Search

A significant proportion of patients with infective endocarditis presents with acute renal failure related to infective endocarditis-associated glomerulonephritis (IEAGN). However, the clinical presentation of IEAGN differs from that of other infection-related glomerulonephritis (IRGN) with anti-neutrophil cytoplasmic antibody (ANCA) positivity occurring in almost onethird of cases; therefore, it may be difficult to establish a definitive diagnosis and provide appropriate treatment. This review article provides a comprehensive understanding of the clinical presentation, investigations, histopathology, and treatment/management of IEAGN so that clinicians can keep this differential in mind for patients with fever of unknown origin accompanied by signs and symptoms of acute renal failure.

A significant proportion of patients with infective endocarditis presents with acute renal failure related to infective endocarditis-associated glomerulonephritis (IEAGN). However, the clinical presentation of IEAGN differs from that of other infection-related glomerulonephritis (IRGN) with anti-neutrophil cytoplasmic antibody (ANCA) positivity occurring in almost onethird of cases; therefore, it may be difficult to establish a definitive diagnosis and provide appropriate treatment. This review article provides a comprehensive understanding of the clinical presentation, investigations, histopathology, and treatment/management of IEAGN so that clinicians can keep this differential in mind for patients with fever of unknown origin accompanied by signs and symptoms of acute renal failure., identifier:https://doi.org/10.33160/yam.2022.02.011

Gamma-glutamyl hydroxymethyl rhodamine green (gGlu-HMRG) is an activatable fluorescent probe that can be activated by γ-glutamyltranspeptidase (GGT). The expression of GGT in the kidney, which is one of the major organs exhibiting enhanced GGT expression, is exclusively localised to the cortex. Here, we aimed to investigate the feasibility of gGlu-HMRG as a probe for the on-site assessment of renal biopsy specimens. gGlu-HMRG fluorescent probe was applied to the renal proximal tubular epithelial cells and cortical collecting duct cells in vitro, mouse kidneys ex vivo, and human biopsy specimens. In addition, the fluorescence intensities in the cortex and the medulla were comparatively evaluated in the biopsy specimens. The fluorescence signal was rapidly detected in the renal proximal tubular epithelial cells, whereas that in the cortical collecting duct cells was not detected. The fluorescence signal was detected in the mouse kidneys ex vivo without markedly affecting the tissue morphology. In the human biopsy specimens, the fluorescence signal in the cortex was significantly distinct from that in the medulla (p?

Background: Chronic kidney disease (CKD) and non-alcoholic steatohepatitis (NASH) are major health burdens closely related to metabolic syndrome. A link between CKD and NASH has been assumed; however, the underlying mechanism is still unknown. Ectopic lipid deposition (ELD) in the hepatocyte results in endoplasmic reticulum (ER) stress, which plays an important role in the development of steatohepatitis. ELD is also assumed to play a role in the development of kidney injury. We aimed to investigate the role of ELD and ER stress in the development of CKD, and evaluate the efficacy of a sodium glucose cotransporter-2 inhibitor, ipragliflozin. Methods: Male FLS-ob/ob mice that closely imitate the pathophysiology of NASH were treated with vehicle or ipragliflozin. Metabolic characteristics, histology of the kidney, ER stress, and apoptotic signals were evaluated. Results: The serum triglyceride was significantly lower in mice treated with ipragliflozin. Ipragliflozin reduced ELD in renal tubules. Ipragliflozin also reduced the expression levels of GRP78 and CHOP, apoptotic cells, and interstitial fibrosis. Conclusions: ELD induced kidney injury through ER stress. Ipragliflozin improved the pathogenesis of CKD by reducing ELD and ER stress in NASH-model mice. Our results suggest ipragliflozin has therapeutic effect on CKD in NASH.

