Search

Increased central venous pressure in congestive heart failure is responsible for renal dysfunction, which is mediated by renal venous congestion. Pericyte detachment from capillaries after renal congestion might trigger renal fibrogenesis via pericyte-myofibroblast transition (PMT). Platelet-derived growth factor receptors (PDGFRs), which are PMT indicators, were upregulated in our recently established renal congestion model. This study was designed to determine whether inhibition of the PDGFR pathway could suppress tubulointerstitial injury after renal congestion.The inferior vena cava between the renal veins was ligated in male Sprague-Dawley rats, inducing congestion only in the left kidney. Imatinib mesylate or vehicle were injected intraperitoneally daily from 1 day before the operation. Three days after the surgery, the effect of imatinib was assessed by physiological, morphological and molecular methods. The inhibition of PDGFRs against transforming growth factor-β1 (TGFB1)-induced fibrosis was also tested in human pericyte cell culture.Increased kidney weight and renal fibrosis were observed in the congested kidneys. Upstream inferior vena cava (IVC) pressure immediately increased to around 20 mmHg after IVC ligation in both the imatinib and saline groups. Although vasa recta dilatation and pericyte detachment under renal congestion were maintained, imatinib ameliorated the increased kidney weight and suppressed renal fibrosis around the vasa recta. TGFB1-induced elevation of fibrosis markers in human pericytes was suppressed by PDGFR inhibitors at the transcriptional level.The activation of the PDGFR pathway after renal congestion was responsible for renal congestion-induced fibrosis. This mechanism could be a candidate therapeutic target for renoprotection against renal congestion-induced tubulointerstitial injury.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a systemic autoimmune disease characterized by necrotizing inflammation of the small blood vessels. ANCA-associated vasculitis is subclassified into three variants: granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, and microscopic polyangiitis (MPA). Myeloperoxidase (MPO) ANCA is a marker antibody for MPA. Interstitial pneumonia (IP) is occasionally complicated with MPA. However, only a few cases of idiopathic IP develop MPO-ANCA-positive conversion and MPA. Therefore, we present a case of a 70-year-old Japanese man with idiopathic IP who developed MPO-ANCA-positive conversion and MPA. We performed renal biopsy, which revealed pauci-immune crescentic glomerulonephritis. The patient was treated with intravenous methylprednisolone pulse therapy and oral prednisone, and the patient's laboratory data gradually improved with steroid therapy. The association between the production of MPO-ANCA and IP remains unclear, and the present case suggests that IP plays a role in inducing MPO-ANCA production. Patients with idiopathic IP should be followed-up carefully for an examination of increased MPO-ANCA levels and MPA development. In addition, early gastric cancer was detected during upper gastrointestinal endoscopy in our case, and it could also be important not to miss malignancy in patients with ANCA-associated vasculitis.

Current contrast-enhanced magnetic resonance angiography (MRA) and non-contrast-enhanced balanced steady-state free precession (bSSFP) MRA cause susceptibility artifacts from metallic devices in assessing endovascular visceral-artery interventions. The aims of this study are to investigate and compare image quality (IQ) and susceptibility artifacts of three-dimensional (3D) ultrashort echo time (UTE) time-spatial labeling inversion pulse (Time-SLIP) with those of 3D bSSFP Time-SLIP and to assess denoising deep learning reconstruction (dDLR) for the improvement of the signal-to-noise ratio (SNR) in 3D UTE with sparse sampling in phantoms and human subjects. This is a prospective type of study. Pulsatile glycerin-water flow phantom with platinum-tungsten-alloy coil, stainless-steel, nitinol, and cobalt-alloy stents were used. Ten healthy volunteers (seven males) and three patients (two males) were included in this study. 3D UTE Time-SLIP and 3D bSSFP Time-SLIP at 3T were used. The phantom-based study compared the signal-intensity ratio of the device levels (SRdevice ) and distal segments (SRdistal ) to the proximal segments. The volunteer-based study measured SNR, contrast ratio (CR), and IQ. The patient study evaluated local artifacts from metallic devices. Statistical tests included paired t-tests, Wilcoxon-signed rank tests, and Kruskal-Wallis tests. In the phantom-based study, SRdevice was small with UTE Time-SLIP, except the stainless-steel stent. SRdistal was greater (49.1%-90.4%) on bSSFP images than UTE images (-11.1% to 9.6%). Among volunteers, dDLR in UTE images improved SNR (p < 0.05) and IQ (p < 0.05), but CR was unaffected. UTE Time-SLIP showed inferior SNR and IQ than bSSFP Time-SLIP in images with and without dDLR (p < 0.05 for each). However, among patients, UTE Time-SLIP showed reduced metal artifacts compared to bSSFP Time-SLIP. Irrespective of the lower SNR and IQ of 3D UTE Time-SLIP than those of 3D bSSFP Time-SLIP, the former appeared to better depict flow after stenting or coiling. This indicates the potential of 3D UTE Time-SLIP to provide suitable diagnostic images of target vessels. dDLR improved SNR with reducing artifacts related to radial sampling, while maintaining the contrast. LEVEL OF EVIDENCE: 2. TECHNICAL EFFICACY STAGE: 2.

