Bone marrow stromal cell antigen-1 deficiency protects from acute kidney injury.

This study aimed to investigate the role of bone marrow stromal cell antigen-1 (Bst1; also known as CD157) in acute kidney injury (AKI). Bst1 is a cell surface molecule with various enzymatic activities and downstream intracellular signaling pathways that modulate the immune response. Previous research has linked Bst1 to diseases such as ovarian cancer, Parkinson's disease, and rheumatoid arthritis. We used bilateral ischemia-reperfusion injury (IRI) as an AKI model and created bone marrow chimeric mice to evaluate the role of Bst1 in bone marrow-derived cells. We also used flow cytometry to identify Bst1/CD157 expression in hematopoietic cells and evaluate immune cell dynamics in the kidney. The findings showed that Bst1-deficient (Bst1-/-) mice were protected against renal bilateral IRI. Bone marrow chimera experiments revealed that Bst1 expression on hematopoietic cells, but not parenchymal cells, induced renal IRI. Bst1 was mainly found in B cells and neutrophils by flow cytometry of the spleen and bone marrow. In vitro, migration of neutrophils from Bst1-/- mice was suppressed, and adoptive transfer of neutrophils from wild-type Bst1+/+ mice abolished the renal protective effect in Bst1 knockout mice. In conclusion, the study demonstrated that Bst1-/- mice are protected against renal IRI and that Bst1 expression in neutrophils plays a crucial role in inducing renal IRI. These findings suggest that targeting Bst1 in neutrophils could be a potential therapeutic strategy for AKI.NEW & NOTEWORTHY Acute kidney injury (AKI), a serious disease for which there is no effective Federal Drug Administration-approved treatment, is associated with high mortality rates. Bone marrow stromal cell antigen-1 (Bst1) is a cell surface molecule that can cause kidney fibrosis, but its role in AKI is largely unknown. Our study showed that Bst1-/- mice revealed a protective effect against renal bilateral ischemia-reperfusion injury (IRI). Adoptive transfer studies confirmed that Bst1 expression in hematopoietic cells, especially neutrophils, contributed to renal bilateral IRI.

Exposure and outcomes of aortic valve change in patients initiating dialysis.

BACKGROUND: Aortic stenosis (AS) and aortic valve calcification (AVC) are occasionally observed in patients receiving maintenance dialysis. However, their prevalence and factors associated with them in patients undergoing dialysis remain unknown. We aimed to elucidate the aortic valve status at the time of dialysis initiation and patient prognosis based on aortic valve status. METHODS: We analyzed 289 patients initiating dialysis (hemodialysis: peritoneal dialysis = 275:14) between 2016 and 2023. "AS and/or AVC" was detected using echocardiography. AS was defined as a maximum transaortic velocity > 2.0 m/s. Statistical analyses including multivariable logistic regression and Cox regression were used to assess the association between patient characteristics and survival outcomes. RESULTS: Aortic valve changes were observed in 121 (42%) patients, among which 33 (11%) met the AS criteria. The mean age of patients in the AS, AVC without AS, and control groups was 79.1 ± 8.9, 75.9 ± 9.2, and 68.3 ± 12.9, respectively (P < 0.001). Multivariable logistic regression models showed that only age was associated with aortic valve changes (P < 0.001). Age and other important factor-adjusted multivariable Cox regression models showed that AS was an independent risk factor for death after dialysis initiation (hazard ratio (HR): 1.95, 95% confidence interval (CI): 1.06 - 3.59, P = 0.04). However, aortic valve changes ("AS and/or AVC") were not a risk factor for death (HR: 1.51, 95% CI 0.95 - 2.39, P = 0.08). CONCLUSIONS: With the growing older population undergoing dialysis, aortic valve changes should be closely monitored. Particularly, AS is crucial because of its impact on patient prognosis.

Neglected Pulmonary Infection Caused by Exophiala dermatitidis Misidentified as Rhodotorula spp.