Background: Rapidly progressive glomerulonephritis (RPGN) is a syndrome characterized by a rapid decline in renal function that often causes end-stage renal disease. Although it is important to predict renal outcome in RPGN before initiating immunosuppressive therapies, no simple prognostic indicator has been reported. The aim of this study was to investigate the associations of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) to renal outcomes in patients with RPGN. Methods: Forty-four patients with a clinical diagnosis of RPGN who underwent renal biopsy were enrolled. The relationships between NLR and PLR and renal outcome after 1 year were investigated. Results: NLR and PLR were significantly higher in patients with preserved renal function in comparison to patients who required maintenance hemodialysis (p < 0.05 and p < 0.01, respectively). An NLR of 4.0 and a PLR of 137.7 were the cutoff values for renal outcome (area under the curve, 0.782 and 0.819; sensitivity, 78.4% and 89.2%; specificity, 71.4% and 71.4%, respectively). Furthermore, an NLR of 5.0 could predict recovery from renal injury in patients requiring hemodialysis (area under the curve, 0.929; sensitivity, 83.3%; specificity, 85.7%). Conclusion: NLR and PLR could be candidates for predicting renal outcomes in patients with RPGN.

[Background] Sarcopenia is a major health issue especially in patients on maintenance hemodialysis. Low skeletal muscle mass is included in the diagnostic criteria for sarcopenia. The skeletal muscle mass is usually evaluated by modalities such as bioimpedance analysis (BIA) or dual-energy X-ray absorptiometry, however the assessment of skeletal muscle mass using computed tomography (CT) images has not been established. The purpose of the study was to investigate the feasibility of the assessment of skeletal muscle mass using CT images in hemodialysis patients. [Methods] Skeletal muscle mass index (SMI) was measured by BIA and psoas muscle index (PMI) was measured by cross-sectional CT images in 131 patients. The relationship between SMI and PMI and the diagnostic ability of PMI for low muscle mass were evaluated. Furthermore, the patients were followed up and long-term survival in patients with low and high PMI were compared. [Results] PMI measured at the L3 vertebral level was strongly correlated with SMI (r = 0.597, p < 0.001). Age, sex, and SMI were the influencing factors for PMI. Patients with low PMI showed higher incidence rates of mortality during the follow up. [Conclusions] PMI assessed by CT image can be an alternative to BIA in patients on hemodialysis.

[Aim] Acoustic radiation force impulse is a noninvasive method for evaluating tissue elasticity on ultrasound. Renal shear wave velocity measured by this technique has not been fully investigated in patients with renal disease. The aim of the present study was to compare renal shear wave velocity in end‐stage renal disease patients and that in patients without chronic kidney disease and to investigate influencing factors. [Methods] Renal shear wave velocities were measured in 59 healthy young subjects (control group), 31 subjects without chronic kidney disease (non‐CKD group), and 39 end‐stage renal disease patients (ESRD group). Each measurement was performed 10 times at both kidneys, and the mean value of eight of 10 measurements, excluding the maximum and minimum values, was compared. [Results] Renal shear wave velocity could be measured in all subjects. Renal shear wave velocity in the control group was higher than in the non‐CKD group and in the ESRD group, and no difference was found between the non‐CKD group and the ESRD group. Age and depth were negatively correlated to the renal shear wave velocity. In multiple regression analysis, age and depth were independent factors for renal shear wave velocity, while renal impairment was not. There was no difference between the non‐CKD group and the ESRD group, even when ages were matched and depth was adjusted. [Conclusion] Renal shear wave velocity was not associated with advanced renal impairment. However, it reflected alteration of renal aging, and this technique may be useful to detect renal impairment in the earlier stages.