Nephrolithiasis is a common renal disease with no effective medication. Sodium-glucose cotransporter-2 (SGLT2) inhibitors, an anti-diabetic agent, have diuretic and anti-inflammatory properties and could prevent nephrolithiasis. Here, we investigated the potential of SGLT2 inhibition against nephrolithiasis using large-scale epidemiological data, animal models, and cell culture experiments.This study included the data of diabetic patients (n = 1,538,198) available in the Japanese administrative database and divided them according to SGLT2 inhibitor prescription status. For animal experiments, renal calcium oxalate stones were induced by ethylene glycol in Sprague-Dawley rats, and phlorizin, an SGLT1/2 inhibitor, was used for the treatment. The effects of SGLT2-specific inhibition for renal stone formation were assessed in SGLT2-deficient mice and a human proximal tubular cell line, HK-2.Nephrolithiasis prevalence in diabetic men was significantly lower in the SGLT2 inhibitor prescription group than in the non-SGLT2 inhibitor prescription group. Phlorizin attenuated renal stone formation and downregulated the kidney injury molecule 1 (Kim1) and osteopontin (Opn) expression in rats, with unchanged water intake and urine volume. It suppressed inflammation and macrophage marker expression, suggesting the role of the SGLT2 inhibitor in reducing inflammation. SGLT2-deficient mice were resistant to glyoxylic acid-induced calcium oxalate stone formation with reduced Opn expression and renal damages. High glucose-induced upregulation of OPN and CD44 and cell surface adhesion of calcium oxalate reduced upon SGLT2-silencing in HK-2 cells.Overall, our findings identified that SGLT2 inhibition prevents renal stone formation and may be a promising therapeutic approach against nephrolithiasis.

The number of patients aged ≥ 75 years and who need renal replacement therapy is steadily increasing. The study aimed to determine the safety of open surgery for peritoneal dialysis (PD) catheter placement in such patients.This prospective cohort study included patients who underwent PD catheter placement by open surgery under dexmedetomidine (DEX) and local anesthesia at our institution from January 2015 to February 2021. Patients were divided into the following two groups according to age at the time of surgery: ≥ 75 years (group A) and 75 years (group B). We compared the perioperative and postoperative complications (i.e., time to the first PD-related peritonitis and catheter obstruction requiring surgical intervention within 1 year) between the groups.A total of 118 patients were categorized into groups A (n = 65) and B (n = 53). No significant intergroup differences were observed in the postoperative fever, total duration of surgery, perioperative hemoglobin decrease, changes in the white blood cell count and C-reactive protein, postoperative catheter leakage, postoperative hospital stay, time to the first PD-related peritonitis, and catheter obstruction requiring surgical intervention within 1 year.The surgery for PD catheter placement by open surgery under DEX and local anesthesia in elderly patients is safe and effective.

Swimming is an extremely popular sport around the world. The streamlined body position is a crucial and foundational position for swimmers. Since the density of lungs is low, the center of buoyancy is always on the cranial side and the center of gravity is always on the caudal side. It has been reported that the greater the distance between the centers of buoyancy and gravity, the swimmer’s legs will sink more. This is disadvantageous to swimming performance. However, the way to reduce the distance between the centers of buoyancy and gravity is yet to be elucidated. Here we show that swimmers with high gliding performance exhibit different abdominal cavity shapes in the streamlined body position, which causes cranial movement of the abdominal organs. This movement can reduce the distance between the centers of buoyancy and gravity, prevent the legs from sinking, and have a positive effect on gliding performance.

