Years of life lost and long-term outcomes due to glomerular disease in a Southeast Asian Cohort.

Death and end-stage kidney disease (ESKD) are major outcomes of glomerular disease. (GD) The years of potential life lost (YLL) may provide additional insight into the disease burden beyond death rates. There is limited data on premature mortality in GD. In this retrospective observational cohort study, we evaluated the mortality, ESKD rates, and YLL in Thais with biopsy-proven GD. The mortality and combined outcome rates were determined by log-rank test and ESKD by using a competing risk model. YLL and premature life lost before age 60 were calculated for different GD based on the life expectancy of the Thai population. Patients with GD (n = 949) were followed for 5237 patient years. The death rate and ESKD rates (95%CI) were 4.2 (3.7-4.9) and 3.3 (2.9-3.9) per 100 patient-years, respectively. Paraprotein-related kidney disease had the highest death rate, and diabetic nephropathy had the highest ESKD rate. Despite not having the highest death rate, lupus nephritis (LN) had the highest YLL (41% of all GD) and premature loss of life before age 60. In conclusion, YLL provided a different disease burden assessment compared to mortality rates and identified LN as the major cause of premature death due to GD in a Southeast Asian cohort.

Metformin-associated lactic acidosis and factors associated with 30-day mortality.

BACKGROUND: Metformin-associated lactic acidosis (MALA) is a rare event but underrecognition may lead to unfavorable outcomes in type 2 diabetes patients. While many risk factors of MALA have been identified, how to reduce mortality from MALA is a matter of debate. This study aimed to explore the factors associated with 30-day mortality amongst MALA patients. METHODS: An observational study enrolled patients diagnosed with MALA between January 2014 and December 2017. MALA was defined by a history of metformin administration, metabolic acidosis (arterial blood gas pH <7.35 or HCO3 <15 mmol/L), and elevated plasma lactate level (>5 mmol/L). We examined risk factors including age, sex, underlying diseases, current medications, blood tests, disease severity, and dialysis data. Mortality status was identified from medical records or report on telephone. RESULTS: We included 105 MALA patients. Most patients (95.2%) were diagnosed acute kidney injury stage 3 according to KDIGO 2012 definition. The 30-day mortality rate was 36.2% and dialysis rate was 85.7%. The survivors had higher proportions of underlying chronic kidney disease, presence of metabolic acidosis, receiving renal replacement therapy within 6 hours, and haemodialysis, whereas the non-survivors had higher percentage of hypertension and disease severity. Lower APACHE II score (HR = 0.95; 95%CI, 0.91-0.99; p = 0.038), time to dialysis < 6 hours (0.31; 0.14-0.69; 0.004), and haemodialysis (0.20;0.06-0.67; 0.010) were associated with lower 30-day mortality, using multivariate Cox-regression analysis. CONCLUSIONS: Mortality rate amongst patients with MALA was high. Early dialysis treatment within 6 hours after admission and haemodialysis were independently associated with lower 30-day mortality. The large scale, well-designed studies need to confirm these encouraging results.

Durability of Humoral and Cellular Immunity after an Extended Primary Series with Heterologous Inactivated SARS-CoV-2 Prime-Boost and ChAdOx1 nCoV-19 in Dialysis Patients (ICON3).

The durability of a three-dose extended primary series of COVID-19 vaccine in dialysis patients remains unknown. Here, we assessed dynamic changes in SARS-CoV-2-specific humoral and cell-mediated immunity at baseline, 3 months, and 6 months after the extended primary series in 29 hemodialyzed (HD), 28 peritoneal dialyzed (PD) patients, and 14 healthy controls. Participants received two doses of inactivated SARS-CoV-2 vaccine followed by a dose of ChAdOx1 nCoV-19 vaccine. At 6 months, median anti-RBD IgG titers (IQR) significantly declined from baseline in the HD (1741 (1136−3083) BAU/mL vs. 373 (188−607) BAU/mL) and PD (1093 (617−1911) BAU/mL vs. 180 (126−320) BAU/mL) groups, as did the mean percent inhibition of neutralizing antibodies (HD: 96% vs. 81%; PD: 95% vs. 73%) (all p < 0.01). Age and post-vaccination serological response intensity were predictors of early humoral seroprotection loss. In contrast, cell-mediated immunity remained unchanged. In conclusion, humoral immunity declined substantially in dialysis patients, while cell-mediated immunity remained stable 6 months after the extended heterologous primary series of two inactivated SARS-CoV-2/ChAdOx1 nCoV-19 vaccine. A booster dose could be considered in dialysis patients 3 months after this unique regimen, particularly in the elderly or those with a modest initial humoral response.

