.

BACKGROUND: The inflammatory mediator calprotectin (CPT, myeloid-related protein 8/14) is known as an endogenous ligand contributing to pathophysiology in inflammatory diseases. Serum CPT reportedly became a potential biomarker in these conditions, though there is no report predicting the prognosis in hemodialysis patients. The aim of this study is to investigate the predictive role of serum CPT on mortality in hemodialysis patients. METHODS: We conducted a multicenter, observational cohort study of 388 Japanese subjects undergoing hemodialysis. Serum CPT were measured using an ELISA. The potential associations between serum CPT and clinical variables were cross-sectionally examined. Multivariate Cox regression was used to estimate the association between serum CPT, high-sensitivity C reactive protein (hs-CRP), white blood cell (WBC) count and mortality. Median follow-up was 6.6 years. RESULTS: The median CPT level was 6108 ng/ml (median in healthy subjects, 2800) at baseline. Serum CPT positively correlated with WBC count (ρ = 0.54, P < 0.001) and hs-CRP values (ρ = 0.35, P < 0.001). In multivariate analysis, hs-CRP was an independent predictor of all-cause mortality after adjusting confounding factors (middle vs. low: hazard ratio [HR] 2.09, 95% confidence interval [CI] 1.23-3.66; high vs. low: 2.47, 1.40-4.47). In the analysis by stratum of phosphate levels, elevated CPT levels were significantly associated with all-cause mortality in the highest tertile (18.1; 3.15-345.9) among the high-phosphate group, but not among the low-phosphate group. CONCLUSIONS: Serum CPT would become a potential predictive marker on mortality in hemodialysis patients with high-phosphate levels.

Rapidly progressive renal failure due to tubulointerstitial infiltration of peripheral T-cell lymphoma, not otherwise specified accompanied by uveitis: a case report.

BACKGROUND: Rapid decline in renal dysfunction due to primary renal lymphoma, or secondary renal lymphoma by infiltration from a primary origin, is extremely rare. There are notably few reports indicating infiltration of T-cell lymphoma into the kidney. CASE PRESENTATION: A 61-year-old woman with a sudden body rash and liver dysfunction was brought to our hospital presenting with a dull headache and blurred vision. Laboratory tests revealed rapidly progressive renal failure. Histological examination of the kidney and skin indicated infiltration of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS). Infiltration of PTCL-NOS to the liver and spleen, and presence of Uveitis masquerade syndrome were suspected. Imaging showed that the lesion was limited to extralymphatic organs. Renal function was improved with administration of steroids, including pulse steroid therapy, before administering cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) therapy. CONCLUSIONS: This is the first reported case of rapidly progressive renal failure caused by perivascular tubulointerstitial nephritis with the direct invasion of PTCL-NOS. In our case, a single steroid dose showed dramatic results with respect to renal symptoms.

Renal infarct volume and renal function decline in acute and chronic phases.

BACKGROUND: Acute renal infarction (ARI) is a rare disease. ARI causes decline in renal function in both the acute and chronic phases. However, the correlation between the volume of the infarction and degree of renal function decline has not been fully investigated. Therefore, we aimed to examine the relationship between the volume of the infarction and degree of renal function decline. METHODS: We performed a single-center, retrospective, observational study investigating clinical parameters and the volume of the infarction. The volume of the infarction was measured using reconstructed computed tomography data. RESULTS: A total of 39 patients (mean age, 72.6 ± 13.2 years; men, 59%) were enrolled. The median infarction volume was 45 mL (interquartile range, 14-91 mL). The volume of the infarction was significantly associated with the peak lactate dehydrogenase (LDH) level (median, 728 IU/L; interquartile range, 491-1227 U/L) (r = 0.58, p < 0.01) and the degree of renal function decline in both acute and chronic phases (r = -0.44, -0.38, respectively, p < 0.05). The peak LDH level was significantly correlated with the degree of renal function decline in the acute phase but not in the chronic phase (r = -0.35, -0.21; p < 0.05, N.S., respectively). CONCLUSIONS: The volume of the infarction may be a factor in the degree of renal function decline in ARI. Therefore, assessment of infarct volume in ARI is important.

