Association between alcohol consumption and chronic kidney disease: a population-based survey.

BACKGROUND: Alcohol consumption is associated with both beneficial and harmful effects, and the role of alcohol consumption in chronic kidney disease (CKD) remains inconclusive. This study aimed to investigate the relationship between alcohol consumption and CKD or estimated glomerular filtration rate (eGFR). METHODS: This study enrolled adults from the second Taiwanese Survey on Prevalences of Hypertension, Hyperglycemia, and Hyperlipidemia, conducted in 2007. Participants were categorized into frequent drinkers, occasional drinkers, and nondrinkers. The amount of alcohol consumption was assessed by standard drinks per week. The primary outcome was the presence of CKD, and the secondary outcome was the eGFR. RESULTS: Among 3967 participants with a mean age of 47.9 years and a CKD prevalence of 11.7%, 13.8% were frequent drinkers, and 23.1% were occasional drinkers. The average amount of alcohol consumed was 3.3 drinks per week. Frequent drinkers (odds ratio [OR] 0.622, 95% confidence interval [CI] 0.443-0.874) and occasional drinkers (OR 0.597 95% CI 0.434-0.821) showed a lower prevalence of CKD than nondrinkers. Consumption of a larger number of standard drinks was associated with a lower prevalence of CKD (OR 0.872, 95% CI 0.781-0.975). Frequent drinkers and those who consumed a larger number of standard drinks per week showed higher eGFRs. CONCLUSION: Within the range of moderate alcohol intake, those who consumed more alcohol had a higher eGFR and reduced prevalence of CKD. The potentially harmful effects of heavy drinking should be taken into consideration, and alcohol intake should be limited to less than light to moderate levels.

Comparative efficacy of treatments for molluscum contagiosum: A systematic review and network meta-analysis.

BACKGROUND AND OBJECTIVES: Various interventions have been applied to treat molluscum contagiosum, but benefits and efficacy remain unclear. To assess the comparative efficacy and safety of interventions for molluscum contagiosum, a network meta-analysis was performed. PATIENTS AND METHODS: Embase, PubMed, and the Cochrane Library were searched for articles published between January 1, 1990, and November 31, 2020. Eligible studies were randomized clinical trials (RCTs) of interventions in immunocompetent children and adults with genital/non-genital molluscum contagiosum lesions. RESULTS: Twelve interventions from 25 RCTs including 2,123 participants were assessed. Compared with the placebo, ingenol mebutate had the most significant effect on complete clearance (odds ratio [OR] 117.42, 95% confidence interval [CI] 6.37-2164.88), followed by cryotherapy (OR 16.81, 95% CI 4.13-68.54), podophyllotoxin (OR 10.24, 95% CI 3.36-31.21), and potassium hydroxide (KOH) (OR 10.02, 95% CI 4.64-21.64). Data on adverse effects were too scarce for quantitative synthesis. CONCLUSIONS: Ingenol mebutate, cryotherapy, podophyllotoxin, and KOH were more effective than the other interventions in achieving complete clearance, but safety concerns regarding ingenol mebutate have recently been reported. Due to the possibility of spontaneous resolution, observation is also justified for asymptomatic infection. Factors including adverse effects, cost, patient preference, and medical accessibility should be considered.

Ultraviolet B phototherapy does not increase the risk of skin cancer among patients with atopic dermatitis: A population-based retrospective cohort study.

BACKGROUND: UV-B phototherapy is a common treatment modality for patients with atopic dermatitis (AD), but its long-term safety in terms of cutaneous carcinogenic risk has not been studied. OBJECTIVE: To investigate the risk of skin cancer among patients with AD receiving UV-B phototherapy. METHODS: We conducted a nationwide population-based cohort study from 2001 to 2018 to estimate the risk of UV-B phototherapy for skin cancer, nonmelanoma skin cancer, and cutaneous melanoma in patients with AD. RESULTS: Among 6205 patients with AD, the risks of skin cancer (adjusted hazard ratio [HR], 0.91; 95% CI, 0.35-2.35), nonmelanoma skin cancer (adjusted HR, 0.80; 95% CI, 0.29-2.26), and cutaneous melanoma (adjusted HR, 0.80; 95% CI, 0.08-7.64) did not increase among patients with AD treated with UV-B phototherapy, compared with those who did not receive UV-B phototherapy. Additionally, the number of UV-B phototherapy sessions was not associated with an increased risk of skin cancer (adjusted HR, 0.99; 95% CI, 0.96-1.02), nonmelanoma skin cancer (adjusted HR, 0.99; 95% CI, 0.96-1.03), or cutaneous melanoma (adjusted HR, 0.94; 95% CI, 0.77-1.15). LIMITATIONS: Retrospective study. CONCLUSION: Neither UV-B phototherapy nor the number of UV-B phototherapy sessions was associated with an increased risk of skin cancers among patients with AD.

