Tasuku Nagasawa

Strain vessel hypothesis : a viewpoint for linkage of albuminuria and cerebro-cardiovascular risk

Albuminuria is closely associated with stroke and cardiovascular diseases (CVDs) as well as the salt sensitivity of blood pressure (BP). Although albuminuria may reflect generalized endothelial dysfunction, there may be more specific hemodynamic mechanisms underlying these associations. Cerebral hemorrhage and infarction occur most frequently in the area of small perforating arteries that are exposed to high pressure and that have to maintain strong vascular tone in order to provide large pressure gradients from the parent vessels to the capillaries. Analogous to the perforating arteries are the glomerular afferent arterioles of the juxtamedullary nephrons. Hypertensive vascular damage occurs first and more severely in the juxtamedullary glomeruli. Therefore, albuminuria may be an early sign of vascular damages imposed on ‘strain vessels’ such as perforating arteries and juxtamedullary afferent arterioles. Coronary circulation also occurs under unique hemodynamic conditions, in which the entire epicardial segments are exposed to very high pressure with little flow during systolic phases. From the evolutionary point of view, we speculate that such circulatory systems in the vital organs are mandatory for survival under the danger of hypoperfusion due to difficult access to salt and water as well as high risks of wound injuries. In addition, albuminuria would indicate an impairment of renal medullary circulation, downstream from the juxtamedullary glomeruli, and therefore an impaired pressure natriuresis, which would lead to salt sensitivity of BP. Our ‘strain vessel hypothesis’ may explain why hypertension and diabetes, unforeseen in the concept of evolution, preferentially affect vital organs such as the brain, heart and kidney.

Albuminuria indicates the pressure-associated injury of juxtamedullary nephrons and cerebral strain vessels in spontaneously hypertensive stroke-prone rats.

Albuminuria is an indicator of renal injury and is closely linked with cardiovascular disease (CVD). However, the mechanism by which albumin is excreted in the urine remains unclear. As the juxtamedullary region of the kidney is highly susceptible to pressure increase, juxtamedullary injury is observed from an early phase in hypertensive rat models. Anatomical similarities are observed between the pre-glomerular vessels of the juxtamedullary nephron and the cerebral vasculature. We previously named these ‘strain vessels’ for their high vascular tone and exposure to higher pressures. The current studies were designed to determine whether albuminuria is the result of juxtamedullary nephron injury, indicating the presence of pressure injury to the strain vessels in spontaneously hypertensive stroke-prone rats (SHR-SP) fed a high-salt diet. Albuminuria was associated with juxtamedullary nephron injury, and the enhanced expression of monocyte chemotactic protein-1 (MCP-1) and tumor growth factor-beta (TGF-β) in 12-week-old SHR-SP rats fed a 4% high-salt diet from the age of 6 weeks. The wall thickness of the pre-glomerular vessels of the juxtamedullary nephron was also associated with that of the perforating artery of the middle cerebral artery. Reducing the blood pressure with nifedipine reduced the degree of albuminuria and juxtamedullary nephron injury as well as MCP-1 and TGF-β expression in the SHR-SP rats fed an 8% high-salt diet from the age of 9 weeks. Nifedipine inhibited stroke events in these animals until they were 14 weeks old. These results indicate that albuminuria is a result of juxtamedullary nephron injury and a marker of pressure-induced injury of the strain vessels.

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.

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.

Clinical Diversity in Patients with Anderson-Fabry Disease with the R301Q Mutation

Anderson-Fabry disease (AFD) is a rare X-linked disorder caused by deficient activity of the lysosomal enzyme α-galactosidase A (α-GAL A). We herein report 10 cases of AFD in 5 families (3 men and 7 women) that were found to have a specific common mutation in R301Q [G-to-A transition in exon 6 (codon 301) resulting in the replacement of a glutamine with an arginine residue]. We evaluated their clinical characteristics, residual enzymatic activity, and plasma concentrations of globotriaosylsphingosine (Lyso-Gb3). Although all 10 cases had cardiac and renal manifestations in common, their clinical manifestations were markedly divergent despite the same genetic abnormality.

Anti-Neutrophil Cytoplasmic Antibody-associated Vasculitis (AAV) Restricted to the Limbs: A Case Report

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.

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

BackgroundAcute 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.MethodsThis 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.ResultsA 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.ConclusionThe 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.

Abdominal involvement in minimal change nephrotic syndrome

A 20-year-old man was hospitalized to undergo methylprednisolone pulse therapy for recurrence of minimal change nephrotic syndrome (MCNS) (serum total protein level, 4.3 g/dL; serum albumin, 1.8 g/dL; proteinuria level, 12.1 g/gCre). On the third day after admission, he complained of epigastric pain. Laboratory tests did not indicate pancreatitis (white blood cell count, 14200/lL; C reactive protein level, 0.05 mg/dL; amylase level, 32 IU/mL; glucose level, 123 mg/dL). An enlarged pancreas, high absorption of the anterior pararenal spaces, and edematous swelling of the small intestine were observed on a computed tomography (CT) scan (Fig. 1a, b). We started intensive therapy for suspected acute pancreatitis (intensive infusions, gabexate mesilate, and antibiotics). The treatment for acute pancreatitis was ineffective, but the patient’s symptom was relieved. We discontinued intensive therapy. The follow-up CT scan showed improvement of the edematous intestine (Fig. 1c, d). Urinary protein diminished 6 days after abdominal pain began. The relief of intestinal edema may be associated with the improvement of nephrotic syndrome. Patients with MCNS often complain of abdominal pain, which sometimes causes a fatal thrombotic event [1]. One possible reason is intestinal angina due to decreased circulating volume, and another is intestinal paralysis due to edema. However, the cause has not been clarified [2]. This case suggests that intestinal edema may cause abdominal pain in patients with MCNS.

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.