Humeral and cellular immune responses to SARS-CoV-2 vaccination in patients on peritoneal dialysis.

BACKGROUND: Patients with chronic kidney disease are at high risk for coronavirus disease 2019. Little is known about immune response to severe acute respiratory syndrome coronavirus 2 vaccination in patients on peritoneal dialysis (PD). METHOD: We prospectively enrolled 306 PD patients receiving two doses of vaccines (ChAdOx1-S: 283, mRNA-1273: 23) from July 2021 at a medical center. Humeral and cellular immune responses were assessed by anti-spike IgG concentration and blood T cell interferon-γ production 30 days after vaccination. Antibody ≥0.8 U/mL and interferon-γ ≥ 100 mIU/mL were defined as positive. Antibody was also measured in 604 non-dialysis volunteers (ChAdOx1-S: 244, mRNA-1273: 360) for comparison. RESULT: PD patients had less adverse events after vaccinations than volunteers. After the first dose of vaccine, the median antibody concentrations were 8.5 U/mL and 50.4 U/mL in ChAdOx1-S group and mRNA-1273 group of PD patients, and 66.6 U/mL and 195.3 U/mL in ChAdOx1-S group and mRNA-1273 group of volunteers, respectively. And after the second dose of vaccine, the median antibody concentrations were 344.8 U/mL and 9941.0 U/mL in ChAdOx1-S group and mRNA-1273 group of PD patients, and 620.3 U/mL and 3845.0 U/mL in ChAdOx1-S group and mRNA-1273 group of volunteers, respectively. The median IFN-γ concentration was 182.8 mIU/mL in ChAdOx1-S group, which was substantially lower than the median concentration 476.8 mIU/mL in mRNA-1273 group of PD patients. CONCLUSION: Both vaccines were safe and resulted in comparable antibody seroconversion in PD patients when compared with volunteers. However, mRNA-1273 vaccine induced significantly higher antibody and T cell response than ChAdOx1-S in PD patients. Booster doses are recommended for PD patients after two doses of ChAdOx1-S vaccination.

Gustatory Dysfunction Is Closely Associated With Frailty in Patients With Chronic Kidney Disease.

OBJECTIVE: Gustatory function is frequently impaired in patients with chronic kidney disease (CKD), and the associated taste dysfunction contributes to compromised nutrition. Whether gustatory dysfunction is an underappreciated risk factor for frailty in patients with CKD remains unclear. The objective of this work was to examine the role of gustatory dysfunction as a risk factor for frailty in patients with CKD. METHODS: We prospectively enrolled patients with stage 3 or higher CKD from a single institute, with their gustatory function assessed using both objective (taste strip method) and subjective approaches, and frailty identified using the Edmonton frail scale, FRAIL scale, and Study of Osteoporotic Fracture (SOF) scale. Multiple regression analyses were performed to investigate whether results from gustatory function tests independently correlated with frailty. RESULTS: Among the enrolled patients with CKD, 14 (17.9%) were found to be frail. We discovered that higher taste strip scores, or better taste function, were significantly associated with a lower frail probability (odds ratio [OR] 0.74 per score, 95% confidence interval [CI] 0.57-0.97), independent of clinical features, while better subjective taste function (OR 0.84 per score, 95% CI 0.74-0.96) and better oral cavity intactness (OR, 0.94; 95% CI, 0.9-0.98) were similarly associated with a lower frail probability among patients with CKD. CONCLUSION: Gustatory dysfunction may be an important risk factor for frailty in patients with CKD. It is tempting to presume that interventions aiming to ameliorate such deficits may bear the potential of reducing frailty severity in this population with a high frailty burden.

Elevated Red Cell Distribution Width Is Independently Associated With a Higher Frailty Risk Among 2,932 Community-Dwelling Older Adults.