Physician Compliance With a Computerized Clinical Decision Support System for Anemia Management of Patients With End-stage Kidney Disease on Hemodialysis: Retrospective Electronic Health Record Observational Study.

BACKGROUND: Previous studies on clinical decision support systems (CDSSs) for the management of renal anemia in patients with end-stage kidney disease undergoing hemodialysis have previously focused solely on the effects of the CDSS. However, the role of physician compliance in the efficacy of the CDSS remains ill-defined. OBJECTIVE: We aimed to investigate whether physician compliance was an intermediate variable between the CDSS and the management outcomes of renal anemia. METHODS: We extracted the electronic health records of patients with end-stage kidney disease on hemodialysis at the Far Eastern Memorial Hospital Hemodialysis Center (FEMHHC) from 2016 to 2020. FEMHHC implemented a rule-based CDSS for the management of renal anemia in 2019. We compared the clinical outcomes of renal anemia between the pre- and post-CDSS periods using random intercept models. Hemoglobin levels of 10 to 12 g/dL were defined as the on-target range. Physician compliance was defined as the concordance of adjustments of the erythropoietin-stimulating agent (ESA) between the CDSS recommendations and the actual physician prescriptions. RESULTS: We included 717 eligible patients on hemodialysis (mean age 62.9, SD 11.6 years; male n=430, 59.9%) with a total of 36,091 hemoglobin measurements (average hemoglobin and on-target rate were 11.1, SD 1.4, g/dL and 59.9%, respectively). The on-target rate decreased from 61.3% (pre-CDSS) to 56.2% (post-CDSS) owing to a high hemoglobin percentage of >12 g/dL (pre: 21.5%; post: 29%). The failure rate (hemoglobin <10 g/dL) decreased from 17.2% (pre-CDSS) to 14.8% (post-CDSS). The average weekly ESA use of 5848 (SD 4211) units per week did not differ between phases. The overall concordance between CDSS recommendations and physician prescriptions was 62.3%. The CDSS concordance increased from 56.2% to 78.6%. In the adjusted random intercept model, the post-CDSS phase showed increased hemoglobin by 0.17 (95% CI 0.14-0.21) g/dL, weekly ESA by 264 (95% CI 158-371) units per week, and 3.4-fold (95% CI 3.1-3.6) increased concordance rate. However, the on-target rate (29%; odds ratio 0.71, 95% CI 0.66-0.75) and failure rate (16%; odds ratio 0.84, 95% CI 0.76-0.92) were reduced. After additional adjustments for concordance in the full models, increased hemoglobin and decreased on-target rate tended toward attenuation (from 0.17 to 0.13 g/dL and 0.71 to 0.73 g/dL, respectively). Increased ESA and decreased failure rate were completely mediated by physician compliance (from 264 to 50 units and 0.84 to 0.97, respectively). CONCLUSIONS: Our results confirmed that physician compliance was a complete intermediate factor accounting for the efficacy of the CDSS. The CDSS reduced failure rates of anemia management through physician compliance. Our study highlights the importance of optimizing physician compliance in the design and implementation of CDSSs to improve patient outcomes.

Short-Term Effects of a Therapeutic Diet on Biochemical Parameters in Hemodialysis Patients: A Randomized Crossover Trial.

