Assessing caregiver burden in advanced kidney disease: protocol for a systematic review of the measurement properties of instruments and tools.

INTRODUCTION: Caregiver burden is a significant issue in the care of patients with advanced kidney disease. Its assessment is crucial for evaluating the needs of caregivers and for the development of interventions to support them. Several instruments have been developed to measure caregiver burden in these patients. However, the measurement properties of these instruments have not been systematically reviewed. METHODS AND ANALYSIS: This systematic review will include a comprehensive search of databases including PubMed, CINAHL, Embase, Cochrane Library, SCOPUS and Web of Science by using keywords and MeSH terms to identify relevant studies starting from each database inception to 1 January 2024 and covering papers in English. The search strategy will combine relevant keywords and database-specific subject headings related to the following concepts: (1) caregivers, (2) burden, stress, distress, (3) chronic kidney disease, end-stage kidney disease, dialysis. Reference lists of eligible articles will also be hand searched. We will include quantitative and qualitative studies evaluating measurement properties of instruments assessing caregiver burden in caregivers of adult patients (aged ≥18 years). Data will be extracted from the selected studies and analysed using the COnsensus-based Standards for the selection of health Measurement INstruments checklist as the study quality assessment tool. Subsequently, the van der Vleuten utility index will be used to critique and categorise the instruments. A narrative that synthesises the utility of all instruments will be presented along with recommendations for the selection of instruments depending on specific clinical contexts. This systematic review will provide an overview of the measurement properties of available instruments, including discussion on reliability, validity and responsiveness. Results from the review may give rise to the subsequent development of most appropriate instrument that could be applied to the assessment of caregiver burden in advanced kidney disease. ETHICS AND DISSEMINATION: Ethics approval is not required as this study will merely synthesise data from published studies. The results will be disseminated through peer-reviewed publications as well as conference presentations. PROSPERO REGISTRATION NUMBER: CRD42023433906.

Disparities in ethnicity and metabolic disease burden in referrals to nephrology.

Introduction: The profile of patients referred from primary to tertiary nephrology care is unclear. Ethnic Malay patients have the highest incidence and prevalence of kidney failure in Singapore. We hypothesised that there is a Malay predominance among patients referred to nephrology due to a higher burden of metabolic disease in this ethnic group. Methods: This is a retrospective observational cohort study. From 2014 to 2018, a coordinator and physician triaged patients referred from primary care, and determined co-management and assignment to nephrology clinics. Key disease parameters were collated on triage and analysed. Results: A total of 6,017 patients were studied. The mean age of patients was 64 ± 16 years. They comprised 57% men; 67% were Chinese and 22% were Malay. The proportion of Malay patients is higher than the proportion of Malays in the general population (13.4%) and they were more likely than other ethnicities to have ≥3 comorbidities, including diabetes mellitus, hypertension, hyperlipidaemia, coronary artery disease and stroke (70% vs. 57%, P < 0.001). Malay and Indian patients had poorer control of diabetes mellitus compared to other ethnicities (glycated haemoglobin 7.8% vs. 7.4%, P < 0.001). Higher proportion of Malay patients compared to other ethnicities had worse kidney function with estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 on presentation (28% vs. 24%, P = 0.003). More ethnic Malay, Indian and younger patients missed appointments. Conclusion: A disproportionately large number of Malay patients are referred for kidney disease. These patients have higher metabolic disease burden, tend to miss appointments and are referred at lower eGFR. Reasons underpinning these associations should be identified to facilitate efforts for targeting this at-risk population, ensuring kidney health for all.

Randomized Controlled Clinical Trial of the Effect of Treatment with Vitamin K2 on Vascular Calcification in Hemodialysis Patients (Trevasc-HDK).

