Disruption in glutathione metabolism and altered energy production in the liver and kidney after ischemic acute kidney injury in mice.

Acute kidney injury (AKI) is a systemic disease that affects energy metabolism in various remote organs in murine models of ischemic AKI. However, AKI-mediated effects in the liver have not been comprehensively assessed. After inducing ischemic AKI in 8-10-week-old, male C57BL/6 mice, mass spectrometry metabolomics revealed that the liver had the most distinct phenotype 24 h after AKI versus 4 h and 7 days. Follow up studies with in vivo [13C6]-glucose tracing on liver and kidney 24 h after AKI revealed 4 major findings: (1) increased flux through glycolysis and the tricarboxylic (TCA) cycle in both kidney and liver; (2) depleted hepatic glutathione levels and its intermediates despite unchanged level of reactive oxygen species, suggesting glutathione consumption exceeds production due to systemic oxidative stress after AKI; (3) hepatic ATP depletion despite unchanged rate of mitochondrial respiration, suggesting increased ATP consumption relative to production; (4) increased hepatic and renal urea cycle intermediates suggesting hypercatabolism and upregulation of the urea cycle independent of impaired renal clearance of nitrogenous waste. Taken together, this is the first study to describe the hepatic metabolome after ischemic AKI in a murine model and demonstrates that there is significant liver-kidney crosstalk after AKI.

Correction: CVVHD results in longer filter life than pre-filter CVVH: Results of a quasi-randomized clinical trial.

[This corrects the article DOI: 10.1371/journal.pone.0278550.].

Blood Pressure, Readmission, and Mortality Among Patients Hospitalized With Acute Kidney Injury.

Importance: Acute kidney injury (AKI) complicates 20% to 25% of hospital admissions and is associated with long-term mortality, especially from cardiovascular disease. Lower systolic blood pressure (SBP) following AKI may be associated with lower mortality, but potentially at the cost of higher short-term complications. Objective: To determine associations of SBP with mortality and hospital readmissions following AKI, and to determine whether time from discharge affects these associations. Design, Setting, and Participants: This retrospective cohort study of adults with AKI during a hospitalization in Veteran Healthcare Association (VHA) hospitals was conducted between January 2013 and December 2018. Patients with 1 year or less of data within the VA system prior to admission, severe or end-stage liver disease, stage 4 or 5 chronic kidney disease, end-stage kidney disease, metastatic cancer, and no blood pressure values within 30 days of discharge were excluded. Data analysis was conducted from May 2022 to February 2024. Exposure: SBP was treated as time-dependent (categorized as <120 mm Hg, 120-129 mm Hg, 130-139 mm Hg, 140-149 mm Hg, 150-159 mm Hg, and ≥160 mm Hg [comparator]). Time spent in each SBP category was accumulated over time and represented in 30-day increments. Main Outcomes and Measures: Primary outcomes were time to mortality and time to all-cause hospital readmission. Cox proportional hazards regression was adjusted for demographics, comorbidities, and laboratory values. To evaluate associations over time, hazard ratios (HRs) were calculated at 60 days, 90 days, 120 days, 180 days, 270 days, and 365 days from discharge. Results: Of 237 409 admissions with AKI, 80 960 (57 242 aged 65 years or older [70.7%]; 77 965 male [96.3%] and 2995 female [3.7%]) were included. The cohort had high rates of diabetes (16 060 patients [20.0%]), congestive heart failure (22 516 patients [28.1%]), and chronic lung disease (27 682 patients [34.2%]), and 1-year mortality was 15.9% (12 876 patients). Overall, patients with SBP between 130 and 139 mm Hg had the most favorable risk level for mortality and readmission. There were clear, time-dependent mediations on associations in all groups. Compared with patients with SBP of 160 mm Hg or greater, the risk of mortality for patients with SBP between 130 and 139 mm Hg decreased between 60 days (adjusted HR, 1.20; 99% CI, 1.00-1.44) and 365 days (adjusted HR, 0.58; 99% CI, 0.45-0.76). SBP less than 120 mm Hg was associated with increased risk of mortality at all time points. Conclusions and Relevance: In this retrospective cohort study of post-AKI patients, there were important time-dependent mediations of the association of blood pressure with mortality and readmission. These findings may inform timing of post-AKI blood pressure treatment.

