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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 β-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. [ABSTRACT FROM AUTHOR]

Although polypharmacy is common among patients on hemodialysis (HD), its association with prognosis remains unclear. This study aimed to elucidate the association between the number of prescribed medicines and all-cause mortality in patients on HD, accounting for essential medicines (i.e., antihypertensives, antidiabetic medicines, and statins) and non-essential medicines. We evaluated 339 patients who underwent maintenance HD at Nagasaki Renal Center between July 2011 and June 2012 and followed up until June 2021. After adjusting for patient characteristics, the number of regularly prescribed medicines (10.0 ± 4.0) was not correlated with prognosis (hazard ratio [HR]: 1.01, 95% confidence interval [CI] 0.97–1.05, p = 0.60). However, the number of non-essential medicines (7.9 ± 3.6) was correlated with prognosis (HR: 1.06, 95% CI 1.01–1.10, p = 0.009). Adjusting for patient characteristics, patients who were prescribed more than 10 non-essential medicines were found to have a significantly higher probability of mortality than those prescribed less than five non-essential medicines, with a relative risk of 2.01 (p = 0.004). In conclusion, polypharmacy of non-essential medicines increases the risk of all-cause mortality in patients on HD. As such, prescribing essential medicines should be prioritized, and the clinical relevance of each medicine should be reviewed by physicians and pharmacists. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Asymptomatic blood pressure (BP) elevation may be associated with cerebral hemorrhage (CH); however, few studies have investigated this association. We aimed to evaluate BP elevation before CH in hemodialysis (HD) patients and elucidate its associated factors. Methods: We reviewed HD patients treated for CH at our hospital between 2008 and 2019 (CH group). The control group comprised HD patients treated at Nagasaki Renal Center between 2011 and 2012. Data were obtained from medical records and three consecutive HD charts, made immediately before CH. HD1 was the session closest to onset, followed by HD2 and HD3. Systolic and mean BP were evaluated at the beginning of HD, and factors associated with BP elevation were investigated. Results: The CH and control groups included 105 and 339 patients, respectively. Systolic and mean BP at HD1 were significantly higher than those at baseline (HD2 + HD3) in the CH group by 5 and 3 mmHg, respectively (P < 0.001). Multiple linear regression analysis showed that lower calcium levels were significantly associated with BP elevation in the CH group (P < 0.05). The CH group was sub-divided by June 2013; the latter group had lower calcium levels (9.2 mg/dL) and a marked systolic BP difference from baseline (+ 10 mmHg) compared with the former (9.5 mg/dL and − 4 mmHg). Conclusion: Asymptomatic BP elevation was observed in HD patients before CH; this elevation was associated with lower serum calcium levels and observed more frequently in the recent era. The precise mechanism underlying this effect remains unknown. [ABSTRACT FROM AUTHOR]

Background: Prothymosin alpha (ProTα) is a nuclear protein expressed in virtually all mammalian tissues. Previous studies have shown that ProTα exhibits protective effects against ischemia-induced cell death in various cell types. Recently, the 6-residue peptide P6Q (NEVDQE), the modified form of the active 6-residue core (51–56) in ProTα, has also been shown to have protective effects against retinal ischemia. However, it remains to be elucidated whether P6Q is effective against acute kidney injury (AKI). Therefore, we investigated the renoprotective effect of P6Q on cisplatin-induced AKI. Methods: Cultured HK-2 cells were treated with cisplatin for 24 h and pretreatment with ProTα or P6Q was carried out 30 min before cisplatin treatment. Cell viability was evaluated using the MTT assay. In an in vivo study, 8-week-old male Wistar rats were divided into control, cisplatin treated, and cisplatin treated with P6Q injection groups. In the last of these, P6Q was injected intravenously before cisplatin treatment. Then, we evaluated the renoprotective effect of P6Q. Results: In the study on cultured cells, pretreatment with ProTα or P6Q prevented cisplatin-induced cell death. In the in vivo study, pretreatment with P6Q significantly attenuated cisplatin-induced increase in serum creatinine and blood urea nitrogen levels, renal tubular cell injury, and apoptosis. Moreover, P6Q attenuated the mitochondrial apoptotic pathway and accelerated Akt phosphorylation after cisplatin-induced renal damage. Conclusion: Taken together, our findings indicate that P6Q can attenuate cisplatin-induced AKI and suppress the mitochondrial apoptotic pathway via Akt phosphorylation. These data suggest that P6Q has potential as a preventative drug for cisplatin-induced AKI. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 m2/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. [ABSTRACT FROM AUTHOR]