Introduction: Vitamin K deficiency among patients on hemodialysis (HD) affects the function of matrix GLA protein (MGP), a potent vitamin K-dependent inhibitor of vascular calcification (VC). Methods: We conducted a single-center randomized controlled trial (RCT) on maintenance HD patients to examine if vitamin K2 supplementation can reduce progression of coronary artery calcification (CAC) over an 18-month study period. Patients were randomized to vitamin K2 group receiving menaquinone-7360 µg 3 times/wk or control group. The primary outcome was CAC scores at the end of the study period. The secondary outcomes were aortic valve calcification (AVC), carotid-femoral pulse wave velocity (cfPWV), aortic augmentation index (AIx), dephosphorylated undercarboxylated MGP (dp-ucMGP) levels, major adverse cardiac events (MACE), and vascular access events. Results: Of the 178 patients randomized, follow-up was completed for 138 patients. The CAC scores between the 2 groups were not statistically different at the end of 18 months (relative mean difference [RMD] 0.85, 95% CI 0.55-1.31). The secondary outcomes did not differ significantly in AVC (RMD 0.82, 95% CI 0.34-1.98), cfPWV (absolute mean difference [AMD] 0.55, 95% CI -0.50 to 1.60), and AIx (AMD 0.13, 95% CI -3.55 to 3.80). Supplementation with vitamin K2 did reduce dp-ucMGP levels (AMD -86, 95% CI -854 to -117). The composite outcome of MACE and mortality was not statistically different between the 2 groups (Hazard ratio = 0.98, 95% CI 0.50-1.94). Conclusion: Our study did not demonstrate a beneficial effect of vitamin K2 in reducing progression of VC in this population at the studied dose and duration.

Extrapulmonary manifestations and complications of severe acute respiratory syndrome coronavirus-2 infection: a systematic review.

Introduction: We aimed to describe the extrapulmonary manifestations of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, including their frequency, onset with respect to respiratory symptoms, pathogenesis and association with disease severity. Methods: We searched the MEDLINE and Embase databases for SARS-CoV-2-related studies. Meta-analysis, observational studies, case series and case reports published in English or Chinese between 1 January 2020 and 1 May 2020 were included. Reports with only paediatric or obstetric cases were excluded. Results: 169 articles were included. Early manifestations (preceding respiratory symptoms until Day 6 of onset) included olfactory and gustatory disturbance (self-reported in up to 68% and 85% of cases, respectively), gastrointestinal symptoms (up to 65.9%) and rash (up to 20.4%). From Day 7 onwards, hypercytokinaemia, paralleled multi-organ complications including acute cardiac injury (pooled incidence of 17.7% in 1,412 patients, mostly with severe disease and 17.4% mortality), kidney and liver injury (up to 17% and 33%, respectively) and thrombocytopenia (up to 30%). Hypercoagulability resulted in venous thromboembolic events in up to 31% of all patients. Uncommon disease presentation and complications comprised Guillain-Barré syndrome, rhabdomyolysis, otitis media, meningoencephalitis and spontaneous pneumomediastinum. Conclusion: Although the systemic manifestations of SARS-CoV-2 infection are variegated, they are deeply interwoven by shared mechanisms. Two phases of extrapulmonary disease were identified: (a) an early phase with possible gastrointestinal, ocular and cutaneous involvement; and (b) a late phase characterised by multiorgan dysfunction and clinical deterioration. A clear, multidisciplinary consensus to define and approach thromboinflammation and cytokine release syndrome in SARS-CoV-2 is needed.

Association of anticoagulation use during continuous kidney replacement therapy and 90-day outcomes: A multicentre study.

Introduction: Anticoagulation is recommended during continuous kidney replacement therapy (CKRT) to prolong the filter lifespan for optimal filter performance. We aimed to evaluate the effect of anticoagulation during CKRT on dialysis dependence and mortality within 90 days of intensive care unit (ICU) admission. Method: Our retrospective observational study evaluated the first CKRT session in critically ill adults with acute kidney injury (AKI) in Singapore from April to September 2017. The primary outcome was a composite of dialysis dependence or death within 90 days of ICU admission; the main exposure variable was anticoagulation use (regional citrate anticoagulation [RCA] or systemic heparin). Multivariable logistic regression was performed to adjust for possible confounders: age, female sex, Acute Physiology and Chronic Health Evaluation (APACHE II) score, liver dysfunction, coagulopathy (international normalised ratio[INR] >1.5) and platelet counts of less than 100,000/uL). Results: The study cohort included 276 patients from 14 participating adult ICUs, of whom 176 (63.8%) experienced dialysis dependence or death within 90 days of ICU admission (19 dialysis dependence, 157 death). Anticoagulation significantly reduced the odds of the primary outcome (adjusted odds ratio [AOR] 0.47, 95% confidence interval [CI] 0.27-0.83, P=0.009). Logistic regression analysis using anticoagulation as a 3-level indicator variable demonstrated that RCA was associated with mortality reduction (AOR 0.46, 95% CI 0.25-0.83, P=0.011), with heparin having a consistent trend (AOR 0.51, 95% CI 0.23-1.14, P=0.102). Conclusion: Among critically ill patients with AKI, anticoagulation use during CKRT was associated with reduced dialysis or death at 90 days post-ICU admission, which was statistically significant for regional citrate anticoagulation and trended in the same direction of benefit for systemic heparin anticoagulation. Anticoagulation during CKRT should be considered whenever possible.