The antioxidant and anti-inflammatory activities of avasopasem manganese in age-associated, cisplatin-induced renal injury.

PURPOSE: Cisplatin contributes to acute kidney injury (AKI) and chronic kidney disease (CKD) that occurs with greater frequency and severity in older patients. Age-associated cisplatin sensitivity in human fibroblasts involves increased mitochondrial superoxide produced by older donor cells. EXPERIMENTAL DESIGN: Young and old C57BL/6 J murine models of cisplatin-induced AKI and CKD were treated with the SOD mimetic avasopasem manganese to investigate the potential antioxidant and anti-inflammatory effects. Adverse event reporting from a phase 2 and a phase 3 randomized clinical trial (NCT02508389 and NCT03689712) conducted in patients treated with cisplatin and AVA was determined to have established the incidence and severity of AKI. RESULTS: Cisplatin-induced AKI and CKD occurred in all mice, however, was more pronounced in older mice. AVA reduced cisplatin-induced mortality, AKI, and CKD, in older animals. AVA also alleviated cisplatin-induced alterations in mitochondrial electron transport chain (ETC) complex activities and NADPH Oxidase 4 (NOX4) and inhibited the increased levels of the inflammation markers, TNFα, IL1, ICAM-1, and VCAM-1. Analysis of age-stratified subjects treated with cisplatin from clinical trials (NCT02508389, NCT03689712) also supported that the incidence of AKI increased with age and AVA reduced age-associated therapy-induced adverse events (AE), including hypomagnesemia, increased creatinine, and AKI. CONCLUSIONS: Older mice and humans are more susceptible to cisplatin-induced kidney injury, and treatment with AVA mitigates age-associated damage. Mitochondrial ETC and NOX4 activities represent sources of superoxide production contributing to cisplatin-induced kidney injury, and pro-inflammatory cytokine production and endothelial dysfunction may also be increased by superoxide formation.

Hepcidin Removal during Continuous Renal Replacement Therapy.

INTRODUCTION: Patients with acute kidney injury (AKI) or end stage kidney disease (ESKD) may require continuous renal replacement therapy (CRRT) as a supportive intervention. While CRRT is effective at achieving solute control and fluid balance, the indiscriminate nature of this procedure raises the possibility that beneficial substances may similarly be removed. Hepcidin, an antimicrobial peptide with pivotal roles in iron homeostasis and pathogen clearance, has biochemical properties amenable to direct removal via CRRT. We hypothesized that serum hepcidin levels would significantly decrease after initiation of CRRT. METHODS: In this prospective, observational trial, we enrolled 13 patients who required CRRT: 11 due to stage 3 AKI, and 2 due to critical illness in the setting of ESKD. Plasma was collected at the time of enrollment, and then plasma and effluent were collected at 10:00 a.m. on the following 3 days. Plasma samples were also collected from healthy controls, and we compared hepcidin concentrations in those with renal disease compared to normal controls, evaluated trends in hepcidin levels over time, and calculated the hepcidin sieving coefficient. RESULTS: Plasma hepcidin levels were significantly higher in patients initiating CRRT than in normal controls (158 ± 60 vs. 17 ± 3 ng/mL respectively, p < 0.001). Hepcidin levels were highest prior to CRRT initiation (158 ± 60 ng/mL), and were significantly lower on day 1 (102 ± 24 ng/mL, p < 0.001) and day 2 (56 ± 14 ng/mL, p < 0.001) before leveling out on day 3 (51 ± 11 ng/mL). The median sieving coefficient was consistent at 0.82-0.83 for each of 3 days. CONCLUSIONS: CRRT initiation is associated with significant decreases in plasma hepcidin levels over the first 2 days of treatment regardless of indication for CRRT, or presence of underlying ESKD. Since reduced hepcidin levels are associated with increased mortality and our data implicate CRRT in hepcidin removal, larger clinical studies evaluating relevant clinical outcomes based on hepcidin trends in this population should be pursued.

Redox Regulation of Nrf2 in Cisplatin-Induced Kidney Injury.

