Renal sinus fat is associated with intrarenal hemodynamic abnormalities independent of visceral fat in patients with chronic kidney disease.

OBJECTIVE: Obesity is a risk factor of chronic kidney disease (CKD), contributing to the rising incidence of cardiometabolic diseases. Renal sinus fat (RSF) is an ectopic fat depot located at the renal cavity that could impair renal function and hemodynamic through compression of renal structures. The major purpose of this study was to explore the relationship between RSF accumulation and renal dysfunction in CKD patients. METHODS: We evaluated the associations between computed tomography measured RSF volume and key clinical and histologic parameters involved in renal function and hemodynamics in 132 well-characterized CKD patients who underwent renal biopsy (median age: 62 years; 63.6% men). RESULTS: RSF volume normalized by renal volume (RSF%) positively correlated with obesity-related traits such body mass index and visceral fat volume (VFV) (all P < 0.001) whereas it negatively correlated with estimated glomerular filtration rate (eGFR) (ρ = -0.42, P < 0.001) and 24-h urinary creatinine clearance (CCr) (ρ = -0.34, P < 0.001). Notably, we found robust positive correlations between RSF% and renal resistive index (RRI) measured by the Doppler ultrasound (ρ = 0.40, P < 0.001), and the histological severity of global glomerular sclerosis (ρ = 0.48, P < 0.001) and interstitial fibrosis and tubular atrophy (IFTA) (ρ = 0.35, P < 0.001). In the multivariate linear regression models, after accounting for potential confounders including VFV, RSF% remained significantly associated with CCr (ß = -0.26, P < 0.001), RRI (ß = 0.17, P = 0.022), global glomerular sclerosis (ß = 0.21, P = 0.002), and IFTA (ß = 0.17, P = 0.012). CONCLUSION: RSF accumulation is associated with renal dysfunction and hemodynamic abnormalities independent of visceral adiposity. Our results suggest that RSF may have a potential unique role in the pathogenesis of CKD.

Association Between Renal Sinus Fat and Cardiometabolic and Renin-Angiotensin System Parameters in Primary Aldosteronism.

Context: Renal sinus fat (RSF) accumulation is associated with cardiometabolic diseases, such as obesity, diabetes, hypertension, and chronic kidney disease. However, clinical implications of RSF in primary aldosteronism (PA) remain unclear. Objective: We aimed to investigate relationships between RSF volume and key cardiometabolic and renin-angiotensin system (RAS) parameters in PA patients and clarify the differences in these relationships between unilateral and bilateral subtypes. Methods: We analyzed data obtained from well-characterized PA patients that involved 45 unilateral (median age: 52 years; 42.2% men) and 92 bilateral patients (51 years; 42.4% men). Results: RSF volume normalized by renal volume (RSF%) was greater in the unilateral group than in the bilateral group (P < .05). RSF% was greater in men than in women (P < .05). RSF% positively correlated with parameters related to cardiometabolic risk, including age, body mass index, visceral fat volume, creatinine, triglycerides/high-density lipoprotein cholesterol ratio, uric acid, fasting glucose, and C-reactive protein regardless of PA subtypes (all P < .05). Intriguingly, RSF% positively correlated with plasma aldosterone concentration (PAC), aldosterone-to-renin ratio, and intact parathyroid hormone (iPTH) (all P < .05) in bilateral patients but did not correlate with RAS parameters and even showed an opposite trend in unilateral patients. In subgroup analyses by sex, these distinctions became more evident in women. After adjustment for potential confounders, RSF% remained positively correlated with PAC and iPTH in bilateral patients. Conclusion: Our results indicate that RSF accumulation is involved in cardiometabolic dysfunction associated with PA. However, there were distinct correlations between RSF volume and RAS parameters according to sex and PA subtypes.

Copterus tyloloricatus (Ciliophora, Suctorea), a new suctorian genus and species.

We present the description of the new suctorian genus Copterus gen. n. with type species Copterus tyloloricatus sp. n. from the family Acinetidae, inhabiting the prosomes and urosomes of calanoid copepods from the northern North Pacific Ocean. The new taxon is characterized by (i) an ellipsoidal to triangular, asymmetric, dorsoventrally flattened cell body, which lies horizontally on the lorica surface; (ii) an unflattened lorica; and (iii) the presence of three to five radially arranged bundles of tentacles positioned at the edge of the body or on actinophores.

Life-threatening gastrointestinal bleeding caused by perforation of a penetrating atherosclerotic ulcer into the esophagus.