Exophiala dermatitidis is an emerging black fungus that causes pulmonary infections that may be underestimated by conventional culture methods. We encountered one case that initially appeared to be yeast and was misidentified as Rhodotorula spp. using a commercial identification kit. Thus, genetic identification and clinical background investigations were conducted on 46 strains of Rhodotorula spp. The sequences of the internal transcribed spacer and large-subunit RNA genes (D1/D2 regions) of 43 isolates, excluding two environmental isolates and one difficult-to-culture isolate, were determined and genetically identified. Notably, 22 isolates were identified as E. dermatitidis and misidentified as Rhodotorula spp. using the conventional method. Based on the exclusion criteria, the clinical information of 11 patients was retrospectively reviewed. Five cases (definite) had definite exacerbation of pulmonary infections due to E. dermatitidis, and six cases (possible) had undeniable infections. Of the 11 cases of pulmonary infection suggested to be caused by E. dermatitidis, comorbidities included two cases of chronic pulmonary aspergillosis (CPA), three cases of pulmonary non-tuberculous mycobacterial (NTM) infection and one case of pulmonary nocardiosis, suggesting a trend towards simultaneous detection of chronic pulmonary infections. Steroid and immunosuppressive drug use was observed in five cases, and ß-D-glucan elevation was observed in three of five definite cases of pulmonary infections due to E. dermatitidis. The possibility of E. dermatitidis infection should be considered when Rhodotorula spp. are isolated from cultures of airway-derived specimens, and, in addition to CPA and NTM, identification of E. dermatitidis may be important in chronic pulmonary infections.

Roxadustat has risks of reversible central hypothyroidism in patients undergoing hemodialysis: a single-center retrospective cohort study.

Roxadustat, a hypoxia-inducible factor-prolyl hydroxylase inhibitor, has proven efficacy in the treatment of renal anemia; however, evidence indicates that it may cause central hypothyroidism. The prevalence and reversibility of roxadustat-induced central hypothyroidism in patients undergoing hemodialysis remain unclear. Here, we retrospectively analyzed thyroid-stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) levels in 51 patients (mean age: 72.3 ± 10.7 years; 58.8% male) undergoing hemodialysis before, during, and after halting roxadustat treatment. TSH levels were significantly decreased from a median of 2.46 (interquartile range:1.60-4.51) mU/L before roxadustat treatment to 1.36 (0.72-2.41) mU/L during treatment (p < 0.001), and improved to 2.56 (1.78-4.63) mU/L after halting roxadustat (p < 0.001). Similarly, FT4 levels decreased from 1.11 (0.97-1.24) ng/dL before roxadustat treatment to 0.92 (0.71-1.03) ng/dL during treatment (p < 0.001) and improved to 1.05 (0.93-1.17) ng/dL after halting roxadustat (p < 0.001). FT3 levels were 2.04 (1.78-2.31) pg/mL before starting roxadustat, 1.97 (1.69-2.27) pg/mL during treatment, and 1.90 (1.63-2.18) pg/mL after halting roxadustat, with no significant difference between each group. Moreover, 2.0% of patients exhibited extremely low TSH levels (≤0.1 mU/L) and low TSH levels (>0.1 mU/L to <0.4 mU/L) before starting roxadustat and that percentage increased to 5.9% and 7.8%, respectively, during treatment. After roxadustat cessation, extremely low or low TSH levels recovered in all patients. Taken together, the results indicate that roxadustat can cause reversible central hypothyroidism in patients undergoing hemodialysis.

Induction of tetraspanin 13 contributes to the synergistic anti-inflammatory effects of parasympathetic and sympathetic stimulation in macrophages.

The autonomic nervous system plays an important role in the regulation of peripheral inflammation. Sympathetic nervous activation stimulates inflammatory gene expression and cytokines, whereas parasympathetic nervous activation suppresses the production of inflammatory cytokines by immune cells. However, most studies on the relationship between the autonomic nervous system and immune processes have analyzed a single branch of the autonomic nerves in isolation. Therefore, this study aimed to examine the effects of sympathetic and parasympathetic stimulation on macrophages, which are controlled by autonomic regulation. Macrophages were stimulated with lipopolysaccharide (LPS) to induce TNF-α. Then, the effects of ß2 adrenergic receptor and α7 nicotinic acetylcholine receptor activation on TNF-α production were assessed using concentration-dependent assays. RNA-seq data were also used to identify genes whose expression was enhanced by parasympathetic and sympathetic stimulation. The simultaneous activation of ß2 adrenergic receptors and α7 nicotinic acetylcholine receptors suppressed LPS-induced TNF-α production in a concentration-dependent manner. Moreover, simultaneous activation of these receptors had synergistic anti-inflammatory effects and induced Tspan13 expression, thereby contributing to anti-inflammatory mechanisms in macrophages. Our study revealed the synergistic anti-inflammatory effects of the parasympathetic and sympathetic stimulation of macrophages. Our results suggest that targeting both sympathetic and parasympathetic signaling is a promising therapeutic approach for inflammatory diseases.