OBJECTIVE: Although unhealthy diets exacerbate nutritional and metabolic derangements in patients with end-stage kidney disease (ESKD), how therapeutic diets that possess a variety of different dietary strategies acutely modify diverse biochemical parameters related to cardiovascular disease remains underexplored. METHODS: Thirty-three adults with end-stage kidney disease undergoing thrice-weekly hemodialysis participated in a randomized crossover trial comparing a therapeutic diet with their usual diets for 7 days, separated by a 4-week washout period. The therapeutic diet was characterized by adequate calorie and protein amounts, natural food ingredients with a low phosphorus-to-protein ratio, higher portions of plant-based food, and high fiber content. The primary outcome measure was the mean difference in the change-from-baseline intact fibroblast growth factor 23 (FGF23) level between the 2 diets. The other outcomes of interest included changes in mineral parameters, uremic toxins, and high-sensitivity C-reactive protein (hs-CRP) levels. RESULTS: Compared with the usual diet, the therapeutic diet lowered intact FGF23 levels (P = .001), decreased serum phosphate levels (P < .001), reduced intact parathyroid hormone (PTH) levels (P = .003), lowered C-terminal FGF23 levels (P = .03), increased serum calcium levels (P = .01), and tended to lower total indoxyl sulfate levels (P = .07) but had no significant effect on hs-CRP levels. Among these changes, reduction in serum phosphate level achieved in 2 days, modifications of intact PTH and calcium levels in 5 days, and reductions in intact and C-terminal FGF23 levels in 7 days of therapeutic diet intervention. CONCLUSION: Within the 1-week intervention period, the dialysis-specific therapeutic diet rapidly reversed mineral abnormalities and tended to decrease total indoxyl sulfate levels in patients undergoing hemodialysis but had no effect on inflammation. Future studies to assess the long-term effects of such therapeutic diets are recommended.

Extremely Low Dose of Erythropoiesis-Stimulating Agent May Be Associated with Increased Mortality in Hemodialysis Patients.

INTRODUCTION: Although high-dose erythropoiesis-stimulating agent (ESA) has been shown to increase mortality risk and adverse cardiovascular events in hemodialysis patients, the safety of extremely low-dose ESA is unclear. METHODS: We retrospectively analyzed the association between ESA dose and mortality in the monthly dosing range of 0-43,000 U of equivalent epoetin alfa in 304 Taiwan hemodialysis patients by using Cox proportional hazard model and cubic spline model. RESULTS: Compared with mean monthly ESA dose of 15,000-25,000 U (mean ± standard deviation 20,609 ± 2,662 U), monthly ESA dose of less than 15,000 U (mean ± standard deviation 7,413 ± 4,510 U) is associated with increased mortality. Monthly ESA dose of 25,001-43,000 U (mean ± standard deviation 31,160 ± 4,304 U) is not associated with higher mortality risk than monthly ESA dose of 15,000-25,000 U. The results were consistent in Cox proportional hazard models and cubic spline models. Subgroup analyses showed no significant heterogeneities among prespecified subgroups. CONCLUSIONS: Extremely low dose of ESA in hemodialysis patients may be associated with increased mortality risk. Future studies are warranted to prove this association.

Adverse events following the first, second and third doses of a COVID-19 vaccine in hemodialysis patients.

BACKGROUND: This study aimed to identify adverse events following the first three doses of COVID-19 vaccines in hemodialysis (HD) patients. Risk factors associated with postvaccination adverse events were explored. METHODS: Postvaccination adverse events in 438 HD patients who received 3 doses of COVID-19 vaccines were prospectively assessed. The adverse events among three doses were compared using generalized linear mixed models. Factors associated with adverse events were assessed with multivariate analyses. RESULTS: The vast majority of participants received Oxford/AstraZeneca ChAdOx1 as their first two doses and Moderna mRNA-1273 as their third dose. Overall, 79%, 50% and 84% of the participants experienced at least one adverse event after their first, second, and third doses, respectively. These adverse events were mostly minor, short-lived and less than 5% reported daily activities being affected. Compared with the first dose, the second dose caused a lower rate of adverse events. Compared with the first dose, the third dose elicited a higher rate of injection site reactions and a lower rate of systemic reactions. Multivariate analyses showed that every 10-year increase of age (odds ratio 0.67, 95% confidence intervals 0.57-0.79) was associated with decreased risk of adverse events, while female sex (2.82, 1.90-4.18) and arteriovenous fistula (1.73, 1.05-2.84) were associated with increased risk of adverse events. Compared with Oxford/AstraZeneca ChAdOx1, Moderna mRNA-1273 was associated with an increased risk of injection site reactions. CONCLUSIONS: COVID-19 vaccination was well tolerated in HD patients. Age, sex, dialysis vascular access and vaccine types were associated with postvaccination adverse events.