We present a case of life-threatening gastrointestinal bleeding caused by a penetrating atherosclerotic ulcer (PAU) that ruptured into the esophagus. A 65-year-old man presented with pyrexia and nausea. Contrast-enhanced computed tomography (CT) performed on admission revealed a hematoma between the lower esophagus and descending aorta due to a contained rupture of a PAU, which was undiagnosed at that time. Esophagogastroduodenoscopy (EGD) performed on the fifth day of admission revealed a subepithelial lesion in the lower esophagus, further complicated by ulcer formation. Biopsy did not reveal any malignant findings. On the eighth day of admission, the patient experienced substantial hematemesis with vital signs indicative of shock. Emergency EGD was performed, which revealed life-threatening bleeding in the lower esophagus. Contrast-enhanced CT revealed an aortoesophageal fistula with massive hematemesis, after which the patient died. An autopsy revealed perforation of the PAU into the esophagus without aortic dissection or a true aneurysm.Patients with atherosclerosis who develop recent-onset gastrointestinal symptoms, progressive anemia, and/or periaortic lesions should be carefully evaluated using contrast-enhanced CT, and PAU should be considered in the differential diagnosis.

Adipocyte NMNAT1 expression is essential for nuclear NAD+ biosynthesis but dispensable for regulating thermogenesis and whole-body energy metabolism.

Nicotinamide adenine dinucleotide (NAD+) functions as an essential cofactor regulating a variety of biological processes. The purpose of the present study was to determine the role of nuclear NAD+ biosynthesis, mediated by nicotinamide mononucleotide adenylyltransferase 1 (NMNAT1), in thermogenesis and whole-body energy metabolism. We first evaluated the relationship between NMNAT1 expression and thermogenic activity in brown adipose tissue (BAT), a key organ for non-shivering thermogenesis. We found that reduced BAT NMNAT1expression was associated with inactivation of thermogenic gene program induced by obesity and thermoneutrality. Next, we generated and characterized adiponectin-Cre-driven adipocyte-specific Nmnat1 knockout (ANMT1KO) mice. Loss of NMNAT1 markedly reduced nuclear NAD+ concentration by approximately 70% in BAT. Nonetheless, adipocyte-specific Nmnat1 deletion had no impact on thermogenic (rectal temperature, BAT temperature and whole-body oxygen consumption) responses to ß-adrenergic ligand norepinephrine administration and acute cold exposure, adrenergic-mediated lipolytic activity, and metabolic responses to obesogenic high-fat diet feeding. In addition, loss of NMNAT1 did not affect nuclear lysine acetylation or thermogenic gene program in BAT. These results demonstrate that adipocyte NMNAT1 expression is required for maintaining nuclear NAD+ concentration, but not for regulating BAT thermogenesis or whole-body energy homeostasis.

Clinical significance of serum urea-to-creatinine ratio in patients undergoing peritoneal dialysis.

INTRODUCTION: We aimed to determine the correlation between the serum urea-to-creatinine ratio and residual kidney function (RKF) in patients undergoing peritoneal dialysis (PD), as well as its predictive value for PD-related outcomes. METHODS: This study included a cross-sectional study to assess the correlation between serum urea-to-creatinine ratio and RKF in 50 patients on PD and a retrospective cohort study to assess the association between serum urea-to-creatinine ratio and PD-related outcomes in 122 patients who initiated PD. RESULTS: Serum urea-to-creatinine ratios had significant positive correlations with renal Kt/V and creatinine clearance values (r = 0.60, p < 0.001 and r = 0.61, p < 0.001, respectively). Additionally, serum urea-to-creatinine ratio was significantly associated with a lower risk of transfer to hemodialysis or PD/hemodialysis hybrid therapy (hazard ratio: 0.84, 95% confidence interval: 0.75-0.95). CONCLUSION: The serum urea-to-creatinine ratio can be an indicator of RKF and a prognostic factor in patients undergoing PD.

The body mass index change is associated with death or hemodialysis transfer in Japanese patients initiating peritoneal dialysis.

A decreased body mass index (BMI) over time is associated with a poor prognosis for patients on hemodialysis. We aimed to examine whether this association also applies to patients with peritoneal dialysis (PD). BMI change was defined as the percentage change in the BMI between the time of PD catheter insertion and six months after its insertion. The association between the BMI change and all-cause mortality or PD discontinuation from six months after PD catheter insertion until October 2021 was investigated. This retrospective cohort study included 122 patients (aged 61.1 ± 12.1 years; 90 males) who underwent PD catheter insertion between January 2008 and March 2020. The median follow-up period was 43.1 (21.2-78.8) months. The median six-month percentage change in the BMI was -2.14 (-5.56-1.84)%, and patients were categorized into tertiles based on their BMI changes. The fully-adjusted Cox regression analysis revealed a significantly higher rate of PD discontinuation or all-cause mortality (hazard ratio (HR): 2.48; 95%; confidence interval (CI): 1.41-4.37) in patients with the lowest tertile (T1, BMI change: < -4.13%) compared to patients with the middle tertile (T2, BMI change: -4.13%-0.67%). The risk was not significantly higher in patients with the highest tertile (T3, BMI change: >0.67%) than those in the T2 group (HR: 1.18; 95% CI: 0.66-2.11). A decreased BMI over time is independently associated with HD transfer or all-cause mortality among patients initiating PD, which highlights the importance of the 6-month BMI change as a novel prognostic marker.