Long-term peritoneal dialysis causes peritoneal fibrosis, and previous reports suggest that inflammation plays a critical role in peritoneal fibrosis. Chondroitin sulfate (CS) suppresses the inflammatory response by preventing activation of nuclear factor (NF)-κB. We examined the effect of CS on the peritoneal fibrosis induced by chlorhexidine gluconate (CG) in mice. CS or water was administered daily. We divided mice into four groups: administered vehicle and water (control); administered vehicle and CS (CS); administered CG and water (CG); and administered CG and CS (CG+CS). Morphologic changes were assessed by Masson's trichrome staining. Inflammation- and fibrosis-associated factors were assessed by immunohistochemistry. Activation of NF-κB was examined by southwestern histochemistry. CS administration suppressed the progression of submesothelial thickening. The numbers of inflammation- and fibrosis-associated factors -positive cells were significantly decreased in the CG+CS group, compared to the CG group. Based on SWH, the CG+CS group contained significantly fewer NF-κB-activated cells than the CG group. Our results indicate that CS suppresses peritoneal fibrosis via suppression of NF-κB activation. These results suggest that CS has therapeutic potential for peritoneal fibrosis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]

Background: Muscle wasting is common and insidious in end-stage renal disease (ESRD). Loss of muscle quantity and quality reduces quality of life and increases mortality in ESRD patients. Additionally, secondary hyperparathyroidism (SHPT) causes muscle atrophy. Meanwhile, vitamin D, which is used for SHPT treatment, plays an essential role in muscle growth. Objectives: We prospectively investigated the effect of active vitamin D administration on muscle mass. Methods: We measured muscle mass based on bioelectrical impedance analysis in 68 hemodialysis patients. Patients were divided into a control group (without active vitamin D administration) and a VitD group (with active vitamin D administration). We compared muscle mass at the beginning of treatment and 1 year later. We also investigated health-related quality of life (HR-QOL) using the Medical Outcome Study Short Form-36 (SF-36). Results: The VitD group experienced a significant increase in the amount of change in total muscle mass and muscle mass percentage in men ( p = 0.025) but not in women ( p = 0.945). By multivariable logistic regression analysis, active vitamin D administration was independently associated with increased muscle mass percentage in men only. In the SF-36, the physical functioning (PF) scores were significantly decreased at the end of the study in the patients without active vitamin D treatment, especially in women. Conclusion: Our results suggested that active vitamin D treatment was associated with increased muscle mass in men, and it might have a favorable effect on maintaining PF in HR-QOL in hemodialysis patients. [ABSTRACT FROM AUTHOR]

We investigated the mechanism of development and repair process of glomerular injury in a rat model of habu snake ( Trimeresurus flavoviridis) venom (HSV)-induced glomerulonephritis. Glomerulonephritis was induced in rats by intravenously injecting HSV at 3 mg/kg. Renal tissue was isolated and subjected to immunohistochemical analysis for expression levels of type IV collagen, heat shock protein 47 (HSP47), transforming growth factor-β (TGF-β), and matrix metalloproteinase-3 (MMP-3), as well as its transcription factor Ets-1. Expression levels of HSP47, TGF-β, and type IV collagen began to increase in the mesangial area starting from day 14 and peaked on day 21, followed by a gradual decrease. Expression levels of MMP-3 and Ets-1 started to increase coinciding with peak production of mesangial matrix on day 21, peaking on day 35, followed by gradual decrease. Expression of MMP-3 and Ets-1 persisted until day 63, whereas that of HSP47 and type IV collagen returned to baseline level at this time point. Time-course changes of extracellular matrix (ECM) accumulation in glomeruli in the HSV-induced glomerulonephritis model were correlated with those of factors involved in both ECM production and degradation systems. Continued expression of factors in the degradation system seems particularly important for the repair process. These findings might lead to new therapies that prevent and repair glomerular injury. [ABSTRACT FROM AUTHOR]

