Nephrologist follow-up care for the acute kidney injury-chronic kidney disease continuum and clinical outcomes: A systematic review and meta-analysis.

BACKGROUND: Acute kidney injury (AKI) to chronic kidney disease (CKD) continuum will increase patients' risk of mortality and long-term dialysis. The aim of the present meta-analysis is to explore the effectiveness of nephrologist care and focus on the follow-up in patients with AKI. METHODS: A systematic search of studies on nephrologist care for the AKI to CKD continuum has been conducted from PubMed and other different databases. Briefly, the primary outcome is the odds ratio of mortality as well as the secondary outcome is de novo renal replacement therapy. RESULTS: This research includes one randomized controlled trial (RCT) and four cohort studies comprised of 15 541 participants in total. The quantitative analysis displays a lower mortality rate with nephrologist care versus non-nephrologist care in patients' discharge after a hospitalization complicated by AKI (odds ratio: 0.768; 95% CI, 0.616-0.956). By means of Trial Sequential Analysis (TSA), we conclude that nephrologist care after an AKI episode declines 30% relative risks of all-cause mortality. CONCLUSION: Nephrologist care for AKI patients after a hospitalization significantly has reduced mortality compared to those followed up by non-nephrologists. There is a trend toward a potentially superior survival rate with nephrologist care has been going well in the recent years.

Characterizing Adeno-Associated Virus Capsids with Both Denaturing and Intact Analysis Methods.

Adeno-associated virus (AAV) capsids are among the leading gene delivery platforms used to treat a vast array of human diseases and conditions. AAVs exist in a variety of serotypes due to differences in viral protein (VP) sequences with distinct serotypes targeting specific cells and tissues. As the utility of AAVs in gene therapy increases, ensuring their specific composition is imperative for the correct targeting and gene delivery. From a quality control perspective, current analytical tools are limited in their selectivity for viral protein (VP) subunits due to their sequence similarities, instrumental difficulties in assessing the large molecular weights of intact capsids, and the uncertainty in distinguishing empty and filled capsids. To address these challenges, we combined two distinct analytical workflows that assess the intact capsids and VP subunits separately. First, a selective temporal overview of resonant ion (STORI)-based charge detection-mass spectrometry (CD-MS) was applied for characterization of the intact capsids. Liquid chromatography, ion mobility spectrometry, and mass spectrometry (LC-IMS-MS) separations were then used for the capsid denaturing measurements. This multimethod combination was applied to three AAV serotypes (AAV2, AAV6, and AAV8) to evaluate their intact empty and filled capsid ratios and then examine the distinct VP sequences and modifications present.

Association between hypomagnesemia and mortality among dialysis patients: a systematic review and meta-analysis.

Background: Malnutrition-inflammation-atherosclerosis (MIA) syndrome is caused by the inflammatory cytokines in end stage renal disease (ESRD) patients, and MIA complex-related factors may be associated with hypomagnesemia and mortality. However, the association between serum magnesium level and mortality for dialysis patients is still not clear. Additionally, no meta-analysis has investigated the impact of serum magnesium on peritoneal dialysis and hemodialysis, separately. Methods: We searched published studies in PubMed, Embase, Cochrane, Collaboration Central Register of Controlled Clinical Trials, and Cochrane Systematic Reviews through April 2022. Studies associated with serum magnesium and all-cause mortality or cardiovascular (CV) mortality in ESRD on kidney replacement therapy (KRT) patients were included. A hazard ratio (HR) with 95% confidence intervals (CI) was used to report the outcomes. Results: Twenty-one studies involving 55,232 patients were included. Overall, there was a significant association between hypomagnesemia and all-cause mortality for dialysis patients (HR: 1.67, 95% CI [1.412-2.00], p < 0.001; certainty of evidence: moderate) using a mixed unadjusted and adjusted HR for analysis. There was also a significantly increased risk of CV mortality for individuals with hypomagnesemia compared with the non-hypomagnesemia group (HR 1.56, 95% CI [1.08-2.25], p < 0.001; certainty of evidence: moderate). In addition, a subgroup analysis demonstrated that hypomagnesemia was associated with a high risk of both all-cause mortality and CV mortality (all-cause mortality, HR:1.80, 95% CI [1.48-2.19]; CV mortality, HR:1.84, 95% CI [1.10-3.07]) in hemodialysis (HD) patients, but not in participants receiving peritoneal dialysis (PD; all-cause mortality, HR:1.26, 95% CI [0.84-1.91]; CV mortality, HR:0.66, 95% CI [0.22-2.00]). The systematic review protocol was prespecified and registered in PROSPERO [CRD42021256187]. Conclusions: Hypomagnesemia may be a significant risk factor for all-cause mortality and CV mortality in KRT patients, especially in those receiving hemodialysis. However, because of the limited certainty of evidence, more studies are required to investigate this association.

