Megalin-related mechanism of hemolysis-induced acute kidney injury and the therapeutic strategy.

Hemolysis-induced acute kidney injury (AKI) is attributed to heme-mediated proximal tubule epithelial cell (PTEC) injury and tubular cast formation due to intratubular protein condensation. Megalin is a multiligand endocytic receptor for proteins, peptides, and drugs in PTECs and mediates the uptake of free hemoglobin and the heme-scavenging protein α1-microglobulin. However, understanding of how megalin is involved in the development of hemolysis-induced AKI remains elusive. Here, we investigated the megalin-related pathogenesis of hemolysis-induced AKI and a therapeutic strategy using cilastatin, a megalin blocker. A phenylhydrazine-induced hemolysis model developed in kidney-specific mosaic megalin knockout (MegKO) mice confirmed megalin-dependent PTEC injury revealed by the co-expression of kidney injury molecule-1 (KIM-1). In the hemolysis model in kidney-specific conditional MegKO mice, the uptake of hemoglobin and α1-microglobulin as well as KIM-1 expression in PTECs was suppressed, but tubular cast formation was augmented, likely due to the nonselective inhibition of protein reabsorption in PTECs. Quartz crystal microbalance analysis revealed that cilastatin suppressed the binding of megalin with hemoglobin and α1-microglobulin. Cilastatin also inhibited the specific uptake of fluorescent hemoglobin by megalin-expressing rat yolk sac tumor-derived L2 cells. In a mouse model of hemolysis-induced AKI, repeated cilastatin administration suppressed PTEC injury by inhibiting the uptake of hemoglobin and α1-microglobulin and also prevented cast formation. Hemopexin, another heme-scavenging protein, was also found to be a novel ligand of megalin, and its binding to megalin and uptake by PTECs in the hemolysis model were suppressed by cilastatin. Mass spectrometry-based semiquantitative analysis of urinary proteins in cilastatin-treated C57BL/6J mice indicated that cilastatin suppressed the reabsorption of a limited number of megalin ligands in PTECs, including α1-microglobulin and hemopexin. Collectively, cilastatin-mediated selective megalin blockade is an effective therapeutic strategy to prevent both heme-mediated PTEC injury and cast formation in hemolysis-induced AKI. © 2024 The Pathological Society of Great Britain and Ireland.

Evaluating the associations between compliance with CKD guideline component metrics and renal outcomes.

Understanding the association between compliance to the Chronic Kidney Disease (CKD) guidelines in real-world clinical settings and renal outcomes remains a critical gap in knowledge. A comprehensive analysis was conducted using data from a national, multicenter CKD registry. This study included 4,455 patients with an estimated glomerular filtration rate (eGFR) measurement on the index date and eight additional metrics recorded within six months. These metrics comprised serum electrolyte levels, low-density lipoprotein cholesterol, hemoglobin, and the use of renin-angiotensin system inhibitors. The primary outcome was a composite of renal events, defined by a decline in eGFR to < 15 mL/min/1.73 m2 or a reduction of ≥ 30% in eGFR, confirmed by follow-up tests. Over a median follow-up of 513 days, 838 renal events were observed. High serum potassium levels (> 5.4 mmol/L) were associated with increased event rates compared to lower levels. Similarly, low serum sodium-chloride levels (< 33) correlated with higher event rates. Usage of renin-angiotensin system inhibitors, low serum calcium (< 8.4 mg/dL), and high uric acid levels (> 7.0 mg/dL) were also linked to increased events. Conversely, higher hemoglobin levels (≥ 13 g/dL) were associated with lower event rates. Compliance to guidelines, categorized into quartiles based on the number of met metrics, revealed a significantly reduced risk of events in the highest compliance group (meeting 8 metrics) compared to the lowest (0-5 metrics). Compliance to CKD guidelines in clinical practice is significantly associated with improved renal outcomes, emphasizing the need for guideline-concordant care in the management of CKD.

Individual dipeptidyl peptidase-4 inhibitors and acute kidney injury in patients with type 2 diabetes: A systematic review and network meta-analysis.