An additional dose of viral vector COVID-19 vaccine and mRNA COVID-19 vaccine in kidney transplant recipients: A randomized controlled trial (CVIM 4 study).

Immunogenicity following an additional dose of Coronavirus disease 2019 (COVID-19) vaccine was investigated in an extended primary series among kidney transplant (KT) recipients. Eighty-five KT participants were randomized to receive either an mRNA (M group; n = 43) or viral vector (V group; n = 42) vaccine. Among them, 62% were male, with a median (IQR) age of 50 (43-59) years and post-transplantation duration of 46 (26-82) months. At 2 weeks post-additional dose, there was no difference in the seroconversion rate between the M and V groups (70% vs. 65%, p = .63). A median (IQR) of anti-RBD antibody level was not statistically different between the M group compared with the V group (51.8 [5.1-591] vs. 28.5 [2.9-119.3] BAU/ml, p = .18). Furthermore, the percentage of participants with positive SARS-CoV-2 surrogate virus neutralization test results was not statistically different between groups (20% vs. 15%, p = .40). S1-specific T cell and RBD-specific B cell responses were also comparable between the M and V groups (230 [41-420] vs. 268 [118-510], p = .65 and 2 [0-10] vs. 2 [0-13] spot-forming units/106 peripheral blood mononuclear cells, p = .60). In conclusion, compared with an additional dose of viral vector COVID-19 vaccine, a dose of mRNA COVID-19 vaccine did not elicit significantly different responses in KT recipients, regarding either humoral or cell-mediated immunity. (TCTR20211102003).

Immunogenicity of ChAdOx1 nCoV-19 vaccine after a two-dose inactivated SARS-CoV-2 vaccination of dialysis patients and kidney transplant recipients.

Vaccination with inactivated SARS-CoV-2 virus produces suboptimal immune responses among kidney transplant (KT), peritoneal dialyzed (PD), and hemodialyzed (HD) patients. Participants were vaccinated with two-dose inactivated SARS-CoV-2 vaccine (V2) and a third dose of ChAdOx1 nCoV-19 vaccine (V3) at 1-2 months after V2. We enrolled 106 participants: 31 KT, 28 PD, and 31 HD patients and 16 controls. Among KT, PD, and HD groups, median (IQR) of anti-receptor binding domain antibody levels were 1.0 (0.4-26.8), 1092.5 (606.9-1927.2), and 1740.9 (1106-3762.3) BAU/mL, and percent neutralization was 0.9 (0-9.9), 98.8 (95.9-99.5), and 99.4 (98.8-99.7), respectively, at two weeks after V3. Both parameters were significantly increased from V2 across all groups (p < 0.05). Seroconversion and neutralization positivity rates in PD, HD, and control groups were 100% but were impaired in KT patients (39% and 16%, respectively). S1-specific T-cell counts were increased in PD and HD groups (p < 0.05) but not in KT patients. The positive S1-specific T-cell responder rate was > 90% in PD, HD, and control groups, which was higher than that in KT recipients (74%, p < 0.05). The heterologous inactivated virus/ChAdOx1 nCoV-19 vaccination strategy elicited greater immunogenicity among dialysis patients; however, inadequate responses remained among KT recipients (TCTR20210226002).

Predicting treatment response and clinicopathological findings in lupus nephritis with urine epidermal growth factor, monocyte chemoattractant protein-1 or their ratios.

