Risk of Tuberculosis Disease in People With Chronic Kidney Disease Without Kidney Failure: A Systematic Review and Meta-analysis.

BACKGROUND: Kidney failure is an established risk factor for tuberculosis (TB), but little is known about TB risk in people with chronic kidney disease (CKD) who have not initiated kidney replacement therapy (CKD without kidney failure). Our primary objective was to estimate the pooled relative risk of TB disease in people with CKD stages 3-5 without kidney failure compared with people without CKD. Our secondary objectives were to estimate the pooled relative risk of TB disease for all stages of CKD without kidney failure (stages 1-5) and by each CKD stage. METHODS: This review was prospectively registered (PROSPERO CRD42022342499). We systematically searched MEDLINE, Embase, and Cochrane databases for studies published between 1970 and 2022. We included original observational research estimating TB risk among people with CKD without kidney failure. Random-effects meta-analysis was performed to obtain the pooled relative risk. RESULTS: Of the 6915 unique articles identified, data from 5 studies were included. The estimated pooled risk of TB was 57% higher in people with CKD stages 3-5 than in people without CKD (adjusted hazard ratio: 1.57; 95% CI: 1.22-2.03; I2 = 88%). When stratified by CKD stage, the pooled rate of TB was highest in stages 4-5 (incidence rate ratio: 3.63; 95% CI: 2.25-5.86; I2 = 89%). CONCLUSIONS: People with CKD without kidney failure have an increased relative risk of TB. Further research and modeling are required to understand the risks, benefits, and CKD cutoffs for screening people for TB with CKD prior to kidney replacement therapy.

Association of an Acute Kidney Injury Follow-up Clinic With Patient Outcomes and Care Processes: A Cohort Study.

RATIONALE & OBJECTIVE: To determine whether attendance at an acute kidney injury (AKI) follow-up clinic is associated with reduced major adverse kidney events. STUDY DESIGN: Propensity-matched cohort study. SETTING & PARTICIPANTS: Patients hospitalized with AKI in Ontario, Canada, from February 1, 2013, through September 30, 2017, at a single clinical center, who were not receiving dialysis when discharged. EXPOSURE: Standardized assessment by a nephrologist. OUTCOMES: Time to a major adverse kidney event, defined as death, initiation of maintenance dialysis, or incident/progressive chronic kidney disease. ANALYTICAL APPROACH: Propensity scores were used to match each patient who attended an AKI follow-up clinic to 4 patients who received standard care. Cox proportional hazards models were fit to assess the association between the care within an AKI follow-up clinic and outcomes. To avoid immortal time bias, we randomly assigned index dates to the comparator group. RESULTS: We matched 164 patients from the AKI follow-up clinic to 656 patients who received standard care. During a mean follow-up of 2.2±1.3 (SD) years, care in the AKI follow-up clinic was not associated with a reduction in major adverse kidney events relative to standard care (22.1 vs 24.7 events per 100 patient-years; HR, 0.91 [95% CI, 0.75-1.11]). The AKI follow-up clinic was associated with a lower risk of all-cause mortality (HR, 0.71 [95% CI, 0.55-0.91]). Patients aged at least 66 years who attended the AKI follow-up clinic were more likely to receive ß-blockers (HR, 1.34 [95% CI, 1.02-1.77]) and statins (HR, 1.35 [95% CI, 1.05-1.74]), but not angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (HR, 1.21 [95% CI, 0.94-1.56]). LIMITATIONS: Single-center study and residual confounding. CONCLUSIONS: Specialized postdischarge follow-up for AKI survivors was not associated with a lower risk of major adverse kidney events but was associated with a lower risk of death and increased prescriptions for some cardioprotective medications.

How I prescribe prolonged intermittent renal replacement therapy.