Background: Older adults are at an increased risk of frailty, but laboratory surrogates for identifying frailty in this population remain controversial and clinicians frequently encounter difficulty during frailty screening. We examined whether having a high red cell distribution width (RDW) was associated with an increased probability of frailty in older adults. Methods: We prospectively included community-dwelling older adults between 2013 and 2016 from a single institute, with their clinical features/laboratory parameters documented. We used the Study of Osteoporotic Fractures index (malnutrition, poor physical performance, and fatigue) to delineate frailty, and harnessed multiple logistic regression to investigate whether having a high RDW (≥ 15.7%) was associated with an increased risk of having frailty among these participants. Results: A total of 2,932 older adults (mean 73.5 ± 6.7 years; 44.6% male) were included, among whom 113 (3.9%) and 76 (2.6%) had a high RDW and presented frailty, respectively. Older adults with a high RDW were more likely to be frail (p = 0.002) and had more positive SOF items than those with normal RDW levels (p = 0.013). Those with a high RDW exhibited a significantly higher risk of having frailty (odds ratio [OR] 2.689, 95% confidence interval [CI] 1.184-6.109) compared to those without. Sensitivity analyses using RDW as a continuous variable similarly showed that RDW levels were positively associated with frailty risk (OR 1.223 per 1% RDW higher). Conclusions: In older adults, higher RDW can be regarded as a frailty indicator, and the readiness in RDW assessment supports its screening utility.

Gustatory Function and the Uremic Toxin, Phosphate, Are Modulators of the Risk of Vascular Calcification among Patients with Chronic Kidney Disease: A Pilot Study.

Patients with chronic kidney disease (CKD) have an increased risk of vascular calcification (VC), including aortic arch calcification (AAC). Few investigated the influence of gustatory function on the probability of having VC. We examined whether gustatory function results modulated the probability of having VC in patients with CKD. We prospectively enrolled adults with CKD (estimated glomerular filtration rate <60 mL/min/1.73 m2), with their AAC rated semi-quantitatively and gustatory function assessed by objective and subjective approaches. Multiple logistic regression was used to analyze the relationship between gustatory function results and AAC. Those with AAC had significantly better objective gustatory function in aggregate scores (p = 0.039) and categories (p = 0.022) and less defective bitter taste (p = 0.045) and scores (p = 0.037) than those without. Multiple regression analyses showed that higher aggregate scores (odds ratio (OR) 1.288, p = 0.032), or better gustatory function, and higher bitter taste scores (OR 2.558, p = 0.019) were each associated with a higher probability of having AAC among CKD patients; such an association was modulated by serum phosphate levels. In conclusion, better gustatory function was independently correlated with having AAC among CKD patients. A follow-up of VC severity may be an underrecognized component of care for CKD patients with a preserved gustatory function.

Impact of Self-Report and eGFR-Based Chronic Kidney Disease on the Risk of Chronic Kidney Disease-Related Complications and Geriatric Syndromes in Community-Dwelling Older Adults.

BACKGROUND/AIMS: Awareness of chronic kidney disease (CKD) has been low among affected patients, particularly the older ones. However, whether such awareness is synonymous with the presence of laboratory-diagnosed CKD among older adults is currently unclear. METHODS: We enrolled community-dwelling old adults (≥ 65 years) who received health examinations between 2013 and 2016 from a regional metropolitan hospital. Clinical information and geriatric syndromes including depression, cognitive impairment, fall, quality of life, and visual disturbance were evaluated during the medical interview. We compared the differences in clinical features between those with and without self-reported or estimated glomerular filtration rate (eGFR)-based CKD and investigated their influences and interactions on the risk of CKD complications and geriatric syndromes. RESULTS: Among the 2932 enrolled older adults (mean 73.4 ± 7 years), 93 (3%) reported that they had CKD by history, while 306 (10%) had an eGFR < 60 mL/min/1.73m2 persisted for over 3 months. The prevalence of hyperlipidemia, body mass index, waist circumference, leukocyte count, and the incidence of fall differed only between those with and without eGFR-based CKD, but not between those with and without self-reported CKD. A synergistic effect was found between self-reported and eGFR-based CKD regarding the CKD complication severity, including malnutrition (albumin), anemia (hemoglobin), dyslipidemia (serum cholesterol), and geriatric syndromes (cognitive and quality of life impairment). Multivariate regression analyses showed that self-reported CKD exhibited better predictive efficacy for lower serum albumin and hemoglobin than eGFR-based CKD, while the latter outperformed the former for predicting lower serum cholesterol and a higher risk of cognitive impairment. CONCLUSION: Among older adults, self-reported CKD may not be a surrogate for laboratory-diagnosed CKD and has an independent effect on CKD-related complications.