INTRODUCTION: There is a need for sensitive and specific biomarkers to predict kidney damage and therapeutic response in lupus nephritis (LN). Monocyte chemoattractant protein-1 (MCP-1) and epidermal growth factor (EGF) are cytokines with divergent roles. EGF or EGF/MCP1 ratio have been shown to correlate with prognosis in primary glomerulonephritis, but there is limited information in lupus nephritis (LN). This study evaluated the roles of MCP-1, EGF or their ratio as biomarkers of histopathology and response to treatment in LN. METHODS: This was a cross-sectional and observational study. Baseline urine MCP-1 and EGF levels in systemic lupus erythematosus (SLE) patients and controls (total n = 101) were compared, and levels were correlated with clinicopathological findings and subsequent response to treatment. RESULTS: MCP-1 was higher in active LN (n = 69) compared to other SLE groups and controls, whereas EGF was not different. MCP-1 correlated with disease activity (proteinuria, renal SLEDAI, classes III/IV/V, and high activity index.) By contrast, EGF correlated with eGFR, but not with proteinuria, activity index, or class III/IV/V. MCP-1 was higher, and EGF was lower in high chronicity index. EGF/MCP-1 decreased with greater clinicopathological severity. In a subgroup with proliferative LN who completed six months of induction therapy (n = 41), EGF at baseline was lower in non-responders compared to responders, whereas MCP-1 was similar. By multivariable analysis, baseline EGF was independently associated with subsequent treatment response. Area under the curve for EGF to predict response was 0.80 (0.66-0.95). EGF ≥ 65.6 ng/ mgCr demonstrated 85% sensitivity and 71% specificity for response. EGF/MCP-1 did not improve the prediction for response compared to EGF alone. CONCLUSION: MCP-1 increased with disease activity, whereas EGF decreased with low GFR and chronic damage. Urine EGF may be a promising biomarker to predict therapeutic response in LN. EGF/MCP-1 did not improve the prediction of response.

Dialysate Magnesium and Coronary Artery Calcification, Bone Mineral Density, and Cramping in Maintenance Hemodialysis: A Quasi-experimental Study.

RATIONALE & OBJECTIVE: Recent evidence suggests a role for magnesium as a calcification inhibitor. Increased magnesium abundance may attenuate vascular calcification and promote bone formation. STUDY DESIGN: Parallel-group, 1:1-allocation-ratio, quasi-experimental study. SETTING & PARTICIPANTS: The study was conducted at hemodialysis centers in Bangkok, Thailand. Patients receiving maintenance hemodialysis were screened for coronary artery calcification (CAC) and bone mineral density (BMD), and those with a CAC score of ≥300 were included and matched according to the initial CAC score. The intervention and control groups consisted of 20 patients in each arm. INTERVENTIONS: A high (1.75 mEq/L) or standard (0.7 mEq/L) dialysate magnesium concentration was delivered for 26 weeks. OUTCOMES: Changes in the CAC score and BMD and the progression of CAC. The safety outcomes included occurrence of cramps recorded as per usual care. RESULTS: The median CAC score of all patients was 1,792. Serum and ionized magnesium concentrations increased substantially in the high dialysate magnesium group. At the end of the study, the CAC score increased significantly in both the groups, with no significant difference between the groups. The number of participants with CAC progression was comparable between the 2 groups. In exploratory subgroup analyses stratified by the median CAC score, a significant decline in CAC and fewer participants with CAC progression were observed in the subgroup with lower CAC scores that received the high dialysis magnesium concentration. Bone mineral density was largely unchanged in both groups. The number of participants experiencing cramps and the number of episodes of muscle cramps were markedly lower among patients who received the high dialysis magnesium concentration. LIMITATIONS: The participants had severe vascular calcification at baseline; therefore, the findings might not apply to those with less-established calcification. Moreover, cramps were not systematically ascertained. CONCLUSIONS: The high dialysis magnesium concentration did not alleviate the progression of CAC or improve BMD in patients with severe calcification receiving hemodialysis; however, muscle cramps were less frequent among those treated with high dialysate magnesium. Further study is required to determine a possible favorable effect of high dialysis magnesium concentration in individuals with mild-to-moderate calcification.

SARS-CoV-2-specific humoral and cell-mediated immune responses after immunization with inactivated COVID-19 vaccine in kidney transplant recipients (CVIM 1 study).

Immunogenicity following inactivated SARS-CoV-2 vaccination among solid organ transplant recipients has not been assessed. Seventy-five patients (37 kidney transplant [KT] recipients and 38 healthy controls) received two doses, at 4-week intervals, of an inactivated whole-virus SARS-CoV-2 vaccine. SARS-CoV-2-specific humoral (HMI) and cell-mediated immunity (CMI) were measured before, 4 weeks post-first dose, and 2 weeks post-second dose. The median (IQR) age of KT recipients was 50 (42-54) years and 89% were receiving calcineurin inhibitors/mycophenolate/corticosteroid regimens. The median (IQR) time since transplant was 4.5 (2-9.5) years. Among 35 KT patients, the median (IQR) of anti-RBD IgG level measured by CLIA after vaccination was not different from baseline, but was significantly lower than in controls (2.4 [1.1-3.7] vs. 1742.0 [747.7-3783.0] AU/ml, p < .01) as well as percentages of neutralizing antibody inhibition measured by surrogate viral neutralization test (0 [0-0] vs. 71.2 [56.8-92.2]%, p < .01). However, the median (IQR) of SARS-CoV-2 mixed peptides-specific T cell responses measured by ELISpot was significantly increased compared with baseline (30 [4-120] vs. 12 [0-56] T cells/106  PBMCs, p = .02) and not different from the controls. Our findings revealed weak HMI but comparable CMI responses in fully vaccinated KT recipients receiving inactivated SARS-CoV-2 vaccination compared to immunocompetent individuals (Thai Clinical Trials Registry, TCTR20210226002).