A 50-year-old woman with a 1-month history of lower extremity edema and a 5 kg weight increase was admitted to our hospital with suspected nephrotic syndrome in October 1999. Urine protein level was 3.5 g per day, 10−15 erythrocytes in urine per high-power field, and serum albumin level 2.5 g/dl. Furthermore, an accumulation of pleural effusion was confirmed by chest X-ray. The results of a renal biopsy indicated slight mesangial proliferation in the glomeruli by light microscopy, and an immunofluorescence study confirmed the deposition of immunoglobulin (Ig) A and C3 in the mesangial area. Diffuse attenuation of foot processes and dense deposits in the mesangial area were observed by electron microscopy. Treatment with 40 mg/day of prednisolone was effective, and proteinuria was negative 1 month later. Because of this course, we diagnosed minimal change nephrotic syndrome complicated by mild-proliferative IgA nephropathy. In November 2000, there was a relapse of nephrotic syndrome, which was believed to be induced by an influenza vaccination, but response to increased steroid treatment was favorable, and proteinuria disappeared on day 13 of steroid increase. A second relapse in May 2001, showed steroid resistance with renal insufficiency, and an increase in the selectivity index to 0.195. Light microscopy revealed focal sclerotic lesions of the glomeruli, and an immunofluorescence study revealed attenuation of mesangial IgA and C3 deposition. These findings led to the diagnosis that minimal change nephrotic syndrome had transitioned to focal segmental glomerulosclerosis, whereby mesangial IgA deposition was reduced by immunosuppressive treatment. Subsequently, her renal function gradually worsened to the point of end-stage renal failure by 27 months after the second relapse of nephrotic syndrome. [ABSTRACT FROM AUTHOR]

Although constipation is very common during pregnancy, the exact mechanism is unknown. We hypothesized that the involvement of estrogen receptor (ER) in the regulation of electrolyte transporter in the colon leads to constipation. In this study, the intestines of normal female ICR mouse and pregnant mice were examined for the expression of ERα and ERβ by immunohistochemistry and in situ hybridization. ERβ, but not ERα, was expressed in surface epithelial cells of the proximal, but not distal, colon on pregnancy days 10, 15, and 18, but not day 5, and the number of ERβ-positive cells increased significantly during pregnancy. Expression of NHE3, the gene that harbors estrogen response element, examined by immunohistochemistry and western blotting, was localized in the surface epithelial cells of the proximal colon and increased in parallel with ERβ expression. In ovariectomized mice, NHE3 expression was only marginal and was up-regulated after treatment with 17β-estradiol (E), but not E + ICI 182,780 (estrogen receptor antagonist). Moreover, knock-down of ERβ expression by electroporetically transfected siRNA resulted in a significant reduction of NHE3 expression. These results indicate that ERβ regulates the expression of NHE3 in the proximal colon of pregnant mice through estrogen action, suggesting the involvement of increased sodium absorption by up-regulated NHE3 in constipation during pregnancy. [ABSTRACT FROM AUTHOR]