Peginterferon alfa-2a with or without low-dose ribavirin for treatment-naive patients with hepatitis C virus genotype 2 receiving haemodialysis: a randomised trial.

OBJECTIVE: Data comparing the efficacy and safety of combination therapy with peginterferon plus low-dose ribavirin and peginterferon monotherapy in treatment-naive haemodialysis patients with hepatitis C virus genotype 2 (HCV-2) infection are limited. DESIGN: In this randomised trial, 172 patients received 24 weeks of peginterferon alfa-2a 135 µg/week plus ribavirin 200 mg/day (n=86) or peginterferon alfa-2a 135 µg/week (n=86). The efficacy and safety endpoints were sustained virological response (SVR) rate and adverse event (AE)-related withdrawal rate. RESULTS: Compared with monotherapy, combination therapy had a greater SVR rate (74% vs 44%, relative risk (RR): 1.68 [95% CI 1.29 to 2.20]; p<0.001). The beneficial effect of combination therapy was more pronounced in patients with baseline viral load ≥800,000 IU/mL than those with baseline viral load <800,000 IU/mL (RR: 3.08 [95% CI 1.80 to 5.29] vs. RR: 1.11 [95% CI 0.83 to 1.45]; interaction p=0.001). Patients receiving combination therapy were more likely to have a haemoglobin level of <8.5 g/dL (70% vs. 8%, risk difference (RD): 62% [95% CI 50% to 73%]; p<0.001) and required a higher dosage [mean: 13,417 vs. 6667 IU/week, p=0.027] of epoetin ß to manage anaemia than those receiving monotherapy. The AE-related withdrawal rates were 6% and 3% in combination therapy and monotherapy groups, respectively (RD: 2% [95% CI -4% to 9%]). CONCLUSIONS: In treatment-naive haemodialysis patients with HCV-2 infection, combination therapy with peginterferon plus low-dose ribavirin achieved a greater SVR rate than peginterferon monotherapy. Most haemodialysis patients can tolerate combination therapy. TRIAL REGISTRATION NUMBER: ClinicalTrial.gov number, NCT00491244.

P-side-up thin-film AlGaInP-based light emitting diodes with direct ohmic contact of an ITO layer with a GaP window layer.

A twice wafer-transfer technique can be used to fabricate high-brightness p-side-up thin-film AlGaInP-based light-emitting diodes (LEDs) with an indium-tin oxide (ITO) transparent conductive layer directly deposited on a GaP window layer, without using postannealing. The ITO layer can be used to improve light extraction, which enhances light output power. The p-side-up thin-film AlGaInP LED with an ITO layer exhibited excellent performance stability (e.g., emission wavelength and output power) as the injection current increased. This stability can be attributed to the following factors: 1) Refractive index matching, performed by introducing ITO between the epoxy and the GaP window layer enhances light extraction; and 2) The ITO layer is used as the current spreading layer to reduce the thermal accumulation in the epilayers.

Pegylated interferon-α2a with or without low-dose ribavirin for treatment-naive patients with hepatitis C virus genotype 1 receiving hemodialysis: a randomized trial.

BACKGROUND: Data are limited on the efficacy and safety of pegylated interferon plus ribavirin for patients with hepatitis C virus genotype 1 (HCV-1) receiving hemodialysis. OBJECTIVE: To compare the efficacy and safety of combination therapy with pegylated interferon plus low-dose ribavirin and pegylated interferon monotherapy for treatment-naive patients with HCV-1 receiving hemodialysis. DESIGN: Open-label, randomized, controlled trial. (ClinicalTrials.gov: NCT00491244). SETTING: 8 centers in Taiwan. PATIENTS: 205 treatment-naive patients with HCV-1 receiving hemodialysis. INTERVENTION: 48 weeks of pegylated interferon-α2a, 135 µg weekly, plus ribavirin, 200 mg daily (n = 103), or pegylated interferon-α2a, 135 µg weekly (n = 102). MEASUREMENTS: Sustained virologic response rate and adverse event-related withdrawal rate. RESULTS: Compared with monotherapy, combination therapy had a greater sustained virologic response rate (64% vs. 33%; relative risk, 1.92 [95% CI, 1.41 to 2.62]; P < 0.001). More patients receiving combination therapy had hemoglobin levels less than 8.5 g/dL than those receiving monotherapy (72% vs. 6%; risk difference, 66% [CI, 56% to 76%]; P < 0.001). Patients receiving combination therapy required a higher dosage (mean, 13 946 IU per week [SD, 6449] vs. 5833 IU per week [SD, 1169]; P = 0.006) and longer duration (mean, 29 weeks [SD, 9] vs. 18 weeks [SD, 7]; P = 0.004) of epoetin-ß than patients receiving monotherapy. The adverse event-related withdrawal rates were 7% in the combination therapy group and 4% in the monotherapy group (risk difference, 3% [CI, -3% to 9%]). LIMITATION: Open-label trial; results may not be generalizable to patients on peritoneal dialysis. CONCLUSION: In treatment-naive patients with HCV-1 receiving hemodialysis, combination therapy with pegylated interferon plus low-dose ribavirin achieved a greater sustained virologic response rate than pegylated interferon monotherapy. PRIMARY FUNDING SOURCE: National Center of Excellence for Clinical Trial and Research.