Remission Induction Therapy with Rituximab for Microscopic Polyangiitis: A Feasibility Study.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is systemic vascular inflammation. Microscopic polyangiitis (MPA) is a major type of AAV in Japan. MPA often affects the kidneys and lungs, leading to death if untreated. Induction therapy (i.e., initial treatment) for MPA has not been optimized, although methylprednisolone and cyclophosphamide are commonly used. Recently, rituximab (RTX) (a monoclonal antibody against the protein CD20) has also been used to treat refractory AAV. RTX at 375 mg/m2/week for 4 weeks (i.e., the conventional lymphoma dosing schedule) is used, but the optimal dosing schedule is controversial. Indeed, a single-dose of RTX successfully controlled nephrotic syndrome. However, to date, the effectiveness of a single RTX dose in treating MPA has not been fully investigated in Japan. This was a retrospective observational study. Six newly diagnosed patients with MPA were initially treated with methylprednisolone and a single dose of RTX (375 mg/m2). We investigated the patients' clinical features, as well as the efficacy and safety of RTX treatment. All patients attained remission on a tapered prednisolone dose of < 10 mg/day during the first 12 months. One patient relapsed after 12 months whereas another required hospitalization owing to infective spondyloarthritis. Adverse reactions to RTX infusion and late-onset neutropenia were not observed. Therefore, a single-dose treatment with RTX induced remission with few complications, and allowed tapering the prednisolone treatment. We conclude that a single dose of RTX is a promising induction therapy for MPA, reducing the cost associated with multiple doses.

A case series of acute renal infarction at a single center in Japan.

BACKGROUND: The prevalence of acute renal infarction (ARI) in Japan remains unclear. We describe the clinical features and renal prognosis of ARI in Japanese patients. METHODS: This single-center, retrospective, observational study included 33 patients with newly diagnosed ARI (2009-2013). Their clinical features and long-term renal outcomes were evaluated. RESULTS: The prevalence of ARI among emergency room patients was 0.013 %. The incidence of ARI among in-patients was 0.003 % (mean age 71.9 ± 13.4 years; men 63 %). Enhanced computed tomography or renal isotope scans were obtained to diagnose ARI. ARI involved the left kidney in 70 %, right kidney in 18 %, and both kidneys in 12 % of patients. Four cases had splenic infarction, and 70 % of patients had atrial fibrillation. We noted abdominal or flank pain in 66 %, fever (>37.6 °C) in 36 %, and nausea/vomiting in 6 % of patients. The white blood cell count, and levels of lactate dehydrogenase and C-reactive protein peaked at 2-4 days after onset. Acute kidney injury due to ARI occurred in 76 % of patients. The estimated glomerular filtration rate decreased to ~70 % and recovered to ~80 % of the original value after 1 year. The mortality rates were 9 and 15 % at 1 month and 1 year, respectively. CONCLUSIONS: We determined the prevalence of ARI among emergency room patients, its incidence among in-patients, and short-term and long-term mortality. The majority of ARI cases were of cardiac origin, and the others were due to trauma or systemic thrombotic disease. Clinicians should recognize ARI as a fatal arterial thrombotic disease.

Efficacy and safety in mice of repeated, lifelong administration of an ANGPTL3 vaccine.

Previously, we reported that an ANGPTL3 vaccine is a hopeful therapeutic option against dyslipidemia. In our current study, we assess durability and booster effects of that vaccine over a period representing a mouse's lifespan. The vaccine remained effective for over one year, and booster vaccination maintained suppression of circulating triglyceride levels thereafter without major adverse effects on lungs, kidneys, or liver, suggesting vaccine efficacy and safety.

Vaccine targeting ANGPTL3 ameliorates dyslipidemia and associated diseases in mouse models of obese dyslipidemia and familial hypercholesterolemia.