This network meta-analysis of randomized controlled trials aimed to determine whether any individual dipeptidyl peptidase-4 (DPP-4) inhibitors increase the risk of acute kidney injury (AKI). The Medical Literature Analysis and Retrieval System Online via PubMed, the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov were systematically searched to identify relevant studies. The primary outcome was AKI. A frequentist network meta-analysis was performed using a random-effects model to account for heterogeneity. Twenty-nine studies involving 56 117 participants were included. There were 918 cases of AKI (1.63%). The risk of bias was generally considered to be low. The only DPP-4 inhibitor that significantly increased the frequency of AKI when compared with placebo was sitagliptin (risk ratio 1.65, 95% confidence interval 1.22-2.23). However, because one study showed significant outliers in the funnel plot, in a highly heterogeneous population composed solely of patients undergoing surgery for coronary artery bypass graft, we conducted a post-hoc sensitivity analysis to exclude this study. The results showed no statistically significant difference in the risk of AKI between sitagliptin and placebo. Individual DPP-4 inhibitors do not appear to increase the risk of AKI. However, sitagliptin may be associated with AKI in patients with underlying severe cardiovascular disease.

Factors affecting the sodium-glucose cotransporter 2 inhibitors-related initial decline in glomerular filtration rate and its possible effect on kidney outcome in chronic kidney disease with type 2 diabetes: The Japan Chronic Kidney Disease Database.

AIM: Sodium-glucose cotransporter 2 (SGLT2) inhibitors often cause a transient decrease in glomerular filtration rate (GFR) shortly after the initiation, referred to as the 'initial drop'. However, the clinical significance of this initial drop in real-world practice remains unclear. MATERIALS AND METHODS: Using the nationwide Japan Chronic Kidney Disease Database, we examined factors that affected the initial drop, in patients with chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM). We also evaluated the effects of the initial drop on a composite kidney outcome (a decline in GFR of ≥50% or progression to end-stage kidney disease). RESULTS: Data from 2053 patients with CKD and T2DM newly prescribed an SGLT2 inhibitor were analysed. The follow-up period after SGLT2 inhibitor administration was 1015 days (interquartile range: 532, 1678). Multivariate linear regression models revealed that the concomitant use of the renin-angiotensin system inhibitors and diuretics, urinary protein levels ≥2+, and changes in GFR before the initiation of the SGLT2 inhibitor were associated with a larger initial GFR decline (ß = -0.609, p = .039; ß = -2.298, p < .001; ß = -0.936, p = .048; ß = -0.079, p < .001, respectively). Patients in the quartile with the largest initial GFR decline experienced a higher incidence of the subsequent composite kidney outcome than those in the other quartiles (p < .001). CONCLUSIONS: The concomitant use of renin-angiotensin system inhibitors and diuretics, higher urine protein levels and pre-treatment GFR changes were associated with a larger initial GFR decline. Of these factors, the use of a diuretic had the largest effect. Furthermore, patients with CKD and T2DM experiencing an excessive initial GFR drop might be at a higher risk of adverse kidney outcomes.

Cigarette smoking and progression of kidney dysfunction: a longitudinal cohort study.

INTRODUCTION: Cigarette smoking is one of the most important life-modifiable risk factors for CVD events. The effect on CKD progression caused by smoking remained uncertain, while the effect on CVD had been established. METHOD: The study population included participants from the specific health check and specific health guidance, an annual health check-up for all inhabitants of Japan who were aged between 40 and 74 years. 149,260 subjects (male, 37.1%; female, 62.9%) were included in this analysis. RESULTS: The relationship between smoking status along with new-onset proteinuria and eGFR deterioration more than 15 mL/min/1.73 m2 was examined. Median observation periods were 1427 days [738, 1813] in males and 1437 days [729, 1816] in females. In male participants, the strongest factor upon kidney dysfunction was new-onset proteinuria (1.41 [1.31 1.51], P < 0.001). The second strongest factor on kidney deterioration was smoking (1.24 [1.16 1.31], P < 0.001). In female participants, strongest factor upon kidney dysfunction was smoking (1.27 [1.16-1.39], P < 0.001). The second strongest factor on kidney deterioration was new-onset proteinuria (1.26 [1.17 1.36], P < 0.001). To reveal the relationship of effects from new-onset proteinuria and smoking on the kidney function, the participants were divided into four groups with and without new-onset proteinuria and smoking. The group with both proteinuria and smoking had significantly worst renal prognosis (P for trend < 0.001). CONCLUSION: Large longitudinal observation study revealed smoking has an evil effect on the progression of CKD. This evil effect could be observed in CKD patients with proteinuria as well as in general population without new-onset proteinuria.