Isolation and Cs+ resistance mechanism of Escherichia coli strain ZX-1.

This research aims to elucidate the physiological mechanisms behind the accidental acquisition of high-concentration cesium ions (Cs+) tolerance of Escherichia coli and apply this understanding to develop bioremediation technologies. Bacterial Cs+ resistance has attracted attention, but its physiological mechanism remains largely unknown and poorly understood. In a prior study, we identified the Cs+/H+ antiporter TS_CshA in Microbacterium sp. TS-1, resistant to high Cs+ concentrations, exhibits a low Cs+ affinity with a Km value of 370 mM at pH 8.5. To enhance bioremediation efficacy, we conducted random mutagenesis of TS_cshA using Error-Prone PCR, aiming for higher-affinity mutants. The mutations were inserted downstream of the PBAD promoter in the pBAD24 vector, creating a mutant library. This was then transformed into E. coli-competent cells. As a result, we obtained a Cs+-resistant strain, ZX-1, capable of thriving in 400 mM CsCl-a concentration too high for ordinary E. coli. Unlike the parent strain Mach1™, which struggled in 300 mM CsCl, ZX-1 showed robust growth even in 700 mM CsCl. After 700 mM CsCl treatment, the 70S ribosome of Mach1™ collapsed, whereas ZX-1 and its derivative ΔZX-1/pBR322ΔAp remained stable. This means that the ribosomes of ZX-1 are more stable to high Cs+. The inverted membrane vesicles from strain ZX-1 showed an apparent Km value of 28.7 mM (pH 8.5) for Cs+/H+ antiport activity, indicating an approximately 12.9-fold increase in Cs+ affinity. Remarkably, the entire plasmid isolated from ZX-1, including the TS_cshA region, was mutation-free. Subsequent whole-genome analysis of ZX-1 identified multiple SNPs on the chromosome that differed from those in the parent strain. No mutations in transporter-related genes were identified in ZX-1. However, three mutations emerged as significant: genes encoding the ribosomal bS6 modification enzyme RimK, the phage lysis regulatory protein LysB, and the flagellar base component protein FlgG. These mutations are hypothesized to affect post-translational modifications, influencing the Km value of TS_CshA and accessory protein expression. This study unveils a novel Cs+ resistance mechanism in ZX-1, enhancing our understanding of Cs+ resistance and paving the way for developing technology to recover radioactive Cs+ from water using TS_CshA-expressing inverted membrane vesicles.

Effect of Tolvaptan in Patients with Chronic Kidney Disease Stage G5, and Impact of Concomitant Use of Thiazide Diuretics: A Retrospective Cohort Study.

BACKGROUND: The diuretic effect of tolvaptan, a vasopressin V2 receptor antagonist, in patients with severe renal dysfunction remains poorly characterized. Thiazide diuretics reduce urinary volume (UV) in patients with nephrogenic diabetes insipidus, which lacks V2 receptor function. OBJECTIVE: This retrospective study investigated the acute urinary effects of tolvaptan in patients with stage G5 chronic kidney disease and congestive heart failure (CHF), and the impact of thiazide diuretics on the urinary effects of tolvaptan. METHODS: UVs 24 h before and after tolvaptan administration and 30-day dialysis initiation rate were compared between patients with and without thiazide diuretic administration. RESULTS: Thiazide diuretics were used in 26 of the 106 recruited patients (age 73.4 ± 13.0 years; estimated glomerular filtration rate 8.07 ± 3.13 mL/min/1.73 m2). The pre- and post-tolvaptan 24-h UVs were significantly higher in patients not administered thiazide diuretics (1043.4 ± 645.6 vs. 1422.2 ± 774.0 mL/day; p < 0.001) than in those administered thiazide diuretics (1177.3 ± 686.5 vs. 1173.1 ± 629.1 mL/day; p = 0.93). In a multivariate regression model, thiazide diuretic use was significantly associated with decreased 24-h UV (ß coefficient - 486.7, 95% confidence interval [CI] - 674.5 to - 298.8); increased urine osmolality (ß coefficient 37.7, 95% CI 17.1-58.4); increased body weight (ß coefficient 0.62, 95% CI 0.31-0.92); and increased 30-day dialysis initiation rate (odds ratio 3.40, 95% CI 1.18-9.82) after tolvaptan administration. CONCLUSIONS: Tolvaptan exhibited significant diuretic effects in patients with CHF, including those with severe renal dysfunction, which were diminished with concomitant thiazide diuretic use.

