Blood Urea Nitrogen/Creatinine Ratio and Response to Tolvaptan in Patients with Decompensated Heart Failure: A Retrospective Analysis

Introduction

Arginine vasopressin-stimulated reabsorption of urea occurs in the collecting duct via increased expression of the urea transporter.

Objective

The aim of this study was to evaluate whether the blood urea nitrogen/creatinine (BUN/Cr) ratio is useful for predicting tolvaptan response in patients with decompensated heart failure (HF).

Methods

Among 71 consecutive patients with HF who received oral tolvaptan between 2010 and 2014, we retrospectively studied 33 patients with decompensated HF without any mechanical circulatory assistance or inotropic support who had already been treated with loop diuretics. A responder to tolvaptan was defined as an individual who experienced a ≥30 % increase in their respective 24-h urine volume.

Results

Among the 33 patients, 21 met the criteria of a responder. The area under the receiver operating characteristic curves of BUN/Cr and BUN were 0.790 and 0.714, respectively, and the respective cut-off values for responders to tolvaptan were 23.8 and 49.0. BUN/Cr and BUN retained their significant relationships with the responder status (odds ratio for BUN/Cr >23.8: 20.9; 95 % confidence interval [CI] 2.7–531.1; p = 0.002; odds ratio for BUN ≥49: 7.7; 95 % CI 1.4–65.8; p = 0.02).

Conclusion

Our results suggest that high BUN/Cr may be a predictor of response to tolvaptan in decompensated HF patients. A prospective study with a large sample size is required to confirm this preliminary finding.

     

Neglect‐induced pseudo‐thrombotic thrombocytopenic purpura due to vitamin B12 deficiency

Although thrombotic thrombocytopenic purpura (TTP) is rare, early diagnosis and treatment are important for decreasing the mortality rate. Acquired vitamin B12 deficiency is frequently overlooked because of its rarity in developed countries, particularly in children and adolescents. The hematological changes in vitamin B12 deficiency present as megaloblastic anemia, increased lactate dehydrogenase, vasoconstriction, increased platelet aggregation, and abnormal activation of the coagulation followed by microangiopathy as well as neutropenia and thrombocytopenia. We report herein the case of a 15‐year‐old girl who had been neglected, which might have caused pseudo‐TTP through malnutrition, particularly vitamin B12 deficiency. When we encounter cases of TTP in children, clinicians must be aware of the possibility of malnutrition, particularly with vitamin B12 deficiency, even in developed countries, and investigate the cause of malnutrition including neglect.     

Asymptomatic chronic intestinal ischemia caused by idiopathic phlebosclerosis of mesenteric vein

Phlebosclerosis of the mesenteric vein is a rare condition causing chronic intestinal ischemia, it has only been reported in Japan. A 56-year-old man with liver cirrhosis and hepatic tumor presented with phlebosclerosis of mesenteric vein without any abdominal symptoms. He was admitted for examination of suspected hepatic tumor. Abdominal plain x-ray films and computed tomography revealed calcification of the mesenteric vein. Barium enema revealed narrowing and thumbprinting from the cecum to transverse colon. On colonoscopic examination, blue-black vessels were visible in the terminal ileum, and hyperemic nodular mucosa with small irregular ulcers surrounded by dark purple mucosa was found from the cecum to transverse colon. The etiology of mesenteric vein phlebosclerosis is unknown, although a physical mechanism rather than inflammatory changes appear to be involved in this rare and usually progressive condition of chronic intestinal ischemia.     

Effect of spironolactone on cardiac sympathetic nerve activity and left ventricular remodeling in patients with dilated cardiomyopathy

OBJECTIVES: We sought to evaluate the effects of spironolactone on cardiac sympathetic nerve activity and left ventricular (LV) remodeling in patients with dilated cardiomyopathy (DCM). BACKGROUND: Aldosterone prevents the uptake of norepinephrine and promotes structural remodeling of the heart. Spironolactone, an aldosterone receptor blocker, improves LV remodeling in patients with DCM, but its influence on cardiac sympathetic nerve activity has not been determined. METHODS: We selected 30 patients with DCM who were treated with an angiotensin-converting enzyme inhibitor and a loop diuretic. Fifteen patients were assigned to receive spironolactone additionally, whereas the remaining 15 patients continued their current regimen. The delayed heart/mediastinum (H/M) count ratio, delayed total defect score (TDS), and washout rate (WR) were determined from iodine-123 ((123)I)-meta-iodobenzylguanidine (MIBG) images before and six months after treatment. The left ventricular end-diastolic volume (LVEDV) and left ventricular ejection fraction (LVEF) were determined by echocardiography, and New York Heart Association (NYHA) functional class was estimated.RESULTS: In the spironolactone group, the TDS decreased from 36 +/- 9 to 24 +/- 13 (p < 0.0001), the H/M ratio increased from 1.64 +/- 0.20 to 1.86 +/- 0.27 (p < 0.0001), and WR decreased from 55 +/- 12% to 41 +/- 15% (p < 0.0005). In addition, the LVEDV decreased from 187 +/- 26 to 154 +/- 41 ml (p < 0.005), and LVEF increased from 33 +/- 6% to 39 +/- 6% (p < 0.005). However, there were no significant changes in these parameters in the control group. There was a significant correlation between changes in the (123)I-MIBG findings and changes in LVEDV with spironolactone treatment (TDS: r = 0.684, p = 0.0038; H/M ratio: r = -0.878, p < 0.0001; and WR: r = 0.737, p = 0.0011). The NYHA functional class improved in both groups but showed a greater improvement in the spironolactone group than in the control group (p < 0.01). CONCLUSIONS: Spironolactone improves cardiac sympathetic nerve activity and LV remodeling in patients with DCM.     