Development of a prognostic risk score to predict early mortality in incident elderly Japanese hemodialysis patients.

BACKGROUND: Information of short-term prognosis after hemodialysis (HD) introduction is important for elderly patients with chronic kidney disease (CKD) and their families choosing a modality of renal replacement therapy. Therefore, we developed a risk score to predict early mortality in incident elderly Japanese hemodialysis patients. MATERIALS AND METHODS: We analyzed data of incident elderly HD patients from a nationwide cohort study of the Japanese Society for Dialysis Therapy Renal Data Registry (JRDR) to develop a prognostic risk score. Candidate risk factors for early death within 1 year was evaluated using multivariate logistic regression analysis. The risk score was developed by summing up points derived from parameter estimate values of independent risk factors. The association between risk score and early death was tested using Cox proportional hazards models. This risk score was validated twice by using an internal validation cohort derived from the JRDR and an external validation cohort collected for this study. RESULTS: Using the development cohort (n = 2,000), nine risk factors were retained in the risk score: older age (>85), yes = 2, no = 0; sex, male = 2, female = 0; lower body mass index (<20), yes = 2, no = 0; cancer, yes = 1, no = 0; dementia, yes = 3, no = 0; lower creatinine (<6.5 mg/dL), yes = 1, no = 0; lower albumin (<3.0 g/dL), yes = 3, no = 0; normal or high calcium (≥8.5 mg/dL), yes = 1, no = 0; and higher C reactive protein (>2.0 mg/dL), yes = 2, no = 0. In the internal and external validation cohorts (n = 739, 140, respectively), the medium- and high-risk groups (total score, 6 to 10 and 11 or more, respectively) showed significantly higher risk of early death than the low-risk group (total score, 0 to 5) (p<0.001). CONCLUSION: We developed a prognostic risk score predicting early death within 1 year in incident elderly Japanese HD patients, which may help detect elderly patients with a high-risk of early death after HD introduction.

Exercise instruction during haemodialysis treatment after changes to the insurance regime: a nationwide questionnaire survey in Japan.

In April 2022, an additional medical fee for exercise instruction during haemodialysis treatment was approved for insurance claims in Japan. We conducted a questionnaire survey to investigate the current situation regarding exercise therapy during haemodialysis treatment after this change. Questionnaires were mailed to 4257 haemodialysis facilities, almost all the haemodialysis facilities in Japan, on January 31, 2023. In total, 1657 facilities responded, of which 550 (33%) provided exercise instruction during haemodialysis treatment, and 65% of these claimed the new fee. Of the 550 facilities that had claimed the fee at the time of survey, 245 (55%) started exercise instruction in April 2022 or later. Exercise instruction focused on resistance training (81%) and aerobic exercise (62%) for 20-30 min (66%) three times a week (80%). The instructors included physicians in 45% of facilities, nurses in 74%, and physical therapists in 36%. Efficacy was evaluated in 76% of the facilities providing instruction, mainly by assessing change in muscle strength (49%). Overall, 39% of facilities had experienced some adverse events, but none were life-threatening. In conclusion, after the change in the insurance regime, exercise instruction during haemodialysis treatment has become more popular, and more patients on haemodialysis are undergoing exercise therapy.

Effect of proteinuria on the rapid kidney function decline in chronic kidney disease depends on the underlying disease: A post hoc analysis of the BRIGHTEN study.

AIMS: It is unclear whether the effect of proteinuria on rapid kidney function decline is equivalent among diabetic kidney disease (DKD), non-DKD with diabetes (NDKD+DM), and nephrosclerosis without diabetes (NS-DM), particularly in advanced chronic kidney disease patients. METHODS: In total, 1038 chronic kidney disease patients who participated in the BRIGHTEN study were included in the present study. A linear mixed effect model was applied to estimate the annual estimated glomerular filtration rate decline in each disease group. RESULTS: The prevalence of rapid decliners (rapid kidney function decline, defined as an eGFR loss of > 5 mL/min/1.73 m2/year) in the DKD group (44.6 %) was significantly higher compared with the NDKD+DM (27.9 %) and NS-DM (27.0 %) groups. By contrast, the prevalence of rapid decliners in different urine total protein to creatinine ratio (UPCR) categories (<0.5, 0.5 to < 1.0, 1.0 to < 3.5, and ≥ 3.5 g/g) were equivalent between the DKD and NS-DM groups. Moreover, the prevalence of a UPCR < 1.0 g/g in rapid decliners of the NS-DM group was more than double than in those of the DKD and NDKD+DM groups. CONCLUSIONS: The risk of rapid kidney function decline in NS-DM patients with low levels of proteinuria may be greater than initially predicted.