[Background] The 5-aminolevulinic acid (ALA)-based photodynamic diagnosis is based on the accumulation of photosensitizing protoporphyrin IX in the tumor after ALA administration. However, the mechanisms connecting exogenous ALA and tumor fluorescence in pancreatic cancer remain unclear. We aimed to elucidate the mechanism underlying the ALA-induced fluorescent. [Methods] Human pancreatic duct epithelial cells (hPDECs) and pancreatic cancer cell lines were used. The expressions of ALA-associated enzymes and membrane transporters in these cell lines were investigated. ALA-induced fluorescence was also investigated. [Results] The expression of oligopeptide transporter-1 (PEPT-1), through which ALA is absorbed, was significantly higher in AsPC-1 cells and lower in MIA PaCa-2 cells than in hPDECs. AsPC-1 cells showed rapid and intense fluorescence after ALA administration, and that was attenuated by PEPT-1 inhibition. ALA-induced fluorescence was not sufficiently strong in MIA PaCa-2 cells to distinguish the cells from hPDECs. [Conclusion] We revealed the association of PEPT-1 with ALA-induced fluorescence. Cancers expressing PEPT-1 could be easily distinguished by this technique from normal cells. These findings help develop novel diagnostic modalities for pancreatic cancer.

Background: Chronic kidney disease (CKD) and non-alcoholic steatohepatitis (NASH) are major health burdens closely related to metabolic syndrome. A link between CKD and NASH has been assumed; however, the underlying mechanism is still unknown. Ectopic lipid deposition (ELD) in the hepatocyte results in endoplasmic reticulum (ER) stress, which plays an important role in the development of steatohepatitis. ELD is also assumed to play a role in the development of kidney injury. We aimed to investigate the role of ELD and ER stress in the development of CKD, and evaluate the efficacy of a sodium glucose cotransporter-2 inhibitor, ipragliflozin. Methods: Male FLS-ob/ob mice that closely imitate the pathophysiology of NASH were treated with vehicle or ipragliflozin. Metabolic characteristics, histology of the kidney, ER stress, and apoptotic signals were evaluated. Results: The serum triglyceride was significantly lower in mice treated with ipragliflozin. Ipragliflozin reduced ELD in renal tubules. Ipragliflozin also reduced the expression levels of GRP78 and CHOP, apoptotic cells, and interstitial fibrosis. Conclusions: ELD induced kidney injury through ER stress. Ipragliflozin improved the pathogenesis of CKD by reducing ELD and ER stress in NASH-model mice. Our results suggest ipragliflozin has therapeutic effect on CKD in NASH., identifier:https://www.mdpi.com/1422-0067/21/1/190

[Background] Sarcopenia is a major health issue especially in patients on maintenance hemodialysis. Low skeletal muscle mass is included in the diagnostic criteria for sarcopenia. The skeletal muscle mass is usually evaluated by modalities such as bioimpedance analysis (BIA) or dual-energy X-ray absorptiometry, however the assessment of skeletal muscle mass using computed tomography (CT) images has not been established. The purpose of the study was to investigate the feasibility of the assessment of skeletal muscle mass using CT images in hemodialysis patients. [Methods] Skeletal muscle mass index (SMI) was measured by BIA and psoas muscle index (PMI) was measured by cross-sectional CT images in 131 patients. The relationship between SMI and PMI and the diagnostic ability of PMI for low muscle mass were evaluated. Furthermore, the patients were followed up and long-term survival in patients with low and high PMI were compared. [Results] PMI measured at the L3 vertebral level was strongly correlated with SMI (r = 0.597, p < 0.001). Age, sex, and SMI were the influencing factors for PMI. Patients with low PMI showed higher incidence rates of mortality during the follow up. [Conclusions] PMI assessed by CT image can be an alternative to BIA in patients on hemodialysis., identifier:https://link.springer.com/article/10.1007%2Fs40620-020-00871-5