Reversible posterior leukoencephalopathy syndrome (RPLS) is a recently identified clinical and radiologic entity. The characteristic radiologic findings are bilateral gray and white matter edema in the posterior regions of the cerebral hemispheres. The typical clinical syndrome includes headache, confusion, visual symptoms, and seizures. RPLS most often occurs in the setting of hypertensive crisis, preeclampsia, or with cytotoxic immunosuppressive therapy, but many other clinical settings are described, such as cryoglobulinemia, hemolytic uremic syndrome, systemic lupus erythematosus, and use of erythropoietin. A 24-year-old man, diagnosed as having anaphylactoid purpura nephritis at 12 years of age and who started peritoneal dialysis (PD) at 23 years of age, was admitted to our hospital with a seizure and consciousness disturbance. His blood pressure (BP) and body fluid volume had not been controlled well because of poor compliance with medication and PD. T2-weighted magnetic resonance imaging (MRI) revealed high signal intensity changes restricted to the cortex and subcortical white matter of the cerebellum. On the other hand, diffusion-weighted imaging showed an isointense signal. From these findings, he was diagnosed as having RPLS. With appropriate control of BP and volume control by PD and hemodialysis, his symptoms improved, and a follow-up cranial MRI 1 month later was almost normal. To the best of our knowledge, this is the first report of RPLS in an adult PD patient. [ABSTRACT FROM AUTHOR]

Role of obesity in renal pathological and structural changes remains poorly investigated, and this study was designed to examine the pathological effects of obesity on renal structural components in patients with chronic kidney diseases (CKD). The study subjects were obese (body mass index, BMI ≥ 25 kg/m2) patients with nonglomerulonephritis (non-GN, n = 26), IgA nephropathy (IgAN, n = 19), benign nephrosclerosis (BNS, n = 15), and thin basement membrane disease (TMD, n = 6), and 65 nonobese controls ( n = 20, 20, 10, and 15, respectively). Patients were evaluated for glomerular lesions (mesangial proliferation and focal segmental/global glomerulosclerosis), glomerular size, and thickness of glomerular basement membrane (GBM). Urinary protein was higher in obese non-GN, IgAN, and BNS groups than in the respective controls. Focal segmental glomerulosclerosis (FSGS) lesions were noted in all obesity groups. The glomeruli were larger in size in obese than in nonobese patients of the non-GN and IgAN groups. The glomeruli of nonobese TMD and BNS patients were significantly larger in size than those of nonobese non-GN patients. GBM were thicker in obese than in nonobese patients irrespective of types of glomerular diseases, but only significantly so in non-GN and BNS groups. In non-GN, IgAN, and BNS, obesity worsens proteinuria and is associated with structural changes such as glomerulomegaly and GBM thickening, similar to changes observed in obesity-related nephropathy. Obesity seems to worsen the renopathological state in CKD. [ABSTRACT FROM AUTHOR]

Peritoneal dialysis (PD) is an established mode of renal replacement therapy based on the exchange of fluid and solutes between blood and a dialysate that has been instilled in the peritoneal cavity. The dialysis process involves osmosis, as well as diffusive and convective transports through the highly vascularized peritoneal membrane. Computer simulations predicted that the membrane contains ultrasmall pores responsible for the selective transport of water across the capillary endothelium during crystalloid osmosis. The distribution of the water channel aquaporin-1 (AQP1), as well as its molecular structure ensuring an exquisite selectivity for water, fit with the characteristics of the ultrasmall pore. Peritoneal transport studies using AQP1 knockout mice demonstrated that the osmotic water flux across the peritoneal membrane is mediated by AQP1. This water transport accounts for 50% of the ultrafiltration during PD. Treatment with high-dose corticosteroids upregulates the expression of AQP1 in peritoneal capillaries, resulting in increased water transport and ultrafiltration in rats. AQP1 may also play a role during inflammation, as vascular proliferation and leukocyte recruitment are both decreased in mice lacking AQP1. These data illustrate the potential of the peritoneal membrane as an experimental model in the investigation of the role of AQP1 in the endothelium at baseline and during inflammation. They emphasize the critical role of AQP1 during PD and suggest that manipulating AQP1 expression could be clinically useful in PD patients. [ABSTRACT FROM AUTHOR]

Discusses a case of primary sclerosing cholangitis associated with lupus nephritis. Case history; Treatment options.

The original article can be found online. [ABSTRACT FROM AUTHOR]

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.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.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).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.Methods: 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.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.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).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.Results: 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.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.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).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.Conclusions: 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.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.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).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. [ABSTRACT FROM AUTHOR]