Elevated Urinary Tissue Inhibitor of Metalloproteinase-2 and Insulin-Like Growth Factor Binding Protein-7 Predict Drug-Induced Acute Kidney Injury.

BACKGROUND: Urinary tissue inhibitor of metalloproteinase-2 (TIMP2) and insulin-like growth factor binding protein-7 (IGFBP7) predict severe acute kidney injury (AKI) in critical illness. Earlier but subtle elevation of either biomarker from nephrotoxicity may predict drug-induced AKI. METHODS: A prospective study involving serial urine collection in patients treated with vancomycin, aminoglycosides, amphotericin, foscarnet, or calcineurin inhibitors was performed. Urinary TIMP2 and IGFBP7, both absolute levels and those normalized with urine creatinine, were examined in days leading to AKI onset by KDIGO criteria in cases or at final day of nephrotoxic therapy in non-AKI controls, who were matched for age, baseline kidney function, and nephrotoxic exposure. RESULTS: Urinary biomarker analyses were performed in 21 AKI patients and 28 non-AKI matched-controls; both groups had comparable baseline kidney function and duration of nephrotoxic drug therapy. Significantly higher absolute, normalized, and composite levels of TIMP2 and IGFBP7 were observed in AKI cases versus controls as early as 2-3 days before AKI onset (all P<0.05); >70% of patients with corresponding levels above 75th percentile developed AKI. Normalized TIMP2 at 2-3 days pre-AKI predicted AKI with the highest average AUROC of 0.81, followed by that of composite [TIMP2]x[IGFBP7] (0.78) after cross-validation. [TIMP2]x[IGFBP7] >0.01 (ng/mL)2/1000 predicted AKI with a sensitivity of 79% and specificity of 60%. CONCLUSION: Elevated urinary TIMP2 or IGFBP7 predicts drug-induced AKI with a lead-time of 2-3 days; an opportune time for interventions to reduce nephrotoxicity.

Biomarker Rule-in or Rule-out in Patients With Acute Diseases for Validation of Acute Kidney Injury in the Emergency Department (BRAVA): A Multicenter Study Evaluating Urinary TIMP-2/IGFBP7.

Background: Urine tissue inhibitor of metalloproteinases-2/insulin-like growth factor-binding protein 7 (TIMP-2/IGFBP7) (NephroCheck, Ortho Clinical Diagnostics, Raritan, NJ, USA) is a US Food and Drug Administration-approved biomarker for risk assessment of acute kidney injury (AKI) in critically ill adult patients in intensive care units; however, its clinical impact in the emergency department (ED) remains unproven. We evaluated the utility of NephroCheck for predicting AKI development and short-term mortality in the ED. Methods: This was a prospective, observational, five-center international study. We consecutively enrolled ED patients admitted with ≥30% risk of AKI development (assessed by ED physician: ED score) or acute diseases. Serum creatinine was tested on ED arrival (T0), day 1, and day 2 (T48); urine for NephroCheck was collected at T0 and T48. We performed ROC curve and reclassification analyses. Results: Among the 529 patients enrolled (213 females; median age, 65 years), AKI developed in 59 (11.2%) patients. The T0 NephroCheck value was higher in the AKI group than in the non-AKI group (median 0.77 vs. 0.29 (ng/m)2/1,000, P=0.001), and better predicted AKI development than the ED score (area under the curve [AUC], 0.64 vs. 0.53; P=0.04). In reclassification analyses, adding NephroCheck to the ED score improved the prediction of AKI development (P<0.05). The T0 NephroCheck value predicted 30-day mortality (AUC, 0.68; P<0.001). Conclusions: NephroCheck can predict both AKI development and short-term mortality in at-risk ED patients. NephroCheck would be a useful biomarker for early ruling-in or ruling-out of AKI in the ED.