Prolonged Intermittent Renal Replacement Therapy (PIRRT) is the term used to define 'hybrid' forms of renal replacement therapy. PIRRT can be provided using an intermittent hemodialysis machine or a continuous renal replacement therapy (CRRT) machine. Treatments are provided for a longer duration than typical intermittent hemodialysis treatments (6-12 h vs. 3-4 h, respectively) but not 24 h per day as is done for continuous renal replacement therapy (CRRT). Usually, PIRRT treatments are provided 4 to 7 times per week. PIRRT is a cost-effective and flexible modality with which to safely provide RRT for critically ill patients. We present a brief review on the use of PIRRT in the ICU with a focus on how we prescribe it in that setting.

BAFF Produced by Neutrophils and Dendritic Cells Is Regulated Differently and Has Distinct Roles in Antibody Responses and Protective Immunity against West Nile Virus.

B cell activating factor (BAFF) is essential for B cells to develop and respond to Ags. Dysregulation of BAFF contributes to the development of some autoimmune diseases and malignancies. Little is known about when, where, and how BAFF is produced in vivo and about which BAFF-producing cells contribute to B cell responses. To better understand BAFF functions, we created BAFF reporter (BAFF-RFP) mice and Baff floxed (Bafffl/fl ) mice. Splenic and bone marrow neutrophils (Nphs) from BAFF-RFP mice expressed the highest constitutive levels of BAFF; other myeloid subsets, including conventional dendritic cells (cDCs) and monocyte (MO) subsets, expressed lower levels. Treatment of BAFF-RFP mice with polyinosinic:polycytidylic acid increased BAFF expression in splenic Ly6Chi inflammatory MOs, CD11bhi activated NK subset, and in bone marrow myeloid precursors. Postinfection with West Nile virus (WNV), BAFF increased in CD8- cDCs and Nphs, and BAFF+ CD11bhi NK cells expanded in draining lymph nodes. The cell- and tissue-specific increases in BAFF expression were dependent on type I IFN signaling. MAVS also was required or contributed to BAFF expression in dendritic cell and MO subsets, respectively. Mice with deletion of Baff in either cDCs or Nphs had reduced Ab responses after NP-Ficoll immunization; thus, BAFF produced by both cDCs and Nphs contributes to T cell-independent Ab responses. Conversely, mice with a cDC Baff deficiency had increased mortality after WNV infection and decreased WNV-specific IgG and neutralizing Ab responses. BAFF produced by Nphs and cDCs is regulated differently and has key roles in Ab responses and protective immunity.

Canadian Association of Radiologists Guidance on Contrast Associated Acute Kidney Injury.

Iodinated contrast media (ICM) is one of the most frequently administered pharmaceuticals. In Canada, over 5.4 million computed tomography (CT) examinations were performed in 2019, of which 50% were contrast enhanced. Acute kidney injury (AKI) occurring after ICM administration was historically considered a common iatrogenic complication which was managed by screening patients, prophylactic strategies, and follow up evaluation of renal function. The Canadian Association of Radiologists (CAR) initially published guidelines on the prevention of contrast induced nephropathy in 2007, with an update in 2012. However, new developments in the field have led to the availability of safer contrast agents and changes in clinical practice, prompting a complete revision of the earlier recommendations. This revised guidance document was developed by a multidisciplinary CAR Working Group of radiologists and nephrologists, and summarizes changes in practice related to contrast administration, screening, and risk stratification since the last guideline. It reviews the scientific evidence for contrast associated AKI and provides consensus-based recommendations for its prevention and management in the Canadian healthcare context. This article is a joint publication in the Canadian Association of Radiologists Journal and Canadian Journal of Kidney Health and Disease, intended to inform both communities of practice.

The RIG-I-like receptor LGP2 controls CD8(+) T cell survival and fitness.

