Renal Embolism Associated with the Atrial Myxoma: A Case Report and Literature Review.

Renal embolisms due to cardiac myxomas are extremely rare; the clinical course, treatment, and prognosis of this disease are not established. A 69-year-old Japanese woman who underwent a nephrectomy for renal cell carcinoma 3 years earlier was hospitalized with a right occipital lobe cerebral infarction. Her renal function suddenly worsened 3 days post-admission: her serum creatinine rose from 1.46 mg/dL to 6.57 mg/dL and then to 8.03 mg/dL the next day, and hemodialysis therapy was started. Abdominal computed tomography (CT) scans showed patchy non-contrasted low-density areas in the right kidney, and chest CT scans and transesophageal ultrasonography revealed a left atrial tumor. We diagnosed renal infarction due to a left atrial myxoma. Hemodialysis and anticoagulant therapy (heparin) were continued, followed by the cardiac myxoma's resection. The patient's renal function gradually improved post-surgery, and the hemodialysis was discontinued. Considering our patient and 19 other case reports of renal infarction associated with cardiac myxoma, the treatment for such a renal infarction and the outcomes differ depending on the embolus site. The poor outcome of abdominal aortic embolism requires a prompt embolectomy, whereas a branch renal artery embolism requires anticoagulation therapy to prevent thrombosis formation around the myxoma.

NT-pro BNP level at dialysis initiation is a useful biomarker for predicting hospitalization for ischemic heart disease.

BACKGROUND: Patients with end-stage kidney disease (ESKD) are at high risk of cardiovascular disease including stroke, heart failure, and ischemic heart disease (IHD). To prevent the occurrence and progression of CVD, a reliable prognostic cardiac biomarker is essential. We investigated the prognostic value of NT-proBNP for each incident type of CVD. METHODS: Male patients from the Ibaraki Dialysis Initiation Cohort (iDIC) study with preserved serum samples from dialysis initiation day (n = 212) were analyzed. Patients were classified into four groups according to quartiles of baseline NT-pro BNP levels. The relationship between NT-proBNP levels at the initiation of dialysis and the subsequent incidence of hospitalization events due to IHD, heart failure, and stroke was analyzed. RESULTS: The incidence rate for hospitalization due to IHD was significantly higher in the highest NT-proBNP category (Log rank p = 0.008); those of stroke and heart failure showed no significant differences among quartiles. Cox proportional hazards regression analysis revealed that serum NT-proBNT was the only prognostic factor for hospitalization for IHD after adjustment by major known IHD risk factors. (HR, 1.008; 95% confidence interval, 1.002-1.014; p = 0.01) The ROC curve analysis for the incidence of hospitalization due to IHD showed that NT-proBNP had an area under the curve (AUC) of 0.759 (95% CI 0.622-0.897; p = 0.004) at a cut-off value of 956.6 pg/mL. CONCLUSION: NT-proBNP measurement at the initiation of dialysis therapy is useful to predict later hospitalization for IHD. TRIAL REGISTRATION: UMIN000010806.

The Immunobiological Agents for Treatment of Antiglomerular Basement Membrane Disease.

Combination therapy with glucocorticoids, cyclophosphamide, and plasmapheresis is recommended as the standard treatment for anti-glomerular basement membrane (anti-GBM) disease, but the prognosis of this disease remains poor. Several immunobiological agents have been administered or are expected to be useful for anti-GBM disease in light of refractory disease or the standard treatments' tolerability. Many data regarding the use of biologic agents for anti-GBM disease have accumulated, verifying the effectiveness and potential of biologic agents as a new treatment option for anti-GBM disease. Tumor necrosis factor (TNF) inhibitors were shown to be useful in animal studies, but these agents have no clinical use and were even shown to induce anti-GBM disease in several cases. Although the efficacy of the TNF-receptor antagonist has been observed in animal models, there are no published case reports of its clinical use. There are also no published reports of animal or clinical studies of anti-B-cell-activating factor, which is a member of the TNF family of agents. Anti-interleukin (IL)-6 antibodies have been demonstrated to have no effect on or to exacerbate nephritis in animal models. Anti-C5 inhibitor was observed to be useful in a few anti-GBM disease cases. Among the several immunobiological agents, only rituximab has been demonstrated to be useful in refractory or poor-tolerance patients or small uncontrolled studies. Rituximab is usually used in combination with steroids and plasma exchange and is used primarily as an alternative to cyclophosphamide, but there is insufficient evidence regarding the efficacy of rituximab for anti-GBM disease, and thus, randomized controlled studies are required.

Treatment of Fabry Nephropathy: A Literature Review.

