Abstract
Endocapillary proliferation occurs in various types of glomerulonephritis (GN), with varying prognoses. We examined 42 renal biopsy samples representing endocapillary proliferative lesions ...from post-streptococcal acute GN (PSAGN), Henoch–Schönlein purpura nephritis (HSPN), and lupus nephritis (LN). In PSAGN, the glomerular capillary network was maintained, although severe lesions displayed dots or short, curved lines, indicating CD34-positive capillaries and suggesting capillary obstruction. Conversely, patients with LN and HSPN displayed obstruction of CD34-positive capillaries with dissociation from the glomerular basement membrane even in mild lesions. According to computer-assisted morphologic analysis, the cell density did not differ between the diseases. However, in PSAGN, the number of capillary loops was significantly increased, with a larger glomerular capillary luminal area than in the other groups. In addition, the number and frequency of CD163-positive cells (M2 macrophages) tended to be higher in PSAGN, while there were no significant differences in the number of CD68-positive (total) macrophages. These results indicate that in PSAGN, endothelial cell damage is less severe, and angiogenesis may be promoted. The severity of endothelial cell injury in each disease may be associated with differences in infiltrating inflammatory cell phenotypes.
Background: Peritonitis is one of the most common complications in patients undergoing peritoneal dialysis, (PD) but it is difficult to predict or prevent. In this study, we analyzed the risk of ...endogenous peritonitis in patients receiving PD. Methods: We included all patients who underwent PD at our hospital from April 2015 to March 2020. There were 22 cases of peritonitis, including 18 cases of endogenous peritonitis without evidence of exit-site infection or technical failure. We evaluated older age, female sex, obesity, diabetes, diverticulosis, and constipation as potential important risk factors for endogenous peritonitis and included these as confounding factors, along with a current or previous history of smoking, in univariate logistic regression models. Results: A previous or current history of smoking (p = 0.0065) was the most significant risk factor for endogenous peritonitis in the univariate logistic regression model. In addition, smoking was the most significant independent risk factor for endogenous peritonitis (p = 0.0034) in multivariate logistic regression models. Diabetes was also significant in univariate and multivariate logistic regression analysis. Conclusions: Smoking is a significant independent risk factor for endogenous peritonitis in patients undergoing PD. Cessation of smoking may lower the risk of endogenous peritonitis in this patient group.
Background: Febuxostat is recommended for lowering serum uric acid (sUA) concentration in chronic kidney disease (CKD) patients with hyperuricemia. However, it remains uncertain how febuxostat ...affects associations between several laboratory variables related to glomerular filtration and renal tubular reabsorption of uric acid. Methods: We retrospectively analyzed the records of 148 patients with CKD and hyperuricemia: 122 were treated with febuxostat, and 26 were not. Clinical and laboratory variables were used to calculate estimated glomerular filtration rate (eGFR), fractional excretion of uric acid (FEUA), and estimated 24-h urinary excretion of uric acid (eEUA). We examined correlations of those variables and compared patients who did and did not receive febuxostat. Results: eGFR and FEUA were significantly inversely regardless of febuxostat-treatment status. eGFR was significantly inversely correlated with sUA in patients who received febuxostat, but not in those who did not. Similarly, there was a significant positive correlation between FEUA and eEUA only in patients treated with febuxostat. Conclusions: FEUA increased as eGFR decreased in our patients. Febuxostat changed correlation patterns for clinical and laboratory variables. Additional administration of uricosuric agents might help further lower sUA by increasing FEUA and eEUA in patients treated with febuxostat.
Background: The number of patients on peritoneal dialysis (PD) in our hospital has increased during the past 5 years, but the number discontinuing PD has also increased. The purpose of this study was ...to identify the risk factors for PD discontinuation by analyzing the association between technical survival period (defined as the duration of PD) and various clinical factors. Methods: We retrospectively investigated 87 patients who were started on PD at our hospital and attended regularly from April 2015 to March 2020, and we analyzed the association between technical survival period and various clinical factors. We also looked for associations between technical survival period and hospitalizations for heart failure, peritonitis, and exit-site infections among patients undergoing PD. Results: The patients using renin-angiotensin-aldosterone system inhibitors (RASi) (P = 0.0218), those with left ventricular ejection fraction (LVEF) > 50% (P = 0.0194) when they started PD, and those with estimated glomerular filtration rate (eGFR) ≥ 6 (mL/min/1.73 m2) (P = 0.0013) at the initiation of PD showed significantly longer technical survival period, and those who were hospitalized for heart failure had significantly shorter period (P = 0.0008). Conclusion: Treatment of RASi, LVEF > 50% and eGFR ≥ 6 mL/ min/1.73 m2 when the initiation of PD and better volume control to prevent ultrafiltration failure and heart failure may improve technical survival period in patients undergoing PD.