Development of Alveolar Hemorrhage After Pfizer-BioNTech COVID-19 mRNA Vaccination in a Patient With Renal-Limited Anti-neutrophil Cytoplasmic Antibody-Associated Vasculitis: A Case Report.

Since the coronavirus disease 2019 (COVID-19) pandemic continues and a new variant of the virus has emerged, the COVID-19 vaccination campaign has progressed. Rare but severe adverse outcomes of COVID-19 vaccination such as anaphylaxis and myocarditis have begun to be noticed. Of note, several cases of new-onset antineutrophil cytoplasmic antibody-associated vasculitis (AAV) after COVID-19 mRNA vaccination have been reported. However, relapse of AAV in remission has not been recognized enough as an adverse outcome of COVID-19 vaccination. We report, to our knowledge, a first case of renal-limited AAV in remission using every 6-month rituximab administration that relapsed with pulmonary hemorrhage, but not glomerulonephritis, following the first dose of the Pfizer-BioNTech COVID-19 vaccine. The patient received the COVID-19 vaccine more than 6 months after the last dose of rituximab according to the recommendations. However, his CD19+ B cell counts were found to be increased after admission, indicating that our case might have been prone to relapse after COVID-19 vaccination. Although our case cannot establish causality between AAV relapse and COVID-19 mRNA vaccination, a high level of clinical vigilance for relapse of AAV especially in patients undergoing rituximab maintenance therapy following COVID-19 vaccination should be maintained. Furthermore, elapsed time between rituximab administration and COVID-19 mRNA vaccination should be carefully adjusted based on AAV disease-activity.

Case report: Importance of early and continuous tocilizumab therapy in nephrotic syndrome associated with idiopathic multicentric Castleman disease: A case series.

Idiopathic multicentric Castleman disease (iMCD) is a systemic and polyclonal lymphoproliferative disease involving multiple organs, including the kidneys, due to the overproduction of interleukin-6 (IL-6). Recently, several reports have suggested that excessive IL-6 actions in iMCD could have a causal relationship with the development of diverse histopathological renal manifestations that cause nephrotic syndrome. However, the treatment for such cases remains unclear. We report a series of three cases of nephrotic syndrome due to iMCD that helps to delineate the importance of early and continuous therapy with the anti-interleukin-6 receptor antibody tocilizumab. First, treatment was suspended for infectious control, and the patient presented with nephrotic syndrome due to diffuse mesangial and endocapillary hypercellularity without immune deposits complicating acute kidney injury. Second, iMCD was treated with prednisolone alone. The patient suddenly developed nephrotic syndrome due to immune-complex glomerulonephritis, not otherwise specified, complicated with acute kidney injury. In the third case, nephrotic syndrome secondary to membranous glomerulonephritis was diagnosed, with a skin rash and IgE antibodies to tocilizumab, and was therefore treated with prednisolone alone. In contrast to the first two cases, the third progressed to end-stage renal disease on hemodialysis. Taken together, this series suggests that clinicians should maintain clinical vigilance for iMCD as a possible underlying component of nephrotic syndrome, since iMCD presents with a variety of renal pathologies. Prompt initiation and continuous administration of tocilizumab are likely key determinants of renal outcomes in such cases. In particular, when tocilizumab is suspended due to infection or in the perioperative period, consideration of its expeditious resumption should be made, taking into account both the withdrawal period and systemic conditions.

Relationships between dissolved black carbon and dissolved organic matter in streams.

Black carbon (BC) is a pyrolyzed product derived from incomplete combustion. A major fraction of BC produced by landscape fires is initially deposited onto onsite soils. Atmospheric deposition of soot is known to be an important source of soil BC, especially in watersheds that are not affected by landscape fires. The transport of the dissolved fraction of oxidized BC in soil, defined as dissolved black carbon (DBC), to streams is considered one of the important loss pathways of BC in soil, but the mechanism is not well documented. We measured the quantity and quality of DBC, determined by a benzenepolycarboxylic acid method, and the quantitative and qualitative parameters of bulk dissolved organic matter (DOM) in streams in Hokkaido, northern Japan, whose catchments were not affected by landscape fire for at least 110 years. DBC with relatively low polycondensed signatures occurred in the streams, irrespective of differences in watershed characteristics and seasons, suggesting that atmospheric deposition of soot into the catchment is probably a major source of stream DBC. The DBC concentration was linearly related to the dissolved organic carbon (DOC) concentration, irrespective of the differences in watershed characteristics and seasons. Furthermore, the polycondensation degree of DBC was observed to correlate with the qualitative parameters of bulk DOM. Such quantitative and qualitative relationships between DBC and bulk DOM imply that the transfer mechanism from soils to streams of soot-derived polycondensed DBC is linked with that of higher plant-derived, high-molecular-weight aromatic DOM.