Microbiota analysis in the hemodialysis population - Focusing on Enterobacteriaceae.

BACKGROUND: Infection is a recognized risk factor for mortality among hemodialysis (HD) population, including infection caused by Enterobacteriaceae. We aimed to investigate Enterobacteriaceae in gut microbiota among HD patients and to analyze associations between microbiota and clinical parameters. METHODS: This prospective study of microbiota analysis in HD patients was conducted in April-May 2019. A control group without recent antibiotic use or hospitalization was used for comparison. Stool samples underwent 16S rRNA sequencing, using Greengenes 16S rRNA database for microbiota analysis. RESULTS: Among 96 hemodialysis (HD) patients, mean age was 61.9 ± 0.8 years and mean duration of HD was 6.5 ± 0.7 years. No significant differences were found in alpha diversity between HD and control groups (HD group 949.5, controls 898; p = 0.16) although significant between-group differences were found in beta diversity (p < 0.001). At phylum level, HD group had a higher abundance of Firmicutes and Proteobacteria, but lower abundance of Bacteriodetes. At genus level, Escherichia-Shigella complex increased among HD patients who had hospitalization with 1 year (median 0.024 vs 0.004, p = 0.054) and Klebsiella was associated with emergency room visit within 1 year among HD patients (p = 0.002). CONCLUSIONS: Alpha diversity in HD patients is not lower than that in healthy controls but significant between-group differences are found in microbiota composition according to beta diversity, due to decreased Bacteriodetes and increased Firmicutes and Proteobacteria. Deeper microbiota analyses for Enterobacteriaceae are necessary. Whether change in dietary components can help to decrease mortality among dialysis population warrants further research.

Cardiovascular and renal efficacy and safety of sodium-glucose cotransporter-2 inhibitors in patients without diabetes: a systematic review and meta-analysis of randomised placebo-controlled trials.

OBJECTIVES: To assess the cardiovascular and renal efficacy and safety of sodium-glucose cotransporter-2 (SGLT2) inhibitors in patients without diabetes. METHODS: We searched PubMed, MEDLINE, Embase and Cochrane Library for publications up to 17 August 2022. Certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation approach. Random-effects meta-analyses were performed to pool effect measures across studies. Risk ratios (RRs) with 95% CIs are expressed for composite cardiovascular outcome of cardiovascular death or hospitalisation for heart failure, cardiovascular death, hospitalisation for heart failure, all-cause mortality and composite renal outcome of ≥50% reduction in estimated glomerular filtration rate (eGFR), end-stage kidney disease or renal death. Annual rate of change in eGFR is expressed as the mean difference with 95% CI. RESULTS: We identified four trials with 8927 patients with heart failure or chronic kidney disease (CKD). Compared with placebo, SGLT2 inhibitors showed favourable effects on the composite cardiovascular outcome (RR: 0.79, 95% CI: 0.71 to 0.87; moderate certainty), cardiovascular death (0.85, 0.74 to 0.99; moderate certainty), hospitalisation for heart failure (0.72, 0.62 to 0.82; moderate certainty), the composite renal outcome (0.64, 0.48 to 0.85; low certainty) and the annual rate of change in eGFR (mean difference: 0.99, 0.59 to 1.39 mL/min/1.73 m2/year; moderate certainty), while there was no significant difference in all-cause mortality (0.88, 0.77 to 1.01; very low certainty). Moderate certainty evidence indicated that SGLT2 inhibitors reduced the risk of serious adverse events and acute renal failure. Low certainty evidence suggested that SGLT2 inhibitors increased the risk of urinary tract infection and genital infection, while there were no differences in discontinuation due to adverse events, amputation, fracture, hypoglycaemia, ketoacidosis or volume depletion. CONCLUSIONS: Evidence of low to moderate certainty suggests that SGLT2 inhibitors provide cardiorenal benefits but have increased risk for urinary tract infection and genital infection in patients without diabetes and with heart failure or CKD. PROSPERO REGISTRATION NUMBER: CRD42021239807.

