Soluble Urokinase Receptor and Acute Kidney Injury.

BACKGROUND: Acute kidney injury is common, with a major effect on morbidity and health care utilization. Soluble urokinase plasminogen activator receptor (suPAR) is a signaling glycoprotein thought to be involved in the pathogenesis of kidney disease. We investigated whether a high level of suPAR predisposed patients to acute kidney injury in multiple clinical contexts, and we used experimental models to identify mechanisms by which suPAR acts and to assess it as a therapeutic target. METHODS: We measured plasma levels of suPAR preprocedurally in patients who underwent coronary angiography and patients who underwent cardiac surgery and at the time of admission to the intensive care unit in critically ill patients. We assessed the risk of acute kidney injury at 7 days as the primary outcome and acute kidney injury or death at 90 days as a secondary outcome, according to quartile of suPAR level. In experimental studies, we used a monoclonal antibody to urokinase plasminogen activator receptor (uPAR) as a therapeutic strategy to attenuate acute kidney injury in transgenic mice receiving contrast material. We also assessed cellular bioenergetics and generation of reactive oxygen species in human kidney proximal tubular (HK-2) cells that were exposed to recombinant suPAR. RESULTS: The suPAR level was assessed in 3827 patients who were undergoing coronary angiography, 250 who were undergoing cardiac surgery, and 692 who were critically ill. Acute kidney injury developed in 318 patients (8%) who had undergone coronary angiography. The highest suPAR quartile (vs. the lowest) had an adjusted odds ratio of 2.66 (95% confidence interval [CI], 1.77 to 3.99) for acute kidney injury and 2.29 (95% CI, 1.71 to 3.06) for acute kidney injury or death at 90 days. Findings were similar in the surgical and critically ill cohorts. The suPAR-overexpressing mice that were given contrast material had greater functional and histologic evidence of acute kidney injury than wild-type mice. The suPAR-treated HK-2 cells showed heightened energetic demand and mitochondrial superoxide generation. Pretreatment with a uPAR monoclonal antibody attenuated kidney injury in suPAR-overexpressing mice and normalized bioenergetic changes in HK-2 cells. CONCLUSIONS: High suPAR levels were associated with acute kidney injury in various clinical and experimental contexts. (Funded by the National Institutes of Health and others.).

AKI Treated with Renal Replacement Therapy in Critically Ill Patients with COVID-19.

BACKGROUND: AKI is a common sequela of coronavirus disease 2019 (COVID-19). However, few studies have focused on AKI treated with RRT (AKI-RRT). METHODS: We conducted a multicenter cohort study of 3099 critically ill adults with COVID-19 admitted to intensive care units (ICUs) at 67 hospitals across the United States. We used multivariable logistic regression to identify patient-and hospital-level risk factors for AKI-RRT and to examine risk factors for 28-day mortality among such patients. RESULTS: A total of 637 of 3099 patients (20.6%) developed AKI-RRT within 14 days of ICU admission, 350 of whom (54.9%) died within 28 days of ICU admission. Patient-level risk factors for AKI-RRT included CKD, men, non-White race, hypertension, diabetes mellitus, higher body mass index, higher d-dimer, and greater severity of hypoxemia on ICU admission. Predictors of 28-day mortality in patients with AKI-RRT were older age, severe oliguria, and admission to a hospital with fewer ICU beds or one with greater regional density of COVID-19. At the end of a median follow-up of 17 days (range, 1-123 days), 403 of the 637 patients (63.3%) with AKI-RRT had died, 216 (33.9%) were discharged, and 18 (2.8%) remained hospitalized. Of the 216 patients discharged, 73 (33.8%) remained RRT dependent at discharge, and 39 (18.1%) remained RRT dependent 60 days after ICU admission. CONCLUSIONS: AKI-RRT is common among critically ill patients with COVID-19 and is associated with a hospital mortality rate of >60%. Among those who survive to discharge, one in three still depends on RRT at discharge, and one in six remains RRT dependent 60 days after ICU admission.

Acute kidney injury in renal transplant recipients undergoing cardiac surgery.