BACKGROUND AND OBJECTIVES: The histopathologic classification for ANCA-associated GN distinguishes four classes on the basis of patterns of injury. In the original validation study, these classes were ordered by severity of kidney function loss as follows: focal, crescentic, mixed, and sclerotic. Subsequent validation studies disagreed on outcomes in the crescentic and mixed classes. This study, driven by the original investigators, provides several analyses in order to determine the current position of the histopathologic classification of ANCA-associated GN. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A validation study was performed with newly collected data from 145 patients from ten centers worldwide, including an analysis of interobserver agreement on the histopathologic evaluation of the kidney biopsies. This study also included a meta-analysis on previous validation studies and a validation of the recently proposed ANCA kidney risk score. RESULTS: The validation study showed that kidney failure at 10-year follow-up was significantly different between the histopathologic classes (P

Purpose To assess changes in left ventricular function and tissue composition by using MRI after chemotherapy-radiation therapy in participants with esophageal cancer. Materials and Methods Between January 2013 and April 2015, this prospective study enrolled 24 participants (42% women; mean age, 63 years; range, 49-73 years) scheduled for chemotherapy-radiation therapy. 3.0-T MRI examinations were performed before, at 0.5 year, and at 1.5 years after chemotherapy-radiation therapy. Myocardial native T1, postcontrast T1, and extracellular volume were measured in basal septum (as irradiated areas) and apical lateral wall (as nonirradiated areas). Left ventricular function, prevalence of late gadolinium enhancement, and T1 and extracellular volume values were compared over the follow-up period by using Friedman or Cochran Q tests, followed by Dunn test. Results In 14 participants who were followed up for 1.5 years, native T1 and extracellular volume in the septum were elevated at 0.5 year compared with baseline (1183 msec ± 46 [standard deviation] vs 1257 msec ± 35; 26% ± 3 vs 32% ± 3; adjusted P.01 for both), but not in the lateral wall. Left ventricular stroke volume index and late gadolinium enhancement changed at 1.5 years compared with baseline (41 mL/m

Fabry disease is a rare X-linked hereditary disorder (Xq22) caused by a deficiency in alpha-galactosidase (α-GAL) activity. This enzyme deficit results in the systemic accumulation of glycophospholipids, leading to multi-organ failure including the heart, kidneys, and brain. Enzyme replacement therapy (ERT) improves the prognosis of patients with Fabry disease. We describe a case showing progressive renal failure despite ERT. An 18-year-old obese male patient (body mass index (BMI) 29.9 kg/m2) was admitted for detailed examination of mild degree hypertension (150/65 mmHg) and proteinuria occurring for 2 years prior to admittance. Laboratory tests revealed mostly normal kidney function (serum creatinine 0.5 mg/dL, estimated glomerular filtration rate 181 mL/min/m2) with low α-GAL activity, a significant level of proteinuria (0.5–1.0 g/day), and the presence of mulberry cells in the urinary sediment. Renal biopsy demonstrated marked glomerulomegaly with diffuse vacuolization of the glomerular epithelial cells and focal segmental glomerulosclerosis. Electron microscopy revealed typical zebra bodies in the glomerular epithelial cells and effacement of foot processes of the epithelium. We could not find any cause of glomerulomegaly except for obesity. α-GAL gene analysis revealed a missense mutation in R301Q. Although ERT with agalsidase α was initiated, his renal function declined, and hemodialysis was initiated at 22 years of age. We present a case of rapid progression of Fabry nephropathy despite ERT. As with other renal diseases, obesity may aggravate the progression of Fabry nephropathy.

The course of rapidly progressive glomerulonephritis (RPGN) caused by antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is often life-threatening, especially in the elderly when pulmonary involvement and/or severely impaired renal function are present. Corticosteroids and cyclophosphamide are the first-line treatment, but ironically infection, not vascular events such as hemorrhage, caused by the vasculitis itself, is the most common cause of death of RPGN patients. Several new treatment strategies, such as leukocytapheresis (LCAP) and intravenous immunoglobulin (IVIg), have become available during the past decade and these treatments have made it possible to treat high-risk RPGN patients without inducing serious immunosuppressive states. In the present paper we review recent clinical trials of LCAP and IVIg therapy in patients with pauci-immune/ANCA-associated RPGN, and show improved clinical outcomes after using these new treatment strategies in our institution.

