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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., (© 2024. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

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., (© 2023. The Author(s), under exclusive licence to The Japanese Society of Nephrology.)

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 m 2 . 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., (© 2022. The Author(s), under exclusive licence to The Japanese Society of Nephrology.)

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., (© 2022. The Author(s), under exclusive licence to The Japanese Society of Nephrology.)

Background: Liposomal amphotericin B (L-AMB), a broad-spectrum antifungicidal drug, is often used to treat fungal infections. However, clinical evidence of its use in patients with renal dysfunction, especially those receiving renal replacement therapy (RRT), is limited. Therefore, we evaluated the usage and occurrence of adverse reactions during L-AMB therapy in patients undergoing RRT., Methods: Using claims data and laboratory data, we retrospectively evaluated patients who were administered L-AMB. The presence of comorbidities, mortality rate, treatment with L-AMB and other anti-infective agents, and the incidence of adverse reactions were compared between patients receiving RRT, including continuous renal replacement therapy (CRRT) and maintenance hemodialysis (HD), and those that did not receive RRT., Results: In total, 900 cases met the eligibility criteria: 24, 19, and 842 cases in the maintenance HD, CRRT, and non-RRT groups, respectively. Of the patients administered L-AMB, mortality at discharge was higher for those undergoing either CRRT (15/19; 79%) or maintenance HD (16/24; 67%) than for those not receiving RRT (353/842; 42%). After propensity score matching, the average daily and cumulative dose, treatment duration, and dosing interval for L-AMB were not significantly different between patients receiving and not receiving RRT. L-AMB was used as the first-line antifungal agent for patients undergoing CRRT in most cases (12/19; 63%). Although the number of subjects was limited, the incidence of adverse events did not markedly differ among the groups., Conclusion: L-AMB may be used for patients undergoing maintenance HD or CRRT without any dosing, duration, or interval adjustments.

Background: The Japanese classification of diabetic nephropathy reflects the risks of mortality, cardiovascular events and kidney prognosis and is clinically useful. Furthermore, pathological findings of diabetic nephropathy are useful for predicting prognoses. In this study, we evaluated the characteristics of pathological findings in relation to the Japanese classification of diabetic nephropathy and their ability to predict prognosis., Methods: The clinical data of 600 biopsy-confirmed diabetic nephropathy patients were collected retrospectively from 13 centers across Japan. Composite kidney events, kidney death, cardiovascular events, all-cause mortality, and decreasing rate of estimated GFR (eGFR) were evaluated based on the Japanese classification of diabetic nephropathy., Results: The median observation period was 70.4 (IQR 20.9-101.0) months. Each stage had specific characteristic pathological findings. Diffuse lesions, interstitial fibrosis and/or tubular atrophy (IFTA), interstitial cell infiltration, arteriolar hyalinosis, and intimal thickening were detected in more than half the cases, even in Stage 1. An analysis of the impacts on outcomes in all data showed that hazard ratios of diffuse lesions, widening of the subendothelial space, exudative lesions, mesangiolysis, IFTA, and interstitial cell infiltration were 2.7, 2.8, 2.7, 2.6, 3.5, and 3.7, respectively. Median declining speed of eGFR in all cases was 5.61 mL/min/1.73 m 2 /year, and the median rate of declining kidney function within 2 years after kidney biopsy was 24.0%., Conclusions: This study indicated that pathological findings could categorize the high-risk group as well as the Japanese classification of diabetic nephropathy. Further study using biopsy specimens is required to clarify the pathogenesis of diabetic kidney disease.