Increased procollagen type I C-terminal peptide levels indicate diastolic dysfunction in end-stage renal disease patients undergoing maintenance dialysis therapy.

BACKGROUND: Cardiac dysfunction is common among patients with end-stage renal disease. The aim of this study was to explore the determinants of diastolic dysfunction in patients with end-stage renal disease on maintenance hemodialysis. METHODS: Patients with asymptomatic end-stage renal disease undergoing hemodialysis underwent Doppler tissue imaging analysis and two-dimensional speckle-tracking echocardiography with strain analysis. Blood studies included albumin, cardiac troponin T, and procollagen type I C-terminal peptide (PICP). RESULTS: All enrolled patients had left ventricular (LV) diastolic dysfunction and were stratified into two groups by a cutoff value of 13 for the ratio of early transmitral flow velocity to the average early diastolic annular velocity (E/e'). Seventy-two of the enrolled patients (87%) had grade 1 diastolic dysfunction, and 11 patients (13%) had higher grades of diastolic dysfunction. The study population did not include a representative sample of patients with the pseudonormal or restrictive filling patterns of diastolic dysfunction. There were no significant differences in gender, age, LV geometric change, ejection fraction, global systolic longitudinal strain and strain rate, and prevalence of comorbidities between groups. Patients with average E/e' ≥ 13 had higher PICP, which was significantly correlated with cardiac troponin T, average E/e', and systolic circumferential strain rate. By multivariate regression analysis, average E/e' level was an independent factor of PICP level (P = .047). CONCLUSIONS: Hemodialysis patients with high average E/e' ratios showed increased levels of LV filling pressure and higher severity levels of cardiac fibrosis, which occurred before the development of systolic dysfunction. PICP was a potential indicator of diastolic dysfunction and increased LV filling pressure.

Transient elastography to assess hepatic fibrosis in hemodialysis chronic hepatitis C patients.

BACKGROUND AND OBJECTIVES: Although percutaneous liver biopsy (PLB) is the gold standard for staging hepatic fibrosis in hemodialysis patients with chronic hepatitis C (CHC) before renal transplantation or antiviral therapy, concerns exist about serious postbiopsy complications. Using transient elastography (TE, Fibroscan(®)) to predict the severity of hepatic fibrosis has not been prospectively evaluated in these patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A total of 284 hemodialysis patients with CHC were enrolled. TE and aspartate aminotransferase-to-platelet ratio index (APRI) were performed before PLB. The severity of hepatic fibrosis was staged by METAVIR scores ranging from F0 to F4. Receiver operating characteristic curves were used to assess the diagnostic accuracy of TE and APRI, taking PLB as the reference standard. RESULTS: The areas under curves of TE were higher than those of APRI in predicting patients with significant hepatic fibrosis (≥F2) (0.96 versus 0.84, P<0.001), those with advanced hepatic fibrosis (≥F3) (0.98 versus 0.93, P=0.04), and those with cirrhosis (F4) (0.99 versus 0.92, P=0.13). Choosing optimized liver stiffness measurements of 5.3, 8.3, and 9.2 kPa had high sensitivity (93-100%) and specificity (88-99%), and 87, 97, and 93% of the patients with a fibrosis stage of ≥F2, ≥F3, and F4 were correctly diagnosed without PLB, respectively. CONCLUSIONS: TE is superior to APRI in assessing the severity of hepatic fibrosis and can substantially decrease the need of staging PLB in hemodialysis patients with CHC.

