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).

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).

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.

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.

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.

Urine epidermal growth factor, monocyte chemoattractant protein-1 or their ratio as predictors of complete remission in primary glomerulonephritis.

BACKGROUND: The balance of several cytokines likely influences the resolution of glomerulonephritis. Monocyte chemoattractant protein-1(MCP-1) is a chemokine that promotes renal inflammation whereas epidermal growth factor (EGF) stimulates protective responses. Previously, high urine MCP-1(MCP-1) and low urine EGF (EGF) levels were found to be associated with tubulointerstitial fibrosis, but there is limited information on the value of these mediators as predictors of therapeutic responses or long term outcome in primary glomerulonephritis. OBJECTIVES: To determine the performance of urine EGF, MCP-1 or their ratio at baseline as biomarkers to predict complete remission, and the relationship of these mediators with subsequent renal function 24 months later in primary glomerulonephritis. METHODS: This is a prospective study of patients with biopsy-proven primary glomerulonephritis. Baseline urine samples were collected at biopsy before therapy. MCP-1 and EGF were analyzed by enzyme-linked immunosorbent assays and expressed as a ratio to urine creatinine (ng/mgCr) or as EGF/MCP-1 ratio (ng/ng). Proteinuria and estimated glomerular filtration rate (eGRF) were monitored after therapy. Complete remission (CR) was defined as proteinuria ≤ 0.3 g/gCr. RESULTS: Median follow-up was 20 months. Of all patients (n = 74), 38 patients (51.4%) subsequently achieved CR. Baseline urine EGF and EGF/MCP-1 levels were significantly higher in CR compared to Not CR. By contrast, MCP-1 was not different. High EGF (EGF > 75 ng/mgCr) was a significant predictor (OR 2.28) for CR by multivariate analysis after adjusting for proteinuria, blood pressure, baseline eGFR. In patients who completed 24 months follow-up (n = 43), baseline EGF correlated inversely with proteinuria and positively with eGFR at 24 months. CONCLUSION: High urine EGF level is a promising biomarker of CR. Baseline EGF levels correlated with kidney function at 2 years. EGF/MCP-1 was not superior to EGF alone. Further studies are necessary to determine the role of urine EGF as a guide to therapy in primary GN.

The Effect of On-Line Hemodiafiltration, Vegetarian Diet, and Urine Volume on Advanced Glycosylation End Products Measured by Changes in Skin Auto-Fluorescence.

Increasing urea clearance by hemodialysis (HD) has not improved patient survival. Hemodiafiltration (HDF) has been reported to reduce cardiovascular mortality. HDF increases middle sized solute clearances. Advanced glycosylation end products (AGEs) are associated with increased cardiovascular mortality. We wished to determine whether HDF reduces AGEs. Skin auto-fluorescence (SAF) measures circulating AGEs deposited in the skin. We compared SAF measurements 12 months apart in high flux HD and HDF patients. At enrollment SAF was not different (HD 3.34 ± 0.71 vs. HDF 3.48 ± 1.05 AU). At seven months after completion of SAF measurement, one hemodiafiltration center returned to hemodialysis, and one hemodialysis center converted to hemodiafiltration. In the 66 patients treated solely by high flux HD, SAF increased (3.36 ± 0.71 to 3.82 ± 0.88 AU, P < 0.001), whereas there was no change for 47 exclusively treated by HDF (3.45 ± 1.13 to 3.44 ± 0.85 AU, P > 0.9). SAF increased in 34 patients switching from HDF to high flux HD (3.52 ± 0.94 vs. 3.88 ± 1.05, P < 0.05), with no significant change for 33 patients converting from high flux HD to HDF (3.32 ± 0.72 to 3.48 ± 1.07 AU, P > 0.3). On multivariate analysis, SAF was associated with older age (ß coefficient 0.013, P = 0.002), prescription of insulin (ß 0.29, P = 0.016), lanthanum (ß 0.36, P = 0.004), and warfarin (ß 0.62, P = 0.012), whereas vegetarian diet and > 250 mL/day residual urine volume were negatively associated with SAF (ß -0.58, P = 0.002 and ß -0.26, P = 0.033 respectively). Residual urine output and vegetarian diet were associated with lower AGE deposition. Whereas SAF increased over time in patients treated with high flux HD, there was no statistical change in SAF in those exclusively treated by HDF.