The RIG-I-like receptors (RLRs) signal innate immune defenses upon RNA virus infection, but their roles in adaptive immunity have not been clearly defined. Here, we showed that the RLR LGP2 was not essential for induction of innate immune defenses, but rather was required for controlling antigen-specific CD8(+) T cell survival and fitness during peripheral T cell-number expansion in response to virus infection. Adoptive transfer and biochemical studies demonstrated that T cell-receptor signaling induced LGP2 expression wherein LGP2 operated to regulate death-receptor signaling and imparted sensitivity to CD95-mediated cell death. Thus, LGP2 promotes an essential prosurvival signal in response to antigen stimulation to confer CD8(+) T cell-number expansion and effector functions against divergent RNA viruses, including West Nile virus and lymphocytic choriomeningitis virus.

The Plasticity of Newly Formed B Cells.

Newly formed B cells (NF-B cells) that emerge from the bone marrow to the periphery have often been referred to as immature or transitional B cells. However, NF-B cells have several striking characteristics, including a distinct BCR repertoire, high expression of AID, high sensitivity to PAMPs, and the ability to produce cytokines. A number of findings do not support their designation as immature because NF-B cells have the potential to become Ab-producing cells and to undergo class-switch recombination. In this review, we provide a fresh perspective on NF-B cell functions and describe some of the signals driving their activation. We summarize growing evidence supporting a role for NF-B cells in protection against infections and as a potential source of autoantibody-producing cells in autoimmune diseases such as systemic lupus erythematosus.

A living donor kidney transplant recipient with mycobacterium senegalense bacteremia: A case report.

Mycobacterium senegalense is primarily known in sub-Saharan Africa to cause bovine farcy, a chronic granulomatous inflammation of the skin and lymphatics in cows. Reports of M. senegalense are rare among humans. We report a unique case of M. senegalense bloodstream infection in a living donor kidney transplant recipient with multiple possible sources of infection.

Targeting Antigens to CD180 but Not CD40 Programs Immature and Mature B Cell Subsets to Become Efficient APCs.

Targeting Ags to the CD180 receptor activates both B cells and dendritic cells (DCs) to become potent APCs. After inoculating mice with Ag conjugated to an anti-CD180 Ab, B cell receptors were rapidly internalized. Remarkably, all B cell subsets, including even transitional 1 B cells, were programed to process, present Ag, and stimulate Ag-specific CD4+ T cells. Within 24-48 hours, Ag-specific B cells were detectable at T-B borders in the spleen; there, they proliferated in a T cell-dependent manner and induced the maturation of T follicular helper (TFH) cells. Remarkably, immature B cells were sufficient for the maturation of TFH cells after CD180 targeting: TFH cells were induced in BAFFR-/- mice (with only transitional 1 B cells) and not in µMT mice (lacking all B cells) following CD180 targeting. Unlike CD180 targeting, CD40 targeting only induced DCs but not B cells to become APCs and thus failed to efficiently induce TFH cell maturation, resulting in slower and lower-affinity IgG Ab responses. CD180 targeting induces a unique program in Ag-specific B cells and to our knowledge, is a novel strategy to induce Ag presentation in both DCs and B cells, especially immature B cells and thus has the potential to produce a broad range of Ab specificities. This study highlights the ability of immature B cells to present Ag to and induce the maturation of cognate TFH cells, providing insights toward vaccination of mature B cell-deficient individuals and implications in treating autoimmune disorders.

Exploring human-guided strategies for reaction network exploration: Interactive molecular dynamics in virtual reality as a tool for citizen scientists.

The emerging fields of citizen science and gamification reformulate scientific problems as games or puzzles to be solved. Through engaging the wider non-scientific community, significant breakthroughs may be made by analyzing citizen-gathered data. In parallel, recent advances in virtual reality (VR) technology are increasingly being used within a scientific context and the burgeoning field of interactive molecular dynamics in VR (iMD-VR) allows users to interact with dynamical chemistry simulations in real time. Here, we demonstrate the utility of iMD-VR as a medium for gamification of chemistry research tasks. An iMD-VR "game" was designed to encourage users to explore the reactivity of a particular chemical system, and a cohort of 18 participants was recruited to playtest this game as part of a user study. The reaction game encouraged users to experiment with making chemical reactions between a propyne molecule and an OH radical, and "molecular snapshots" from each game session were then compiled and used to map out reaction pathways. The reaction network generated by users was compared to existing literature networks demonstrating that users in VR capture almost all the important reaction pathways. Further comparisons between humans and an algorithmic method for guiding molecular dynamics show that through using citizen science to explore these kinds of chemical problems, new approaches and strategies start to emerge.