Short-Term Immunogenicity Profiles and Predictors for Suboptimal Immune Responses in Patients with End-Stage Kidney Disease Immunized with Inactivated SARS-CoV-2 Vaccine.

INTRODUCTION: Patients with end-stage kidney disease (ESKD) are at risk of severe coronavirus disease and mortality. Immunogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inactivated whole-virus vaccine in patients with ESKD has never been explored. METHODS: We conducted a prospective cohort study of 60 patients with ESKD and 30 healthy controls. All participants received two doses of an inactivated whole-virus SARS-CoV-2 vaccine (Sinovac Biotech Ltd) 4 weeks apart. SARS-CoV-2-specific humoral and cell-mediated immune responses were investigated and referenced with healthy controls. RESULTS: After two doses, an anti-receptor-binding domain immunoglobulin G of 50 AU/ml or greater was present in 53 of 60 patients (88%) in the ESKD group and all participants (100%) in the control group (P = 0.05). The percentage of patients with ESKD and controls with neutralizing antibodies of 35% threshold or greater was 58% and 88%, respectively (P = 0.01). Furthermore, the proportion of patients with ESKD and S1-specific T cell response was comparable with controls (82% vs. 77%, P = 0.45). Old age, high ferritin level, and low absolute lymphocyte count were independently associated with poor humoral immune responses. CONCLUSIONS: Patients with ESKD could develop similar SARS-CoV-2-specific cell-mediated immune responses compared to healthy controls, although suboptimal humoral immune responses were observed following two doses of SARS-CoV-2 vaccination. Therefore, patients with ESKD and the abovementioned factors are at risk of generating inadequate humoral immune responses, and a vaccine strategy to elicit greater immunogenicity among these relatively immunocompromised patients is warranted. (Thai Clinical Trials Registry, TCTR20210226002).

Pilot study to investigate differences in middle molecules, oxidative stress and markers of peripheral vascular disease in patients treated by high flux haemodialysis and haemodiafiltration.

BACKGROUND: Dialysis patients have an increased risk of mortality. Recently treatment with haemodiafiltration (HDF) has been reported to reduce mortality, particularly cardiovascular mortality, compared to standard high-flux haemodialysis (HD). However, why HDF may offer a survival advantage remains to be determined. So, we conducted a pilot study to explore differences in middle-molecules, inflammation and markers of vascular disease in patients treated by HD and HDF. METHODS: Observational cross-sectional study measuring serum ß2-microglobulin (ß2M), Advanced Glycosylation End Products (AGEs) by skin autofluorescence (SAF), oxidative stress with ischaemia modified albumin ratio (IMAR) and peripheral vascular disease assessment using Ankle-Brachial Index (ABI), and arterial stiffness using Cardio-Ankle Vascular Index (CAVI). RESULTS: We studied 196 patients, mean age 69.1 ± 12.4 years, 172 (87.8%) treated by HD and 24 (12.2%) by HDF. Age, body mass index, co-morbidity and dialysis vintage were not different between HD and HDF groups. Middle molecules; ß2M (31±9.9 vs 31.2±10 ug/mL) and SAF (2.99±0.72 vs 3.0±0.84 AU), ABI (1.06±0.05 vs 1.07±0.10) and CAVI (9.34±1.55 vs 9.35±1.23) were not different, but IMAR was higher in the HD patients (38.4±14.8 vs 31.3 ± 17.4, P = 0.035). CONCLUSIONS: In this pilot observational study, we found patients treated by HDF had lower oxidative stress as measured by IMAR, with no differences in middle molecules. Lower oxidative stress would be expected to have diverse protective effects on the cardiovascular system Although we found no differences in ABI and CAVI, future studies are required to determine whether reduced oxidative stress translates into clinically relevant differences over time.

Masked hypertension and its associations with glycemic variability metrics in children and adolescents with type 1 diabetes.