Urine Epidermal Growth Factor, Monocyte Chemoattractant Protein-1 or Their Ratio as Biomarkers for Interstitial Fibrosis and Tubular Atrophy in Primary Glomerulonephritis.

BACKGROUND/AIMS: The degree of tubular atrophy and interstitial fibrosis (IFTA) is an important prognostic factor in glomerulonephritis. Imbalance between pro-inflammatory cytokines such as monocyte chemoattractant protein- 1 (MCP-1) and protective cytokines such as epidermal growth factor (EGF) likely determine IFTA severity. In separate studies, elevated MCP-1 and decreased EGF have been shown to be associated with IFTA severity. In this study, we aim to evaluate the predictive value of urinary EGF/MCP-1 ratio compared to each biomarker individually for moderate to severe IFTA in primary glomerulonephritis (GN). METHODS: Urine samples were collected at biopsy from primary GN (IgA nephropathy, focal and segmental glomerulosclerosis, minimal change disease, membranous nephropathy). MCP-1 and EGF were analyzed by enzyme-linked immunosorbent assay. RESULTS: EGF, MCP-1 and EGF/MCP-1 ratio from primary GN, all correlated with IFTA (n=58). By univariate analysis, glomerular filtration rate, EGF, and EGF/MCP-1 ratio were associated with IFTA. By multivariate analysis, only EGF/MCP-1 ratio was independently associated with IFTA. EGF/MCP-1 ratio had a sensitivity of 88% and specificity of 74 % for IFTA. EGF/MCP-1 had good discrimination for IFTA (AUC=0.85), but the improvement over EGF alone was not significant. CONCLUSION: EGF/MCP-1 ratio is independently associated IFTA severity in primary glomerulonephritis, but the ability of EGF/MCP-1 ratio to discriminate moderate to severe IFTA may not be much better than EGF alone.

Increased postdialysis systolic blood pressure is associated with extracellular overhydration in hemodialysis outpatients.

Recently, intradialytic hypertension was reported to be associated with increased mortality for hemodialysis patients. To determine whether volume status plays a role in dialysis-associated hypertension, we prospectively audited 531 patients that had volume assessments measured by multiple-frequency bioelectrical impedance during their midweek dialysis session. Mean pre- and postdialysis weights were 73.2 vs 71.7 kg, and systolic blood pressures (SBPs) 140.5 vs. 130.3 mm Hg, respectively. Patients were divided into groups based on a fall in SBP of 20 mm Hg or more (32%), an increased SBP of 10 mm Hg or more (18%), and a stable group (50%). There were no differences in patient demographics, dialysis prescriptions, predialysis weight, total body (TBW), and extracellular (ECW) and intracellular water (ICW). However, the change in weight was significantly less in the increased blood pressure group (1.01 kg vs. stable 1.65, and 1.7 hypotensive). The ratio of ECW to TBW was significantly higher in the increased blood pressure group, particularly post dialysis (39.1 vs. stable 38.7% and fall in blood pressure group 38.7%). ECW overhydration was significantly greater in the increased blood pressure group post dialysis (0.7 (0.17 to 1.1) vs. stable 0.39 (-0.2 to 0.95) and fall in blood pressure group 0.38 (-0.19 to 0.86) liter). We found that patients who had increased blood pressure post dialysis had greater hydration status, particularly ECW. Thus, patients who increase their blood pressure post dialysis should have review of target weight, consideration of lowering the post-dialysis weight, and may benefit from increasing dialysis session time or frequency.