目的; 血液浄化療法時の一時的ブラッドアクセスとしてのオブチュレーター式カテーテル留置例に対して, ウロキナーゼ未処理オブチュレーターの臨床的有用性と安全性について検討した. また, カテーテル留置中の凝固線溶系マーカーの変動について検討した. 対象は血液浄化療法に際して一時的ブラッドアクセスを必要とする患者で, 無作為にウロキナーゼ固定化オブチュレーター群 (UK+OBT群) とウロキナーゼ未処理オブチュレーター群 (UK-OBT群) の2群に割り付けした. 両群で脱血不良の有無, 感染やカテーテル閉塞等のトラブルによる抜去例について比較検討し, さらにカテーテル挿入時, 1週間後, および抜去時におけるCRP, プラスミン・アンチプラスミン複合体 (PIC), トロンビン・アンチトロンビンIII複合体 (TAT), D-dimerの推移について比較検討した.結果; オブチュレーターへの血栓付着はウロキナーゼ未処理オブチュレーター群で有意に増加していた (UK+OBT群; 5/12例, UK-OBT群; 15/18例, p

Currently, there are no detailed reports on the effects of vitamin E-bonded polysulfone (PS) membrane dialyzers on intradialytic hypotension (IDH) in diabetic hemodialysis (HD) patients. This study was designed to evaluate changes in intradialytic systolic blood pressure (SBP) using "VPS-HA" vitamin E-bonded super high-flux PS membrane dialyzers. The subjects were 62 diabetic HD patients whose intradialytic SBP fell by more than 20%. Group A comprised patients who required vasopressors to be able to continue treatment or who had to discontinue therapy due to their lowest intradialytic SBP being observed at 210 min (28 patients). Group B comprised patients who showed no symptoms and required no vasopressors but showed a gradual reduction in blood pressure, with the lowest intradialytic SBP seen at the end of dialysis (34 patients). The primary outcome was defined as the lowest intradialytic SBP after 3 months using VPS-HA. Secondary outcomes included changes in the following: lowest intradialytic diastolic blood pressure, pulse pressure, pulse rate, plasma nitric oxide and peroxynitrite, serum albumin, and hemoglobin A1c. Group A's lowest intradialytic SBP had significantly improved at 3 months (128.0 ± 25.1 mm Hg vs. 117.1 ± 29.2 mm Hg; P = 0.017). Group B's lowest intradialytic SBP had significantly improved at 1 month (134.4 ± 13.2 mm Hg vs. 121.5 ± 25.8 mm Hg; P = 0.047) and 3 months (139.1 ± 20.9 mm Hg vs. 121.5 ± 25.8 mm Hg; P = 0.011). We conclude that VPS-HA may improve IDH in diabetic HD patients.

Sulfated portions of glycosaminoglycan (GAG) side chains in heparan sulfate proteoglycan (HSPG) are thought to play an important role in charge-dependent selectivity of glomerular filtration against plasma proteins. Heparan sulfate N-acetylglucosamine N-deacetylase/adenosine 3'-phosphate 5'-phosphosulfate: unsubstituted glucosamine N-sulfotransferase (NDST) is the key enzyme regulating sulfation of GAG chains. In this study we investigated transcriptional expression of NDST-1, 1 of 4 isozymes of NDST, in glomeruli of rats with puromycin aminonucleoside (PAN) nephrosis. Nephrosis was induced in rats with a single intraperitoneal injection of 150 mg/kg PAN. On days 10 and 35, expression of NDST-1 messenger RNA (mRNA) in glomeruli was analyzed with the use of Northern-blot analysis. Immunohistochemical studies were also performed with the use of monoclonal antibodies that react specifically with the N-sulfated portion of the GAG chain of HSPG and agrin, a major core protein of HSPG in glomerular basement membrane (GBM). In addition, we studied the expression of NDST-1 mRNA in cultured glomerular epithelial cells (GECs) and glomerular mesangial cells in the presence of PAN. On day 10, when significant proteinuria developed, the ratios of glomerular expression of NDST-1 mRNA against glyceraldehyde-phosphate dehydrogenase mRNA in PAN-treated rats were decreased to 48% +/- 6% of those in controls (P