Prognosis of Transplant-Ineligible Patients with Cirrhosis and Acute Kidney Injury Who Initiate Renal Replacement Therapy.

BACKGROUND: Data to guide dialysis decision-making for transplant-ineligible patients with cirrhosis are lacking. AIMS: We aimed to describe the processes, predictors, and outcomes of renal replacement therapy (RRT) initiation for transplant-ineligible patients with cirrhosis at a single liver transplantation center. METHODS: We conducted a mixed-methods study of a retrospective cohort of 372 transplant-ineligible inpatients with cirrhosis with acute kidney injury (AKI) due to hepatorenal syndrome (HRS-AKI) or acute tubular necrosis (ATN) between 2008 and 2015. We performed survival analyses to evaluate 6-month survival and renal recovery and examined end-of-life care outcomes. We used a consensus-driven medical record review to characterize processes leading to RRT initiation. RESULTS: We identified 266 (71.5%) patients who received RRT and 106 (28.5%) who did not receive RRT (non-RRT). Median survival was 12.5 days (RRT) vs. 2.0 days (non-RRT) (HR 0.36, 95%CI 0.28-0.46); 6-month survival was 15% (RRT) vs. 0% (non-RRT). RRT patients were more likely to die in the intensive care unit (88% vs. 32%, p < 0.001). HRS-AKI patients were more likely to be RRT dependent at 6 months than ATN patients (86% vs. 27%, p = 0.007). The most common reasons for RRT initiation were unclear etiology of AKI on presentation (32%) and belief of likely reversibility of ATN (82%). CONCLUSION: Most transplant-ineligible patients who were initiated on RRT experienced very short-term mortality and received intensive end-of-life care. However, approximately 1 in 6 were alive at 6 months. Our findings underscore the critical need for structured clinical processes to support high-quality serious illness communication and RRT decision-making for this population.

Harnessing basic and clinic tools to evaluate SGLT2 inhibitor nephrotoxicity.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors are a new class of medications that target the transporter that reabsorbs ~90% of glucose in the S1 segment of the proximal convoluted tubule. As a result, SGLT2 inhibition increases urinary glucose excretion, effectively lowering plasma glucose levels. In addition to reducing hemoglobin A1c levels, these drugs also lower body weight, blood pressure, and uric acid levels in Type 2 diabetes mellitus (T2DM) patients. Importantly, empagliflozin has been observed to slow progression of kidney disease and reduce dialysis requirements in T2DM patients. However, the Food and Drug Administration (FDA) Adverse Events Reporting System (FAERS) has collected over 100 cases of acute kidney injury (AKI) for canagloflozin and dapagliflozin since their approval. Of the 101 patients, 96 required hospitalization, 22 required intensive care unit admission, and 15 underwent hemodialysis. The FDA now requires that AKI be listed as a potential side effect of the SGLT2 inhibitors along with cautious prescription of these drugs with other medications, such as renin-angiotensin-system antagonists, diuretics, and NSAIDs. It is unclear, however, whether this FAERS reported "AKI" actually represents structural kidney injury, as randomized, controlled trials of these drugs do not describe AKI as an adverse event despite coprescription with RAS blockers and diuretics. As a result of this FDA warning, diabetic patients with early-stage CKD may not be prescribed an SGLT2 inhibitor for fear of AKI. Thus, it is imperative to ascertain whether the reported AKI represents true structural kidney injury or a functional decline in glomerular filtration rate. We propose using readily available clinical tools with experimental biomarkers of kidney injury and kidney-on-a-chip technology to resolve this question and provide solid evidence about the AKI risk of these drugs for healthcare providers.

Association of HRS-AKI with Mortality in Patients with Cirrhosis Requiring Renal Replacement Therapy: Results from the HRS-HARMONY Consortium.