Pegylated interferon alfa-2a monotherapy for hemodialysis patients with acute hepatitis C.

BACKGROUND: Hemodialysis patients are at risk of hepatitis C virus (HCV) infection. However, little is known about the efficacy and safety of pegylated interferon (IFN) therapy for hemodialysis patients with acute hepatitis C. METHODS: From 2005 through 2008, 35 hemodialysis patients with acute hepatitis C who did not have spontaneous clearance of HCV by 16 weeks were treated with pegylated IFN alfa-2a at a dosage of 135 microg weekly for 24 weeks. In contrast, 7 patients with clearance of HCV by 16 weeks were under observation only. Thirty-six hemodialysis patients from 2002-2005 who had acute hepatitis C but did not receive treatment served as historical controls. The primary efficacy and safety end points were sustained virologic response (undetectable HCV RNA levels at 24 weeks after therapy) by intention-to-treat analysis and treatment-related withdrawal. RESULTS: The rate of sustained virologic response in the treatment group was significantly higher than the rate of spontaneous HCV clearance in the control group (88.6% vs 16.7%; P < .001). Two patients (5.7%) prematurely terminated treatment at 8 and 10 weeks because of constitutional symptoms, and both did not have sustained virologic response. All but one patient had rapid virologic response (undetectable HCV RNA levels at 4 weeks of therapy), and all patients who received >12 weeks of therapy had early and end-of-treatment virologic responses. All patients who had clearance of HCV by 16 weeks had undetectable HCV RNA levels until the end of follow-up. CONCLUSIONS: Pegylated IFN alfa-2a monotherapy is safe and efficacious for hemodialysis patients with acute hepatitis C. It is suggested that patients without spontaneous clearance of HCV by week 16 should receive therapy.

The ratio of aminotransferase to platelets is a useful index for predicting hepatic fibrosis in hemodialysis patients with chronic hepatitis C.

Percutaneous liver biopsy is the gold standard for staging hepatic fibrosis of hemodialysis patients with chronic hepatitis C before renal transplantation or antiviral therapy. Concerns exist, however, about serious post-biopsy complications. To evaluate a more simple approach using standard laboratory tests to predict hepatic fibrosis and its evolution, we studied 279 consecutive hemodialysis patients with chronic hepatitis C and a baseline biopsy. Among them, 175 receiving antiviral therapy underwent follow-up biopsy to evaluate the histological evolution of fibrosis. Multivariate analysis of routine laboratory tests at baseline showed the aspartate aminotransferase-to-platelet ratio index was an independent predictor of significant hepatic fibrosis. The areas under curves of this ratio to predict fibrosis stages F2-4 were 0.83 and 0.71 in the baseline and follow-up sets; and 0.75 and 0.80 respectively, for patients with sustained or non-sustained virological response groups in the follow-up sets. By a judicious setting of cut-off levels for the baseline and non-sustained groups, and the sustained virological response group, almost half and 60 percent of the baseline and follow-up sets could be correctly diagnosed without biopsy. Our study found the aminotransferase-to-platelet ratio index is accurate and reproducible for assessing hepatic fibrosis in hemodialysis patients with chronic hepatitis C. Applying this simple index could decrease the need of percutaneous liver biopsy in this clinical setting.

Residual urine output and postoperative mortality in maintenance hemodialysis patients.