Health Care Analytics With Time-Invariant and Time-Variant Feature Importance to Predict Hospital-Acquired Acute Kidney Injury: Observational Longitudinal Study.

BACKGROUND: Acute kidney injury (AKI) develops in 4% of hospitalized patients and is a marker of clinical deterioration and nephrotoxicity. AKI onset is highly variable in hospitals, which makes it difficult to time biomarker assessment in all patients for preemptive care. OBJECTIVE: The study sought to apply machine learning techniques to electronic health records and predict hospital-acquired AKI by a 48-hour lead time, with the aim to create an AKI surveillance algorithm that is deployable in real time. METHODS: The data were sourced from 20,732 case admissions in 16,288 patients over 1 year in our institution. We enhanced the bidirectional recurrent neural network model with a novel time-invariant and time-variant aggregated module to capture important clinical features temporal to AKI in every patient. Time-series features included laboratory parameters that preceded a 48-hour prediction window before AKI onset; the latter's corresponding reference was the final in-hospital serum creatinine performed in case admissions without AKI episodes. RESULTS: The cohort was of mean age 53 (SD 25) years, of whom 29%, 12%, 12%, and 53% had diabetes, ischemic heart disease, cancers, and baseline eGFR <90 mL/min/1.73 m2, respectively. There were 911 AKI episodes in 869 patients. We derived and validated an algorithm in the testing dataset with an AUROC of 0.81 (0.78-0.85) for predicting AKI. At a 15% prediction threshold, our model generated 699 AKI alerts with 2 false positives for every true AKI and predicted 26% of AKIs. A lowered 5% prediction threshold improved the recall to 60% but generated 3746 AKI alerts with 6 false positives for every true AKI. Representative interpretation results produced by our model alluded to the top-ranked features that predicted AKI that could be categorized in association with sepsis, acute coronary syndrome, nephrotoxicity, or multiorgan injury, specific to every case at risk. CONCLUSIONS: We generated an accurate algorithm from electronic health records through machine learning that predicted AKI by a lead time of at least 48 hours. The prediction threshold could be adjusted during deployment to optimize recall and minimize alert fatigue, while its precision could potentially be augmented by targeted AKI biomarker assessment in the high-risk cohort identified.

Calcium, Vitamin D, and Bone Derangement in Nephrotic Syndrome.

INTRODUCTION: Derangement in calcium homeostasis is common in nephrotic syndrome (NS). It is postulated that low serum total calcium and vitamin D levels are due to loss of protein-bound calcium and vitamin D. It is unclear if free calcium and free vitamin D levels are truly low. The guideline is lacking with regards to calcium and vitamin D supplementation in NS. This study aims to examine calcium and vitamin D homeostasis and bone turnover in NS to guide practice in calcium and vitamin D levels supplementation. METHODOLOGY: This is a prospective pilot study of ten patients diagnosed with NS, and eight healthy controls. Calcium, vitamin D, and bone turnover-related analytes were assessed at baseline, partial and complete remission in NS patients and in healthy controls. RESULTS: NS patients had low free and total serum calcium, low total 25(OH)D, normal total 1,25(OH)D levels and lack of parathyroid hormone response. With remission of disease, serum calcium and vitamin D metabolites improved. However, nephrotic patients who do not attain complete disease remission continue to have low 25(OH)D level. CONCLUSION: In this study, the vitamin D and calcium derangement observed at nephrotic syndrome presentation trended towards normalisation in remission. This suggested calcium and vitamin D replacement may not be indicated in early-phase nephrotic syndrome but may be considered in prolonged nephrotic syndrome.

Neutrophil-to-Lymphocyte Ratio Predicts Development of Immune-Related Adverse Events and Outcomes from Immune Checkpoint Blockade: A Case-Control Study.

