1317P Renal toxicity in black patients with non-squamous non-small cell lung cancer treated with combination platinum-pemetrexed-pembrolizumab therapy

Background: In Keynote 189, an increased incidence of renal toxicity was observed with combination platinum-pemetrexed-pembrolizumab (PPP) therapy compared to chemotherapy alone. Studies have shown that compared to White Americans, Black Americans are at higher risk of morbidity and mortality associated with chronic kidney disease (CKD). We conducted a retrospective analysis of patients treated with PPP to assess the rate of renal toxicity in Black and White patients. Methods: Data of self-identified non-hispanic (NH) Black and NH White patients with advanced NS-NSCLC who were treated with PPP between January 1, 2017, and November 1, 2020, at the Henry Ford Health System was analyzed. Serum creatinine (Cr) and calculated glomerular filtration rate (GFR) before the first cycle of PPP and over the duration of PPP therapy were assessed. Acute kidney injury (AKI) was defined as an increase in Cr 1.5 times the baseline value. Reduction in GFR of ≥ 30% was considered significant. Multiple variables and outcomes were analyzed by two-group comparisons, univariate analysis, and Cox regression. Results: A total of 134 patients were included in the analysis. The mean age was 66.5 (SD 8.6) years, and 65 (48.5%) patients were men. A total of 33 (24%) patients were NH Black and 101 (75.4%) were NH White. There were 10 (8.1%) patients who developed AKI, and the median time to development of AKI was 4.5 months. No significant association of Black (3) or White (7) ethnicity with AKI was observed (p =.57). The odds of developing AKI was not increased in patients with a history of hypertension (p =.67), diabetes mellitus (p =.33), cardiovascular disease (p =.68), or CKD (p =.33). A total of 17 out of 127 (13.4%) patients had significantly reduced GFR, and patients with CKD were more likely to have reduced GFR (OR 4.8, p =.02). At the median follow-up of 24.5 months, the median survival was 15.2 months (95% CI, 12.7-22.2). Black ethnicity (HR 1.21, p =.46) and development of AKI (HR 1.13; 95% CI, 0.45–2.86) were not associated with increased mortality. Conclusions: Black patients with NS-NSCLC treated with PPP are not at higher risk of AKI or death than White patients. Development of AKI after PPP therapy was not associated with increased mortality

In-Hospital and 1-Year Mortality Trends in a National Cohort of US Veterans with Acute Kidney Injury

BACKGROUND AND OBJECTIVES: AKI, a frequent complication among hospitalized patients, confers excess short- and long-term mortality. We sought to determine trends in in-hospital and 1-year mortality associated with AKI as defined by Kidney Disease Improving Global Outcomes consensus criteria. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This retrospective cohort study used data from the national Veterans Health Administration on all patients hospitalized from October 1, 2008 to September 31, 2017. AKI was defined by Kidney Disease Improving Global Outcomes serum creatinine criteria. In-hospital and 1-year mortality trends were analyzed in patients with and without AKI using Cox regression with year as a continuous variable. RESULTS: We identified 1,688,457 patients and 2,689,093 hospitalizations across the study period. Among patients with AKI, 6% died in hospital, and 28% died within 1 year. In contrast, in-hospital and 1-year mortality rates were 0.8% and 14%, respectively, among non-AKI hospitalizations. During the study period, there was a slight decline in crude in-hospital AKI-associated mortality (hazard ratio, 0.98 per year; 95% confidence interval, 0.98 to 0.99) that was attenuated after accounting for patient demographics, comorbid conditions, and acute hospitalization characteristics (adjusted hazard ratio, 0.99 per year; 95% confidence interval, 0.99 to 1.00). This stable temporal trend in mortality persisted at 1 year (adjusted hazard ratio, 1.00 per year; 95% confidence interval, 0.99 to 1.00). CONCLUSIONS: AKI associated mortality remains high, as greater than one in four patients with AKI died within 1 year of hospitalization. Over the past decade, there seems to have been no significant progress toward improving in-hospital or long-term AKI survivorship

Dementia and catheter dysfunction as under identified and documented risk factors for catheter related blood stream infections.

Hemodialysis associated infections are a prominent cause of morbidity and mortality in patients with end-stage renal disease, second only to cardiovascular events, along with increased costs and hospitalization. Among vascular access types, central catheters have the highest risk of infection. We conducted a retrospective study involving 70 patients with dialysis catheter related blood stream infection (CABSI) to identify certain risk factors for infection. After IRB approval, clinical variables collected included age, gender, race, prior tissue plasminogen activator use, number of prior catheter exchanges, and diagnosis of dementia. We compared the prevalence of those risk factors in the study population with that of the general population based on prior published data that shared the same data collection methodology. A total 10 patients were diagnosed with dementia and the proportion of dementia was 14.29%. This was significantly higher than the general prevalence rate of 4% found on a cohort study of 16694 patients (p-value \u3c 0.0001). There were 53 patients who had catheter replacements/exchanges due to catheter thrombosis, the average number of replacement/exchanges was 2.57 per patient. The catheter thrombosis rate of 75.7% was significantly higher than the general prevalence of catheter thrombosis of 51% based on a cohort of over 50000 patients (p-value \u3c 0.0001). Dementia and prior catheter dysfunction may be under recognized and under documented risk factors for CABSI. Patients with dementia may have higher rates of CABSI due to lack of proper care and hygiene technique. Improved identification may lead to earlier intervention which may ultimately lead to lower mortality, hospitalizations and cost of care. Prevalence based on chart review seems to be much lower than prevalence based on more objective methodology, and implementation of more sensitive methods for detection will likely result in better patient outcomes