BACKGROUND: Masked hypertension defined as having normal office blood pressure (BP) but hypertension detected by continuous BP monitoring has been observed in children and adolescents with type 1 diabetes (T1D). However, no study has evaluated whether masked hypertension is associated with glycemic variability (GV) in these patients. We hypothesized that masked hypertension might be associated with high GV in patients with T1D. METHODS: This cross-sectional study performed continuous glucose monitoring (CGM) in parallel with ambulatory blood pressure monitoring (ABPM) in T1D patients aged 6-21 years. Patients who had known hypertension were excluded. CGM data from the same day as ABPM was calculated for GV including standard deviation (SD), coefficient of variation (CV) of glucose levels, and unstable glycemia which was defined as having a CV of glucose levels ≥ 36%. RESULTS: Thirty-three patients had complete ABPM and CGM data. Mean (SD) age was 13.8 (3.8) years and mean (SD) duration of T1D was 5.4 (3.6) years. All patients had normal office BP, but ABPM showed masked hypertension in 9 patients (27%). In comparison with normotensive patients, patients with masked hypertension had longer duration of T1D (7.4 vs. 4.6 years, p = 0.049), higher insulin requirement (1.2 vs. 0.9 units/kg/day, p = 0.049), and higher SD of glucose (70.3 vs. 47.9 mg/dl, p = 0.038). Masked hypertension group had a greater number of patients (71% vs. 19%, p = 0.02) with unstable glycemia. Multivariate analysis revealed that unstable glycemia was associated with masked hypertension. CONCLUSIONS: The presence of unstable glycemia in children and adolescents with T1D is associated with masked hypertension. Graphical abstract.

Double-Filtration Plasmapheresis Plus Low-Dose Anti-thymocyte Globulin and Tacrolimus in Asian Living-Donor Kidney Transplantation With Donor-Specific Anti-HLA Antibody.

BACKGROUND: Pretransplant desensitization protocols, including plasmapheresis, intravenous immunoglobulin, induction antibody therapy, and intensive maintenance immunosuppression, are generally employed in kidney transplant recipients who have positive status for donor-specific anti-HLA antibody (DSA). To avoid serious infectious complications, the authors designed a novel low-dose protocol in Thai patients undergoing DSA+ living-related kidney transplantation (LRKT). METHODS: A retrospective cohort study of the patients who underwent DSA+ LRKT was conducted. The novel protocol consisted of 3 to 5 sessions of pretransplant double-filtration plasmapheresis (DFPP) with or without low-dose intravenous immunoglobulin together with low-dose anti-thymocyte globulin (ATG) induction (1-1.5 mg/kg/d for 3-4 days) and low-dose tacrolimus (Tac) (trough level 5-10 ng/mL), mycophenolate, and prednisolone. RESULTS: The study included 17 patients. The lymphocyte crossmatch via complement-dependent cytotoxicity was negative in 12 patients and positive for B cell immunoglobulin M in 5 patients. The novel desensitization protocol resulted in a decrease of at least 50% of DSA mean fluorescence intensity from baseline (from 4320 ± 549 before DFPP to 1601 ± 350 before transplantation, P < .005) and successful kidney transplantation with good allograft function in all cases. Early DSA rebound was observed in 3 patients after transplantation, and kidney biopsy revealed subclinical antibody-mediated rejection in 1 patient and diffuse C4d staining without cell infiltration in 2 patients. There were good long-term outcomes in patient and graft survival (100% and 94.1%, respectively). Only 1 allograft loss occurred because of nonadherence. The majority of patients have stable allograft function with serum creatinine less than 1.5 mg/dL. However, infections, including CMV and other organisms, were commonly observed. CONCLUSIONS: Desensitization protocol with DFPP, low-dose ATG, and Tac provides excellent outcomes in living donor kidney transplantation in highly sensitized Asian populations.

Risk and impact of delayed renal impairment in patients with locally advanced head and neck squamous cell carcinoma receiving chemoradiotherapy with cisplatin.