Dyslipidemia is a risk factor for cardiovascular disease (CVD), a major cause of death worldwide. Angiopoietin-like protein 3 (ANGPTL3), recognized as a new therapeutic target for dyslipidemia, regulates the metabolism of low-density lipoprotein-cholesterol (LDL-C) and triglycerides. Here, we design 3 epitopes (E1-E3) for use in development of a peptide vaccine targeting ANGPTL3 and estimate effects of each on obesity-associated dyslipidemia in B6.Cg-Lepob /J (ob/ob) mice. Vaccination with the E3 (32EPKSRFAMLD41) peptide significantly reduces circulating levels of triglycerides, LDL-C, and small dense (sd)-LDL-C in ob/ob mice and decreases obese-induced fatty liver. Moreover, E3 vaccination does not induce cytotoxicity in ob/ob mice. Interestingly, the effect of E3 vaccination on dyslipidemia attenuates development of atherosclerosis in B6.KOR/StmSlc-Apoeshl mice fed a high-cholesterol diet, which represent a model of severe familial hypercholesterolemia (FH) caused by ApoE loss of function. Taken together, ANGPTL3 vaccination could be an effective therapeutic strategy against dyslipidemia and associated diseases.

Hyperglycemia and Thrombocytopenia　- Combinatorially Increase the Risk of Mortality in Patients With Acute Myocardial Infarction Undergoing Veno-Arterial Extracorporeal Membrane Oxygenation.

Background: Patients with cardiogenic shock due to acute myocardial infarction (AMI) can rapidly undergo veno-arterial extracorporeal membrane oxygenation (VA-ECMO) therapy to recover cardiac output and decrease mortality. However, the clinical indicators predictive of mortality in these patients remain unknown. Methods and Results: We conducted a single-center retrospective cohort study targeting AMI patients undergoing VA-ECMO. All 63 patients undergoing VA-ECMO for AMI at the Japanese Red Cross Kumamoto Hospital between January 1, 2010 and June 30, 2020 were enrolled. An exploratory analysis was conducted using a survival tree model and variables selected in a univariate Cox proportional hazard model. The median survival time from the start of VA-ECMO was 6.3 days, and 77.8% (n=49) of patients died. Survival analysis divided patients into 3 groups based on 2 parameters at the initial medical examination: Group 1, patients with neither hyperglycemia (blood glucose ≥213 mg/dL) nor thrombocytopenia (platelets ≤145,100/µL); Group 2, patients with hyperglycemia; and Group 3, patients with hyperglycemia plus thrombocytopenia. Relative to Group 1, the risk of in-hospital mortality was significantly increased in Group 2 (hazard ratio [HR] 2.25; 95% confidence interval [CI] 1.13-4.46), and that risk further increased in Group 3 (HR 7.60; 95% CI 3.21-17.95). Conclusions: Hyperglycemia plus thrombocytopenia on initial medical examination combinatorially increase the risk of mortality in patients with cardiogenic shock due to AMI undergoing VA-ECMO.

Circulating angiopoietin-like protein 2 levels and arterial stiffness in patients receiving maintenance hemodialysis: A cross-sectional study.

BACKGROUND AND AIMS: Chronic low-grade inflammation is receiving much attention as a critical pathology that induces various aging phenotypes, a concept known as "inflammaging". Uremic patients undergoing hemodialysis therapy show vascular aging phenotypes characterized by greater arterial stiffness and calcification compared to healthy controls of the same generation. In the current study, we investigated whether levels of inflammaging markers in the circulation were associated with vascular aging phenotypes in hemodialysis patients, as estimated by the cardio-ankle vascular index (CAVI). METHODS: We conducted a multicenter cross-sectional study of 412 patients receiving hemodialysis and evaluated the relationship between circulating hs-CRP or ANGPTL2 levels, as markers of inflammaging, and CAVI. RESULTS: Of 412 patients, 376 were analyzed statistically. While circulating hs-CRP levels had no significant association with CAVI, generalized linear models revealed that high circulating ANGPTL2 levels were significantly associated with increasing CAVI after adjustment for classical metabolic factors and hemodialysis-related parameters [ß 0.63 (95%CI 0.07-1.18)]. Exploratory analysis revealed that high circulating ANGPTL2 levels were also strongly associated with increased CAVI, particularly in patients with conditions of increased vascular mechanical stress, such elevated blood pressure [ß 1.00 (95%CI 0.23-1.76)], elevated pulse pressure [ß 0.75 (95%CI 0.52-0.98)], or excess body fluid [ß 1.25 (95%CI 0.65-1.84)]. CONCLUSIONS: We conclude that circulating levels of ANGPTL2 rather than hs-CRP are positively associated with CAVI in the uremic population and that ANGPTL2 could be a unique marker of progression of vascular aging in patients receiving hemodialysis.

