Urinary (U)-complement components have been detected in patients with proteinuric renal diseases, and complement activation via the alternative pathway (AP) is believed to play a role in renal tubular damage. The present study aimed to examine the regulation of complement AP activation in patients with renal tubular damage by focusing on the balance between properdin (P) and factor H (fH). In the in vivo studies, U concentrations of P, fH and membrane attack complex (MAC) were measured in patients with renal diseases using an enzyme-linked immunosorbent assay (ELISA), and their relationships with the clinical data were evaluated. In the in vitro studies, human proximal tubular epithelial cells (PTECs) were incubated with normal human serum (NHS), P-depleted serum (PDS), purified P and/or fH. Changes in cell morphology and phenotype were assessed by microscopy, real-time polymerase chain reaction (PCR), immunostaining and a cell viability assay. The U-P, fH and MAC concentrations were significantly higher in patients with renal disease than in normal controls and correlated with the U-protein and tubular damage markers. Furthermore, multivariate analysis revealed a relationship between P levels and tubular damage markers. There were no significant changes in morphology and mRNA expression in the AP components (P, fH, fB, C3, C5 and C9) after the addition of up to 25% NHS. Dose-dependent depositions of P or fH were observed after the addition of P or fH on PTECs. Depositions of P were not inhibited by fH in a mixture of a fixed concentration of P and a variable concentration of fH, and vice versa. Preincubation with the fixed concentration of P before the addition of NHS or PDS increased the depositions of P, C3 and MAC compared with incubation with intact NHS or intact PDS only; the depositions of C3 and MAC showed a serum-dependent trend. Preincubation with P before NHS addition significantly suppressed cell viability without causing morphological changes. In the pathogenesis of renal tubular damage, P can directly bind to PTECs and may accelerate AP activation by surpassing fH regulation.

Background: The complement system is vital for innate immunity and is implicated in the pathogenesis of inflammatory diseases and the mechanism of host defense. Complement deficiencies occasionally cause life-threatening diseases. In hemodialysis (HD) patients, profiles on complement functional activity and deficiency are still obscure. The objectives of the present study were to measure the functional complement activities of the classical pathway (CP), lectin pathway (LP) and alternative pathway (AP) using a novel method and consequently to elucidate the rates of deficiencies among HD patients. Methods: In the present study, 244 HD patients at one dialysis center and 204 healthy controls were enrolled. Functional complement activities were measured simultaneously using the Wielisa^®-kit. The combination of the results of these three pathway activities allows us to speculate which candidate complement is deficient; subsequently, the deficient complement was determined. Results: All three functional complement activities were significantly higher in the HD patients than in the control group (P < 0.01 for all cases). After identifying candidates in both groups with complement deficiencies using the Wielisa^®-kit, 16 sera (8.8%) with mannose-binding lectin (MBL) deficiency, 1 serum (0.4%) with C4 deficiency, 1 serum (0.4%) with C9 deficiency, and 1 serum (0.4%) with B deficiency were observed in the HD group, and 18 sera (8.8%) with MBL deficiency and 1 serum (0.5%) with B deficiency were observed in the control group. There were no significant differences in the 5-year mortality rate between each complement-deficient group and the complement-sufficient group among the HD patients. Conclusion: This is the first report that profiles complement deficiencies by simultaneous measurement of functional activities of the three complement pathways in HD patients. Hemodialysis patients frequently suffer from infections or malignancies, but functional complement deficiencies do not confer additional risk of mortality.

This study aimed to identify the ideal timing and setting for measuring blood pressure (BP) and determine whether the left ventricular mass index (LVMI) is an independent risk factor associated with increased cardiovascular events in hemodialysis (HD) patients. BP and LVMI were measured at baseline and at 6 and 12 months after HD initiation. BP was monitored and recorded at nine different time points, including before and after HD over a one-week period (HDBP). The mean BP measurement was calculated as the weekly averaged BP (WABP). LVMI was significantly correlated with home BP, in-office BP, HDBP, and WABP. Receiver operating characteristic analysis indicated that the cutoff LVMI value for cardiovascular events was 156 g/m². LVMI and diabetes mellitus were significant influencing factors for cardiovascular events (hazards ratio (95% confidence interval): diabetes mellitus, 2.84 (1.17,7.45); LVMI > 156 g/m², 2.86 (1.22,6.99)). Pre-HDBP, post-HDBP, and WABP were independently associated with higher LVMI in the follow-up periods. Hemoglobin and human atrial natriuretic peptide (hANP) levels were associated with LVMI beyond 12 months after HD initiation. Treatment of hypertension, overhydration based on hANP, and anemia may reduce the progression of LVMI and help identify HD patients at high risk for cardiovascular events.