The utility of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) utility in predicting immune-related adverse events (irAEs) and survival have not been well studied in the context of treatment with immune checkpoint inhibitors (ICIs). We performed a case-control study of cancer patients who received at least one dose of ICI in a tertiary hospital. We examined NLR and PLR in irAE cases and controls. Logistic and Cox regression models were used to identify independent risk factors for irAEs, progression-free survival (PFS), and overall survival (OS). The study included 91 patients with irAEs and 56 controls. Multiple logistic regression showed that NLR < 3 at baseline was associated with higher occurrence of irAEs. Multivariate Cox regression showed that development of irAEs and reduction in NLR from baseline to week 6 were associated with longer PFS. Higher NLR values at baseline and/or week 6 were independently associated with shorter OS. A reduction in NLR from baseline to week 6 was associated with longer OS. In this study of cancer patients treated with ICIs, NLR has a bidirectional relationship with adverse outcomes. Lower NLR was associated with increased occurrence of irAEs while higher NLR values were associated with worse clinical outcomes.

Filter life and safety of heparin-grafted membrane for continuous renal replacement therapy - A randomized controlled trial.

Polyethyleneimine-layered membrane with grafted heparin (oXiris) may improve filter life during continuous renal replacement therapy (CRRT) in addition to its immunoadsorptive capability, compared with that of conventional membrane. In this single center, prospective, open-label pilot study, we randomized critically ill patients with bleeding risk who underwent anticoagulation-free CRRT, to commence with oXiris or M150 filter with sequential crossover. We examined the filter life with each circuit and its effect on systemic coagulation parameters. We randomized 11 and nine patients to commence CRRT with oXiris and M150 respectively, with 19 oXiris and 20 M150 filter-circuits in all. Patient profiles in both arms were comparable for illness severity and comorbidities. Median filter lives for oXiris versus M150 circuits were 13 h versus 18 h (p = 0.10). Among 11 patients with paired crossover filters, filter lives for 14 oXiris-M150 circuit pairs were 13 h versus 16 h (p = 0.27), and corresponding transmembrane pressures increased to 111 mmHg versus 75 mmHg by 12 h (p = 0.02). Patients' coagulation parameters were comparable following both filter-circuits. CRRT with oXiris (vs. M150) was independently associated with shorter filter life, adjusted for prescribed dose, vascular access, and coagulopathy. Use of oXiris did not prolong filter life over conventional membrane with no evidence of systemic heparin exposure; significant membrane clogging is observed by 12 h with oXiris.

Cumulative iodinated contrast exposure for computed tomography during acute kidney injury and major adverse kidney events.

OBJECTIVES: To determine if contrast-enhanced CT imaging performed in patients during their episode of AKI contributes to major adverse kidney events (MAKE). METHODS: A propensity score-matched analysis of 1127 patients with AKI defined by KDIGO criteria was done. Their mean age was 63 ± 16 years with 56% males. A total of 419 cases exposed to CT contrast peri-AKI were matched with 798 non-exposed controls for 14 covariates including comorbidities, acute illnesses, and initial AKI severity; outcomes including MAKE and renal recovery in hospital were compared using bivariate analysis and logistic regression. MAKE was a composite of mortality, renal replacement therapy, and doubling of serum creatinine on discharge over baseline; renal recovery was classified as early versus late based on a 7-day timeline from AKI onset to nadir creatinine or cessation of renal replacement therapy in survivors. RESULTS: Sixty-two patients received cumulatively > 100 mL of CT contrast, 143 patients had > 50-100 mL, and 214 patients had 50 mL or less; MAKE occurred in 34%, 17%, and 21%, respectively, as compared with 20% in non-exposed controls (p = 0.008 for patients with > 100 mL contrast versus none). More contrast-exposed patients experienced late renal recovery (27% versus 20%) and longer hospital days (median 10 versus 8) than non-exposed patients (all p < 0.01). On multivariate analysis, cumulative CT contrast > 100 mL was independently associated with MAKE (odds ratio 2.39 versus non-contrast, adjusted for all confounders, p = 0.005); cumulative CT contrast under 100 mL was not associated with MAKE. CONCLUSIONS: High cumulative volume of CT contrast administered to patients with AKI is associated with worse short-term renal outcomes and delayed renal recovery. KEY POINTS: • Cumulative intravenous iodinated contrast for CT imaging of more than 100 mL, during an episode of acute kidney injury, was independently associated with worse renal outcomes and less renal recovery. • These adverse outcomes including renal replacement therapy were not more frequent in similar patients who received cumulatively 100 mL or less of CT contrast, compared with non-exposed patients. • More patients with CT contrast exposure during acute kidney injury experienced delayed renal recovery.