Fasting influences aquaporin expression, water transport and adipocyte metabolism in the peritoneal membrane.

BACKGROUND: The water channels aquaporin-1 (AQP1) and AQP7 are abundantly expressed in the peritoneal membrane. While AQP1 facilitates water transport during peritoneal dialysis (PD), the role of AQP7, which mediates glycerol transport during fasting, remains unknown. METHODS: We investigated the distribution of AQP7 and AQP1 and used a mouse model of PD to investigate the role of AQP7 in the peritoneal membrane at baseline and after fasting. RESULTS: Single nucleus RNA-sequencing revealed that AQP7 was mostly detected in mature adipocytes, whereas AQP1 was essentially expressed in endothelial cells. Fasting induced significant decreases in whole body fat, plasma glucose, insulin and triglycerides, as well as higher plasma glycerol and corticosterone levels in mice, paralleled by major decreases in adipocyte size and levels of fatty acid synthase and leptin, and increased levels of hormone-sensitive lipase mRNAs in the peritoneum. Mechanistically, fasting upregulated the expression of AQP1 and AQP7 in the peritoneum, with increased ultrafiltration but no change in small solute transport. Studies based on Aqp1 and Aqp7 knockout mice and RU-486 inhibition demonstrated that the glucocorticoid induction of AQP1 mediates the increase in ultrafiltration whereas AQP7 regulates the size of adipocytes in the peritoneum. CONCLUSIONS: Fasting induces a coordinated regulation of lipolytic and lipogenic factors and aqua(glycero)porins in the peritoneum, driving structural and functional changes. These data yield novel information on the specific roles of aquaporins in the peritoneal membrane and indicate that fasting improves fluid removal in a mouse model of PD.

Long-term effectiveness of a primary care practice facilitation program for chronic kidney disease management: an extended follow-up of a cluster-randomized FROM-J study.

BACKGROUND: Practice facilitation program by multidisciplinary care for primary care physicians (PCPs) is expected to improve chronic kidney disease (CKD) outcomes, but there is no clear evidence of its long-term effectiveness. We have previously performed a cluster-randomized controlled trial for 3.5 years (the Frontier of Renal Outcome Modifications in Japan (FROM-J) study) with two arms-group A without the program and group B with the program. We aimed to assess the long-term effectiveness of the practice facilitation program on CKD outcomes via an extended 10-year follow-up of the FROM-J study. METHODS: We enrolled patients who were in the FROM-J study. The primary composite endpoint comprised cardiovascular disease (CVD), renal replacement therapy initiation and a 50% decrease in the estimated glomerular filtration rate (eGFR). The secondary endpoints were survival rate, eGFR decline rate and collaboration rate between PCPs and nephrologists. RESULTS: The occurrence of the primary composite endpoint tended to be lower in group B (group A: 27.1% versus group B: 22.1%, P = 0.051). Furthermore, CVD incidence was remarkably lower in group B (group A: 10.5% versus group B: 6.4%, P = 0.001). Although both mortality and the rate of eGFR decline were identical between both groups, the eGFR decline rate was significantly better in group B than in group A only in patients with stage G3a at enrollment (group A: 2.35 ± 3.87 mL/min/1.73 m2/year versus group B: 1.68 ± 2.98 mL/min/1.73 m2/year, P = 0.02). The collaboration rate was higher in group B. CONCLUSIONS: The CKD practice facilitation program for PCPs reliably decreases CVD events and may reduce the progression of cases to end-stage kidney disease.

Anorexia Assessed by Simplified Nutritional Appetite Questionnaire and Association with Medication in Older Patients Undergoing Hemodialysis.