More than ever, efficient evaluation of potential living kidney donors is needed.

In this issue, Habbous et al. reported that simultaneously evaluating multiple potential living kidney donors for the same intended recipient, rather than sequentially, is more effective and less expensive. This important study highlighted how quicker living kidney donor evaluations benefit patients and lower costs by reducing time spent on dialysis. Given the backlog precipitated by the coronavirus disease 2019 pandemic, devoting resources to ensure efficient living kidney donor evaluations is a better investment than ever before.

Protection of mice deficient in mature B cells from West Nile virus infection by passive and active immunization.

B cell activating factor receptor (BAFFR)-/- mice have a profound reduction in mature B cells, but unlike µMT mice, they have normal numbers of newly formed, immature B cells. Using a West Nile virus (WNV) challenge model that requires antibodies (Abs) for protection, we found that unlike wild-type (WT) mice, BAFFR-/- mice were highly susceptible to WNV and succumbed to infection within 8 to 12 days after subcutaneous virus challenge. Although mature B cells were required to protect against lethal infection, infected BAFFR-/- mice had reduced WNV E-specific IgG responses and neutralizing Abs. Passive transfer of immune sera from previously infected WT mice rescued BAFFR-/- and fully B cell-deficient µMT mice, but unlike µMT mice that died around 30 days post-infection, BAFFR-/- mice survived, developed WNV-specific IgG Abs and overcame a second WNV challenge. Remarkably, protective immunity could be induced in mature B cell-deficient mice. Administration of a WNV E-anti-CD180 conjugate vaccine 30 days prior to WNV infection induced Ab responses that protected against lethal infection in BAFFR-/- mice but not in µMT mice. Thus, the immature B cells present in BAFFR-/- and not µMT mice contribute to protective antiviral immunity. A CD180-based vaccine may promote immunity in immunocompromised individuals.

Acute Kidney Injury Due to Ovarian Hyperstimulation Syndrome.

Ovarian hyperstimulation syndrome (OHSS) is a complication of assisted reproductive treatments such as in vitro fertilization (IVF). The pathophysiology of severe OHSS includes a humorally mediated capillary leak syndrome that is predominantly centered on the intra-abdominal space. Severe OHSS is frequently complicated by acute kidney injury (AKI), which can be due to any of a variety of mechanisms, each requiring a different management strategy. Mechanisms of AKI in severe OHSS include intravascular volume depletion, kidney edema due to capillary leak, intra-abdominal hypertension or compartment syndrome, and obstructive uropathy due to ovarian enlargement. We present a teaching case of severe OHSS complicated by AKI in a woman with underlying stage 4 chronic kidney disease. She had been undergoing IVF with plans to subsequently use a gestational carrier (surrogate) for pregnancy. We use this case to review the presentation and pathophysiology of OHSS complicated by AKI. In addition, we review the management of AKI in OHSS, in particular, the role of paracentesis and/or culdocentesis to manage tense ascites. Last, we highlight that similar cases may occur more frequently in the future given that IVF with subsequent use of a gestational carrier is increasingly being used for patients with comorbid conditions that can be exacerbated by pregnancy, such as advanced chronic kidney disease.

WITHDRAWN: Death and Recovery of Kidney Function Among Patients Continued on Dialysis After Discharge From Hospital Stays Complicated by Acute Kidney Injury: A Cohort Study.

This article has been withdrawn at the request of the authors and editors because after publication of the Article in Press, the authors discovered that there had been an error in the programming of the statistical analysis. Once the error was corrected, the conclusions of the article were no longer supported. The Publisher and authors apologize for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

Common errors in temporary hemodialysis catheter insertion.