Background: Nephrosclerosis is an increasingly reason for dialysis in Japan. However, kidney biopsy specimens for hypertensive nephrosclerosis are very limited; thus, the pathologic evaluation of hypertensive nephrosclerosis currently remains unclear., Methods: Clinical and pathologic data of a total of 184 biopsy-confirmed hypertensive nephrosclerosis patients were collected from 13 centers throughout Japan. Seven pathological findings were assessed in this study. The outcomes of interest for this study were dialysis, composite kidney events, cardiovascular events, and all-cause mortality., Results: The Green and Yellow (G&Y), Orange, and Red groups of the chronic kidney diseases (CKD) heat map contained 36, 57, and 91 cases, respectively. The mean observation period was 7.3 ± 5.2 (median, IQR; 6.1, 2.6-9.7) years. Global glomerulosclerosis (GScle), interstitial fibrosis and tubular atrophy (IFTA), arteriolar hyalinosis in Red exhibited higher scores than those in G&Y and Orange. The incidence rates of the composite kidney end points in 100 person-years for the G&Y, Orange, and Red groups were 1.42, 2.16, and 3.98, respectively. In the univariate Cox analysis for the composite kidney end points, GScle, IFTA and interstitial cell infiltration exhibited statistically significant high hazard ratios (1.18, 1.84, 1.69, respectively). However, after adjustment for clinical and medication data, the Red group in the CKD heat map category was risk factor for the composite kidney end points (HR 9.51)., Conclusions: In summary, although pathologic findings had minor impacts on the prediction of composite outcomes in this study, the clinical stage of the CKD heat map is a good predictor of composite kidney events.

Background: Medical intervention for patients with IgA nephropathy and mild proteinuria (<1.0 g/day) is controversial, and the effectiveness of tonsillectomy plus steroid pulse therapy (TSP) for such patients remains obscure., Methods: Among 323 patients in our multicenter cohort study, 79 who had mild proteinuria (0.4-1.0 g/day) at diagnosis were eligible to participate in this study. We compared the clinicopathological findings at diagnosis, a decline in renal function defined as a 50 or 100% increase in serum creatinine (sCr) and clinical remission (CR) defined as the disappearance of hematuria and proteinuria (<0.3 g/day) among groups given TSP (n = 46), steroid therapy (ST) (n = 9), and non-ST (n = 24). Factors contributing to CR were also evaluated using multivariate analysis., Results: Background factors at diagnosis including age, ratio (%) of patients with hypertension, sCr, proteinuria, and histological severity did not significantly differ among the groups. Only two patients each in the TSP (4.3%) and non-ST (8.3%) groups achieved a 50% increase in sCr during a mean follow-up period of 4.7 years. At the final observation, 71.7, 44.4, and 41.7% of patients in the TSP, ST, and non-ST groups, respectively, achieved CR (p = 0.032). Cox proportional hazards models revealed that TSP led to CR more effectively than non-TSP by a factor of about threefold (hazard ratio, 2.74; p = 0.008)., Conclusion: TSP therapy has potential for inducing CR in patients with IgAN and mild proteinuria (<1.0 g/day).

Background: In addition to corticosteroids and inhibition of the renin-angiotensin-aldosterone system, tonsillectomy with steroid pulse therapy (TSP) may have a beneficial impact on the clinical course of IgA nephropathy (IgAN). However, there is still much uncertainty regarding the indications for therapy, treatment protocol, and therapeutic options for IgAN., Methods: In this multicenter retrospective cohort study, we enrolled 284 patients with biopsy-proven IgAN who received TSP or corticosteroid therapy or conservative therapy. The effects of TSP on clinical remission (CR) were evaluated after a median follow-up period of 4.1 years in relation to histological classifications., Results: Among the 284 participants, 161 patients received TSP. During the observation time, 141 patients (49.6%) achieved CR, with a median time to remission of 397 days. In multivariate Cox regression analyses, TSP had an impact on achieving CR in only the group with histological grade 3 defined as glomerulosclerosis, crescent formation or adhesion to Bowman's capsule in 10-30% of all biopsied glomeruli, or mild cellular infiltration in the interstitium (hazard ratio (HR) 4.29, 95% confidence interval (95%CI) 1.88-11.19, P < 0.001). TSP independently contributed to a higher incidence of CR, particularly in the patient group showing evident mesangial hypercellularity (HR 2.54, 95%CI 1.38-5.08, P = 0.002)., Conclusions: TSP may have a beneficial effect on the clinical course in IgAN patients with mild to moderate glomerular and interstitial lesions, particularly with distinct mesangial cell proliferation.