IgG4-Related Disease Manifesting as Interstitial Nephritis Accompanied by Hypophysitis.

BACKGROUND IgG4-related disease is a systemic disease with marked infiltration of IgG4-positive plasma cells into affected organs and elevated serum IgG4. On clinical examination, swelling, nodules, and hypertrophic lesions might appear simultaneously or metachronously in different organs. CASE REPORT An 85-year-old man with sudden-onset polydipsia and polyuria insipidus was transported to our hospital because of hypothermia and general malaise. Laboratory tests revealed renal failure and central diabetes insipidus. According to his serum IgG4 level, the patient was diagnosed with possible IgG4-related kidney disease accompanied by IgG4-related hypophysitis. Abdominal contrast-enhanced computed tomography, hypophysis magnetic resonance imaging, and histological examination of the kidney were performed. Glucocorticoid therapy was administered and his renal function improved gradually. However, his central diabetes insipidus did not improve. CONCLUSIONS Glucocorticoid therapy showed different therapeutic effects on the kidney and posterior lobe of the hypophysis. It is possible that glucocorticoid therapy needs to be supported by other immunomodulatory therapies to have an effect on all affected organs.

Pre-Dialysis Neutrophil-Lymphocyte Ratio, a Novel and Strong Short-Term Predictor of All-Cause Mortality in Patients With Diabetic Nephropathy: Results From a Single-Center Study.

Neutrophil-lymphocyte ratio (NLR) is an inflammatory marker affecting the prognosis of end-stage renal disease (ESRD) patients. This study aimed to evaluate NLR levels predicting all-cause mortality in ESRD patients with diabetic nephropathy (DN), which have not been evaluated. We recruited 151 isolated DN patients who started hemodialysis between January 2009 and December 2014 at the Japanese Red Cross Ishinomaki Hospital. The primary outcomes were 1- and 3-year survival rates. The association between NLR and survival rate was evaluated using the Kaplan-Meier method and Cox proportional hazard regression analysis. Patients with an NLR ≥ 3.5 had a significantly higher mortality rate than did those with an NLR < 3.5 (log rank P = 0.02). The area under the curve (AUC) of 1-year survival for NLR was significantly larger than that for other commonly used nutritional and inflammatory variables. NLR was a more accurate predictor than other well-known markers.

Perirenal fat stranding is not a powerful diagnostic tool for acute pyelonephritis.

PURPOSE: Pyelonephritis, an upper urinary tract infection, is a serious infection that often requires hospitalization. However, the accurate diagnosis of acute pyelonephritis can be difficult, especially among older individuals who can present with unusual symptoms. Imaging with computed tomography (CT) is not unusual in the diagnosis of pyelonephritis, with some clinicians regarding perirenal fat stranding (PFS) as a characteristic finding. However, the sensitivity and specificity of PFS in diagnosing pyelonephritis are currently unknown. We therefore sought to clarify the relevance of PFS in diagnosing acute pyelonephritis. PATIENTS AND METHODS: We conducted a case-controlled retrospective analysis of medical records. The pyelonephritis group included 89 patients who had been diagnosed with acute pyelonephritis, while the control group included 319 patients who had undergone percutaneous renal biopsy. CT findings were available for both groups. The frequency of PFS and its sensitivity and specificity for the diagnosis of acute pyelonephritis were investigated. RESULTS: The mean ages of the pyelonephritis and control groups were 74±15 years and 63±16 years, respectively. A total of 28% of men were in the pyelonephritis group vs 61% of men in the control group. The frequency of PFS was 72% in the pyelonephritis group vs 39% in the control group. Age and renal dysfunction were associated with an increased frequency of PFS. After adjusting for age, sex, and renal function using a propensity score analysis, the sensitivity, specificity, and positive likelihood ratio of PFS for diagnosing acute pyelonephritis were 72%, 58%, and 1.7, respectively. CONCLUSION: The presence of PFS was not useful in diagnosing acute pyelonephritis.

The influence of the Great East Japan earthquake on microscopic polyangiitis: A retrospective observational study.