Peritonitis is a common complication of peritoneal dialysis (PD) and can result in PD catheter removal, permanent hemodialysis, and, potentially, death. Prediction and prevention of PD-related ...peritonitis are thus extremely important. In 2016, the International Society for Peritoneal Dialysis published guidelines for patients with peritonitis undergoing PD. The guidelines cover most cases of PD-related peritonitis caused by bacteria and include clear indications for catheter removal. However, difficulties often arise when deciding the timing of catheter removal. When multiple enteric organisms are identified in a culture of dialysis effluent, peritonitis may be caused by intra-abdominal pathology, which is associated with substantial mortality. In such cases, catheter removal is considered. In this report, we describe a case in which, during antibiotic therapy for PD-related peritonitis due to Enterococcus faecalis alone, the patient developed a relapse of peritonitis caused by a newly detected Gram-negative, rod-like Pseudomonas aeruginosa. He required catheter removal because of the possibility of peritonitis recurrence. Although additional study is required, early catheter removal may be effective when a new organism is detected during antibiotic therapy for PD-related peritonitis caused by an organism not meeting the definition of refractory peritonitis.
Currently, cellular senescence has emerged as a fundamental contributor to chronic organ diseases. Radiation is one of the stress factors that induce cellular senescence. Although the kidney is known ...as a radiosensitive organ, whether and how radiation-induced cellular senescence is associated with kidney diseases remains unclear. In this study, we performed experiments on 7-8-week-old male rats that received a single dose of 18-Gy radiation in the unilateral kidney. The irradiated kidneys showed hallmarks of cellular senescence, including increased SA-β-gal activity, upregulation of cyclin-dependent kinase inhibitor (p53, p21, and p16), and absence of DNA proliferation marker (Ki-67). Furthermore, combined with in-vitro experiments, we demonstrated that radiation-induced senescent glomerular endothelial cells acquired altered gene expression, namely, senescence-associated secretory phenotype (particularly, IL-6), which might be triggered by NF-kB signaling pathway. Pathological analysis suggested severe glomerular endothelial cell injury, as evidenced by thrombotic microangiopathy, collapsing glomeruli, and reduced endothelial cell numbers. We suggested that glomerular endothelial cells were more susceptible to radiation-induced cellular senescence. In conclusion, the current study is the first to identify the important role of radiation-induced cellular senescence, mainly derived from glomerular endothelial cells, for the development of glomerular injury.
A 44-year-old woman was admitted due to gross hematuria and progressive renal dysfunction. Poststreptococcal acute glomerulonephritis (PSAGN) was suspected due to her elevated anti-streptolysin O and ...anti-streptokinase titers and hypocomplementemia. A renal biopsy showed crescent formation and endocapillary hypercellularity with neutrophil infiltrate. An immunofluorescence analysis showed granular immunoglobulin G and C3 deposition, suggesting immune-complex-type glomerulonephritis. However, myeloperoxidase anti-neutrophil cytoplasmic antibody (ANCA) was positive, and peritubular capillaritis was observed. Furthermore, citrullinated histone H3-positive neutrophils were detected as markers for neutrophil extracellular trap formation. Therefore, she was diagnosed with ANCA-associated vasculitis superimposed on PSAGN that was the main contributor to her progressive renal injury.