Humoral antibody response to the first dose of the ChAdOx1 nCoV-19 vaccine in Asian patients undergoing hemodialysis.

BACKGROUND AND OBJECTIVES: The immunogenicity of vaccines is known to be attenuated in patients with end-stage kidney disease due to uremia. Patients on dialysis were excluded from coronavirus disease 2019 (COVID-19) vaccine trials; thus, the effectiveness of vaccines for this population is unclear. The aim of this study was to explore whether Asian dialysis patients can effectively produce an immune response after being vaccinated with the first dose of the ChAdOx1 nCoV-19 vaccine. DESIGN SETTING, PARTICIPANTS, AND MEASUREMENTS: In this prospective cohort study, we included Asian hemodialysis patients who received the ChAdOx1 nCoV-19 vaccine. At 3 weeks after the first dose of vaccination, we assessed the humoral immune response by measuring anti-SARS-CoV-2 S antibody titers. The primary outcome was the seropositive rate following vaccination, defined as an antibody titer greater than or equal to 0.8 U/ml. Factors associated with seropositivity were explored in multivariate logistic regression analyses. RESULTS: In total, 434 participants were included. The mean age was 64 years, the mean dialysis vintage was 6 years, and 61% of the participants were men. At a mean time of 22 days from vaccination, 56% of the participants were seropositive. The vast majority (88%) had low antibody titers (< 15 U/ml). The multivariate logistic regression analyses showed that older age (every increase of 10 years, odds ratio [OR] 0.80, 95% CI 0.65-0.98, p = 0.03) was negatively associated with seropositivity and that higher Kt/V (every increase of 0.1, OR 1.14, 95% CI 1.01-1.28, p = 0.03) and higher serum albumin level (every increase of 0.1 g/dl, OR 1.09, 95% CI 1.02-1.18, p = 0.02) were positively associated with seropositivity. CONCLUSIONS: In Asian hemodialysis patients, the seropositive rate was low, and most had low antibody titers after the first dose of the ChAdOx1 nCoV-19 vaccine. Younger age, better dialysis adequacy, and higher albumin levels were associated with seropositivity.

Boiling for 15 minutes improves nutrient profiles in fishes included in the diets of dialysis patients.

INTRODUCTION: Little is known about the effects of boiling on nutrient levels in fishes that have a relatively high phosphorus-to-protein ratio (PPR), which are important sources of omega-3 polyunsaturated fatty acids. We hypothesized that the beneficial effects of boiling for a shorter duration (15 min) on nutrient contents in fishes were similar to those of boiling for a longer duration (30 min), which has been shown to decrease the PPR in meat. METHODS: The protein, fat, and phosphorus contents and the PPR of three cooked fish species and their corresponding fish broths were chemically analyzed. The effects of boiling on changes in protein, fat, phosphorus, and the PPR was examined by comparing fish that were prepared with usual cooking methods (no boiling), boiled for 15 min, and boiled for 30 min. The nutrients in fish broths that were boiled for 15 min were also compared with those boiled for 30 min. FINDINGS: There were no significant differences in the changes in phosphorus, PPR, protein, and fat content in fish and fish broths prepared with the two boiling methods. In the fish boiled for 15 min, the phosphorus content was 24% lower (p = 0.001), and the PPR was 20% lower (p = 0.04) than those in nonboiled fish. Additionally, boiling for 30 min reduced the phosphorus content by 31% (p = 0.001), and the PPR by 27% (p = 0.04) compared to nonboiled fish, but the protein and fat contents were unchanged after both 15 and 30 min of boiling. DISCUSSION: The 15- and 30-min boiling methods resulted in a similar reduction in phosphorus and the PPR in fish, with minimal effects on protein and fat. A shorter duration of boiling is recommended to achieve better nutrient profiles in fishes consumed by dialysis patients.

Altered Monocytic Phenotypes are Associated with Uraemic Pruritus in Patients Receiving Haemodialysis.