BACKGROUND: An incidence of cisplatin-induced acute kidney injury (AKI) of 34% has been reported in patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC). However, delayed cisplatin-induced nephrotoxicity and long-term renal outcomes remain poorly studied. METHODS: Patients with LA-HNSCC who underwent definitive or postoperative cisplatin-based chemoradiotherapy (CRT) were included. Acute kidney disease (AKD) was defined as newly developed estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2 for < 3 months, ≥ 35% decrease in eGFR, or > 50% increase in serum creatinine for <3 months from baseline. RESULTS: A total of 509 patients were analyzed. AKD and AKI occurred in 27.9% and 13.4% of patients, respectively. Most patients had primary prophylactic feeding tube (95%) and definitive CRT (83%). More AKD patients had an ECOG status of 0 (p = 0.017), diabetes (p = 0.044), and hypertension (p < 0.001). AKI, but not AKD, was significantly associated with cumulative cisplatin dose, delay, dose reduction, termination, and hospitalization during CRT. GFR percentage in patients with AKD declined significantly during CRT (- 36%), worsened at 3 months (- 39%), and had not recovered to baseline at 12 months after CRT (- 29%). Multivariate analysis identified ECOG status 0 and hypertension as significantly associated with the development of AKD. CONCLUSION: Almost one third of LA-HNSCC patients who underwent CRT with cisplatin developed AKD, and their eGFR did not recover to baseline even after 1 year. ECOG 0 and hypertension were associated with AKD. These findings may have been due to the physician's awareness of AKD and underestimation of its potential complications in fit patients.

Epidemiology, Risk Factors, and Outcome of Bloodstream Infection Within the First Year After Kidney Transplantation.

BACKGROUND: Multi-drug resistant organisms have been emerging among kidney transplant (KT) recipients with bloodstream infections (BSI). The investigation for epidemiology, risk factors and outcome of these infections following KT was initiated. MATERIALS AND METHODS: A retrospective study of all adult KT recipients who developed a BSI within the first year after KT in 2016 at a single transplant center was conducted. The cumulative incidence of BSI was estimated with Kaplan-Meier methodology. Clinical characteristics and outcome were extracted. Risk factors were analyzed with Cox proportional hazards models. RESULTS: Among 171 KT recipients, there were 26 (15.2%) episodes of BSI. Fifty-nine percent were men and the mean ± SD age was 43 ± 12 years. The cumulative incidence of BSIs was 10.1% at 1 month, 13.5% at 6 months, and 15.2% at 12 months. Gram-negative bacteria were responsible for 92% of BSIs, Escherichia coli was the most common pathogen (65%) followed by Klebsiella pneumoniae (11%). Among those, 71% were resistant to extended-spectrum cephalosporins. The genitourinary tracts were the predominant source of BSIs (85%). The second kidney transplantation (HR, 4.55; 95% CI, 1.24-16.79 [P = 0.02]) and receiving induction therapy (HR, 3.05; 95% CI, 1.15-8.10 [P < 0.03]) were associated with BSI in a multivariate analysis. One patient (4%) developed allograft rejection, allograft failure and death from septic shock. CONCLUSIONS: One out of six KT recipients could develop BSI from gram-negative bacteria within the first year after transplant, particularly in those that received the second transplantation or induction therapy.

Causes of hypercalcemia in people living with HIV in the HAART era.

BACKGROUND: Hypercalcemia is an uncommon finding in people living with HIV (PLHIV). Causes of hypercalcemia in PLHIV have not been well documented. As such, we studied the causes of hypercalcemia in PLHIV. METHODS: We conducted a retrospective review of PLHIV who had corrected serum calcium of ≥10.5 mg/dL between 2010 and 2019. Demographic data, associated diseases, and treatment details were collected. Corrected serum calcium levels were compared among the causes of hypercalcemia. RESULTS: A total of 70 of 2168 (3.2%) PLHIV had hypercalcemia. Forty-nine (70.0%) were male with a mean age of 47.7 ± 4.7 years. Only two (2.9%) had symptoms of hypercalcemia. Fifty-four patients had identifiable causes of hypercalcemia; 21 infections (30.0%), 17 solid organ malignancies (24.3%), 14 hematologic malignancies (20.0%), and two other specific causes (2.9%). Mean corrected serum calcium concentrations of PLHIV who had solid organ malignancy, hematologic malignancy, infection, and unknown causes were 12.8 ± 2.1, 11.4 ± 1.0, 11.2 ± 0.6, and 10.8 ± 0.2 mg/dL, respectively. Corrected serum calcium levels were significantly greater in patients who had solid organ malignancy comparing to those with other causes of hypercalcemia (p < 0.05, all). Logistic regression identified solid organ malignancy as the only factor associated with moderate to severe hypercalcemia (odds ratio 12.72, 95% confidence interval 3.11-52.08; p < 0.001). CONCLUSIONS: Hypercalcemia in PLHIV is associated with solid organ malignancy, hematologic malignancy, and infection. Most PLHIV with hypercalcemia are asymptomatic. Solid organ malignancy is associated with moderate to severe hypercalcemia, and as such PLHIV presenting with moderate to severe hypercalcemia should be investigated for solid organ malignancy.