BACKGROUND: The relationship between residual urine output and postoperative survival in maintenance hemodialysis patients is unknown. OBJECTIVE: To explore the relationship between amount of urine before surgery and postoperative mortality and differences between postoperative nonanuria and anuria in maintenance hemodialysis patients. METHODS: A total of 109 maintenance hemodialysis patients underwent major operations. Anuria was defined as urine output <30 mL in the 8 hours before the first session of postoperative dialysis. Propensity scores for postoperative anuria were developed. RESULTS: Postoperative residual urine output was 159.2 mL/8 h (SD, 115.1) in 33 patients; 76 patients were anuric. Preoperative residual urine output and adequate perioperative blood transfusion were positively related to postoperative urine output. Propensity-adjusted 30-day mortality was associated with postoperative anuria (odds ratio [OR], 4.56; 95% confidence interval [CI], 1.16-17.96; P = .03), prior stroke (OR, 4.46; 95% CI, 1.43-13.89; P = .01) and higher disease severity (OR, 1.10; 95% CI, 1.00-1.21; P = .049) at the first postoperative dialysis. OR of 30-day mortality was 5.38 for nonanuria to anuria vs nonanuria to nonanuria (P = .03) and 5.13 for preoperative anuria vs nonanuria to nonanuria (P = .01). By Kaplan-Meier analysis, 30-day mortality differed significantly among patients for nonanuria to nonanuria, anuria, and nonanuria to anuria (log rank, P = .045). CONCLUSION: Patients with preoperative nonanuria and postoperative anuria had higher mortality than did patients with no anuria before and after surgery and patients with anuria before surgery. Postoperative residual urine output is an important surrogate marker for disease severity.

Effects of low- and high-flux dialyzers on oxidative stress and insulin resistance.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of mortality in patients with end-stage renal disease (ESRD). The cornerstone of high CVD incidence in ESRD patients is endothelial dysfunction which results from inflammation, oxidative stress and insulin resistance. Although various modalities of hemodialysis (HD) have been presumed to exert different effects on oxidative stress and insulin resistance, solid evidence is still lacking. METHODS: 40 ESRD patients undergoing HD were prospectively enrolled and divided randomly into two groups. Patients in each group received either F8 HPS (low-flux) (Group A) or FX80 (high-flux) (Group B) as HD dialyzers for 2 consecutive months. Diet pattern and medications were kept as usual in both groups to avoid considerable blood glucose change during study period. Blood samples were taken at the start and end of the study. RESULTS: A total of 38 patients (18 and 20 for Groups A and B, respectively) completed the study. Within each group, there was no change in adiponectin, plasma 8-iso-prostaglandin F(2)(alpha), high-sensitivity C-reactive protein, blood glucose and insulin after 2 months of treatment except a significant change of HOMA(IR) (p = 0.02) in high-flux group. The significant change of HOMA(IR) between the two groups (p = 0.017) mainly results from the parallel change of insulin between the two groups (p = 0.03). CONCLUSION: For patients receiving HD, the high-flux dialyzer with synthetic polysulfone membranes fails to provide a better anti-inflammatory or antioxidative effect than the low-flux dialyzer; however, the high-flux dialyzer does significantly improve insulin resistance in this short-term study. This result implies that the high-flux dialyzer might provide better cardiovascular protection than the low-flux dialyzer. Therefore, the low-flux dialyzer might be considered for patients who only need short-term HD therapy. Regarding patients under long-term maintenance HD therapy, a high-flux dialyzer might be the choice of dialyzer.

Clinical characteristics of patients with segmental renal infarction.

BACKGROUND: Renal infarction is usually an underestimated disease due to its rare and non-specific presentations; the renal survival of these patients is not well studied. The aim of the present analysis is to study the clinical features and outcome in patients who had documented renal infarction. METHODS: Twenty-two patients (12 men and 10 women, mean age of 57.7 +/- 3.44 years (28.4-83.3 years)) with image-confirmed segmental renal infarction in the past 15 years were enrolled. All patients were followed up at outpatient department with a median of 4 years (1-14 years). Initial and follow-up clinical characteristics and laboratory results were recorded. RESULTS: The most common underlying disease was cardiovascular disease. Renal infarction often presented with non-specific symptoms, including flank pain (55%), vague abdominal pain (50%), nausea/vomiting (46%) and fever (27%). The levels of leucocytes, lactate dehydrogenase, blood urea nitrogen and serum creatinine were all elevated at admission. The early diagnosis group (12/22) had more obvious flank pain, nausea/vomiting (P < 0.001) and higher alanine transaminase (P = 0.02). It also predisposed to undergo antiplatelet or anticoagulant therapy (all P < 0.04). During follow up, there was no recurrence in the whole study group, and a trend of better recovery of renal function was noted in the early diagnosis group. CONCLUSION: The serum creatinine level correlates with longer hospitalization length (P < 0.05). As regards long-term prognosis, no definite factor or treatment was found to have significant effect in segmental renal infarction patients. However, early diagnosis and early initiation of treatment seems to have a positive effect on future renal outcome.