Fabry Disease with Pacemaker Implantation as the Initial Event.

Fabry disease (FD) is a rare X-linked hereditary disorder (Xq22) caused by a deficiency in alpha-galactosidase activity. A 34-year-old man was referred to our hospital because of renal dysfunction. He had previously undergone pacemaker implantation at 24 years of age. Investigations revealed undetectable alpha-galactosidase A activity levels. Renal biopsy results indicated vacuolization of podocytes. A genetic analysis revealed that the patient carried the W340X mutation. Enzyme replacement therapy with agalsidase beta was started. This case is novel because most cases of FD nephropathy precede cardiac disease. In our patient, the cardiac event was the initial event, and renal impairment followed.

Manual compression and reflex syncope in native renal biopsy.

BACKGROUND: Complications associated with diagnostic native percutaneous renal biopsy (PRB) must be minimized. While life threatening major complications has been extensively investigated, there is little discussion regarding minor bleeding complications, such as a transient hypotension, which directly affect patients' quality of life. There is also little evidence supporting the need for conventional manual compression following PRB. Therefore, this study evaluated the relationship between minor and major complications incidence in patients following PRB with or without compression. METHODS: This single-center, retrospective study included 456 patients (compression group: n = 71; observation group: n = 385). The compression group completed 15 min of manual compression and 4 h of subsequent strict bed rest with abdominal bandage. The observation group completed 2 h of strict bed rest only. The primary outcome of interest was transient symptomatic hypotension (minor event). RESULTS: Of the 456 patients, 26 patients encountered intraoperative and postoperative transient hypotension, which were considered reflex syncope without tachycardia. Univariate analysis showed that symptomatic transient hypotension was significantly associated with compression. This association remained significant, even after adjustment of covariates using multivariate logistic regression analysis (adjusted odds ratio 3.27; 95% confidential interval 1.36-7.82; P = 0.0078). CONCLUSION: Manual compression and abdominal bandage significantly increased the frequency of reflex syncope during native PRB. It is necessary to consider the potential benefit and risk of compression maneuvers for each patient undergoing this procedure.

The size of the renal artery orifice contributes to laterality of acute renal infarction.

BACKGROUND: Acute renal infarction (ARI) is a rare disease with atrial fibrillation being its main cause. The possible laterality of ARI is controversial. This study aimed to evaluate the association between anatomical features of the renal arteries and ARI. METHODS: This was a single-center cross-sectional study that evaluated the anatomical and clinical features of renal arteries. The anatomical features of the renal arteries were assessed using computed tomography. RESULTS: A total of 46 patients (mean age 71.3 ± 14.0 years; men, 59%) were enrolled. ARI involved the left kidney in 63%, right kidney in 28%, and both kidneys in 9% of patients. The right renal artery orifice was often higher than that of the left renal artery (71%). The angle of divergence from the abdominal aorta was similar on both sides. The left renal artery orifice was larger than that of the right (83 ± 24, 72 ± 24 mm2; p = 0.03, respectively). A larger left orifice was present in 72% of all cases. ARI involved the side with the larger orifice in 64% of patients. CONCLUSION: The size of the renal artery orifice may be a factor that contributes to the laterality of ARI. Assessment of anatomical features is important when considering the laterality of the disease.

Unexpected delayed bleeding after native renal biopsy: a case report.

Percutaneous native renal biopsy is recognized as a safe procedure. The majority of bleeding events occur within 24 h after the procedure, and reports of delayed major complications are very limited. We report a patient presenting with sudden flank pain 7 days after renal biopsy, in whom abdominal computed tomography showed increased hematoma size with extravasation and who was treated with radiological intervention. Careful attention should be paid to diagnose and treat delayed major complications in patients undergoing native renal biopsy.

Anti-neutrophil Cytoplasmic Antibody-associated Vasculitis (AAV) Restricted to the Limbs.

A previously healthy 58-year-old man was admitted for muscle pain and weakness [manual muscle testing (MMT) of 4/4 for upper and lower limbs]. We detected elevated levels of inflammatory makers and PR3-anti-neutrophil cytoplasmic antibody (ANCA). Subsequently, the muscle weakness rapidly progressed to an MMT of 2 for all limbs. Magnetic resonance imaging indicated muscle edema, and the creatine kinase (CK) level increased to 29,998 U/L. Methylprednisolone (mPSL) and cyclophosphamide pulse therapy improved the patient symptoms. MMT recovered to 4 for all limbs. A muscle biopsy showed degenerated muscle fibers surrounded by neutrophil-predominant infiltration. In addition, lamina elastic breakdown and fibrinoid necrosis of arterioles were observed. A final diagnosis of microscopic polyangiitis (MPA) limited to the muscles was made.

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.

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.

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.

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.

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.

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.

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.

Cytokines induce NF-κB, Nurr1 and corticotropin-releasing factor gene transcription in hypothalamic 4B cells.

OBJECTIVE: In the hypothalamus, corticotropin-releasing factor (CRF) plays a central role in regulating stress responses. Cytokines are important mediators of the interaction between the neuroendocrine and immune systems, and are implicated in the regulation of CRF expression. Following inflammatory challenges, interleukin (IL)-1 or IL-6 stimulates the hypothalamic-pituitary-adrenal axis. CRF promoter contains multiple nuclear factor (NF)-kappaB and Nurr1 binding sites. In the present study, we determined the ability of the signaling pathways to activate the CRF gene in the hypothalamic paraventricular nucleus following inflammatory challenge. METHODS: Cytokine-induced changes in CRF gene expression were examined in the hypothalamic system. Luciferase assay and Western blotting were performed to assess transcriptional activity and the nuclear translocation of transcriptional factors. RESULTS: IL-1beta, IL-6 and tumor necrosis factor (TNF)-alpha stimulated the nuclear expression levels of NF-kappaB, NF-kappaB-dependent Nurr1 and c-Fos proteins. Direct stimulatory effects of TNF-alpha and IL-1beta, in addition to IL-6, were found on the transcriptional activity of the CRF gene in hypothalamic 4B cells. CONCLUSION: These cytokines are involved in the regulation of CRF gene activity in hypothalamic cells.