identifier:https://onlinelibrary.wiley.com/doi/10.1111/1744-9987.13459

Background: Rapidly progressive glomerulonephritis (RPGN) is a syndrome characterized by a rapid decline in renal function that often causes end-stage renal disease. Although it is important to predict renal outcome in RPGN before initiating immunosuppressive therapies, no simple prognostic indicator has been reported. The aim of this study was to investigate the associations of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) to renal outcomes in patients with RPGN. Methods: Forty-four patients with a clinical diagnosis of RPGN who underwent renal biopsy were enrolled. The relationships between NLR and PLR and renal outcome after 1 year were investigated. Results: NLR and PLR were significantly higher in patients with preserved renal function in comparison to patients who required maintenance hemodialysis (p < 0.05 and p < 0.01, respectively). An NLR of 4.0 and a PLR of 137.7 were the cutoff values for renal outcome (area under the curve, 0.782 and 0.819; sensitivity, 78.4% and 89.2%; specificity, 71.4% and 71.4%, respectively). Furthermore, an NLR of 5.0 could predict recovery from renal injury in patients requiring hemodialysis (area under the curve, 0.929; sensitivity, 83.3%; specificity, 85.7%). Conclusion: NLR and PLR could be candidates for predicting renal outcomes in patients with RPGN., identifier:https://www.mdpi.com/2077-0383/9/4/1128

Uromodulin is a zona pellucida-type protein essentially produced in the thick ascending limb (TAL) of the mammalian kidney. It is the most abundant protein in normal urine. Defective uromodulin processing is associated with various kidney disorders. The luminal release and subsequent polymerization of uromodulin depend on its cleavage mediated by the serine protease hepsin. The biological relevance of a proper cleavage of uromodulin remains unknown. Here we combined in vivo testing on hepsin-deficient mice, ex vivo analyses on isolated tubules and in vitro studies on TAL cells to demonstrate that hepsin influence on uromodulin processing is an important modulator of salt transport via the sodium cotransporter NKCC2 in the TAL. At baseline, hepsin-deficient mice accumulate uromodulin, along with hyperactivated NKCC2, resulting in a positive sodium balance and a better adaptation to water deprivation. In conditions of high salt intake, defective uromodulin processing predisposes hepsin-deficient mice to a salt-wasting phenotype, with a decreased salt sensitivity. These modifications are associated with intracellular accumulation of uromodulin, endoplasmic reticulum-stress and signs of tubular damage. These studies expand the physiological role of hepsin and uromodulin and highlight the importance of hepsin-mediated processing of uromodulin for kidney tubule homeostasis and salt sensitivity.

Uromodulin is a zona pellucida-type protein essentially produced in the thick ascending limb (TAL) of the mammalian kidney. It is the most abundant protein in normal urine. Defective uromodulin processing is associated with various kidney disorders. The luminal release and subsequent polymerization of uromodulin depend on its cleavage mediated by the serine protease hepsin. The biological relevance of a proper cleavage of uromodulin remains unknown. Here we combined in vivo testing on hepsin-deficient mice, ex vivo analyses on isolated tubules and in vitro studies on TAL cells to demonstrate that hepsin influence on uromodulin processing is an important modulator of salt transport via the sodium cotransporter NKCC2 in the TAL. At baseline, hepsin-deficient mice accumulate uromodulin, along with hyperactivated NKCC2, resulting in a positive sodium balance and a better adaptation to water deprivation. In conditions of high salt intake, defective uromodulin processing predisposes hepsin-deficient mice to a salt-wasting phenotype, with a decreased salt sensitivity. These modifications are associated with intracellular accumulation of uromodulin, endoplasmic reticulum-stress and signs of tubular damage. These studies expand the physiological role of hepsin and uromodulin and highlight the importance of hepsin-mediated processing of uromodulin for kidney tubule homeostasis and salt sensitivity.