Trends in the Incidence of Renal Replacement Therapy due to Rapidly Progressive Glomerulonephritis in Japan, 2006-2021.

Objective Patients with rapidly progressive glomerulonephritis (RPGN) are at a high risk of progression to end-stage kidney disease (ESKD), requiring renal replacement therapy (RRT). The present study examined recent trends in the incidence of RRT due to RPGN in Japan. Methods The number of patients with incident RRT due to RPGN by sex from 2006 to 2021 was extracted from the Japanese Society of Dialysis Therapy Registry. The incidence rates of RRT were calculated for four-year periods with the census population as the denominator. Standardized incidence ratios (SIRs) and age-specific incidence rates were also calculated. Results From 2006 to 2021, the crude number of patients with incident RRT due to RPGN increased by 34% and 58% in men and women, respectively. The SIRs decreased significantly in 2010-2013 relative to the first period (2006-2009) for both men (0.90 [95% confidence interval {CI} 0.85-0.96]) and women (0.92 [0.86-0.99]) but then increased to 1.01 (0.96-1.07) for men and 1.20 (1.13-1.27) for women in 2018-2021. In the older age groups (≥70 years old), age-specific incidence rates initially decreased in 2010-2013 but increased thereafter, peaking in 2018-2021. Conclusion From 2006 to 2021, the number of patients with incident RRT due to RPGN increased, with an increase in the age-specific incidence of RRT due to RPGN in the older age groups (≥70 years old), suggesting that the number of patients with incident RRT due to RPGN will continue to increase as the population ages in Japan.

Association of serum magnesium levels with renal prognosis in patients with chronic kidney disease.

BACKGROUND: Magnesium deficiency is associated with various health conditions, but its impact on the progression of chronic kidney disease (CKD) remains unclear. This study aimed to investigate the association between serum magnesium levels and prognosis of renal function in CKD patients. METHODS: This is an analysis of the Japan Chronic Kidney Disease Database Ex　(J-CKD-DB-Ex), which is a multicenter prospective cohort including CKD patients enrolled from January 1, 2014 to December 31, 2020. We included adult outpatients with CKD stage G3 and G4 at the time of initial magnesium measurement. Patients were classified by magnesium levels as low (<1.7 mg/dl), normal (1.7-2.6 mg/dl), or high (>2.6 mg/dl). The primary outcomes were the composite of an eGFR < 15 ml/min/1.73 m2 or a ≥30% reduction in eGFR from the initial measurement, which was defined as CKD progression. We applied the Kaplan-Meier analysis and Cox regression hazard model to examine the association between magnesium levels and CKD progression. RESULTS: The analysis included 9868 outpatients during the follow-up period. The low magnesium group was significantly more likely to reach CKD progression. Cox regression, adjusting for covariates and using the normal magnesium group as the reference, showed that the hazard ratio for the low magnesium group was 1.20 (1.08-1.34). High magnesium was not significantly associated with poor renal outcomes compared with normal magnesium. CONCLUSION: Based on large real-world data, this study demonstrated that low magnesium levels are associated with poorer renal outcomes.

Protein intake and its relationship with frailty in chronic kidney disease.