Fabry disease is an X-linked inherited lysosomal storage disorder with a deficiency of α-galactosidase A activity, which results in the intracellular accumulation of globotriaosylceramide (Gb3) and related glycosphingolipids in various organs. Fabry nephropathy is one of the major complications of Fabry disease, and kidney damage is often related to cardiovascular disease and mortality. The treatment of Fabry nephropathy thus helps prolong life expectancy. Two treatment options for Fabry nephropathy and cardiopathy are now commercially available: enzyme replacement therapy (agalsidase α agalsidase ß, and a biosimilar of agalsidase ß) and pharmacological chaperone therapy (migalastat). In this review, we summarize the efficacy of these treatment options for Fabry nephropathy with respect to renal function, proteinuria, and renal pathological findings. We also describe the importance of adjunctive therapy for Fabry nephropathy.

The effect of sodium-glucose cotransporter 2 inhibitor (tofogliflozin) on renal tubular damage in diabetic patients without albuminuria.

PURPOSE: The sodium-glucose cotransporter 2 (SGLT2) inhibitors comprise a new class of glucose-lowering drugs for individuals with diabetes. Large-scale clinical trials indicated that SGLT2 inhibitors have both a cardiovascular-protective and renal-protective effects. A reduction in glomerular hyperfiltration and a decrease in albuminuria are suspected as the main causes of SGLT2 inhibitors' renoprotective effect. The effects of SGLT2 inhibitors on tubular damage in non-albuminuric diabetic patients are unclear. METHODS: The SGLT2 inhibitor tofogliflozin (20 mg, 1 × /day) was orally administered to 14 non-albuminuric diabetic patients. Serum and urine samples were collected at baseline (before) and after the start of tofogliflozin treatment. Hemoglobin A1c, hemoglobin, estimated glomerular filtration rate (eGFR), body weight, and blood pressure (BP) were analyzed as clinical parameters at baseline and 1, 3, and 6 months later. Urinary neutrophil gelatinase-associated lipocalin (NGAL) and N-acetyl-ß-D-glucosaminidase were measured as tubular damage markers and the urinary 8-hidroxydeoxyguanosine (8-OHdG) values were measured as an oxidative stress marker at baseline and at 1 and 3 months. RESULTS: Compared to baseline, the patients' HbA1c values and body weights were significantly decreased post-tofogliflozin administration, and their eGFR values were decreased at 3 months but recovered at 6 months; the hemoglobin concentrations were significantly increased at 3 and 6 months and the urinary NGAL level tended to be decreased at 3 months. No significant changes in blood urea nitrogen, BP, NAG, urine sodium concentration, or urinary 8-OHdG values occurred. The effect of this SGLT2 inhibitor was not influenced by the use of an angiotensin receptor blocker or dipeptidyl-peptidase 4 inhibitor. CONCLUSION: For individuals with non-albuminuric diabetes, tofogliflozin has a good glucose-lowering effect and might have a tubular-protective effect.

Health state utility values in people living with HTLV-1 and in patients with HAM/TSP: The impact of a neglected disease on the quality of life.

BACKGROUND: HTLV-1 is a neglected sexually transmitted infection despite being the cause of disabling neurological disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). There is no treatment for this infection and public health policies are essential to reduce its transmission. However, there are no data to support adequate cost-effective analysis in this field. The aim of this study was to obtain health state utility values for individuals with HAM/TSP and HTLV-1 asymptomatic carriers (AC). The impact of both states on quality of life (QoL) is described and compared to other diseases. METHODS: A cross-sectional observational study of 141 individuals infected with HTLV-1 (79 with HAM/TSP and 62 AC) from three Brazilian states (Rio de Janeiro, São Paulo and Alagoas) and from the United Kingdom. Participants completed a validated general health questionnaire (EQ-5D, Euroqol) from which country specific health state utility values are generated. Clinical and epidemiological data were collated. PRINCIPAL FINDINGS: Health state utility value for HAM/TSP was 0.2991. QoL for 130 reported clinical conditions ranges from 0.35 to 0.847. 12% reported their quality of life as worse as death. Low QoL was associated with severity rather than duration of disease with a moderate inverse correlation between QoL and Osame's Motor Disability Score (-0.4933) Patients who are wheelchair dependent had lowest QoL whilst those still walking unaided had the highest. AC also reported impaired QoL (0.7121) compared to general population. CONCLUSION: HTLV-1 and its associated neurological disease has a marked impact on QoL. This study provides robust data to support the development of cost-utility analysis of interventions for HTLV-1.

Serum 20S proteasome levels are associated with disease activity in MPO-ANCA-associated microscopic polyangiitis.