Euglycemic Ketosis During Continuous Kidney Replacement Therapy With Glucose-Free Solution: A Report of 8 Cases.

In this report, we describe 8 patients with critical illness and diabetes mellitus who developed euglycemic ketosis during continuous kidney replacement therapy (CKRT) with a glucose-free CKRT solution. Two patients had chronic kidney disease stage 5, while the rest had acute kidney injury. The patients had improvement in all metabolic parameters following CKRT commencement, except for a worsening high anion gap metabolic acidosis, in spite of improvement in serum lactate. This led to detection of elevated serum ß-hydroxybutyrate in the setting of normoglycemia. Following diagnosis of ketosis, the patients' caloric intake was increased from a median of 15 (IQR, 10-20) to 25 (IQR, 20-29) kcal/kg/d by adding a dextrose infusion. This allowed for a corresponding increase in the insulin administered, from a median of 0.2 (IQR, 0-0.2) to 3.0 (IQR, 2.3-3.9) U/h. These contributed to a complete resolution of ketosis. This report of 8 cases demonstrates that critically ill patients are at risk of developing euglycemic ketosis during CKRT, which can be mitigated by providing adequate caloric intake and using glucose-containing CKRT solutions with appropriate insulin therapy. We recommend vigilance in evaluating for euglycemic ketosis in patients who have a persistent metabolic acidosis despite improvements in solute control during CKRT.

Nitrates in combination with hydralazine in cardiorenal syndrome: a randomized controlled proof-of-concept study.

AIMS: Cardiorenal syndrome (CRS) is a common problem of great morbidity and mortality. Hydralazine-isosorbide dinitrate (H-ISDN) may be used in renal failure and may improve exercise capacity in heart failure (HF). Our proof-of-concept study aimed to evaluate early evidence of efficacy, safety, and feasibility of H-ISDN compared with standard of care in CRS. METHODS AND RESULTS: This multi-centre, single-blind, randomized trial in Singapore enrolled CRS patients, defined as chronic HF with concomitant renal failure [estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2 ]. The primary outcome was 6 min walk test (6MWT) distance measured at 6 months. Secondary outcomes included study feasibility; efficacy outcomes which included renal, cardiac, and endothelial functions, health-related quality of life using Short Form-36, clinical outcomes; and adverse events. Forty-four patients [71 ± 10 years; 75% male; median (inter-quartile range) N-terminal prohormone brain natriuretic peptide 1346 (481-2272) pg/mL] with CRS (left ventricular ejection fraction 42 ± 12% and eGFR 46 ± 15 ml/min/1.73 m2 ) were randomized into two equal groups. Of these, 39 (89%) had hypertension, 27 (61%) had diabetes mellitus, and 17 (39%) had atrial fibrillation. Six (27%) discontinued H-ISDN owing to intolerance and poor compliance. There was a trend towards improved 6MWT distance with H-ISDN compared with standard of care at 6 months (mean difference 27 m; 95% CI, -12 to 66), with little differences in secondary efficacy outcomes. Giddiness and hypotension occurred more frequently with H-ISDN, but HF hospitalizations and mortality were less. CONCLUSIONS: Our pilot study does not support the addition of H-ISDN on top of standard medical therapy to improve exercise capacity in patients with CRS.

Treatment to reduce vascular calcification in hemodialysis patients using vitamin K (Trevasc-HDK): A study protocol for a randomized controlled trial.