INTRODUCTION: Patients with chronic kidney disease (CKD) are susceptible to frailty because of a range of nutrition-related factors. While protein restriction is commonly advised to preserve kidney function in patients with CKD, insufficient protein intake could potentially exacerbate frailty risk. This study aimed to elucidate the relationship between frailty and protein intake in patients with CKD. METHODS: This cross-sectional study enrolled patients with CKD stage 3-5. Frailty and prefrailty were assessed using the Japanese version of the Cardiovascular Health Study (J-CHS) criteria. To estimate dietary protein intake, Maroni's formula based on 24-h urine collection was used. The potential association between frailty/pre-frailty and protein intake was investigated using a logistic regression analysis. RESULTS: Ninety-seven individuals with CKD were included in the study, with a median age of 73.0 years (interquartile range: 67.0, 82.0). Among them, 34 were women (35.1%), and the estimated glomerular filtration rate (eGFR) was 36.3 mL/min/1.73 m2 (interquartile range: 26.9, 44.1). Frailty and pre-frailty were identified in 13.4% and 55.7% of participants, respectively. Comparing the groups, protein intake in the frailty/pre-frailty group (0.83 g/kgBW/day [0.72, 0.93]) was lower than that in the robust group (0.89 g/kgBW/day [0.84, 1.19], p = 0.002). Upon logistic regression analysis, protein intake exhibited an independent association with frailty/pre-frailty (odds ratio: 0.72, 95% confidence interval: 0.59-0.89, p = 0.003). CONCLUSION: Reduced protein intake in patients with CKD is associated with frailty and pre-frailty. It is advisable to ensure that patients with CKD who are at risk of frailty consume an adequate amount of protein.

A Case of Adult-Onset Still's Disease With Hypocomplementemia.

Adult-onset Still's disease (AOSD) causes fever, rash, pharyngalgia, and arthralgia through autoinflammation. Its complement titer has not previously received attention because this usually increases during the inflammatory process. Our female patient in her 60s was admitted to the hospital with fever, rash, arthralgia, and pharyngalgia. Her white blood cell count was 19,130/µL, hemoglobin was 11.0 g/dL, platelet count was 26.0 × 104/µL, and ferritin titer was 6,175 ng/mL. Anti-nuclear antibodies and anti-neutrophil cytoplasmic antibodies were negative. The presence of infectious diseases and malignancies was excluded. She was diagnosed with hypocomplementemia at the onset of AOSD because of her low complement component 4 (C4) titer (<5.0 mg/dL). Her complement component 3 (C3) titer was 104.5 mg/dL, which was within normal limits. There was no sign of thrombotic microangiopathy (TMA) or hemophagocytosis. She was treated with high-dose corticosteroids, including pulse methylprednisolone therapy, cyclosporine, methotrexate, and intravenous immunoglobulin, but was resistant to these, and her disease repeatedly flared up. Treatment with intravenous cyclophosphamide eventually led to remission. Post-treatment, her C4 titer increased to within the normal range. Although hypocomplementemia with TMA or hemophagocytosis has been reported in AOSD patients, our patient showed no sign of either at disease onset. Hypocomplementemia of AOSD may be a sign of high disease activity and could be a predictive marker for resistance to standard therapy.

Mass spectrometry-based proteomic analysis of proteins adsorbed by hexadecyl-immobilized cellulose bead column for the treatment of dialysis-related amyloidosis.

BACKGROUND: Dialysis-related amyloidosis (DRA) is a severe complication in end-stage kidney disease (ESKD) patients undergoing long-term dialysis treatment, characterized by the deposition of ß2-microglobulin-related amyloids (Aß2M amyloid). To inhibit DRA progression, hexadecyl-immobilized cellulose bead (HICB) columns are employed to adsorb circulating ß2-microglobulin (ß2M). However, it is possible that the HICB also adsorbs other molecules involved in amyloidogenesis. METHODS: We enrolled 14 ESKD patients using HICB columns for DRA treatment; proteins were extracted from HICBs following treatment and identified using liquid chromatography-linked mass spectrometry. We measured the removal rate of these proteins and examined the effect of those molecules on Aß2M amyloid fibril formation in vitro. RESULTS: We identified 200 proteins adsorbed by HICBs. Of these, 21 were also detected in the amyloid deposits in the carpal tunnels of patients with DRA. After passing through the HICB column and hemodialyzer, the serum levels of proteins such as ß2M, lysozyme, angiogenin, complement factor D and matrix Gla protein were reduced. These proteins acted in the Aß2M amyloid fibril formation. CONCLUSIONS: HICBs adsorbed diverse proteins in ESKD patients with DRA, including those detected in amyloid lesions. Direct hemoperfusion utilizing HICBs may play a role in acting Aß2M amyloidogenesis by reducing the amyloid-related proteins.

A case of non-lupus full-house nephropathy diagnosed by kidney biopsy but observed IgA nephropathy on second biopsy.