Anorexia is a common symptom in older patients undergoing hemodialysis (HD) and has become a serious problem in dialysis facilities with the aging of patients. Polypharmacy, defined as the prescription of several medications, is known to cause drug-induced anorexia. Although polypharmacy is also common in older patients undergoing HD, only a few studies have examined the association between anorexia and polypharmacy. This study used the Simplified Nutritional Appetite Questionnaire for Japanese Elderly (SNAQ-JE) to evaluate patients' appetite, and examined its association with medications. This cross-sectional study included 233 patients (aged ≥65 years) who underwent HD in October 2021. Among the 233 patients (median age, 73.0 [interquartile range (IQR), 69.0-80.5] years; men, 57.3%; median dialysis vintage, 62.0 [IQR, 30.0-122.0] months), 116 and 117 were classified into the poor (SNAQ-JE total score ≤14) and good (>14) appetite groups, respectively. Although the total number of medications prescribed was not significantly different between the two groups (p = 0.12), the number of antihypertensive drugs was significantly lower (p = 0.03), and that of sleeping medications was significantly higher (p = 0.002) in the poor appetite group. Multivariable logistic regression analysis showed that the number of sleeping medications was associated with poor appetite (odds ratio, 2.08; 95% confidence interval, 1.32-3.27; p < 0.001). The findings suggest that the number of sleeping medications is an important contributing factor to poor appetite in older patients undergoing HD. A proper and regular review of prescriptions may be necessary to improve anorexia.

Association between COVID-19 vaccination and relapse of glomerulonephritis.

BACKGROUND: Vaccines for coronavirus disease 2019 (COVID-19) have been developed and are recommended for patients with chronic kidney disease; however, it has been reported that glomerulonephritis worsens after vaccination. We aimed to elucidate the incidence and association between COVID-19 vaccination and glomerulonephritis relapse. METHODS: We investigated the onset of renal events and adverse reactions after COVID-19 vaccination in 111 patients diagnosed with glomerulonephritis. Renal events were defined as worsening hematuria, increased proteinuria, and an increased creatine level over 1.5-fold from baseline. RESULTS: Patients were 57 ± 18 years old (55.9% female) and had an estimated glomerular filtration rate of 57.0 ± 25.0 ml/min/1.73 m2. A pathological diagnosis of IgA nephropathy was confirmed in 55.0%, minimal change disease in 22.5%, and membranous nephropathy in 10.8% of the patients. The BNT162b2 (Pfizer) and mRNA-1273 (Moderna) vaccines were administered in 88.2% and 11.7% of the cases, respectively. Renal events were observed in 22.5% of patients, 10.8% had increased proteinuria, 12.6% had worsening hematuria, and 1.8% received additional immunosuppressive treatment. Only 0.9% required temporary hemodialysis from exacerbation of renal dysfunction. Renal events were higher in younger patients (P = 0.02), being highest in those with IgA nephropathy, but there was no difference in the incidence between pathological diagnoses. There was a significantly higher incidence of renal events in patients with fever (P = 0.02). CONCLUSIONS: COVID-19 vaccination and glomerulonephritis relapse may be related, but further research is needed.

Association between annual variability of potassium levels and prognosis in patients undergoing hemodialysis.

BACKGROUND: Hyperkalemia and hypokalemia are associated with mortality in patients undergoing hemodialysis. However, there are few reports on the association between potassium level fluctuations and mortality. We retrospectively investigated the association between serum potassium level variability and mortality in patients undergoing hemodialysis. METHODS: This study was conducted at a single center. Variability in serum potassium levels was evaluated using the standard deviation of potassium level from July 2011 to June 2012, and its association with prognosis was examined by following up the patients for 5 years. Serum potassium variability was assessed as the coefficient of variation, and the statistical analysis was performed after log transformation. RESULTS: Among 302 patients (mean age 64.9 ± 13.3; 57.9% male; and median dialysis vintage 70.5 months [interquartile range, IQR 34-138.3]), 135 died during the observation period (median observation period 5.0 years [2.3-5.0]). Although the mean potassium level was not associated with prognosis, serum potassium level variability was associated with prognosis, even after adjustments for confounding factors such as age and dialysis time (hazard ratio: 6.93, 95% confidence interval [Cl] 1.98-25.00, p = 0.001). After the adjustments, the coefficient of variation of potassium level in the highest tertile (T3) showed a higher relative risk for prognosis than that in T1 (relative risk: 1.98, 95% CI 1.19-3.29, p = 0.01). CONCLUSIONS: Variability in serum potassium levels was associated with mortality in patients undergoing hemodialysis. Careful monitoring of potassium levels and their fluctuations is necessary for this patient population.