BACKGROUND: While AKI requiring renal replacement therapy (AKI-RRT) is associated with increased mortality in heterogeneous inpatient populations, the epidemiology of AKI-RRT in hospitalized patients with cirrhosis is not fully known. Herein, we evaluated the association of etiology of AKI with mortality in hospitalized patients with cirrhosis and AKI-RRT in a multicentric contemporary cohort. METHODS: This is a multicenter retrospective cohort study using data from the HRS-HARMONY consortium, which included 11 U.S. hospital network systems. Consecutive adult patients admitted in 2019 with cirrhosis and AKI-RRT were included. The primary outcome was 90-day mortality, and the main independent variable was AKI etiology, classified as hepatorenal syndrome (HRS-AKI) vs. other (non-HRS-AKI). AKI etiology was determined by at least two independent adjudicators. We performed Fine and Gray sub-distribution hazard analyses adjusting for relevant clinical variables. RESULTS: Of 2,063 hospitalized patients with cirrhosis and AKI, 374 (18.1%) had AKI-RRT. Among these, 65 (17.4%) had HRS-AKI and 309 (82.6%) non-HRS-AKI, which included ATN in most cases (62.6%). Continuous RRT (CRRT) was used as the initial modality in 264 (71%) of patients, while intermittent hemodialysis (IHD) was utilized in 108 (29%). The HRS-AKI (vs. non-HRS-AKI) group received more vasoconstrictors for HRS management (81.5% vs. 67.9%), while the non-HRS-AKI group received more mechanical ventilation (64.3% vs. 50.8%) and more CRRT (vs. IHD) as the initial RRT modality (73.9% vs. 56.9%). In the adjusted model, HRS-AKI (vs. non-HRS-AKI) was not independently associated with increased 90-day mortality (sHR=1.36, 95% CI: 0.95-1.94). CONCLUSIONS: In this multicenter contemporary cohort of hospitalized adult patients with cirrhosis and AKI-RRT, HRS-AKI was not independently associated with an increased risk of 90-day mortality when compared to other AKI etiologies. The etiology of AKI appears less relevant than previously considered when evaluating the prognosis of hospitalized adult patients with cirrhosis and AKI requiring RRT.

Comfort Measures Only in Myocardial Infarction: Prevalence of This Status, Change Over Time, and Predictors From a Nationwide Study.

BACKGROUND: Patients hospitalized with acute myocardial infarction (AMI) have a high mortality rate. Despite increasing recognition of the role for comfort focused care, little is known about the prevalence of comfort measures only (CMO) care among patients with AMI. The objective of this study was to investigate patient- and hospital-level patterns and predictors of CMO care among patients admitted with AMI. METHODS: This retrospective cohort study used the National Cardiovascular Data Registry Chest Pain-MI Registry, which contains data on patients admitted with AMI. Data were analyzed in 6-month increments from January 2015 to June 2018. RESULTS: Among 483 696 patients with AMI across 827 hospitals, 13 955 (2.9%) had CMO status at discharge (2.6% non-ST-segment-elevation myocardial infarction and 3.4% ST-segment-elevation myocardial infarction). There was a modest decline in CMO rates over time (3.0% to 2.8%). Independent patient characteristics associated with CMO status included male gender, White race, nonprivate insurance, frailty, and higher estimated bleeding and mortality risks. There was substantial variation in CMO rates across hospitals, with the proportion of CMO patients ranging from 0% to 17.1% and a median odds ratio of 1.59 (95% CI, 1.56-1.62). Among the 13 955 patients who were CMO by discharge, 8134 (58.3%) underwent diagnostic catheterization. This is despite significantly elevated risks predicted using precatheterization models, specifically the ACTION Registry GWTG in-hospital major bleeding and mortality risk scores. Patients who were initially managed invasively but later made CMO experienced high rates of procedural complications, including cardiogenic shock (38.3%), dialysis (10.1%), and bleeding (33.3%). CONCLUSIONS: Most patients with AMI who were CMO by discharge had aggressive initial management and became CMO following in-hospital complications of their care. Early identification of high-risk patients and appropriate transition of such patients to CMO, if aligned with their values, remain important areas for future quality programs in AMI.

Renal Cell Cancer and Chronic Kidney Disease.

The association between chronic kidney disease (CKD) and renal cell carcinoma (RCC) is bidirectional and multifactorial. Risk factors such as hypertension, diabetes mellitus, obesity, and smoking increase the risk of both CKD and RCC. CKD can lead to RCC via an underlying cystic disease or oxidative stress. RCC can cause CKD because of the tumor itself, surgical reduction of renal mass (either partial or radical nephrectomy), and perioperative acute kidney injury. Medical therapies such as immune checkpoint inhibitors and vascular endothelial growth factor inhibitors can lead to acute kidney injury and resultant CKD. Clinicians need to be aware of the complex, bidirectional interplay between both diseases.