BACKGROUND: Acute kidney injury (AKI) is a key risk factor for chronic kidney disease in the general population, but has not been investigated in detail among renal transplant recipients (RTRs). We investigated the incidence, severity and risk factors for AKI following cardiac surgery among RTRs compared with non-RTRs with otherwise similar clinical characteristics. METHODS: We conducted a retrospective cohort study of RTRs (n = 83) and non-RTRs (n = 83) who underwent cardiac surgery at two major academic medical centers. Non-RTRs were matched 1:1 to RTRs by age, preoperative (preop) estimated glomerular filtration rate and type of cardiac surgery. We defined AKI according to Kidney Disease: Improving Global Outcomes criteria. RESULTS: RTRs had a higher rate of AKI following cardiac surgery compared with non-RTRs [46% versus 28%; adjusted odds ratio 2.77 (95% confidence interval 1.36-5.64)]. Among RTRs, deceased donor (DD) versus living donor (LD) status, as well as higher versus lower preop calcineurin inhibitor (CNI) trough levels, were associated with higher rates of AKI (57% versus 33% among DD-RTRs versus LD-RTRs; P = 0.047; 73% versus 36% among RTRs with higher versus lower CNI trough levels, P = 0.02). The combination of both risk factors (DD status and higher CNI trough level) had an additive effect (88% AKI incidence among patients with both risk factors versus 25% incidence among RTRs with neither risk factor, P = 0.004). CONCLUSIONS: RTRs have a higher risk of AKI following cardiac surgery compared with non-RTRs with otherwise similar characteristics. Among RTRs, DD-RTRs and those with higher preop CNI trough levels are at the highest risk.

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. RESULTS: Lower baseline eGFR, proton pump inhibitor use, and combination immune checkpoint inhibitor therapy were each independently associated with an increased risk of immune checkpoint inhibitor-associated AKI. Median (interquartile range) time from immune checkpoint inhibitor initiation to AKI was 14 (6-37) weeks. Most patients had subnephrotic proteinuria, and approximately half had pyuria. Extrarenal immune-related adverse events occurred in 43% of patients; 69% were concurrently receiving a potential tubulointerstitial nephritis-causing medication. Tubulointerstitial nephritis was the dominant lesion in 93% of the 60 patients biopsied. Most patients (86%) were treated with steroids. Complete, partial, or no kidney recovery occurred in 40%, 45%, and 15% of patients, respectively. Concomitant extrarenal immune-related adverse events were associated with worse renal prognosis, whereas concomitant tubulointerstitial nephritis-causing medications and treatment with steroids were each associated with improved renal prognosis. Failure to achieve kidney recovery after immune checkpoint inhibitor-associated AKI was independently associated with higher mortality. Immune checkpoint inhibitor rechallenge occurred in 22% of patients, of whom 23% developed recurrent associated AKI. CONCLUSIONS: This multicenter study identifies insights into the risk factors, clinical features, histopathologic findings, and renal and overall outcomes in patients with immune checkpoint inhibitor-associated AKI.

Iron Chelation as a Potential Therapeutic Strategy for AKI Prevention.

AKI remains a major public health concern. Despite years of investigation, no intervention has been demonstrated to reliably prevent AKI in humans. Thus, development of novel therapeutic targets is urgently needed. An important role of iron in the pathophysiology of AKI has been recognized for over three decades. When present in excess and in nonphysiologic labile forms, iron is toxic to the kidneys and multiple other organs, whereas iron chelation is protective across a broad spectrum of insults. In humans, small studies have investigated iron chelation as a novel therapeutic strategy for prevention of AKI and extrarenal acute organ injury, and have demonstrated encouraging initial results. In this review, we examine the existing data on iron chelation for AKI prevention in both animal models and human studies. We discuss practical considerations for future clinical trials of AKI prevention using iron chelators, including selection of the ideal clinical setting, patient population, iron chelating agent, and dosing regimen. Finally, we compare the key differences among the currently available iron chelators, including pharmacokinetics, routes of administration, and adverse effects.

Early Flexible Sigmoidoscopy Improves Clinical Outcomes in Acute Severe Ulcerative Colitis.

Objectives: Guidelines recommend performing a flexible sigmoidoscopy in patients hospitalized with acute severe ulcerative colitis (ASUC). However, it is unclear if time to sigmoidoscopy affects relevant clinical outcomes. We aimed to assess the impact of early sigmoidoscopy on clinical outcomes using a well-characterized cohort of patients with ASUC. Methods: This is a single-center, retrospective study of all patients hospitalized with ASUC from January 1, 2012 to November 1, 2021. Early sigmoidoscopy was defined as occurring within 72 hours of admission while delayed sigmoidoscopy was defined as occurring >72 hours after admission. Primary outcomes were cumulative days of intravenous (IV) corticosteroid (CS) use, length of hospital stay, and colectomy rates. Secondary outcomes were time to infliximab (IFX) rescue and inpatient opioid medication use. Results: A total of 112 patients hospitalized with ASUC who underwent sigmoidoscopy were included in the analysis. Eighty-seven patients (78%) had early sigmoidoscopy and 25 (22%) had delayed sigmoidoscopy. Patients in the early sigmoidoscopy group were exposed to significantly fewer days of IV CS (4.5 vs 9.2 days; P < .001), had shorter hospital stays (6.4 vs 19.3 days; P < .001), and shorter time to IFX rescue (3.5 vs 6.4 days; P = .004). Rates of colectomy in the early and delayed sigmoidoscopy groups were 17% versus 28%, respectively (P = .23). Longer time to sigmoidoscopy was associated with a 16% increased risk of colectomy (HR = 1.16, P = .002). Conclusions: In this well-characterized cohort, early sigmoidoscopy in ASUC was associated with favorable clinical outcomes. These findings highlight the benefits of early sigmoidoscopy in patients with ASUC. Larger prospective studies are needed to corroborate these findings.