Bioimpedance Analysis-Guided Volume Expansion for the Prevention of Contrast-Induced Acute Kidney Injury (the BELIEVE Pilot Randomized Controlled Trial).

INTRODUCTION: Peri-procedural i.v. fluid administration is important for the prevention of contrast-induced acute kidney injury (CI-AKI). However, standardized fluid management protocols may not be suitable for all patients. We therefore wished to determine whether an individualized fluid administration protocol guided by measuring extracellular water (ECW) using bioimpedance analysis (BIA) would be safe and would reduce the incidence CI-AKI compared to a standardized fluid administration prescription. METHODS: In this pilot, randomized, parallel-group, single-blind, controlled trial, we compared the effect of BIA-guided isotonic bicarbonate administration according to the ratio of ECW to total body water (ECW/TBW) to our standard isotonic bicarbonate protocol in regard to the safety and efficacy of preventing CI-AKI in chronic kidney disease patients undergoing elective cardiac angiography. Our primary outcome was the incidence of CI-AKI, which was defined as a ≥0.3 mg/dl or 150% increase in serum creatinine concentration within 48 to 72 hours after cardiac angiography. RESULTS: We studied 61 patients, 30 in the bioimpedance group and 31 in the control group. Age was similar (72.5 ± 7 vs. 71.4 ± 7.9 years), as were body mass index (25.5 vs. 25.8 kg/m2) and baseline serum creatinine (1.3 ± 0.3 vs. 1.4 ± 0.4 mg/dl). The peri-procedural fluid volume administered was significantly greater in the BIA-guided hydration group (899.0 ± 252.7 ml vs. 594.4 ± 125.9 ml, P < .01). The incidence of CI-AKI was 3.3% in BIA-guided hydration group and 6.5% in the control group (relative risk = 0.52, 95% confidence interval = 0.05-5.40, P = 1.00). Adverse events reported were comparable between groups (6.7% vs. 6.5%, P = 1.00). CONCLUSIONS: The overall incidence of CI-AKI after cardiac angiography in our patients with mild-to-moderate renal insufficiency was lower than anticipated. Isotonic bicarbonate administration guided by bioimpedance measurements was safe, and probably led to a lower incidence of CI-AKI, although this not reach statistical significance.

Immune response to influenza vaccination in ESRD patients undergoing hemodialysis vs. hemodiafiltration.

BACKGROUND: On-line hemodiafiltration (HDF) clears more azotemic toxins compared to high-flux hemodialysis (HD). The response to vaccination is impaired in dialysis patients. We wished to determine whether the immune responses to influenza vaccine in dialysis patients treated by HDF were stronger than those treated by HD. MATERIALS AND METHODS: We conducted a prospective cohort study in chronic dialysis patients during the 2016 and 2017 influenza seasons. All participants received a single standard dose of trivalent influenza vaccine, and we studied the elicited humoral immune response by hemagglutination inhibition test, and cell-mediated immune response by enumeration of lymphocyte cellular markers and proliferation assays. RESULTS: We immunized 60 end-stage renal disease (ESRD) patients: 42 (70%) treated with HD and 18 patients (30%) with HDF. The median (interquartile range) age was 65.0 (55.0-74.5) years. All patients developed seroprotection to at least one influenza vaccine strain at one month post-vaccination, and did not differ between groups. By logistic regression, age was the only factor independently associated with seroconversion to all vaccine strains (odds ratio 0.89, 95% confidence interval 0.80-0.98; p = 0.022). Seroprotection to all vaccine strains was sustained for longer in patients treated with HDF, and the results remained the same after age adjustment. For cellular immune response, patients who seroconverted to all vaccine strains had higher CD38+ T cell subpopulations pre-vaccination. Patients treated by HDF had higher lymphocyte proliferation to circulating influenza A strains. CONCLUSIONS: Seroconversion to all influenza vaccine strains was associated with age. Patients treated with HDF demonstrated seroprotection was sustained for longer compared to those treated by HD and greater lymphocyte proliferation to circulating influenza A strains. These encouraging results for HDF require confirmation in a larger dialysis population. TRIAL REGISTRATION: ClinicalTrial.gov, NCT04122222.