We describe a case of full-house nephropathy without any underlying disease, including systemic lupus erythematosus. A 40-year-old woman was referred to our hospital with mild proteinuria and microscopic hematuria. The patient was diagnosed with immune complex-mediated glomerulonephritis with a predominant mesangioproliferative pattern based on renal histopathological results using full-house immunofluorescence staining. She showed no clinical criteria for the diagnosis of systemic lupus erythematosus, except for kidney disorders, and tested negative for antinuclear antibodies throughout her clinical course. However, in the second kidney biopsy, no C1q or C4 were detected in the immunofluorescence study, suggesting an immunoglobulin A nephropathy-like pattern. The patient responded favorably to corticosteroid treatment. We found a heterozygous CFHR3-CFHR1 deletion. The association between full-house nephropathy and CFHR3-CFHR1 deletion is unknown, but its influence on the histological pattern in our case is suspected. This indicates the diversity in the pathogenesis of non-lupus full-house nephropathy and warrants further investigation.

Appropriate Anthropometric Indices for Geriatric Nutritional Risk Index in Predicting Mortality in Older Japanese Patients: A Comparison of the Lorentz Formula and Body Mass Index.

The Geriatric Nutritional Risk Index (GNRI) is a popular nutritional screening tool. However, the calculation of ideal body weight (IBW) differs among studies. We aimed to compare GNRI calculated using the Lorentz formula (LF) with a body mass index (BMI) and to investigate the cutoffs based on original or quartile criteria for the association with mortality in elderly patients in Japan. This retrospective study enrolled patients aged 65 and older in a long-term care hospital. The GNRI was calculated using two different IBW methods: the LF and a BMI of 22 kg/m2. We categorized GNRI results based on the original criteria or quartile criteria. Mortality outcomes were analyzed using the GNRI based on IBW (LF or BMI) and its classification (original criteria or quartile) through Cox proportional hazard regression. There were 262 participants, including 160 women, with a median age of 86. There was a notable difference between GNRI-BMI and GNRI-LF. The GNRI-LF original and quartile criteria did not show an association with mortality. A significant association with mortality was found between Q1 and Q4 in the GNRI-BMI quartile criteria (hazard ratio: 2.60; 95% confidence interval: 1.66-4.07, p < 0.01), but not the GNRI-BMI original criteria. The GNRI calculated using BMI with quartile criteria proved to be a reliable predictor of mortality for Japanese elderly inpatients. The calculation method of GNRI and the appropriate cutoff point should be considered based on the patient's background.

Clinicopathological prognostic stratification for proteinuria and kidney survival in IgA nephropathy: a Japanese prospective cohort study.

Background: We require a clinicopathological risk stratification method for immunoglobulin A nephropathy (IgAN) to predict kidney outcomes. We examined a renal failure risk group (RF-RG) classification system created following a prior multicentre, retrospective study to determine if RF-RG could predict kidney outcomes. Methods: We collected data from Japanese patients with IgAN registered between 1 April 2005 and 31 August 2015. The primary outcome was a composite 50% increase in serum creatinine from baseline or dialysis induction. The secondary outcomes were times to proteinuria remission (ProR) and haematuria remission (HemR). Results: The enrolled 991 patients from 44 facilities were followed for a median of 5.5 years (interquartile range 2.5-7.5), during which 87 composite events (8.8%) occurred. RF-RG was significantly associated with the primary outcome {hazard ratio [HR] II 2.78 [95% confidence interval (CI) 1.12-6.93], III 7.15 (2.90-17.6), IV 33.4 (14.1-79.0), I as a reference, P < .001}.The discrimination performance was good [C-statistic 0.81 (95% CI 0.76-0.86)] and the time-dependent C-statistics exceeded 0.8 over 10 years. Among the 764 patients with proteinuria and 879 patients with haematuria at baseline, 515 and 645 patients showed ProR and HemR, respectively. ProR was significantly less frequent in patients with advanced disease [subdistribution HR: II 0.79 (95% CI 0.67-0.94), III 0.53 (0.41-0.66), IV 0.15 (0.09-0.23), I as a reference, P < .001]. We also observed an association between HemR and RF-RG. Conclusions: RF-RG demonstrated good predictive ability for kidney outcomes.

Pruritus and protein-bound uremic toxins in patients undergoing hemodialysis: a cross-sectional study.