INTRODUCTION: End stage renal failure patients on hemodialysis have significant vascular calcification This is postulated to be related to sub-clinical vitamin K deficiency, which is prevalent in hemodialysis patients. Vitamin K deficiency result in the failure of the matrix GLA protein (MGP) to undergo carboxylation. MGP is a natural local inhibitor of vascular calcification and the lack of functional carboxylated MGP may contribute to increase vascular calcification. Vitamin K supplement should therefore correct this anomaly and decrease the rate or severity of vascular calcification in this population of patients on long-term maintenance hemodialysis. Our study seeks to evaluate the prevalence and the progression of vascular calcification in a cohort of maintenance hemodialysis patients. It will also evaluate the efficacy of vitamin K supplementation in reducing the progression of vascular calcification in this group of patients. METHODS: This will be a single-center randomized, prospective and open-label interventional clinical trial of end stage renal failure patients on hemodialysis. We aim to recruit 200 patients. Eligible patients will be randomized to either the standard care arm or active treatment arm. Active treatment arm patients will receive standard care plus supplementation with oral vitamin K2 isoform 360 mcg 3 times weekly for a total duration of 18 months. Primary outcome measured will be absolute difference in coronary artery calcification score at 18-month between control and intervention arms. Secondary outcomes will be to compare absolute difference in aortic valve calcification, percentage of patients with regression of coronary artery calcification of at least 10%, absolute difference in aortic and systemic arterial stiffness, mortality from any cause and major adverse cardiovascular over the same period. DISCUSSION: Evidence of successful regression or retardation of vascular calcification will support the conduct of larger and longer-term trials aimed at reducing cardiovascular disease mortality and major adverse cardiovascular events in this high-risk population using a safe and inexpensive strategy TRIAL REGISTRATION:: ClinicalTrials.gov NCT02870829. Registered on 17 August 2016 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02870829National University Hospital's Institutional Review Board (2015/01000).

Myocardial ischemia by radionuclide imaging and long-term outcomes after kidney transplantation.

PURPOSE: We examined the incidence of myocardial ischemia (MI) in kidney transplant recipients (KTR) using myocardial perfusion imaging (MPI), and its association with long-term outcomes after transplantation. METHODS: A retrospective observational study was conducted of asymptomatic KTRs who underwent post-transplant MPI screening for MI, as defined by moderate to severe myocardial perfusion defects, post-stress myocardial stunning or balanced ischemia. A composite outcome of all-cause mortality, graft loss, and major adverse cardiovascular events (MACE) was examined over minimum 5 years. RESULTS: We studied 135 KTRs who underwent 226 MPIs, with follow-up duration of 10 (7-13) years. 110 (81%) patients had normal MPIs, 11 (8%) had mild perfusion defects, and 14 (10%) had MI. Correspondingly, composite outcome developed in 6%, 27%, and 43% (p = 0.04), and MACE occurred in 7%, 0%, and 21% (p = 0.11), of the respective subgroups. Twenty-six patients developed the composite outcome after 5 (3-7) years post-transplantation, including 11 patients with MACE. On multivariate analysis, MI, higher low-density lipoprotein levels, and proteinuria > 0.3 g/day independently predicted the composite outcome; only MI predicted MACE (all p < 0.05). Ninety-one patients had two serial MPIs, which increased the positive predictive value for MACE from 17 to 25%. Absence of MI had negative predictive value of 83% for MACE and 93% for the composite outcome. CONCLUSION: MI that is detected early post-kidney transplantation predicts long-term mortality, graft loss, and MACE in KTRs, with excellent negative but poor positive predictive values.

Ensuring Sustainability of Continuous Kidney Replacement Therapy in the Face of Extraordinary Demand: Lessons From the COVID-19 Pandemic.

With the exponential surge in patients with coronavirus disease 2019 (COVID-19) worldwide, the resources needed to provide continuous kidney replacement therapy (CKRT) for patients with acute kidney injury or kidney failure may be threatened. This article summarizes subsisting strategies that can be implemented immediately. Pre-emptive weekly multicenter projections of CKRT demand based on evolving COVID-19 epidemiology and routine workload should be made. Corresponding consumables should be quantified and acquired, with diversification of sources from multiple vendors. Supply procurement should be stepped up accordingly so that a several-week stock is amassed, with administrative oversight to prevent disproportionate hoarding by institutions. Consumption of CKRT resources can be made more efficient by optimizing circuit anticoagulation to preserve filters, extending use of each vascular access, lowering blood flows to reduce citrate consumption, moderating the CKRT intensity to conserve fluids, or running accelerated KRT at higher clearance to treat more patients per machine. If logistically feasible, earlier transition to intermittent hemodialysis with online-generated dialysate, or urgent peritoneal dialysis in selected patients, may help reduce CKRT dependency. These measures, coupled to multicenter collaboration and a corresponding increase in trained medical and nursing staffing levels, may avoid downstream rationing of care and save lives during the peak of the pandemic.