Uraemic pruritus is one of the most bothersome symptoms in patients receiving haemodialysis. A total of 175 patients receiving maintenance haemodialysis, with 74 patients experiencing uraemic pruritus, were prospectively recruited to assess the influence of the phenotype of blood monocytes and various cytokines on uraemic pruritus. The phenotype of blood monocytes was determined by flow cytometry as classical (CD14++CD16-) monocytes, non-classical (CD14+CD16++) monocytes, and intermediate (CD14++CD16+) monocytes. Eight cyto-kines, including interleukin (IL)-2, interferon-γ, IL-12p70, IL-4, IL-5, IL-6, tumour necrosis factor-α, and IL-10, were simultaneously detected with a multi-plex bead-based immunoassay. Multivariate linear regression analysis showed that a higher percentage of intermediate monocytes (effect estimate 0.08; 95% confidence interval 0.01-0.16) were independent predictors of a higher visual analogue scale score for pruritus intensity. No differences were noted for all 8 cytokines between patients with and without uraemic pruritus. The results of this study indicate that altered monocytic phenotypes could play a role in uraemic pruritus.

Risk of Skin Cancer among Patients with Chronic Kidney Disease Treated with Ultraviolet B Phototherapy for Uraemic Pruritus: A Nationwide Cohort Study.

The safety of ultraviolet B (UVB) phototherapy with respect to cutaneous carcinogenesis has not been established for patients with chronic kidney disease. To investigate this issue, a nationwide cohort study of 10,805 patients with advanced chronic kidney disease was conducted using data from the National Health Insurance of Taiwan, the Taiwan Cancer Registry, and the national death registry. After a median follow-up of 75 months, 16 of 2,161 patients in the UVB group and 63 of 8,644 patients in the non-UVB group developed skin cancers. Compared with the non-UVB group, patients in the UVB group did not show an increased risk of skin cancer (hazard ratio 1.066; 95% confidence interval 0.584-1.944), non-melanoma skin cancer (hazard ratio 1.067; 95% confidence interval 0.571-1.996), or cutaneous melanoma (hazard ratio 1.009; 95% confidence interval 0.115-8.879). In addition, patients who received more UVB phototherapy did not show an increased risk of skin cancer. UVB phototherapy appears to be a safe treatment for uraemic pruritus in patients with chronic kidney disease.

Acute effects of dietary phosphorus intake on markers of mineral metabolism in hemodialysis patients: post hoc analysis of a randomized crossover trial.

BACKGROUND: Long-term dietary phosphorus excess influences disturbances in mineral metabolism, but it is unclear how rapidly the mineral metabolism responds to short-term dietary change in dialysis populations. METHODS: This was a post hoc analysis of a randomized crossover trial that evaluated the short-term effects of low-phosphorus diets on mineral parameters in hemodialysis patients. Within a 9-day period, we obtained a total of 4 repeated measurements for each participant regarding dietary intake parameters, including calorie, phosphorus, and calcium intake, and markers of mineral metabolism, including phosphate, calcium, intact parathyroid hormone (iPTH), intact fibroblast growth factor 23 (iFGF23), and C-terminal fibroblast growth factor 23 (cFGF23). The correlations between dietary phosphorus intake and serum mineral parameters were assessed by using mixed-effects models. RESULTS: Thirty-four patients were analyzed. In the fully adjusted model, we found that an increase in dietary phosphorus intake of 100 mg was associated with an increase in serum phosphate of 0.3 mg/dL (95% confidence intervals [CI], 0.2-0.4, p < .001), a decrease in serum calcium of 0.06 mg/dL (95% CI, -0.11 to -0.01, p = .01), an increase in iPTH of 5.4% (95% CI, 1.4-9.3, p = .01), and an increase in iFGF23 of 5.0% (95% CI, 2.0-8.0, p = .001). Dietary phosphorus intake was not related to cFGF23. CONCLUSIONS: Increased dietary phosphorus intake acutely increases serum phosphate, iPTH, and iFGF23 levels and decreases serum calcium levels, highlighting the important role of daily fluctuations of dietary habits in disturbed mineral homeostasis in hemodialysis patients.

Emergence of T cell immunosenescence in diabetic chronic kidney disease.