Non-tunneled hemodialysis catheter (NTHC) insertion is an essential skill for nephrology practice and remains a requirement of training. However, improper insertion technique can increase the risk of potentially fatal infectious and mechanical complications. Evidence-based strategies can reduce the rates of such complications and should be integrated into practice and training. Ultrasound (US) guidance should routinely be used for NTHC insertion at the femoral and internal jugular sites (with avoidance of the subclavian site). Nephrologists should receive proper training in the use of US for line insertion. With respect to other aspects of the procedure, proper insertion technique readily prevents guidewire-induced arrhythmias. In addition, adherence to infection-control guidelines results in a sustainable reduction in bloodstream infections. All these aspects of NTHC insertion may be best taught and evaluated through a program that includes simulation-based mastery learning (SBML) training. As a separate issue, nephrologists (and intensivists) should be aware that a dysfunctional catheter should be replaced at a new site rather than being changed over a guidewire. This review of common errors related to NTHC insertion seeks to highlight evidence-based approaches to practice and training.

Death due to delirium: a case of a self-cut hemodialysis dialysis catheter - a case report.

BACKGROUND: Neuropsychiatric conditions such as depression, delirium and cognitive impairment are common in patients with end-stage kidney disease (ESKD) and individuals suffering from ESKD are more likely to commit suicide than members of the general population. Self-harm gestures are not infrequent for ESKD patients suffering from depression, but not well described in other conditions. CASE PRESENTATION: We present a case of self-harm in a patient with ESKD suffering from acute delirium. A man in his mid-seventies was admitted with fungal peritoneal dialysis (PD) associated peritonitis. On the first day post operatively, he was found with absent vital signs due to exsanguination from newly inserted central catheter which he which had self-severed. He died a few days later as a result of the self-harm gesture. CONCLUSION: This case highlights that delirium may lead to self-harm events in ESKD and identifies a few strategies to help reduce the risk of self-harm events.

Regulation of B-lineage cells by caspase 6.

The caspase (Casp) family of proteases regulate both lymphocyte apoptosis and activation. Here, we show that Casp6 regulates early B-cell development. One-week-old Casp6 knockout (Casp6 KO) mice have significantly more splenic B-cell subsets than wild-type (WT) mice. Adult Casp6 KO mice have normal levels of total splenic B cells but have increased numbers of B1a B cells and CD43+ "transitional" or splenic red pulp (RP) B cells. These results suggested that Casp6 may function to control B-cell numbers under nonhomeostatic conditions and during B-cell development. Consistent with this model, reconstitution of B cells was dysregulated in Casp6 KO mice after sublethal irradiation. Furthermore, bone marrow pro-B, pre-B and immature B-cell numbers were significantly higher in 1-week-old Casp6 KO mice than in 1-week-old WT mice. Casp6 KO pro-B cells proliferated more in response to IL-7 than WT pro-B cells, suggesting that Casp6 regulates early B-cell responses to IL-7. Indeed, adult and aged Casp6 KO mice had elevated numbers of IL-7αR+ Sca1+ precursors of common lymphoid progenitors, suggesting Casp6 may help regulate progenitors of B cells and early B-lineage cells. Casp6 regulates B-cell programs both during early development and after antigen stimulation in the periphery.

Interventions to prevent hemodynamic instability during renal replacement therapy in critically ill patients: a systematic review.