The effect of vegetarian diet on skin autofluorescence measurements in haemodialysis patients.

CVD remains the major cause of death for dialysis patients. Dialysis patients have both traditional and nontraditional risk factors, including the retention of advanced glycation end products (AGE). Tissue AGE can be measured by skin autofluorescence (SAF) and are a reliable measurement of chronic exposure. Dietary intake of AGE may be lower in vegetarian patients than in non-vegetarian patients, so we determined whether vegetarian patients had lower SAF than non-vegetarian patients. We measured SAF in 332 adult haemodialysis patients using a UV technique in a standardised manner. Information about patients' demographic data, laboratory results and current medicinal prescriptions was collected retrospectively from the hospital's computerised database. The mean patient age was 65·2 (SD 15·1) years, 64 % were men, 42 % were diabetic, and 66 % were Caucasian. The mean SAF was 3·26 (SD 0·95) arbitrary units (AU), and SAF was lower in vegetarians as compared to non-vegetarians (2·71 (SD 0·6) v. 3·31 (SD 0·97) AU, P= 0·002). SAF was negatively correlated on both univariate (r -0·17, P= 0·002) and multiple linear regression (ß coefficient -0·39, 95 % CI -0·7, -0·07, P= 0·019). SAF, a marker of tissue AGE deposition, was reduced in vegetarian haemodialysis patients after correction for known confounders, which suggests that a vegetarian diet may reduce exposure to preformed dietary AGE. Dietary manipulation could potentially reduce tissue AGE and SAF as well as CVD risk, but further prospective studies are warranted to confirm the present findings.

Skin autofluorescence advanced glycosylation end products as an independent predictor of mortality in high flux haemodialysis and haemodialysis patients.

AIM: Haemodialysis (HD) patients have an increased risk of cardiovascular death. In addition to the standard cardiovascular disease (CVD) risk factors, HD patients have additional risk factors including bone mineral disorders, anaemia and uraemic toxins, including advance glycosylation end product (AGEs). AGEs increase in HD patients due to reduced renal clearance and increased production. Tissue AGEs measured by skin autofluorescence (SAF) have been shown to be more reliable and reproducible to asses AGE accumulation in HD patients compared with serum levels. We wished to determine whether increasing SAF due to AGEs was associated with reduced survival in HD patients. METHODS: We measured SAF in the non-fistula arm in a cross-sectional study of 332 thrice weekly HD outpatients who were then followed prospectively for 30 months. RESULTS: Mean patient age was 65.7 ± 15.1 years, 64.2% male, 41.9% diabetic, mean dialysis vintage 65.1 (range 1-413) months, with an average sessional Kt/Vurea of 1.43 ± 0.34. A percentage of 61.1 had a history of hypertension, 32.2% had CVD, 16% had peripheral vascular disease (PVD) and 37% was current smokers. The mean SAF was 3.27 ± 0.96 IU, and patients with SAF above the mean (>3.27 IU) had a higher risk of death, and higher SAF was independently associated with increased mortality: hazard ratio 12.95 (1.60-104.8), P = 0.016. CONCLUSION: Accumulation of AGEs, measured by SAF, was independently associated with higher risk of death in HD patients. Additional studies are required to determine whether a reduction in tissue AGEs in dialysis patients may reduce mortality in this high-risk population.

Predialysis NTproBNP predicts magnitude of extracellular volume overload in haemodialysis patients.

