Localized K63 ubiquitin signaling is regulated by VCP/p97 during oxidative stress.

Under stress conditions, cells reprogram their molecular machineries to mitigate damage and promote survival. Ubiquitin signaling is globally increased during oxidative stress, controlling protein fate and supporting stress defenses at several subcellular compartments. However, the rules driving subcellular ubiquitin localization to promote these concerted response mechanisms remain understudied.

Too big not to fail: emerging evidence for size-induced senescence.

Cellular senescence refers to a permanent and stable state of cell cycle exit. This process plays an important role in many cellular functions, including tumor suppression. It was first noted that senescence is associated with increased cell size in the early 1960s; however, how this contributes to permanent cell cycle exit was poorly understood until recently.

Genome homeostasis defects drive enlarged cells into senescence.

Cellular senescence refers to an irreversible state of cell-cycle arrest and plays important roles in aging and cancer biology. Because senescence is associated with increased cell size, we used reversible cell-cycle arrests combined with growth rate modulation to study how excessive growth affects proliferation. We find that enlarged cells upregulate p21, which limits cell-cycle progression.

Hemoglobinuria in the Early Poststem-Cell-Transplant Period: Risk Factors and Association with Outcomes.

Background: Information on risk factors of hemoglobinuria after hematopoietic stem-cell transplant (HSCT) and its association with AKI, mortality, and engraftment is limited.

Methods: We conducted a retrospective cohort study on all consecutive adults that underwent HSCT from January 6, 1999, to November 6, 2017. The study included 6039 patients that underwent bone marrow transplantation (BMT), umbilical cord blood, and peripheral blood stem-cell transplantation (PBSCT).

Telehealth versus face-to-face visits: A comprehensive outpatient perspective-based cohort study of patients with kidney disease.

Background: Telenephrology has become an important health care delivery modality during the COVID-19 pandemic. However, little is known about patient perspectives on the quality of care provided via telenephrology compared to face-to-face visits. We aimed to use objective data to study patients' perspectives on outpatient nephrology care received via telenephrology (phone and video) versus face-to-face visits.

Immunotherapy-Related Acute Kidney Injury.

Nephrotoxicity associated with immunotherapy is increasingly being encountered in clinical practice. Drugs that augment the immune system to eradicate cancer are revolutionary in the field of oncology. Older generation immunotherapies such as high-dose interleukin and interferon-alpha are now being replaced with more effective immune checkpoint inhibitors and chimeric antigen receptor T-cell therapies, which have shown promising results in numerous clinical trials.

Rituximab-Associated Flare of Cryoglobulinemic Vasculitis.

Background: Patients with cryoglobulinemic vasculitis (CV) can develop disease flare after rituximab administration. The objective of our study was to describe the prevalence, clinical characteristics, predisposing factors, and outcomes of patients with rituximab-associated flare of CV.

Methods: We conducted a retrospective study in a tertiary referral center until March 25, 2020.

Ultrasonographic Assessment of Extravascular Lung Water in Hospitalized Patients Requiring Hemodialysis: A Prospective Observational Study.

Introduction: Sonographic technologies can estimate extravascular lung water (EVLW) in hemodialysis (HD) patients. This study investigated the suitability of a handheld scanner in contrast to a portable scanner for quantifying EVLW in hospitalized patients requiring HD.

Methods: In this prospective study, 54 hospitalized HD patients were enrolled.

Biomarkers, Clinical Features, and Rechallenge for Immune Checkpoint Inhibitor Renal Immune-Related Adverse Events.

Introduction: Immune checkpoint inhibitors (ICIs) are effective in treating several cancers; however, acute kidney injury (AKI) can occur as part as an immune-related adverse event (iRAE). Biomarkers at the time of AKI diagnosis may help determine whether they are ICI- related and guide therapeutic strategies.

Methods: In this retrospective study, we reviewed patients with cancer treated with ICI therapy between 2014 and 2020 who developed AKI (defined as a ≥1.

The Insulin Receptor Adaptor IRS2 is an APC/C Substrate That Promotes Cell Cycle Protein Expression and a Robust Spindle Assembly Checkpoint.

Insulin receptor substrate 2 (IRS2) is an essential adaptor that mediates signaling downstream of the insulin receptor and other receptor tyrosine kinases. Transduction through IRS2-dependent pathways is important for coordinating metabolic homeostasis, and dysregulation of IRS2 causes systemic insulin signaling defects. Despite the importance of maintaining proper IRS2 abundance, little is known about what factors mediate its protein stability.

Systematic Review of the Safety of Immune Checkpoint Inhibitors Among Kidney Transplant Patients.

Introduction: Kidney transplant (Ktx) recipients are excluded from clinical trials of immune checkpoint inhibitors. The aim of this systematic review was to assess the safety of immune checkpoint inhibitors among Ktx patients.