Cisplatin, a potent chemotherapeutic agent, is marred by severe nephrotoxicity that is governed by mechanisms involving oxidative stress, inflammation, and apoptosis pathways. The transcription factor Nrf2, pivotal in cellular defense against oxidative stress and inflammation, is the master regulator of the antioxidant response, upregulating antioxidants and cytoprotective genes under oxidative stress. This review discusses the mechanisms underlying chemotherapy-induced kidney injury, focusing on the role of Nrf2 in cancer therapy and its redox regulation in cisplatin-induced kidney injury. We also explore Nrf2's signaling pathways, post-translational modifications, and its involvement in autophagy, as well as examine redox-based strategies for modulating Nrf2 in cisplatin-induced kidney injury while considering the limitations and potential off-target effects of Nrf2 modulation. Understanding the redox regulation of Nrf2 in cisplatin-induced kidney injury holds significant promise for developing novel therapeutic interventions. This knowledge could provide valuable insights into potential strategies for mitigating the nephrotoxicity associated with cisplatin, ultimately enhancing the safety and efficacy of cancer treatment.

Critical illness myopathy and trajectory of recovery in acute kidney injury requiring continuous renal replacement therapy: a prospective observational trial protocol.

INTRODUCTION: Acute kidney injury requiring renal replacement therapy (AKI-RRT) is common in the intensive care unit (ICU) and is associated with significant morbidity and mortality. Continuous RRT (CRRT) non-selectively removes large amounts of amino acids from plasma, lowering serum amino acid concentrations and potentially depleting total-body amino acid stores. Therefore, the morbidity and mortality associated with AKI-RRT may be partly mediated through accelerated skeletal muscle atrophy and resulting muscle weakness. However, the impact of AKI-RRT on skeletal muscle mass and function during and following critical illness remains unknown. We hypothesise that patients with AKI-RRT have higher degrees of acute muscle loss than patients without AKI-RRT and that AKI-RRT survivors are less likely to recover muscle mass and function when compared with other ICU survivors. METHODS AND ANALYSIS: This protocol describes a prospective, multicentre, observational trial assessing skeletal muscle size, quality and function in ICU patients with AKI-RRT. We will perform musculoskeletal ultrasound to longitudinally evaluate rectus femoris size and quality at baseline (within 48 hours of CRRT initiation), day 3, day 7 or at ICU discharge, at hospital discharge, and 1-3 months postdischarge. Additional skeletal muscle and physical function tests will be performed at hospital discharge and postdischarge follow-up. We will analyse the effect of AKI-RRT by comparing the findings in enrolled subjects to historical controls of critically ill patients without AKI-RRT using multivariable modelling. ETHICS AND DISSEMINATION: We anticipate our study will reveal that AKI-RRT is associated with greater degrees of muscle loss and dysfunction along with impaired postdischarge recovery of physical function. These findings could impact the in-hospital and postdischarge treatment plan for these patients to include focused attention on muscle strength and function. We intend to disseminate findings to participants, healthcare professionals, the public and other relevant groups via conference presentation and publication without any publication restrictions. TRIAL REGISTRATION NUMBER: NCT05287204.

The prevalence and treatment of hypertension in Veterans Health Administration, assessing the impact of the updated clinical guidelines.

OBJECTIVE: Hypertension is the most common risk factor for cardiovascular disease (CVD). Several guidelines have lowered diagnostic blood pressure (BP) thresholds and treatment targets for hypertension. We evaluated the impact of the more stringent guidelines among Veterans, a population at high risk of CVD. METHODS: We conducted a retrospective analysis of Veterans with at least two office BP measurements between January 2016 and December 2017. Prevalent hypertension was defined as diagnostic codes related to hypertension, prescribed antihypertensive drugs, or office BP values according to the BP cutoffs at least 140/90 mmHg (Joint National Committee 7 [JNC 7]), at least 130/80 mmHg [American College of Cardiology/American Heart Association (ACC/AHA)], or the 2020 Veterans Health Administration (VHA) guideline (BP ≥130/90 mmHg). Uncontrolled BP was defined per the VHA guideline as mean SBP ≥130 mmHg or DBP ≥90 mmHg. RESULTS: The prevalence of hypertension increased from 71% for BP at least 140/90 to 81% for BP at least 130/90 mmHg and further to 87% for BP at least 130/80 mmHg. Among Veterans with known hypertension ( n  = 2 768 826), a majority [ n  = 1 818 951 (66%)] were considered to have uncontrolled BP per the VHA guideline. Lowering the treatment targets for SBP and DBP significantly increased the number of Veterans who would require initiation of or intensification of pharmacotherapy. The majority of Veterans with uncontrolled BP and at least one CVD risk factor remained uncontrolled after 5 years of follow-up. CONCLUSION: Lowering the BP diagnostic and treatment cutoffs increases the burden on healthcare systems significantly. Targeted interventions are needed to achieve the BP treatment goals.