High-sensitivity Troponin I Predicts Galectin-3 in Chronic Kidney Disease Patients.

PURPOSE: Plasma galectin-3 (pG3) regulates inflammation. B-type natriuretic peptide (BNP), high-sensitivity Troponin I (hsTnI), and pG3 concentrations are elevated in chronic kidney disease (CKD) patients. The associations of pG3 with hsTnI/BNP are unclear. We explored the relationship of hsTnI and BNP with pG3 in Asian CKD patients and healthy controls. METHODS: We retrieved prospectively collected frozen plasma samples from 163 stable CKD patients and 105 healthy controls. BNP, hsTnI and pG3 were assayed. pG3 was assessed for associations with age, gender, ethnicity, blood pressures; height, weight, body mass index (BMI), previously diagnosed CKD, diabetes, hypertension, coronary artery disease, estimated glomerular filtration rate (eGFR); C-reactive protein, beta-trace protein, 24 h urine protein, serum albumin, uric acid and cystatin C. We created two models predicting pG3 using multiple linear regression. Akaike Information Criterion (AIC) was used for comparison. Significance was taken at P < 0.05. RESULTS: CKD versus healthy participants: mean BMI (28.2 vs. 24.9 kg/m2), median serum creatinine (159 vs. 69 µmol/L; 1.8 vs. 0.78 mg/dL), median eGFR (49 vs. 104 mL/min/1.73m2), median pG3 (29.4 vs. 15.4 ng/mL), median BNP (136 vs. 23 pg/mL), and median hsTnI (12.5 vs. 2.6 pg/mL). By univariate analysis, all variables are associated with pG3 except weight, gender and diagnosis of cerebrovascular or peripheral vascular diseases. A parsimonious model selected for hsTnI, BMI, serum albumin, cystatin C and eGFR (AIC = 77.6). CONCLUSION: BNP and hsTnI are associated with pG3 in Asian CKD patients. hsTnI is a better predictor of pG3.

Extended Mortality and Chronic Kidney Disease After Septic Acute Kidney Injury.

PURPOSE: To evaluate 1-year mortality in patients with septic acute kidney injury (AKI) and to determine association between initial AKI recovery patterns (reversal within 5 days, beyond 5 days but recovery, or nonrecovery) and chronic kidney disease (CKD) progression. METHODS: Prospective observational study, with retrospective evaluation of initial nonconsenters, of critically ill patients with septic AKI. RESULTS: We studied 207 patients (age, mean [SD]: 64 [16] years, 39% males), of which 56 (27%), 18 (9%), and 9 (4%) died in intensive care unit (ICU), post-ICU in hospital, and posthospitalization, respectively. Infections (including pneumonia) and major adverse cardiac events accounted for 64% and 12% of deaths, respectively. Factors independently associated with 1-year mortality include older age, ischemic heart disease, higher Simplified Acute Physiology Score II, central nervous system or musculoskeletal primary infections, higher daily fluid balance (FB), and frusemide administration during ICU stay (all P < .05). Among 63 patients receiving renal replacement therapy (RRT), hospital mortality was higher with cumulative median FB >8 L versus ≤8 L at RRT initiation (57% vs 24%; P = .009); there was trend for less ICU- and RRT-free days at day 28 in patients with higher FB pre-RRT (P = NS). Chronic kidney disease progression over 1 year developed in 21%, 30%, and 79% of 105 initial survivors with AKI reversal, recovery, and nonrecovery, respectively (P < .001). Acute kidney injury nonrecovery during hospitalization independently predicted CKD progression (P = .001). CONCLUSIONS: Patients with septic AKI had 40% 1-year mortality, mainly associated with infections. High FB and frusemide administration were modifiable risk factors. Risk of CKD progression is high especially with initial AKI nonrecovery.