An experimentally-induced acute hepatic failure model in various strains of mice

When BALB/cAJcl mice are intravenously injected with heat-killedPropionibacterium acnes (P. acnes) followed by an intravenous injection of lipopolysaccharide (LPS) 7 days later, massive necrosis is induced in the liver tissue and most of the mice die within 24 hours of LPS injection. Using this experimental model, acute hepatic failure was induced in various strains of mice and the difference in the response was studied. As a result, as in BALB/cAJcl mice, acut hepatic failure was also induced in BALB/ cAJcl-nu, AKR/J, C3H/HeNJcl, C57BL/6NJcl and DDy mice. However, as an exception, hepatic cell necrosis was hardly seen and the survival rate was remarkable high in C3H/HeJ mice, which genetically do not respond to LPS stimulation. These results indicate that for this experimental induction of acute hepatic failure, macrophages must be activated by the two-step stimulation ofP. acnes and LPS.     

Immunohistochemical analysis of retinoblastoma gene product (pRB) expression in malignant and non-malignant liver diseases

ABSTRACT: The retinoblastoma gene product is a nuclear phosphoprotein that undergoes cell cycle-dependent changes in its phosphorylation status. To analyze the expression of retinoblastoma gene product in the process of liver regeneration and the initiation of hepatocellular carcinoma, we studied immunohistochemically the expression of retinoblastoma gene product and DNA polymerase alpha (DPA) in 33 patients with various liver diseases. Only a few hepatocytes positive for retinoblastoma gene product were found in undamaged, nonregenerating liver tissues, whereas many hepatocytes positive for retinoblastoma gene product were detected in specimens of regenerating liver obtained from patients with acute or chronic liver diseases. Similarities were found between distribution patterns of hepatocytes positive for retinoblastoma gene product and those of hepatocytes positive for DPA, and a highly significant positive correlation was found between the number of hepatocyte nuclei stained for retinoblastoma gene product per 1000 nuclei examined (R-LI) and the number of hepatocyte nuclei stained for DPA per 1000 nuclei examined (D-LI) in tissues obtained from patients with nonmalignant liver disease. Hepatocellular carcinoma cells positive for DPA were detected in the 14 hepatocellular carcinoma specimens tested. In ten of these specimens, hepatocellular carcinoma cells positive for retinoblastoma gene product were found but not in the other four. For all hepatocellular carcinoma specimens, R-LI was proportional to D-LI. Thus in both nonmalignant and malignant liver, retinoblastoma gene product increased in proportion to proliferation of hepatocytes or hepatocellular carcinoma cells.     

Acute disseminated encephalomyelitis during treatment for idiopathic thrombocytopenic purpura

A 54-year-old woman had an episode of sudden oral bleeding and generalized petechiae 1 week after a sore throat and diarrhea. On admission, the platelet count was 0.1 x 10(4)/microl, and the platelet-associated IgG level was elevated. Hyperplasia of megakaryocytes in a bone marrow specimen and aberrant Epstein-Barr virus (EBV) antibody patterns led to a diagnosis of EBV-associated idiopathic thrombocytopenic purpura (ITP). Prednisolone (PSL) promptly restored her platelet count; however, she developed disorientation and affective lability soon after PSL was tapered. Subsequently, she ran a high fever and developed convulsive seizures. T2-weighted MRI demonstrated a high signal area in the subcortical white matter, and no abnormal findings were found on examination of the cerebrospinal fluid. The diagnosis of acute disseminated encephalomyelitis (ADEM) was made and steroid pulse therapy was started, which resulted in remission of the symptoms without recurrence in the following months. This is the first reported case of ADEM following EBV infection during treatment for ITP. Administration of PSL for ITP might mask the presenting clinical picture of ADEM. The possibility of ADEM should be investigated in patients of ITP following viral infection who develop acute encephalopathy.