Deprescription of aspirin for primary prevention is uncommon at discharge in hospitalised patients with gastrointestinal bleeding.

BACKGROUND: Guidelines recommend against aspirin for primary prevention of cardiovascular events in individuals with a history of gastrointestinal bleeding (GIB). It is unknown how often patients on primary prevention aspirin hospitalised with GIB have aspirin discontinued at discharge. AIMS: To determine the rate of aspirin deprescription and explore long-term outcomes in patients taking aspirin for primary prevention of cardiovascular events. METHODS: We evaluated all patients hospitalised at Yale-New Haven Hospital between January 2014 and October 2021 with GIB who were on aspirin for primary prevention. Our primary endpoint was the frequency of aspirin deprescription at discharge. Our secondary endpoints were post-discharge hospitalisations for major adverse cardiovascular events (MACE) or GIB. Time-to-event analysis was performed using Kaplan-Meier curves and the log-rank test. RESULTS: We identified 320 patients with GIB on aspirin for primary prevention: median age was 72 (interquartile range [IQR] 61-81) years and 297 (92.8%) were on aspirin 81 mg daily. Only 25 (9.0%) patients surviving their hospitalisation were deprescribed aspirin at discharge. Among 260 patients with follow-up (median 1103 days; IQR 367-1670), MACE developed post-discharge in 2/25 (8.0%) with aspirin deprescription versus 37/235 (15.7%) with aspirin continuation (log-rank p = 0.28). 0/25 patients with aspirin deprescription had subsequent hospitalisation for GIB versus 17/235 (7.2%) who continued aspirin (log-rank p = 0.13). CONCLUSIONS: Aspirin for primary cardiovascular prevention was rarely deprescribed at discharge in patients hospitalised with GIB. Processes designed to ensure appropriate deprescription of aspirin are crucial to improve adherence to guidelines, thereby improving the risk-benefit ratio in patients at high risk of subsequent GIB hospitalisations with minimal increased risk of MACE.

Management of acute colonic pseudo-obstruction in a neutropenic patient.

Acute colonic pseudo-obstruction, also known as Ogilvie's syndrome, is a rare condition involving acute large bowel dilatation without mechanical obstruction. Management begins with conservative treatment and may include pharmacological therapy, colonoscopic decompression and surgery. Timely resolution is important due to the increased risk of bowel perforation and ischaemia associated with colonic dilatation. However, conditions such as neutropenia that place patients at an elevated risk of infection may limit treatment options. We report a case of acute colonic pseudo-obstruction in a neutropenic elderly man resistant to conservative measures and neostigmine and discuss the additional management considerations in an immunocompromised patient.

Cardiac tamponade as the initial presentation of autoimmune polyglandular syndrome Type 2: a case report.

Background: Cardiac tamponade is a rare but serious manifestation of autoimmune polyglandular syndrome Type 2 (APS 2). Patients often present with symptoms of thyroid dysfunction and adrenal insufficiency, but the insidious onset of the disease may lead to delayed diagnosis, which can progress rapidly to haemodynamic instability requiring urgent intervention. Case summary: A 39-year-old previously healthy male was admitted with cardiac tamponade complicated by cardiac arrest requiring emergent pericardiocentesis. An extensive work up revealed primary adrenal insufficiency and Hashimoto's thyroiditis. His positive autoantibodies to thyroid peroxidase and 21-hydroxylase combined with rapid improvement with initiation of corticosteroids and levothyroxine confirmed a diagnosis of APS 2. Discussion: Although this disease is often difficult to diagnose given its vague symptoms, it should be considered in the differential diagnosis for young patients presenting with pericardial effusion or cardiac tamponade of unknown origin. Early diagnosis and management are critical and often result in rapid improvement after appropriate treatment.

Broken Scalpel Blade During Emergent Cricothyroidotomy: An Unexpected Complication in a Critical Situation.

Scalpel-bougie cricothyroidotomy is the most common surgical procedure to obtain emergency airway access when routine methods fail. We present a case of a broken scalpel blade during emergency cricothyroidotomy further complicating respiratory access.

The deteriorating patient-physician relationship in India: Is it time to look within?

The patient-physician relationship in India is in a state of rapid decline with fresh incidents of violence highlighting the scale of the problem. The medical fraternity needs to reflect on certain issues plaguing its conduct with patients and colleagues and embark on steps to address them. In this article, I highlight some major points which could help us arrest the deteriorating trust and heightened violence in hospitals.