BACKGROUND: Antineutrophil cytoplasmic antibody-associated vasculitis is triggered by environmental factors, including silica dust exposure. Repeated tsunami waves brought a large volume of silica-containing sludge inland after the Great East Japan earthquake in 2011. We aimed to determine if the serious disaster influenced the clinical features of the microscopic polyangiitis. METHODS: This is an observational retrospective study conducted in a single institute. A total of 43 patients were included based on the CHCC2012 criteria for microscopic polyangiitis from 2007 to 2015. We used the Poisson regression model to determine the incidence of microscopic polyangiitis within the annual population of the medical district. The participants were selected during a 3-year period from before (N = 13) to after the disaster (N = 20). The differences of parameters and the overall survival between the groups were analyzed. RESULTS: The incidence of microscopic polyangiitis increased after the disaster (λ = 17.4/million/year [95%CI: 7.66-39.6] before the disaster and λ = 33.1/million/year [17.7-61.7] after the disaster, P = 0.044). A high Birmingham Activity Score was associated with a high incidence of microscopic polyangiitis after the disaster. The overall survival of the patients with microscopic polyangiitis declined significantly after the disaster. CONCLUSIONS: The Great East Japan earthquake influenced the development of the microscopic polyangiitis in our restricted area. The patients who developed after the disaster had severe symptoms and a high mortality rate.

Evaluation of the Predictive Value of the Serum Calcium-Magnesium Ratio for All-Cause and Cardiovascular Mortality in Incident Dialysis Patients.

BACKGROUND/AIM: Cardiovascular disease is the most serious cause of death in patients on hemodialysis. Low serum magnesium (Mg) and high serum calcium (Ca) levels have been associated with poor outcome and cardiovascular mortality in patients on maintenance and initiation dialysis. As a more accurate marker is warranted, we evaluated the efficacy of a novel serum Ca-Mg marker of all-cause and cardiovascular mortality that indicates vessel calcification. METHODS: We recruited 378 consecutive patients with end-stage renal disease who started dialysis between January 2009 and December 2015 at the Japanese Red Cross Ishinomaki Hospital. We collected data of patients' demographic characteristics and comorbidities from their electronic medical records. We retrospectively examined the association of the serum Ca-Mg ratio with all-cause and cardiovascular mortality using the Cox proportional hazard model, and determined the value that predicted cardiovascular death using the receiver operating characteristic (ROC) curve. RESULTS: Overall, 253 patients with serum Mg and Ca data were analyzed. The 3-year survival rate of this group was 0.70 (95% confidence interval [CI] 0.55-0.80), and the hazard ratio for the risk of death was 3.94 (95% CI 1.37-11.31). The 3-year cardiovascular mortality rate was 0.12 (95% CI 0.05-0.23), which was significantly higher than that of the other groups. The ROC curve of cardiovascular mortality with the Ca-Mg ratio was greater than that of Mg (area under the curve 0.75 vs. 0.69, p = 0.037). CONCLUSION: A high Ca-Mg ratio was significantly associated with all-cause and cardiovascular mortality, and it was more accurate than serum Mg.

Quantification of bleeding volume using computed tomography and clinical complications after percutaneous renal biopsy.

Background: The aim of this study was to investigate specific bleeding volume after percutaneous renal biopsy (PRB) and the correlation between bleeding volume and clinical parameters. Methods: A retrospective study of 252 consecutive patients (153 male patients and 99 female patients) who underwent PRB at the Department of Nephrology, Japanese Red Cross Ishinomaki Hospital, between July 2013 and January 2016 was conducted. PRB was performed under ultrasound guidance using an automated spring-loaded biopsy device and a 16-cm, 16-gauge needle. Patients underwent computed tomography (CT) the day after PRB. Bleeding volume after PRB was evaluated using reconstructed CT data. Results: The median bleeding volume after PRB was 38 mL (25th-75th percentile, 18-85 mL), with ≥4 punctures identified as a risk factor for massive bleeding. The incidence rates of macrohematuria, transient hypotension and bladder obstruction were 14.3, 8.7 and 4.7%, respectively. Post-PRB blood transfusion and intervention were required in 4.7 and 0.8% of patients, respectively. Conclusion: Although it is difficult to assess the risk for massive bleeding prior to PRB, we do provide evidence of a specific increased risk with ≥4 puncture attempts, and recommend careful follow-up of these patients.