Effect of bioelectrical impedance analysis-guided dry weight adjustment, in comparison to standard clinical-guided, on the sleep quality of chronic haemodialysis patients (BEDTIME study): a randomised controlled trial.

BACKGROUND: Sleep disturbance is common among chronic haemodialysis patients, which leads to poor quality of life, in addition to increased instances of morbidity and mortality. Hypervolemia has been linked to sleep problems observed in chronic haemodialysis patients, which suggests that optimising one's fluid status could improve the sleep quality of this patient group. In our study, we subjectively examined and objectively measured sleep parameters, using actigraphy recordings, the Pittsburgh Sleep Quality Index (PSQI) questionnaire, and Epworth Sleepiness Scale (ESS), in order to compare bioelectrical impedance analysis (BIA)-guided and standard clinical-guided dry weight adjustment. METHODS: We randomly selected 19 chronic haemodialysis patients with subclinical hypervolemia, defined as a clinically euvolemic status, despite the ratio of extracellular water to total body water being more than 0.4 in BIA. Furthermore, these patients, who were poor sleepers (PSQI > 5), were assigned to either a BIA-guided dry weight group (BIA group) or a standard clinical-guided one (clinical group). The primary outcome was changes in sleep actigraphy parameters between the groups at 1, 3, and 6 months. Changes observed in the PSQI and ESS score between the two groups over the same period of time were the secondary endpoints. RESULTS: The mean age of the participants was 63.53 ± 11.12 years, and 42% of them were male. All sleep parameters measured by means of actigraphy were not significantly different between the two groups. Interestingly, at 3 and 6 months, the subjective sleep quality significantly improved in the BIA group, as reflected by a greater decline in the PSQI score, in comparison with the clinical group (3 months: mean difference - 1.82 [- 3.13 to - 0.51], P = 0.006; 6 months: mean difference - 3.16 [- 4.49 to - 1.83], P <  0.001). However, sleepiness assessed by the ESS was not significantly different between the groups throughout the study. CONCLUSIONS: Optimisation of the fluid status by employing BIA did not improves sleep actigraphy parameter, however, it significantly ameliorates the subjective sleep quality of chronic haemodialysis patients. This observation should be further explored in larger samples and longer clinical trials. TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov ( NCT02825589 ) on July 7, 2016.

The impact of introducing the early warning scoring system and protocol on clinical outcomes in tertiary referral university hospital.

PURPOSE: The aim of this study was to evaluate the impact of a hospital protocol in response to patient deterioration in general wards, stratified using the national early warning score (NEWS), on primary patient outcomes of in-hospital mortality and percentage of patients transferred to the intensive care unit (ICU). PATIENTS AND METHODS: We conducted a prospective observational cohort study among adult medical patients admitted to a university hospital in Bangkok. A 4-month pre-protocol period (November 2015 to February 2016) was assigned to a control group and a protocol period (March 2016 to June 2016) was allocated to a protocol group. On admission, vital signs (respiratory rate, pulse rate, systolic blood pressure, and temperature), oxygen saturation, presence of oxygen supplementation, and neurological status were used to calculate NEWS. Patients were categorized as low, moderate, or high risk based on the NEWS. During protocol period, when patients' conditions are critical and they are at imminent risk, the NEWS detects the event and triggers a systematic response. The response enables closed monitoring and early treatment by expert physicians to rapidly stabilize and triage the patient to a location where services meet the patient's needs. Primary outcomes were compared between the pre-protocol and protocol groups using historical controls for the intervention, which is the availability of NEWS to staff and an associated escalation pathway. RESULTS: A total of 1,145 patients were included in the analysis: 564 patients in the pre-protocol group and 581 in the protocol group. The mean NEWS of patients at admission was higher in the protocol group than in the pre-protocol group (2.4±2.4 vs 1.77±2.158; P<0.001). There was no significant difference for in-hospital mortality and percentage of patients transferred to ICU between the groups. Among 95 (8.3%) patients at moderate risk, in-hospital mortality and ICU transfer percentage were lower in the protocol group than in the pre-protocol group (2.9 vs 15.4%; P=0.026; RR 0.188, 95% CI 0.037%-0.968% and 8.7 vs 26.9%; P=0.021; RR 0.322, 95% CI 0.12-0.87, respectively). CONCLUSION: Implementing the NEWS with the hospital protocol did not change the overall patient's outcomes.