［Background］Diuretics are essential for treating acute decompensated heart failure (ADHF), but the response is inconsistent. This study aimed to clarify whether kidney volume as assessed by ultrasound (US) predicts diuretic resistance in patients with ADHF. ［Methods］We enrolled 29 patients with ADHF and 32 controls. Height-adjusted kidney volume was assessed by US. We divided patients into two groups based on the median value of total daily use of furosemide (intravenous dose plus 0.5 × oral dose of furosemide equivalents) during 3 days from admission. ［Results］Patients with ADHF had a significantly smaller left kidney volume than did control subjects (27.7 ± 10.0 vs. 32.8 ± 8.8 mL/m, P < 0.05). Patients in the highdose furosemide group (? 51.7 mg/d) had a significantly lower estimated glomerular filtration rate (eGFR) and a significantly smaller kidney volume than did those in the low-dose furosemide group (eGFR: 43.9 ± 20.4 vs. 60.8± 21.6 mL/min/1.73 m2, left kidney volume: 23.2 ± 5.2vs. 32.6 ± 11.0 mL/m, right kidney volume: 26.5 ± 7.5vs. 32.6 ± 7.9 mL/m, all P < 0.05). Multivariate logistic analysis showed that left kidney volume, but not eGFR,was independently associated with the requirement of high-dose furosemide (odds ratio: 0.856, 95% confidence interval: 0.735?0.997, P < 0.05). ［Conclusion］Kidney volume as assessed by US is a useful predictor of diuretic resistance in patients with ADHF.

Uromodulin, the most abundant protein in normal urine, is essentially produced by the cells lining the thick ascending limb. There it regulates the activity of the cotransporter NKCC2 and is involved in sodium chloride handling and blood pressure regulation. Conflicting reports suggested that uromodulin may also be expressed in the distal convoluted tubule (DCT) where its role remains unknown. Using microdissection studies combined with fluorescent in situ hybridization and co-immunostaining analyses, we found a significant expression of uromodulin in mouse and human DCT at approximately 10% of thick ascending limb expression levels, but restricted to the early part of the DCT (DCT1). Genetic deletion of Umod in mouse was reflected by a major shift in NCC activity from the DCT1 to the downstream DCT2 segment, paralleled by a compensatory expansion of DCT2. By increasing the distal sodium chloride and calcium ion load with chronic furosemide administration, an intrinsic compensatory defect in the DCT from Umod-/- compared to wild type mice was found manifested as sodium wasting and hypercalciuria. In line, co-expression studies in HEK cells suggested a facilitating role for uromodulin in NCC phosphorylation, possibly via SPAK-OSR1 modulation. These experiments demonstrate a significant expression of uromodulin in the early part of mouse and human DCT. Thus, biosynthesis of uromodulin in the DCT1 is critical for its function, structure and plasticity, suggesting novel links between uromodulin, blood pressure control and risk of kidney stones.

[Aim] Acoustic radiation force impulse is a noninvasive method for evaluating tissue elasticity on ultrasound. Renal shear wave velocity measured by this technique has not been fully investigated in patients with renal disease. The aim of the present study was to compare renal shear wave velocity in end‐stage renal disease patients and that in patients without chronic kidney disease and to investigate influencing factors. [Methods] Renal shear wave velocities were measured in 59 healthy young subjects (control group), 31 subjects without chronic kidney disease (non‐CKD group), and 39 end‐stage renal disease patients (ESRD group). Each measurement was performed 10 times at both kidneys, and the mean value of eight of 10 measurements, excluding the maximum and minimum values, was compared. [Results] Renal shear wave velocity could be measured in all subjects. Renal shear wave velocity in the control group was higher than in the non‐CKD group and in the ESRD group, and no difference was found between the non‐CKD group and the ESRD group. Age and depth were negatively correlated to the renal shear wave velocity. In multiple regression analysis, age and depth were independent factors for renal shear wave velocity, while renal impairment was not. There was no difference between the non‐CKD group and the ESRD group, even when ages were matched and depth was adjusted. [Conclusion] Renal shear wave velocity was not associated with advanced renal impairment. However, it reflected alteration of renal aging, and this technique may be useful to detect renal impairment in the earlier stages., identifier:https://onlinelibrary.wiley.com/doi/full/10.1111/nep.12701