Hydroxychloroquine suppresses anti-GBM nephritis via inhibition of JNK/p38 MAPK signaling.

BACKGROUND: Anti-glomerular basement membrane (anti-GBM) nephritis, characterized by glomerular crescent formation, requires early treatment because of poor prognosis. Hydroxychloroquine (HCQ) is an antimalarial drug with known immunomodulatory, anti-inflammatory, and autophagy inhibitory effects; it is recognized in the treatment of autoimmune diseases such as systemic lupus erythematosus. However, its effect on anti-GBM nephritis remains unknown. In this study, we investigated the effect of HCQ on anti-GBM nephritis in rats. METHODS: Seven-weeks-old male WKY rats were administered anti-GBM serum to induce anti-GBM nephritis. Either HCQ or vehicle control was administered from day 0 to day 7 after the induction of nephritis. Renal function was assessed by measuring serum creatinine, proteinuria, and hematuria. Renal histological changes were assessed by PAS staining and Masson trichrome staining, and infiltration of macrophages was assessed by ED-1 staining. Mitogen-activated protein kinase (MAPK) was evaluated by western blotting, while chemokine and inflammatory cytokines were evaluated by enzyme-linked immunosorbent assay using urine sample. RESULTS: HCQ treatment suppressed the decline in renal function. Histologically, extracapillary and intracapillary proliferations were observed from day 1, while fibrinoid necrosis and ED-1 positive cells were observed from day 3. Rats with anti-GBM nephritis showed high levels of monocyte chemotactic protein-1 and tumor necrosis factor-α. These changes were significantly suppressed following HCQ treatment. In addition, HCQ suppressed JNK/p38 MAPK phosphorylation. CONCLUSION: HCQ attenuates anti-GBM nephritis by exerting its anti-inflammatory effects via the inhibition of JNK/p38 MAPK activation, indicating its therapeutic potential against anti-GBM nephritis.

Prognoses of patients undergoing hemodialysis administered 23-valent pneumococcal polysaccharide versus 13-valent pneumococcal protein conjugate vaccines.

INTRODUCTION: Sequential vaccination with the 13-valent pneumococcal protein conjugate vaccine (PCV13) and 23-valent pneumococcal polysaccharide vaccine (PPSV23) is recommended for patients undergoing hemodialysis; however, evidence for the efficacy of these pneumococcal vaccines for patients undergoing hemodialysis is limited to a single dose. We aimed to evaluate the prognosis of patients undergoing hemodialysis who received vaccination with PPSV23 alone versus sequential vaccination with PCV13 and PPSV23. METHODS: Patients undergoing hemodialysis who were vaccinated with PPSV23 alone (PPSV23 group) or PCV13 followed by PPSV23 (PCV13+PPSV23 group) between 2014 and 2016 were included; the observation period was three years from the first injection. Patients who underwent hemodialysis between 2011 and 2012 were included as controls. After propensity score matching using age, sex, dialysis vintage, diabetes history, pneumonia history, and serum albumin and creatinine levels, survival analysis was performed. RESULTS: The study included 89, 71, and 319 patients in the PPSV23, PCV13+PPSV23, and control groups, respectively. After propensity score matching, the PPSV23 and control group 1 (79 patients each) and the PCV13+PPSV23 and control group 2 (61 patients each) were compared. Significant differences were observed in the survival rate between the PPSV23 group and control group 1 (p = 0.005) but not between the PCV13+PPSV23 group and control group 2. Pneumonia-related mortality in the two vaccinated groups did not differ significantly during the observation period. CONCLUSIONS: Patients who received PPSV23 had a favorable prognosis; however, no positive effect was demonstrated in the PCV13+PPSV23 group.