Methods: A literature search was conducted using MEDLINE, EMBASE, and Cochrane Database from inception through April 2019.

Acute Interstitial Nephritis and Checkpoint Inhibitor Therapy: Single Center Experience of Management and Drug Rechallenge.

Background: The objective of this case cohort study was to describe our experience in the care of patients with immune checkpoint inhibitor-related acute interstitial nephritis (ICI-AIN) including rechallenge.

Methods: A descriptive case series of patients that received an ICI and had an AKI (defined as a ≥1.5-fold increase in serum creatinine) as an immune-related adverse event (irAE), with biopsy-proven or clinically suspected ICI-AIN from January 1, 2014 to December 1, 2018 at Mayo Clinic, Rochester.

Clinical Features and Outcomes of Immune Checkpoint Inhibitor-Associated AKI: A Multicenter Study.

Background: Despite increasing recognition of the importance of immune checkpoint inhibitor-associated AKI, data on this complication of immunotherapy are sparse.

Methods: We conducted a multicenter study of 138 patients with immune checkpoint inhibitor-associated AKI, defined as a ≥2-fold increase in serum creatinine or new dialysis requirement directly attributed to an immune checkpoint inhibitor. We also collected data on 276 control patients who received these drugs but did not develop AKI.

Polyubiquitin Chains Linked by Lysine Residue 48 (K48) Selectively Target Oxidized Proteins .

Ubiquitin is a highly conserved protein modifier that heavily accumulates during the oxidative stress response. Here, we investigated the role of the ubiquitination system, particularly at the linkage level, in the degradation of oxidized proteins. The function of ubiquitin in the removal of oxidized proteins remains elusive because of the wide range of potential targets and different roles that polyubiquitin chains play.

Crystalglobulin-Induced Nephropathy and Keratopathy.

Crystalglobulinemia, a rare manifestation of monoclonal gammopathy, results from vascular deposition of crystallized monoclonal proteins leading to tissue injury. A 56-year-old man initially presented several years earlier with migratory polyarthralgias and blurry vision with no unifying diagnosis. Following an acute episode of malignant hypertension and rapidly progressive kidney failure, kidney biopsy was performed and was interpreted as idiopathic thrombotic microangiopathy.

Programmed cell death protein 1 inhibitor treatment is associated with acute kidney injury and hypocalcemia: meta-analysis.

Background: The aim of this meta-analysis was to assess the risks and incidence of nephrotoxicity and electrolyte abnormalities in patients receiving programmed cell death protein 1 (PD-1) inhibitors.

Methods: We conducted a meta-analysis of clinical trials that monitored electrolyte levels and kidney functions during treatment with nivolumab or pembrolizumab by searching MEDLINE, EMBASE and the Cochrane Database from inception through April 2017. Our protocol is registered with International Prospective Register of Systematic Reviews; no.

Light Chain Cast Nephropathy: Practical Considerations in the Management of Myeloma Kidney-What We Know and What the Future May Hold.

Purpose Of Review: To update and evaluate the current knowledge on pathogenesis and management of light chain cast nephropathy. Light chain cast nephropathy (LCCN) is the leading cause of acute renal failure in patients with multiple myeloma and is currently recognized as a myeloma defining event.

Recent Findings: The immunoglobulin free light chain plays an integral role in the pathogenesis of LCCN.

Total Renal Artery Occlusion: Recovery of Function After Revascularization.

Current trends in managing atherosclerotic renal artery stenosis favor medical therapy, on account of negative results from prospective trials of revascularization, such as CORAL and ASTRAL. One result of this trend has been encountering occasional patients with progressive disease, sometimes leading to total arterial occlusion. We illustrate a case of accelerated hypertension with complete renal artery occlusion in which the patient recovered function after surgical bypass and we review the clinical approach used and the advanced imaging modalities available to us.

Association between urologic malignancies and end-stage renal disease: A meta-analysis.

Aim: Previous studies have suggested a higher incidence of urologic malignancies in end-stage renal disease (ESRD) patients. However, incidence trends of urologic malignancies in ESRD patients remain unclear. The aims of the present study were: (i) to investigate the pooled incidence/incidence trends; and (ii) to assess the risk of urologic malignancies in ESRD patients.

Therapeutic Approach to the Management of Severe Asymptomatic Hyponatremia.

Hyponatremia is an electrolyte imbalance encountered commonly in the hospital and ambulatory settings. It can be seen in isolation or present as a complication of other medical conditions. It is therefore a challenge to determine the appropriate therapeutic intervention.

Associations of rotational shift work and night shift status with hypertension: a systematic review and meta-analysis.

Background: The reported risks of hypertension (HTN) in rotating shift and night shift workers are controversial. The objective of this meta-analysis was to assess the association between shift work status and HTN.

Methods: A literature search was performed using MEDLINE, EMBASE and Cochrane Database from inception through October 2016.