Nephrotoxin Exposure and Acute Kidney Injury in Adults.

BACKGROUND: Rates of nephrotoxic AKI are not well described in adults due to lack of a clear definition, debate over which drugs should be considered nephrotoxins, and illness-related confounding. Nephrotoxic Injury Negated by Just-in Time Action (NINJA), a program that reduces rates of nephrotoxic AKI in pediatric populations, may be able to address these concerns, but whether NINJA can be effectively applied to adults remains unclear. METHODS: In this retrospective cohort study conducted at the University of Iowa Hospital, we included adult patients admitted to a general hospital floor for ≥48 hours during 2019. The NINJA algorithm screened charts for high nephrotoxin exposure and AKI. After propensity score matching, Cox proportional hazard modeling was used to evaluate the relationship between nephrotoxic exposure and all-stage AKI, stage 2-3 AKI, or death. Additional analyses evaluated the most frequent nephrotoxins used in this population. RESULTS: Of 11,311 patients, 1527 (16%) had ≥1 day of high nephrotoxin exposure. Patients with nephrotoxic exposures subsequently developed AKI in 29% of cases, and 22% of all inpatient AKI events met nephrotoxic AKI criteria. Common nephrotoxins were vancomycin, iodinated contrast dye, piperacillin-tazobactam, acyclovir, and lisinopril. After propensity score matching, Cox proportional hazard models for high nephrotoxin exposure were significantly associated with all AKI (hazard ratio [HR] 1.43, 1.19-1.72, P<0.001), stage 2-3 AKI (HR 1.78, 1.18-2.67, P=0.006), and mortality (HR 2.12, 1.09-4.11, P=0.03). CONCLUSIONS: Nephrotoxin exposure in adults is common and is significantly associated with AKI development, including stage 2-3 AKI.

Point-of-Care Testing in Chronic Kidney Disease of Non-Traditional Origin: Considerations for Clinical, Epidemiological, and Health Surveillance Research and Practice.

Purpose: As the prevalence of chronic kidney disease of non-traditional origin (CKDnt) rises in low-resource settings, there is a need for reliable point-of-care creatinine testing. The purpose of this analysis was to assess the accuracy of two commonly used point-of-care creatinine devices, the i-STAT handheld (Abbott, Princeton, NJ, USA) and the StatSensor Creatinine (Nova Biomedical, Waltham, MA, USA) in comparison to venipuncture serum creatinine measures. The affordability, sensitivity, specificity, ease of use, and other considerations for each device are also presented. Methods: Three paired data sets were compared. We collected 213 paired i-STAT and venipuncture samples from a community study in Nicaragua in 2015-2016. We also collected 267 paired StatSensor Creatinine and venipuncture samples, including 158 from a community setting in Nicaragua in 2014-2015 and 109 from a Guatemala sugarcane worker cohort in 2017-2018. Pearson correlation coefficients, Bland-Altman plots, and no intercept linear regression models were used to assess agreement between point-of-care devices and blood samples. Results: The i-STAT performed the most accurately, overestimating creatinine by 0.07 mg/dL (95% CI: 0.02, 0.12) with no evidence of proportional bias. The StatSensor Creatinine performed well at low levels of creatinine (Mean (SD): 0.87 (0.19)). Due to proportional bias, the StatSensor Creatinine performed worse in the Nicaragua community setting where creatinine values ranged from 0.31 to 7.04 mg/dL. Discussion: Both devices provide acceptable sensitivity and specificity. Although adequate for routine surveillance, StatSensor Creatinine is less accurate as the values of measured creatinine increase, a consideration when using the point-of-care device for screening individuals at risk for CKDnt. Research, clinical, and screening objectives, cost, ease of use, and background prevalence of disease must all be carefully considered when selecting a point-of-care creatinine device. Conclusion: POC testing can be more accessible in resource-limited settings. The selection of the appropriate device will depend on the use-case.