The Transfer of the Hepatocyte Growth Factor Gene by Macrophages Ameliorates the Progression of Peritoneal Fibrosis in Mice.

Growing evidence indicates that hepatocyte growth factor (HGF) possesses potent antifibrotic activity. Furthermore, macrophages migrate to inflamed sites and have been linked to the progression of fibrosis. In this study, we utilized macrophages as vehicles to express and deliver the HGF gene and investigated whether macrophages carrying the HGF expression vector (HGF-M) could suppress peritoneal fibrosis development in mice. We obtained macrophages from the peritoneal cavity of mice stimulated with 3% thioglycollate and used cationized gelatin microspheres (CGMs) to produce HGF expression vector-gelatin complexes. Macrophages phagocytosed these CGMs, and gene transfer into macrophages was confirmed in vitro. Peritoneal fibrosis was induced by intraperitoneal injection of chlorhexidine gluconate (CG) for three weeks; seven days after the first CG injection, HGF-M was administered intravenously. Transplantation of HGF-M significantly suppressed submesothelial thickening and reduced type III collagen expression. Moreover, in the HGF-M-treated group, the number of α-smooth muscle actin- and TGF-ß-positive cells were significantly lower in the peritoneum, and ultrafiltration was preserved. Our results indicated that the transplantation of HGF-M prevented the progression of peritoneal fibrosis and indicated that this novel gene therapy using macrophages may have potential for treating peritoneal fibrosis.

[A Retrospective Study on the Malignancies after Renal Transplantation].

Detection of post-transplant malignant tumors and the analysis of the associated risk factors is important for monitoring the progress after renal transplantation. In this study, we retrospectively examined the medical records of 298 patients who underwent renal transplantation at two facilities in Nagasaki Prefecture (Nagasaki University Hospital and National Hospital Organization Nagasaki Medical Center). Of the 298 patients, 45 (15.1%) patients had developed malignant tumors with 50 lesions. The most common type of malignant tumor was skin cancer (eight patients; 17.8%), followed by renal cancer (six patients; 13.3%), and pancreatic cancer and colorectal cancer, (four patients; 9.0% each). Five patients (11.1%) had multiple cancers, four of whom had skin cancer. The cumulative incidence within 10 and 20 years after renal transplantation was 6.0 and 17.9%, respectively. Univariate analysis identified age at transplantation and administration of cyclosporine and rituximab as risk factors, while multivariate analysis identified age at transplantation and administration of rituximab as independent factors. The administration of rituximab was associated with the development of malignant tumors. However, further investigation is required to establish the association with post-transplant malignant neoplasms.

Serum hemoglobin concentration and risk of renal function decline in early stages of diabetic kidney disease: a nationwide, biopsy-based cohort study.

BACKGROUND: Prognosticating disease progression in patients with diabetic kidney disease (DKD) is challenging, especially in the early stages of kidney disease. Anemia can occur in the early stages of kidney disease in diabetes. We therefore postulated that serum hemoglobin (Hb) concentration, as a reflection of incipient renal tubulointerstitial impairment, can be used as a marker to predict DKD progression. METHODS: Drawing on nationally representative data of patients with biopsy-proven DKD, 246 patients who had an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 at renal biopsy were identified: age 56 (45-63) years; 62.6% men; Hb 13.3 (12.0-14.5) g/dL; eGFR 76.2 (66.6-88.6) mL/min/1.73 m2; urine albumin-to-creatinine ratio 534 (100-1480) mg/g Crea. Serum Hb concentration was divided into quartiles: ≤12, 12.1-13.3, 13.4-14.5 and ≥14.6 g/dL. The association between serum Hb concentration and the severity of renal pathological lesions was explored. A multivariable Cox regression model was used to estimate the risk of DKD progression (new onset of end-stage kidney disease, 50% reduction of eGFR or doubling of serum creatinine). The incremental prognostic value of DKD progression by adding serum Hb concentration to the known risk factors of DKD was assessed. RESULTS: Serum Hb levels negatively correlated with all renal pathological features, especially with the severity of interstitial fibrosis (ρ = -0.52; P < 0.001). During a median follow-up of 4.1 years, 95 developed DKD progression. Adjusting for known risk factors of DKD progression, the hazard ratio in the first, second and third quartile (the fourth quartile was reference) were 2.74 [95% confidence interval (CI) 1.26-5.97], 2.33 (95% CI 1.07-5.75) and 1.46 (95% CI 0.71-3.64), respectively. Addition of the serum Hb concentration to the known risk factors of DKD progression improved the prognostic value of DKD progression (the global Chi-statistics increased from 55.1 to 60.8; P < 0.001). CONCLUSIONS: Serum Hb concentration, which reflects incipient renal fibrosis, can be useful for predicting DKD progression in the early stages of kidney disease.