Background: Patients undergoing hemodialysis frequently experience pruritus; its severity is associated with poor quality of life and mortality. Recent progress in hemodialysis treatment has improved the removal of small- and middle-molecular-weight molecules; however, the removal of protein-bound uremic toxins (PBUTs) remains difficult. It is possible that pruritus is associated with serum PBUTs in patients undergoing hemodialysis. Methods: We conducted a multicenter cross-sectional study in patients undergoing hemodialysis (n = 135). The severity of pruritus was assessed using the 5D-itch scale and medication use. Serum PBUTs, including indoxyl sulfate, p-cresyl sulfate, indole acetic acid, phenyl sulfate, and hippuric acid, were measured using mass spectrometry; the PBUT score was calculated from these toxins using principal component analysis. Univariate and multiple regression analyses were performed to examine independent predictors of pruritus. Results: Pruritus was reported by 62.2%, 21.5%, and 13.3%, 1.5% and 0.7% as 5 (not at all), 6-10, 11-15, 16-20, and 21-25 points, respectively. The PBUT score was higher in patients undergoing dialysis having pruritus than those without pruritus (0.201 [-0.021 to 0.424] vs -0.120 [-0.326 to 0.087]; P = 0.046). The PBUT score was shown to have an association with the presence of pruritus (coefficient 0.498[Formula: see text]0.225, odds ratio: 1.65 [1.06-2.56]; P = 0.027). Conclusion: Uremic pruritus was frequently found and associated with the PBUT score in patients undergoing hemodialysis. Further studies are required to clarify the impact of PBUTs on uremic pruritus and to explore therapeutic strategies in patients undergoing hemodialysis.

Association between dry eye and periodontal disease in community-dwelling Japanese adults: data from the Uonoma cohort study.

BACKGROUND: While research has explored the risk of periodontal disease in various eye conditions, the link between dry eye and periodontal disease remains underexplored, especially in Japanese adults. This study aims to investigate the association between dry eye and periodontal disease in community-dwelling Japanese adults. METHODS: This study is a subset of the Uonuma cohort study, which includes Japanese adults aged 40 years and older residing in the Uonuma area of Niigata Prefecture, Japan. Participants completed a self-administered, paper-based questionnaire. Statistical analyses, including the chi-square test, independent t test, ANOVA test, and logistic regressions, were employed to assess the association of periodontal disease with independent variables. RESULTS: Among 36,488 participants (average age 63.3 years, 47.4% men), 39.3% had a history of periodontal disease, and gender differences were statistically significant (p < 0.001). Significant associations were found between periodontal disease and dry eye diagnosis or symptoms. Univariable logistic regression revealed links between periodontal disease and age, gender, living status, alcohol consumption, remaining teeth, bite molar availability, and history of dry eye disease or symptoms. Multiple-adjusted regression found that doctor-diagnosed dry eye was associated with a higher likelihood of periodontal disease (odds ratio, 1.12; 95% confidence interval, 1.03-1.22). Participants who never experienced dryness or foreign body sensation had lower ORs of periodontal disease than those who always experienced such symptoms across all models. CONCLUSION: A significant correlation was found between dry eye and periodontal disease in Japanese adults. Regular check-ups, early detection, and effective management of both conditions are strongly recommended.

Fatal acute portal vein thrombosis associated with hepatic cysts in a patient with autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) often involves polycystic liver disease (PLD). In severe cases, PLD can develop various complications. However, fatal acute portal vein thrombosis (APVT) associated with PLD has not been reported. A 64-year-old male reported mild consciousness disorder. He had been under maintenance hemodialysis for end-stage renal disease due to ADPKD with PLD. Because of recurring hepatic cyst infections, he had sustained high levels of C-reactive protein. Regarding the mild consciousness disorder, a diagnosis of hepatic encephalopathy was made based on an elevation of serum ammonia without any other abnormal liver function tests. Several days after his admission, hepatobiliary enzymes elevated, and acute liver failure progressed. Enhanced abdominal computed tomography suggested the possibility of complete occlusion of the portal vein by a thrombus. Based on an absence of obvious portosystemic collaterals, a diagnosis of APVT was made. The patient died 19 days after admission. Patients with PLD with repeated cystic infections have been seen to develop liver failure, and APVT formation may be one cause of the rapid progression of fatal liver failure. In conclusion, this is the first paper to report on the involvement of APVT in patients with PLD.