BACKGROUND: Proteasomes are found in both the cell nucleus and cytoplasm and play a major role in the ubiquitin-dependent and -independent non-lysosomal pathways of intracellular protein degradation. Proteasomes are also involved in the turnover of various regulatory proteins, antigen processing, cell differentiation, and apoptosis. To determine the diagnostic value of serum proteasome in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), we investigated patients with AAV at various stages of the disease. METHODS: Serum 20S-proteasome was measured by ELISA in 44 patients with MPO-ANCA-associated microscopic polyangiitis (MPA) and renal involvement. Thirty of the patients provided serum samples before the initial treatment, and 30 provided samples during remission; 16 provided samples at both time points. RESULTS: The mean serum 20S-proteasome level was significantly higher in the active-vasculitis patients (3414.6 ± 2738.9 ng/mL; n = 30) compared to the inactive-vasculitis patients (366.4 ± 128.4 ng/mL; n = 30; p <  0.0001) and 40 controls (234.9 ± 90.1 ng/mL; p <  0.0001). There were significant positive correlations between the serum 20S-proteasome level and the Birmingham Vasculitis Activity Score (BVAS) (r = 0.581, p <  0.0001), the ANCA titer (r = 0.384, p <  0.0001), the white blood cell (WBC) count (r = 0.284, p = 0.0042), the platelet count (r = 0.369, p = 0.0002), and the serum C-reactive protein (CRP) level (r = 0.550, p < 0.0001). There were significant negative correlations between the serum 20S-proteasome level and both the hemoglobin concentration (r = - 0.351, p = 0.0003) and the serum albumin level (r = - 0.460, p < 0.0001). In a multiple regression analysis, there was a significant positive correlation between the serum 20S-proteasome level and only the BVAS results (ß = 0.851, p = 0.0009). In a receiver operating curve analysis, the area under the curve for the serum 20S-proteasome level was 0.996, which is higher than those of the WBC count (0.738) and the serum CRP level (0.963). CONCLUSION: The serum level of 20S-proteasome may be a useful marker for disease activity in AAV.

An Adult Patient with Alagille Syndrome Showing Mainly Renal Failure and Vascular Abnormality without Liver Manifestation.

Alagille syndrome is an inherited multisystemic disorder. We herein report an atypical case of a Japanese adult patient with Alagille syndrome. He had been diagnosed with Alagille syndrome as an infant based on a liver biopsy. At 27 years of age, he needed to start hemodialysis therapy, but an arteriovenous fistula was not created because his peripheral blood vessels were too narrow. He also had a recurrent brain infarction due to cerebral vascular stenosis. Alagille syndrome is generally recognized as a pediatric hepatic disease, but general physicians should be aware of its potential existence with renal involvement and vascular abnormalities.

Clinical course and pathological findings of two late-onset Fabry hemizygous patients including mulberry cell counts after enzyme replacement therapy.

Fabry disease is an X-linked inherited lysosomal storage disorder caused by a deficiency of α-galactosidase A activity, resulting in the intracellular accumulation of globotriaosylceramide and related glycosphingolipids. The phenotypes of Fabry disease in both males and females are grouped into two categories: the classical type and the late-onset type. The classical type shows general symptoms including angiokeratoma(s), acroparesthesia, hypohidrosis, corneal opacity, and gastrointestinal symptoms from an early age. The late-onset type shows cardiac or renal (or both) symptoms from a late age. We present herein the clinical course and pathological findings of two late-onset hemizygous Fabry patients after the initiation of enzyme replacement therapy (ERT), along with their mulberry cell counts during treatment. One patient's case was a renal-variant type without general symptoms; he showed stable renal function and mild proteinuria but little histological improvement with no change in the mulberry cell count during ERT. The other patient had a cardiac-variant type with renal pathological abnormality. He achieved a mild improvement of renal pathological findings, and his mulberry cell count gradually decreased during the treatment. These findings indicate that monitoring the mulberry cell count might help assess the efficacy of ERT, as a renal pathology tool.

The relationship between serum magnesium levels and mortality in non-diabetic hemodialysis patients: A 10-year follow-up study.

Introduction Recently, although there are many reports showing that serum magnesium concentration is a predictor of mortality in dialysis patients, the observation periods of those reports were of short duration, typically around 12 months. Thus, we investigated this relationship over a longer follow-up period. Methods This retrospective, observational study included a total of 83 non-diabetic hemodialysis patients. The follow-up period was 120 months. Patients were divided into two groups, those with serum magnesium ≥2.5 mg/dL (Mg ≥2.5 mg/dL group) and serum magnesium <2.5 mg/dL (Mg <2.5 mg/dL group), and Kaplan-Meier analysis and Cox proportional hazards analysis were conducted. In addition to the above analysis, single and multiple regression analysis were performed at baseline to reveal the relationship between serum magnesium and clinical parameters. Findings During the follow-up period, 31 out of 83 patients died. Kaplan-Meier analysis showed a significantly higher incidence of death in the Mg <2.5 mg/dL group (log-rank test 4.951, P = 0.026). Multivariate Cox proportional hazards analysis showed a 62% decreased risk of mortality in the Mg ≥2.5 mg/dL group compared to the Mg <2.5 mg/dL group after adjustment for several confounding factors. Simple correlation coefficient analysis showed positive correlations of serum magnesium levels with serum creatinine, phosphorus, high-density lipoprotein, ankle-brachial index and KT/V, and a negative correlation with age. Multiple linear regression analysis showed that the ankle-brachial index was the only parameter that had a positive and significant correlation with the serum magnesium level. Conclusion Our study demonstrated that higher serum magnesium levels were associated with improved survival in non-diabetic hemodialysis patients.