Parameters affecting prognosis after hemodialysis withdrawal: experience from a single center.

INTRODUCTION: Withdrawal from maintenance hemodialysis is unavoidable in some patients due to their poor general condition; however, their survival days vary depending on their health status. The factors associated with life prognosis in the terminal phase in patients undergoing hemodialysis remain unclear. METHODS: Patients who died after withdrawal from hemodialysis between 2011 and 2021 at Nagasaki Renal Center were included. Patient background data were collected, and the association between the patients' clinical features and survival duration was analyzed. RESULTS: The withdrawal group included 174 patients (79.8 ± 10.8 years old; 50.6% male; median dialysis vintage, 3.6 years). The most common reason for withdrawal (95%) was that hemodialysis was more harmful than beneficial because of the patient's poor general condition. The median time from withdrawal to death was 4 days (interquartile range, 3-10 days). Multivariable Cox proportional regression analysis showed that oral nutrition (hazard ratio (HR), 1.98; 95% confidence interval (CI), 1.12-3.50; P = 0.03), hypoxemia (HR, 2.32; 95% CI, 1.55-3.47; P < 0.01), ventilator use (HR, 0.26; 95% CI, 0.11-0.58; P < 0.01), and pleural effusion (HR, 1.54; CI, 1.01-2.37; P = 0.04) were associated with increased survival duration. In contrast, antibiotics and vasopressor administration were not associated with the survival duration. CONCLUSION: In this study, we explored the parameters affecting the survival of patients who withdrew from hemodialysis. Physicians could use our results to establish more accurate predictions, which may help the patient and their family to emotionally accept and implement the desired care plan.

Deep learning analysis of clinical course of primary nephrotic syndrome: Japan Nephrotic Syndrome Cohort Study (JNSCS).

BACKGROUND: Prognosis of nephrotic syndrome has been evaluated based on pathological diagnosis, whereas its clinical course is monitored using objective items and the treatment strategy is largely the same. We examined whether the entire natural history of nephrotic syndrome could be evaluated using objective common clinical items. METHODS: Machine learning clustering was performed on 205 cases from the Japan Nephrotic Syndrome Cohort Study, whose clinical parameters, serum creatinine, serum albumin, dipstick hematuria, and proteinuria were traceable after kidney biopsy at 5 measured points up to 2 years. The clinical patterns of time-series data were learned using long short-term memory (LSTM)-encoder-decoder architecture, an unsupervised machine learning classifier. Clinical clusters were defined as Gaussian mixture distributions in a two-dimensional scatter plot based on the highest log-likelihood. RESULTS: Time-series data of nephrotic syndrome were classified into four clusters. Patients in the fourth cluster showed the increase in serum creatinine in the later part of the follow-up period. Patients in both the third and fourth clusters were initially high in both hematuria and proteinuria, whereas a lack of decline in the urinary protein level preceded the worsening of kidney function in fourth cluster. The original diseases of fourth cluster included all the disease studied in this cohort. CONCLUSIONS: Four kinds of clinical courses were identified in nephrotic syndrome. This classified clinical course may help objectively grasp the actual condition or treatment resistance of individual patients with nephrotic syndrome.

Association between fluid infusions and the recovery from acute kidney injury in patients administered liposomal amphotericin B: a nationwide observational study.