A Systematic Review of Depression and Anxiety in Patients with Atrial Fibrillation: The Mind-Heart Link

Atrial fibrillation (AF) is the most commonly seen arrhythmia in clinical practice. At present, few studies have been conducted centering on depression and anxiety in AF patients. Our aim in this systematic review is to use the relevant literature to (1) describe the prevalence of depression and anxiety in AF patients, (2) assess the impact that depression and anxiety have on illness perception in patients with AF, (3) provide evidence to support a hypothetical connection between the pathophysiology of AF and depression and anxiety, (4) evaluate the benefit of treatment of AF on depression and anxiety, and (5) give insight on medically managing a patient with AF and concomitant depression and anxiety

Regional citrate anticoagulation “non-shock” protocol with pre-calculated flow settings for patients with at least 6 L/hour liver citrate clearance

Abstract Background Regional citrate anticoagulation (RCA) for the prevention of clotting of the extracorporeal blood circuit during continuous kidney replacement therapy (CKRT) has been employed in limited fashion because of the complexity and complications associated with certain protocols. Hypertonic citrate infusion to achieve circuit anticoagulation results in variable systemic citrate- and sodium load and increases the risk of citrate accumulation and hypernatremia. The practice of “single starting calcium infusion rate for all patients” puts patients at risk for clinically significant hypocalcemia if filter effluent calcium losses exceed replacement. A fixed citrate to blood flow ratio, personalized effluent and pre-calculated calcium infusion dosing based on tables derived through kinetic analysis enable providers to use continuous veno-venous hemo-diafiltration (CVVHDF)-RCA in patients with liver citrate clearance of at least 6 L/h. Methods This was a single-center prospective observational study conducted in intensive care unit patients triaged to be treated with the novel pre-calculated CVVHDF-RCA “Non-shock” protocol. RCA efficacy outcomes were time to first hemofilter loss and circuit ionized calcium (iCa) levels. Safety outcomes were surrogate of citrate accumulation (TCa/iCa ratio) and the incidence of acid-base and electrolyte complications. Results Of 53 patients included in the study, 31 (59%) had acute kidney injury and 12 (22.6%) had the diagnosis of cirrhosis at the start of CVVHDF-RCA. The median first hemofilter life censored for causes other than clotting exceeded 70 h. The cumulative incidence of hypernatremia (Na > 148 mM), metabolic alkalosis (HCO3- > 30 mM), hypocalcemia (iCa  1.5 mM) were 1/47 (1%), 0/50 (0%), 1/53 (2%), 1/53 (2%) respectively and were not clinically significant. The median (25th–75th percentile) of the highest TCa/iCa ratio for every 24-h interval on CKRT was 1.99 (1.91–2.13). Conclusions The fixed citrate to blood flow ratio, as opposed to a titration approach, achieves adequate circuit iCa (< 0.4 mm/L) for any hematocrit level and plasma flow. The personalized dosing approach for calcium supplementation based on pre-calculated effluent calcium losses as opposed to the practice of “one starting dose for all” reduces the risk of clinically significant hypocalcemia. The fixed flow settings achieve clinically desirable steady state systemic electrolyte levels.http://deepblue.lib.umich.edu/bitstream/2027.42/173575/1/12882_2021_Article_2443.pd

SARS-CoV-2 receptor networks in diabetic and COVID-19–associated kidney disease

COVID-19 morbidity and mortality are increased via unknown mechanisms in patients with diabetes and kidney disease. SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2) for entry into host cells. Because ACE2 is a susceptibility factor for infection, we investigated how diabetic kidney disease and medications alter ACE2 receptor expression in kidneys. Single cell RNA profiling of kidney biopsies from healthy living donors and patients with diabetic kidney disease revealed ACE2 expression primarily in proximal tubular epithelial cells. This cell-specific localization was confirmed by in situ hybridization. ACE2 expression levels were unaltered by exposures to renin-angiotensin-aldosterone system inhibitors in diabetic kidney disease. Bayesian integrative analysis of a large compendium of public -omics datasets identified molecular network modules induced in ACE2-expressing proximal tubular epithelial cells in diabetic kidney disease (searchable at hb.flatironinstitute.org/covid-kidney) that were linked to viral entry, immune activation, endomembrane reorganization, and RNA processing. The diabetic kidney disease ACE2-positive proximal tubular epithelial cell module overlapped with expression patterns seen in SARS-CoV-2–infected cells. Similar cellular programs were seen in ACE2-positive proximal tubular epithelial cells obtained from urine samples of 13 hospitalized patients with COVID-19, suggesting a consistent ACE2-coregulated proximal tubular epithelial cell expression program that may interact with the SARS-CoV-2 infection processes. Thus SARS-CoV-2 receptor networks can seed further research into risk stratification and therapeutic strategies for COVID-19–related kidney damage