High salt intake is a primary cause of over-hydration in chronic kidney disease (CKD) patients. Inflammatory markers are predictors of CKD mortality; however, the pathogenesis of inflammation remains ...unclear. Sodium storage in tissues has recently emerged as an issue of concern. The binding of sodium to tissue glycosaminoglycans and its subsequent release regulates local tonicity. Many cell types express tonicity-responsive enhancer-binding protein (TonEBP), which is activated in a tonicity-dependent or tonicity-independent manner. Macrophage infiltration was observed in the heart, peritoneal wall, and para-aortic tissues in salt-loading subtotal nephrectomized mice, whereas macrophages were not prominent in tap water-loaded subtotal nephrectomized mice. TonEBP was increased in the heart and peritoneal wall, leading to the upregulation of inflammatory mediators associated with cardiac fibrosis and peritoneal membrane dysfunction, respectively. Reducing salt loading by a diuretic treatment or changing to tap water attenuated macrophage infiltration, TonEBP expression, and inflammatory marker expression. The role of TonEBP may be crucial during the cardiac fibrosis and peritoneal deterioration processes induced by sodium overload. Anti-interleukin-6 therapy improved cardiac inflammation and fibrosis and peritoneal membrane dysfunction. Further studies are necessary to establish a strategy to regulate organ dysfunction induced by TonEBP activation in CKD patients.
Background: The COVID-19 pandemic has had an enormous impact on hemodialysis patients. This study investigated changes in hemodialysis treatment at our hospital after the start of the pandemic. ...Methods: We analyzed data from the Diagnosis Procedure Combination (DPC) system. Data for inpatients receiving dialysis during collection periods A (before the COVID-19 pandemic) and B (after the start of the COVID-19 pandemic) were extracted and compared. The numbers of inpatients and new patients, the number of patients admitted (by department), duration of stay, mortality, place of residence, surgical procedures, and DPC classification were compared. Results: There were no significant differences between periods in patient age, duration of hospital stay, number of new patients, number of ambulance transports, number of deaths, body mass index, comorbidities, laboratory variables before the first dialysis after hospitalization, or patient area of residence. Although differences were observed among the departments, the numbers of emergency dialysis inpatients and maintenance dialysis inpatients increased. The number of surgeries also increased overall, particularly for maintenance dialysis patients (p = 0.0273). The percentage of DPC III patients was significantly higher in period B (p = 0.0368). Conclusions: The number of surgeries performed on maintenance dialysis patients and the overall DPC III rate significantly increased after the start of the COVID-19 pandemic at our hospital, suggesting that COVID-19 worsened the condition of maintenance dialysis patients and prolonged hospital stays.
Cardiovascular disease is the most common comorbidity in patients with chronic kidney disease (CKD), affecting both their prognosis and quality of life. Cardiac fibrosis is common in patients with ...CKD with left ventricular diastolic dysfunction, and it is associated with increased risk of heart failure and mortality. Recent evidence suggests that high salt intake activates immune responses associated with local accumulation of sodium. We reported that high salt intake promotes cardiac inflammation in subtotal nephrectomized (Nx) mice. We investigated the effects of administration of MR16-1, a rat anti-mouse monoclonal interleukin (IL)-6 receptor antibody, in Nx mice with salt loading (Nx-salt). Expression of monocyte chemoattractant protein-1, tumor necrosis factor-α, IL-1β, and IL-6 mRNAs and macrophage infiltration was significantly reduced in the heart of Nx-salt mice treated with MR16-1 (Nx-salt-MR16-1) compared with Nx-salt mice treated with control rat rat IgG1 (Nx-salt-rat IgG1). Correspondingly, cardiac fibrosis was significantly attenuated in Nx-salt-MR16-1 mice compared with Nx-salt-rat IgG1 mice. Furthermore, in the heart of Nx-salt-MR16-1 mice, expression of mRNA for nicotinamide adenine dinucleotide phosphate oxidase-2, an oxidative stress marker, was significantly downregulated compared with Nx-salt-rat IgG1 mice. Increases in cardiac metabolites, including histidine and γ-butyrobetaine, were also reversed by IL-6 blockade treatment. In conclusion, IL-6 blockade exerts anti-inflammatory, antifibrotic, and partial antioxidative effects in the heart of Nx-salt mice.
In the present study, IL-6 blockade exerted anti-inflammatory, antifibrotic, and partial antioxidative effects on the hearts of mice with CKD on a high-salt diet. Therefore, IL-6 potentially mediates cardiac fibrosis induced by high salt intake in patients with CKD, a finding with therapeutic implications. Of note, the next therapeutic implication may simply be the reinforcement of low-salt diets or diuretics and further research on the anti-inflammatory effects of these measures rather than IL-6 blockade with high-salt diet.
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