Acute kidney injury (AKI) often develops during the administration of liposomal amphotericin B (L-AMB), a broad-spectrum antifungal drug. However, clinical recovery approaches for AKI patients administered L-AMB are not well established. This retrospective analysis used the data obtained from hospitals throughout Japan. AKI was defined as a ≥ 1.5-fold increase within 7 days or ≥0.3 mg/dL increase within 2 days in serum creatinine. AKI recovery was defined as a return to creatinine levels below or equal to those recorded before AKI onset. Ninety patients were assessed for recovery from AKI as per the three stages. The incidence of recovery from AKI regardless of its stage was higher, though not significant, in patients administered ≥10 mL/kg/day fluid for 7 consecutive days from AKI onset (63%) than in those who did not (35%, p = 0.053). However, if limited to AKI stage 1 patients, the former group had a significantly higher incidence of recovery (91%) than the latter group (50%, p = 0.017), even after adjusting for confounding factors (odds ratio: 10.135, 95% confidence interval: 1.148-89.513, p = 0.037). The daily fluid volume administered during the 7 consecutive days from AKI onset positively correlated with the recovery from AKI of all stages (p = 0.043). Daily consecutive fluid infusion from AKI onset may be associated with recovery from stage 1 AKI in patients administered L-AMB, with daily fluid volume positively correlating with the incidence of AKI recovery.

Comparison of bone microstructures via high-resolution peripheral quantitative computed tomography in patients with different stages of chronic kidney disease before and after starting hemodialysis.

Chronic kidney disease (CKD) negatively affects bone strength; however, the osteoporotic conditions in patients with CKD are not fully understood. Moreover, the changes in bone microstructure between pre-dialysis and dialysis are unknown. High-resolution peripheral quantitative computed tomography (HR-pQCT) reveals the three-dimensional microstructures of the bone. We aimed to evaluate bone microstructures in patients with different stages of CKD. This study included 119 healthy men and 40 men admitted to Nagasaki University Hospital for inpatient education or the initiation of hemodialysis. The distal radius and tibia were scanned with HR-pQCT. Patient clinical characteristics and bone microstructures were evaluated within 3 months of initiation of hemodialysis (in patients with CKD stage 5 D), patients with CKD stage 4-5, and healthy volunteers. Cortical bone parameters were lower in the CKD group than in healthy controls. Tibial cortical and trabecular bone parameters (cortical thickness, cortical area, trabecular volumetric bone mineral density, trabecular-bone volume fraction, and trabecular thickness) differed between patients with CKD stage 5 D and those with CKD stage 4-5 (p < 0.01). These differences were also observed between patients with CKD stage 5 and those with CKD stage 5 D (p < 0.017), but not between patients with CKD stage 4 and those with CKD stage 5, suggesting that the bone microstructure rapidly changed at the start of hemodialysis. Patients with CKD stage 5 D exhibited tibial microstructural impairment compared with those with CKD stage 4-5. HR-pQCT is useful for elucidation of the pathology of bone microstructures in patients with renal failure.

Mitochonic acid-5 ameliorates chlorhexidine gluconate-induced peritoneal fibrosis in mice.

Peritoneal fibrosis is a serious complication of long-term peritoneal dialysis, attributable to inflammation and mitochondrial dysfunction. Mitochonic acid-5 (MA-5), an indole-3-acetic acid derivative, improves mitochondrial dysfunction and has therapeutic potential against various diseases including kidney diseases. However, whether MA-5 is effective against peritoneal fibrosis remains unclear. Therefore, we investigated the effect of MA-5 using a peritoneal fibrosis mouse model. Peritoneal fibrosis was induced in C57BL/6 mice via intraperitoneal injection of chlorhexidine gluconate (CG) every other day for 3 weeks. MA-5 was administered daily by oral gavage. The mice were divided into control, MA-5, CG, and CG + MA-5 groups. Following treatment, immunohistochemical analyses were performed. Fibrotic thickening of the parietal peritoneum induced by CG was substantially attenuated by MA-5. The number of α-smooth muscle actin-positive myofibroblasts, transforming growth factor ß-positive cells, F4/80-positive macrophages, monocyte chemotactic protein 1-positive cells, and 4-hydroxy-2-nonenal-positive cells was considerably decreased. In addition, reduced ATP5a1-positive and uncoupling protein 2-positive cells in the CG group were notably increased by MA-5. MA-5 may ameliorate peritoneal fibrosis by suppressing macrophage infiltration and oxidative stress, thus restoring mitochondrial function. Overall, MA-5 has therapeutic potential against peritoneal fibrosis.