BACKGROUND: Type 2 diabetes is an important challenge given the worldwide epidemic and is the most important cause of end-stage renal disease (ESRD) in developed countries. It is known that patients with ESRD and advanced renal failure suffer from immunosenescence and premature T cell aging, but whether such changes develop in patients with less severe chronic kidney disease (CKD) is unclear. METHOD: 523 adult patients with type 2 diabetes were recruited for this study. Demographic data and clinical information were obtained from medical chart review. Immunosenescence, or aging of the immune system was assessed by staining freshly-obtained peripheral blood with immunophenotyping panels and analyzing cells using multicolor flow cytometry. RESULT: Consistent with previously observed in the general population, both T and monocyte immunosenescence in diabetic patients positively correlate with age. When compared to diabetic patients with preserved renal function (estimated glomerular filtration rate > 60 ml/min), patients with impaired renal function exhibit a significant decrease of total CD3+ and CD4+ T cells, but not CD8+ T cell and monocyte numbers. Immunosenescence was observed in patients with CKD stage 3 and in patients with more severe renal failure, especially of CD8+ T cells. However, immunosenescence was not associated with level of proteinuria level or glucose control. In age, sex and glucose level-adjusted regression models, stage 3 CKD patients exhibited significantly elevated percentages of CD28-, CD127-, and CD57+ cells among CD8+ T cells when compared to patients with preserved renal function. In contrast, no change was detected in monocyte subpopulations as renal function declined. In addition, higher body mass index (BMI) is associated with enhanced immunosenescence irrespective of CKD status. CONCLUSION: The extent of immunosenescence is not significantly associated with proteinuria or glucose control in type 2 diabetic patients. T cells, especially the CD8+ subsets, exhibit aggravated characteristics of immunosenescence during renal function decline as early as stage 3 CKD. In addition, inflammation increases since stage 3 CKD and higher BMI drives the accumulation of CD8+CD57+ T cells. Our study indicates that therapeutic approaches such as weight loss may be used to prevent the emergence of immunosenescence in diabetes before stage 3 CKD.

Short-Term Effects of Very-Low-Phosphate and Low-Phosphate Diets on Fibroblast Growth Factor 23 in Hemodialysis Patients: A Randomized Crossover Trial.

BACKGROUND AND OBJECTIVES: The short-term effects of low-phosphate diets on fibroblast growth factor 23 (FGF23) level and the optimal amount of dietary phosphate restriction in patients undergoing hemodialysis remain unknown. DESIGN SETTING, PARTICIPANTS, & MEASUREMENTS: This was a randomized, active-controlled trial with a crossover design that included 35 adults with ESKD undergoing thrice-weekly hemodialysis and with a serum phosphate level >5.5 mg/dl or between 3.5 and 5.5 mg/dl with regular phosphate binder use at a hemodialysis unit of tertiary teaching hospital in Taiwan. Subjects were randomized 1:1 to receive a very-low-phosphate diet, with a phosphate-to-protein ratio of 8 mg/g, or a low-phosphate diet, with a phosphate-to-protein ratio of 10 mg/g for 2 days, each with a 5-day washout during which subjects adhered to their usual diet. The primary outcome measure was mean difference in change-from-baseline intact FGF23 level between intervention groups. Secondary outcomes included difference in change-from-baseline serum phosphate, intact parathyroid hormone (PTH), and C-terminal FGF23 level between intervention groups. RESULTS: There was no significant difference in the mean change-from-baseline in intact FGF23 levels between the two study diets. The very-low-phosphate diet significantly lowered serum phosphate (mean difference, 0.6 mg/dl; 95% confidence interval [95% CI], 0.2 to 1.0; P=0.002). There were no significant differences in change-from-baseline intact PTH and C-terminal FGF23 levels between the two study diets. CONCLUSIONS: Over the 2-day period, the FGF23-lowering effect of the very-low-phosphate diet is similar to that of the low-phosphate diet. The very-low-phosphate diet has an additional phosphate-lowering effect compared with the low-phosphate diet.

Accuracy of a Nutrient Database in Estimating the Dietary Phosphorus-to-Protein Ratio and Using a Boiling Method in Low-Phosphate Hospital Diets.