Stability and Dissociation of Adeno-Associated Viral Capsids by Variable Temperature-Charge Detection-Mass Spectrometry.

Adeno-associated viral (AAV) vectors have emerged as gene therapy and vaccine delivery systems. Differential scanning fluorimetry or differential scanning calorimetry is commonly used to measure the thermal stability of AAVs, but these global methods are unable to distinguish the stabilities of different AAV subpopulations in the same sample. To address this challenge, we combined charge detection-mass spectrometry (CD-MS) with a variable temperature (VT) electrospray source that controls the temperature of the solution prior to electrospray. Using VT-CD-MS, we measured the thermal stabilities of empty and filled capsids. We found that filled AAVs ejected their cargo first and formed intermediate empty capsids before completely dissociating. Finally, we observed that pH stress caused a major decrease in thermal stability. This new approach better characterizes the thermal dissociation of AAVs, providing the simultaneous measurement of the stabilities and dissociation pathways of different subpopulations.

Accelerated versus watchful waiting strategy of kidney replacement therapy for acute kidney injury: a systematic review and meta-analysis of randomized clinical trials.

Background: Critically ill patients with severe acute kidney injury (AKI) requiring kidney replacement therapy (KRT) have a grim prognosis. Recently, multiple studies focused on the impact of KRT initiation time [i.e., accelerated versus watchful waiting KRT initiation (WWS-KRT)] on patient outcomes. We aim to review the results of all related clinical trials. Methods: In this systematic review, we searched all relevant randomized clinical trials from January 2000 to April 2021. We assessed the impacts of accelerated versus WWS-KRT on KRT dependence, KRT-free days, mortality and adverse events, including hypotension, infection, arrhythmia and bleeding. We rated the certainty of evidence according to Cochrane methods and the GRADE approach. Results: A total of 4932 critically ill patients with AKI from 10 randomized clinical trials were included in this analysis. The overall 28-day mortality rate was 38.5%. The 28-day KRT-dependence rate was 13.0%. The overall incident of KRT in the accelerated group was 97.4% and 62.8% in the WWS-KRT group. KRT in the accelerated group started 36.7 h earlier than the WWS-KRT group. The two groups had similar risks of 28-day [pooled log odds ratio (OR) 1.001, P = 0.982] and 90-day (OR 0.999, P = 0.991) mortality rates. The accelerated group had a significantly higher risk of 90-day KRT dependence (OR 1.589, P = 0.007), hypotension (OR 1.687, P < 0.001) and infection (OR 1.38, P = 0.04) compared with the WWS-KRT group. Conclusions: This meta-analysis revealed that accelerated KRT leads to a higher probability of 90-day KRT dependence and dialysis-related complications without any impact on mortality rate when compared with WWS-KRT. Therefore, we suggest the WWS-KRT strategy for critically ill patients.

Correction to: Accelerated versus watchful waiting strategy of kidney replacement therapy for acute kidney injury: a systematic review and meta-analysis of randomized clinical trials.

[This corrects the article DOI: 10.1093/ckj/sfac011.].

Surface Modified Nano-Electrospray Needles Improve Sensitivity for Native Mass Spectrometry.

Native mass spectrometry (MS) and charge detection-mass spectrometry (CD-MS) have become versatile tools for characterizing a wide range of proteins and macromolecular complexes. Both commonly use nanoelectrospray ionization (nESI) from pulled borosilicate needles, but some analytes are known to nonspecifically adsorb to the glass, which may lower sensitivity and limit the quality of the data. To improve the sensitivity of native MS and CD-MS, we modified the surface of nESI needles with inert surface modifiers, including polyethylene-glycol. We found that the surface modification improved the signal intensity for native MS of proteins and for CD-MS of adeno-associated viral capsids. Based on mechanistic comparisons, we hypothesize that the improvement is more likely due to an increased flow rate with coated ESI needles rather than less nonspecific adsorption. In any case, these surface-modified needles provide a simple and inexpensive method for improving the sensitivity of challenging analytes.

Protein Modification via Mild Photochemical Isomerization of Triazenes to Release Aryl Diazonium Ions.

This work describes the development of phenyl diazenyl piperidine triazene derivatives that can be activated to release aryl diazonium ions for labeling of proteins using light. These probes show marked bench stability at room temperature and can be photoisomerized via low-intensity UVA irradiation at physiological pH. Upon isomerization, the triazenes are rendered more basic and readily protonate to release reactive aryl diazonium ions. It was discovered that the intensity and duration of the UV light was essential to the observed diazonium ion reactivity in competition with the traditionally observed photolytic radical pathways. The combination of their synthetic efficiency coupled with their overall stability makes triazenes an attractive candidate for use in bioconjugation applications. Bioorthogonal handles on the triazenes are used to demonstrate the ease by which proteins can be modified.