CVVHD results in longer filter life than pre-filter CVVH: Results of a quasi-randomized clinical trial.

BACKGROUND: Filter clotting is a major issue in continuous kidney replacement therapy (CKRT) that interrupts treatment, reduces delivered effluent dose, and increases cost of care. While a number of variables are involved in filter life, treatment modality is an understudied factor. We hypothesized that filters in pre-filter continuous venovenous hemofiltration (CVVH) would have shorter lifespans than in continuous venovenous hemodialysis (CVVHD). METHODS: This was a single center, pragmatic, unblinded, quasi-randomized cluster trial conducted in critically ill adult patients with severe acute kidney injury (AKI) at the University of Iowa Hospitals and Clinics (UIHC) between March 2020 and December 2020. Patients were quasi-randomized by time block to receive pre-filter CVVH (convection) or CVVHD (diffusion). The primary outcome was filter life, and secondary outcomes were number of filters used, number of filters reaching 72 hours, and in-hospital mortality. RESULTS: In the intention-to-treat analysis, filter life in pre-filter CVVH was 79% of that observed in CVVHD (mean ratio 0.79, 95% CI 0.65-0.97, p = 0.02). Median filter life (with interquartile range) in pre-filter CVVH was 21.8 (11.4-45.3) and was 26.6 (13.0-63.5) for CVVHD. In addition, 11.8% of filters in pre-filter CVVH were active for >72 hours, versus 21.2% in the CVVHD group. Finally, filter clotting accounted for the loss of 26.7% of filters in the CVVH group compared to 17.5% in the CVVHD group. There were no differences in overall numbers of filters used or mortality between groups. CONCLUSIONS: Among critically patients with severe AKI requiring CKRT, use of pre-filter CVVH resulted in significantly shorter filter life compared to CVVHD. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04762524. Registered 02/21/21-Retroactively registered, https://clinicaltrials.gov/ct2/show/NCT04762524?cond=The+Impact+of+CRRT+Modality+on+Filter+Life&draw=2&rank=1.

Risk Factors for Death Among Veterans Following Acute Kidney Injury.

BACKGROUND: Acute kidney injury is prevalent among hospitalized veterans, and associated with increased risk of death following discharge. However, risk factors for death following acute kidney injury have not been well defined. We developed a mortality prediction model using Veterans Health Administration data. METHODS: This retrospective cohort study included inpatients from 2013 through 2018 with a creatinine increase of ≥0.3 mg/dL. We evaluated 45 variables for inclusion in our final model, with a primary outcome of 1-year mortality. Bootstrap sampling with replacement was used to identify variables selected in >60% of models using stepwise selection. Best sub-sets regression using Akaike information criteria was used to identify the best-fitting parsimonious model. RESULTS: A total of 182,683 patients were included, and 38,940 (21.3%) died within 1 year of discharge. The 10-variable model to predict mortality included age, chronic lung disease, cancer within 5 years, unexplained weight loss, dementia, congestive heart failure, hematocrit, blood urea nitrogen, bilirubin, and albumin. Notably, acute kidney injury stage, chronic kidney disease, discharge creatinine, and proteinuria were not selected for inclusion. C-statistics in the primary validation cohorts were 0.77 for the final parsimonious model, compared with 0.52 for acute kidney injury stage alone. CONCLUSION: We identified risk factors for long-term mortality following acute kidney injury. Our 10-variable model did not include traditional renal variables, suggesting that non-kidney factors contribute to the risk of death more than measures of kidney disease in this population, a finding that may have implications for post-acute kidney injury care.

Intensive Care Unit-Acquired Weakness in Patients With Acute Kidney Injury: A Contemporary Review.