Sarcopenia is a poor prognostic factor in patients with chronic kidney disease (CKD). Adequate dietary patterns are important for preventing sarcopenia; however, evidence regarding the underlying association between sarcopenia and diet is insufficient. Therefore, in this study, we aimed to investigate the association between sarcopenia and dietary patterns in CKD patients receiving conservative treatment. In this cross-sectional study, 441 patients with conservative CKD were examined using the Asian Working Group for Sarcopenia diagnostic criteria. CKD was defined as an eGFR of 3 months. The participants were divided into sarcopenia and non-sarcopenia groups, and dietary patterns were compared between the two groups using the dietary variety score, a simple dietary survey method that investigates the weekly frequency of consumption of 10 food groups. Logistic regression analysis for CKD G3 showed that female sex (odds ratio (OR): 0.166, 95% confidence interval (CI): 0.086–0.320), increased body mass index (OR: 0.663, 95% CI: 0.590–0.745), and almost daily consumption of green/yellow vegetables (OR: 0.350, 95% CI: 0.176–0.695) were positively associated with non-sarcopenia. Although further prospective studies are required, the results suggest that low frequent consumption of vegetables is associated with sarcopenia in patients with CKD.

Background/Objectives: Reports on oral frailty as a risk factor for chronic constipation are scarce. In this study, we examined the relationship between Oral Frailty Index-8 (OFI-8) and constipation severity. Methods: This cross-sectional analysis involved patients aged ≥65 years (outpatients between November 2020 and November 2021). Patient background (age, sex, body mass index, medical history, lifestyle history, and oral medications), a constipation severity questionnaire (Constipation Scoring System [CSS]), grip strength, walking speed, skeletal muscle mass index (dual-energy X-ray absorptiometry), a frailty questionnaire, an oral frailty questionnaire (OFI-8), an abdominal symptoms quality of life (QOL) questionnaire (Izumo scale), a swallowing evaluation questionnaire (10-item Eating Assessment Tool [EAT-10]), a chronic obstructive pulmonary disease (COPD) evaluation questionnaire (COPD assessment test [CAT]), a simplified QOL evaluation (EuroQol-five dimensions [EQ-5D]), the Dietary Variety Score, a nutritional evaluation (CONtrolling NUTritional Status [CONUT] score), and the 15-item Geriatric Depression Scale (GDS-15) were analyzed. Risk factors for constipation severity (CSS) were examined using multivariate analysis. Patients with advanced gastrointestinal cancer, inflammatory bowel disease, and active gastroduodenal ulcer were excluded. Results: In total, 1029 patients (male/female: 450/579; mean age: 78.3 ± 6.1 years; mean body mass index: 22.9 ± 3) were included. Multivariate analysis demonstrated a significant association between CSS and OFI-8 (β = 0.065), EAT-10 (β = 0.061), sarcopenia (β = 0.050), laxative (β = 0.126), constipation-related QOL score (β = 0.625), diarrhea-related QOL score (β = −0.064), and CAT (β = 0.061). Conclusions: Comprehensive risk factors associated with CSS included a high oral frailty score, impaired swallowing (EAT-10), sarcopenia, laxative use, a high constipation QOL score, a low diarrhea QOL score, and COPD assessment through CAT.

Objective: To determine the prevalence of frailty and examine its association with gastrointestinal-related quality of life (QOL) among older outpatients in a geriatric hospital. Methods: This cross-sectional study involved 1042 outpatients (age: ≥65 years) diagnosed using the revised Japanese version of the cardiovascular health study criteria. Data collection was performed by a multidisciplinary team. Results: Of the 1039 eligible subjects (male: n = 460 [44.3%]; mean age: 78.2 ± 6.1 years), 172 (16.6%) had frailty (male: n = 77 [44.8%]; mean age: 80.9 ± 6.2 years). The multivariate analysis revealed that age (odds ratio [OR]: 1.070, p < 0.001), QOL (OR: 0.982, p = 0.009), a history of falls (OR: 1.702, p = 0.029), sarcopenia (OR: 4.708, p < 0.001), steroid use (OR: 3.741, p = 0.001), analgesic drug use (OR: 2.056, p = 0.014), Mini Mental State Examination (OR: 0.915, p = 0.011), Geriatric Depression Scale 15 (OR: 1.101, p = 0.008), fullness-related QOL score (OR: 1.119, p = 0.010), chronic obstructive pulmonary disease assessment test (OR: 1.048, p = 0.007), and 10-item Eating Assessment Tool (OR: 1.071, p = 0.009) were related to frailty. Conclusions: The prevalence rate of frailty in older outpatients at a university hospital specializing in geriatric medicine was higher than that previously reported in community-dwelling individuals. Our study clarified that the fullness-related QOL score was related to frailty.