BACKGROUND: Hemodynamic instability related to renal replacement therapy (HIRRT) may increase the risk of death and limit renal recovery. Studies in end-stage renal disease populations on maintenance hemodialysis suggest that some renal replacement therapy (RRT)-related interventions (e.g., cool dialysate) may reduce the occurrence of HIRRT, but less is known about interventions to prevent HIRRT in critically ill patients receiving RRT for acute kidney injury (AKI). We sought to evaluate the effectiveness of RRT-related interventions for reducing HIRRT in such patients across RRT modalities. METHODS: A systematic review of publications was undertaken using MEDLINE, MEDLINE in Process, EMBASE, and Cochrane's Central Registry for Randomized Controlled Trials (RCTs). Studies that assessed any intervention's effect on HIRRT (the primary outcome) in critically ill patients with AKI were included. HIRRT was variably defined according to each study's definition. Two reviewers independently screened abstracts, identified articles for inclusion, extracted data, and evaluated study quality using validated assessment tools. RESULTS: Five RCTs and four observational studies were included (n = 9; 623 patients in total). Studies were small, and the quality was mostly low. Interventions included dialysate sodium modeling (n = 3), ultrafiltration profiling (n = 2), blood volume (n = 2) and temperature control (n = 3), duration of RRT (n = 1), and slow blood flow rate at initiation (n = 1). Some studies applied more than one strategy simultaneously (n = 5). Interventions shown to reduce HIRRT from three studies (two RCTs and one observational study) included higher dialysate sodium concentration, lower dialysate temperature, variable ultrafiltration rates, or a combination of strategies. Interventions not found to have an effect included blood volume and temperature control, extended duration of intermittent RRT, and slower blood flow rates during continuous RRT initiation. How HIRRT was defined and its frequency of occurrence varied widely across studies, including those involving the same RRT modality. Pooled analysis was not possible due to study heterogeneity. CONCLUSIONS: Small clinical studies suggest that higher dialysate sodium, lower temperature, individualized ultrafiltration rates, or a combination of these strategies may reduce the risk of HIRRT. Overall, for all RRT modalities, there is a paucity of high-quality data regarding interventions to reduce the occurrence of HIRRT in critically ill patients.

A discrete-choice experiment to elicit preferences of patients with epilepsy for self-management programs.

BACKGROUND: There is an increasing number of self-management programs developed for patients with epilepsy, with the goal of supporting treatment management and improving their quality of life. With the aim of increasing medication adherence and effectiveness of self-management programs, it is important to design programs that are engaging to, and align with the preferences of patients with epilepsy. This study aimed to evaluate and compare the preferences of patients with epilepsy for self-management programs in three European countries. This is the first cross-border evaluation of the preferences of patients with epilepsy in Europe for such programs. METHODS: Using a discrete-choice experiment, patients with epilepsy from Germany, France, and the Netherlands were surveyed, and chose repetitively between two hypothetical self-management programs. These differed in the following six characteristics: i) the thematic area which would be the main focus of the program, ii) the method of interaction, iii) the source of information or provider of the program, iv) the amount of time spent on the program per week, v) the cost, and vi) whether the program would start immediately, or if there would be a delay of 3weeks before its initiation. A Bayesian efficient design was used to construct 15 choice sets, and a mixed panel logit model was used to estimate patients' preferences. Subgroup analyses were conducted according to socioeconomic status, burden of disease, and previous activation in self-management. RESULTS: A total of 299 people with epilepsy were included in the study, with a mean age of 45.5years. Only 15% had previously made use of a self-management program, although 44.5% reported having previously heard of them. In all three countries, all attributes barring the content were significant at 10%. The cost attribute - i.e., an out-of-pocket expenditure for a program - was reported as the most important feature in each country and across subgroups (significant at 1%). This was followed by the length of program sessions per week, which ranged from 20 to 90min per week. Although there was some heterogeneity between countries and subgroups, the patients, overall, had a preference for a face-to-face meeting with a doctor. In the Netherlands, a preference for online programs and physician assistants was observed when compared with the other countries. Other attributes, including the information source - whether a program was led by a physician, another patient with epilepsy, or another combination - was also important to patients, who appear willing to trade preferences in order to gain their favored attribute level. However, 20% of the population chose consistently to not participate in any self-management program. CONCLUSION: Given the heterogeneity of the epilepsies, preferences, and dispreferences across subgroups, our study highlights that if full account is not taken of different segmentation strategies when designing a self-management program, a large proportion of the population may not be attracted to it.