The use of the dietary phosphorus-to-protein ratio (PPR) to reduce dietary phosphorus while maintaining protein intake is valuable for nutritional management in the dialysis population, but the actual PPR values in hospital meals have not been determined. We aimed to determine the accuracy of a nutrient database for estimating the PPR in low-phosphate hospital diets compared with the accuracy of chemical analysis and produce hospital diets with low-phosphate content by boiling meat for 30 minutes before cooking. The phosphorus and protein content of 26 cooked dishes selected from the hospital menu was estimated using a food composition table (FCT) and sent for chemical analysis. Comparisons of FCT-based estimated values with measured values for every 100 g of tested foods revealed an overestimation for the PPR both in plant-based dishes (mean difference ± SD, 4.1 ± 14.6 mg/g, P = 0.06), and in meats (2.1 ± 2.3 mg/g, P = 0.06). By boiling meats, we crafted diets with PPR as low as 8 mg/g. Caution should be exercised in estimating the PPR using a FCT in hospital diets and boiling should be used to prepare hospital meals. Such diets will be promoted for dialysis patients in both inpatient and outpatient settings.

Prognostic importance and determinants of uremic pruritus in patients receiving peritoneal dialysis: A prospective cohort study.

BACKGROUND: Uremic pruritus is a common and frustrating symptom among patients receiving peritoneal dialysis (PD). This study aimed to examine the prognostic importance of uremic pruritus and to identify the determinants for higher pruritus intensity in PD patients. METHODS: We conducted a prospective cohort study of patients receiving maintenance PD. A visual analogue scale (VAS) score was used to measure the intensity of uremic pruritus. The composite endpoint of PD technique failure or all-cause death was assessed using a multivariable Cox proportional hazards model. The determinants for the VAS score of uremic pruritus was assessed using a multivariable linear regression model. RESULTS: Among the 85 PD patients, 24 (28%) had uremic pruritus. During a median follow-up of 28.0 months, 12 patients experienced technique failure, and 7 died. We found that a higher VAS score of pruritus intensity was an independent risk factor for technique failure or death (hazard ratio, 1.64; 95% confidence interval, 1.18 to 2.28; P = 0.003) after adjusting for a variety of confounding factors. We also found that a weekly total Kt/V of less than 1.88, a longer duration of dialysis, a higher dietary protein intake, and higher blood levels of intact parathyroid hormone and high-sensitivity C-reactive protein were independent determinants of higher VAS scores of pruritus intensity. CONCLUSIONS: Our results show that uremic pruritus is an independent risk factor of technique failure and death in patients receiving PD. We also found that a weekly total Kt/V < 1.88 is associated with higher intensity of uremic pruritus in PD patients.

Anti-cytomegalovirus IgG antibody titer is positively associated with advanced T cell differentiation and coronary artery disease in end-stage renal disease.

BACKGROUND: Accumulating evidence indicates that persistent human cytomegalovirus (HCMV) infection is associated with several health-related adverse outcomes including atherosclerosis and premature mortality in individuals with normal renal function. Patients with end-stage renal disease (ESRD) exhibit impaired immune function and thus may face higher risk of HCMV-related adverse outcomes. Whether the level of anti-HCMV immune response may be associated with the prognosis of hemodialysis patients is unknown. RESULTS: Among 412 of the immunity in ESRD study (iESRD study) participants, 408 were HCMV seropositive and were analyzed. Compared to 57 healthy individuals, ESRD patients had higher levels of anti-HCMV IgG. In a multivariate-adjusted logistic regression model, the log level of anti-HCMV IgG was independently associated with prevalent coronary artery disease (OR = 1.93, 95% CI = 1.2~ 3.2, p = 0.01) after adjusting for age, sex, hemoglobin, diabetes, calcium phosphate product and high sensitivity C-reactive protein. Levels of anti-HCMV IgG also positively correlated with both the percentage and absolute number of terminally differentiated CD8+ and CD4+ CD45RA+ CCR7- TEMRA cells, indicating that immunosenescence may participate in the development of coronary artery disease. CONCLUSION: This is the first study showing that the magnitude of anti-HCMV humoral immune response positively correlates with T cell immunosenescence and coronary artery disease in ESRD patients. The impact of persistent HCMV infection should be further investigated in this special patient population.