INTRODUCTION: Increased natriuretic peptides are associated with increased cardiovascular and all-cause mortality for haemodialysis (HD) patients. However, debate continues whether these biomarkers are increased by extracellular water (ECW) excess and can be used to aid clinical assessment of volume status and help determine target weight. METHODS: We measured N terminal probrain natriuretic peptide (NT-proBNP) predialysis in 375 stable haemodialysis outpatients with corresponding pre and postdialysis multifrequency bioelectrical impedance assessments (MFBIA) of (ECW)/total body water (TBW). RESULTS: Median age 64 (51-75), 63.9% male, 42.9% diabetic, 43.2% Caucasoid, 14.4% with a history of myocardial infarction, 8.4% coronary artery bypass surgery, dialysis vintage 28.2 (12.3-55.5) months. Median predialysis NT-proBNP 283 (123-989) pmol/l, and predialysis ECW/TBW ratio 0.397 ± 0.029. On multivariate analysis, predialysis log NT-proBNP was associated with predialysis systolic blood pressure (ß 0.007, p = 0.000), weight (ß -0.008, p = 0.001), valvular heart disease (ß 0.342, p = 0.015, ECW/TBW (ß 1.3, p = 0.019) and log CRP (ß 0.145, p = 0.037). Dividing patients into NTproBNP quartiles, %ECW/TBW and relative ECW overhydration were significantly greater for the highest quartile vs. lowest (40.5 ± 4.1 vs. 39.0 ± 1.1, and 1.51 ± 1.24 vs. 0.61 ± 0.69 l, respectively, p < 0.001). CONCLUSION: In this study, predialysis NTproBNP values were associated with direct assessments of the extracellular volume excess measured by MFBIA and systolic arterial blood pressure. This suggests that predialysis NTproBNP values can potentially be used to aid clinical assessment of volume status in dialysis patients to determine target weight.

Brain-kidney crosstalk.

Encephalopathy and altered higher mental functions are common clinical complications of acute kidney injury. Although sepsis is a major triggering factor, acute kidney injury predisposes to confusion by causing generalised inflammation, leading to increased permeability of the blood-brain barrier, exacerbated by hyperosmolarity and metabolic acidosis due to the retention of products of nitrogen metabolism potentially resulting in increased brain water content. Downregulation of cell membrane transporters predisposes to alterations in neurotransmitter secretion and uptake, coupled with drug accumulation increasing the risk of encephalopathy. On the other hand, acute brain injury can induce a variety of changes in renal function ranging from altered function and electrolyte imbalances to inflammatory changes in brain death kidney donors.

Mineral metabolism and outcomes in chronic kidney disease stage 2-4 patients.

BACKGROUND: Marked hyperphosphatemia, hyperparathyroidism and 25-hydroxyvitamin D deficiency are associated with mortality in dialysis patients. Such data in chronic kidney disease stage 2-4 population are limited. It has been suggested that high-normal serum phosphate predicts worse renal and patient outcomes. The data regarding parathyroid hormone and outcomes in this population is limited. The present study examined mineral metabolism and its association with the development of end-stage renal disease and mortality in stage 2-4 chronic kidney disease patients. METHODS: This is a prospective cohort study that included 466 non-dialysis chronic kidney disease stage 2-4 patients. Mineral parameters were obtained at the time of enrollment and the patients were followed prospectively for 25 (1-44) months or until they reached the endpoints of end-stage renal disease or mortality. RESULTS: Hyperparathyroidism and 25-hydroxyvitamin D deficiency began to occur in the early stages of chronic kidney disease, whereas significant hyperphosphatemia only developed in the later stages. High-normal and mildly elevated serum phosphate (>4.2 mg/dL) predicted the composite outcome of end-stage renal disease or mortality after adjustments for cardiovascular risk factors, chronic kidney disease stage and other mineral parameters. Parathyroid hormone levels above the upper limit of normal (>65 pg/mL) predicted the future development of end-stage renal disease and the composite outcome of end-stage renal disease or mortality after adjustments. 25-hydroxyvitamin D deficiency (<15 ng/mL) was also associated with worse outcomes. CONCLUSIONS: In chronic kidney disease, hyperparathyroidism developed prior to significant hyperphosphatemia confirming the presence phosphate retention early in the course of chronic kidney disease. High-normal serum phosphate and mildly elevated parathyroid hormone levels predicted worse renal and patient outcomes. This data emphasizes the need for early intervention in the care of chronic kidney disease stage 2-4 patients.

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.

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.

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.

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.

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).