Acute kidney injury (AKI) and intensive care unit-acquired weakness (ICU-AW) are 2 frequent complications of critical illness that, until recently, have been considered unrelated processes. The adverse impact of AKI on ICU mortality is clear, but its relationship with muscle weakness-a major source of ICU morbidity-has not been fully elucidated. Furthermore, improving ICU survival rates have refocused the field of intensive care toward improving long-term functional outcomes of ICU survivors. We begin our review with the epidemiology of AKI in the ICU and of ICU-AW, highlighting emerging data suggesting that AKI and AKI treated with kidney replacement therapy (AKI-KRT) may independently contribute to the development of ICU-AW. We then delve into human and animal data exploring the pathophysiologic mechanisms linking AKI and acute KRT to muscle wasting, including altered amino acid and protein metabolism, inflammatory signaling, and deleterious removal of micronutrients by KRT. We next discuss the currently available interventions that may mitigate the risk of ICU-AW in patients with AKI and AKI-KRT. We conclude that additional studies are needed to better characterize the epidemiologic and pathophysiologic relationship between AKI, AKI-KRT, and ICU-AW and to prospectively test interventions to improve the long-term functional status and quality of life of AKI survivors.

Creatinine elevations from baseline at the time of cardiac surgery are associated with postoperative complications.

OBJECTIVES: Baseline kidney function is a key predictor of postoperative morbidity and mortality. Whether an increased creatinine at the time of surgery, compared with the lowest creatinine in the 3 months before surgery, is associated with poor outcomes has not been evaluated. We examined whether creatinine elevations from "baseline" were associated with adverse postoperative outcomes. METHODS: A total of 1486 patients who underwent cardiac surgery at the University of Colorado Hospital between January 2011 and May 2016 met inclusion criteria. "Change in creatinine from baseline" was defined as the difference between the immediate presurgical creatinine value and the lowest creatinine value within 3 months preceding surgery. Outcomes evaluated were in-hospital mortality, postoperative infection, postoperative stroke, development of stage 3 acute kidney injury, intensive care unit length of stay, and hospital length of stay. Outcomes were adjusted using a balancing score to account for differences in patient characteristics. RESULTS: There were significant increases in the odds of postoperative infection (odds ratio, 1.17; confidence interval, 1.02-1.34; per 0.1 mg/dL increase in creatinine), stage 3 acute kidney injury (odds ratio, 1.44; confidence interval; 1.18-1.75), intensive care unit length of stay (odds ratio, 1.13; confidence interval, 1.01-1.26), and hospital length of stay (odds ratio, 1.09; confidence interval, 1.05-1.13). There was a significant increase in mortality in the unadjusted analysis, although not after adjustment using a balancing score. There was no association with postoperative stroke. CONCLUSIONS: Elevations in creatinine at the time of surgery above the "baseline" level are associated with increased postoperative morbidity. Baseline creatinine should be established before surgery, and small changes in creatinine should trigger heightened vigilance in the postoperative period.

Platelet Decreases following Continuous Renal Replacement Therapy Initiation as a Novel Risk Factor for Renal Nonrecovery.

BACKGROUND: Continuous renal replacement therapy (CRRT) is a form of dialysis used in critically ill patients, and has recently been associated with renal nonrecovery. Decreases in platelets following CRRT initiation are common and are associated with mortality, but associations with renal recovery are unclear. Our objective was to determine if platelet nadir or the degree of platelet decrease following CRRT initiation was associated with renal nonrecovery. METHODS: This is a secondary analysis of the Randomized Evaluation of Normal versus Augmented Level (RENAL) trial. Primary predictors were platelet nadir discretized by median value and percent platelet decrease following CRRT initiation, with cut points evaluated by decile from 30 to 60%. The 2 primary outcomes were time to RRT-independence and RRT-free days. Secondary outcomes were 28-day mortality, 90-day mortality, intensive care unit (ICU)-free, and hospital-free days. RESULTS: Time to RRT independence censored for death was achieved less frequently in patients with low platelet nadir (hazard ratio [HR] 0.77, confidence interval [CI] 0.66-0.91) and in those with >50% platelet decrease (HR 0.84, CI 0.72-0.97). RRT-free days were lower in both low platelet nadir (odds ratio [OR] 0.94, CI 0.90-0.97) and >50% platelet decrease (OR 0.91, CI 0.88-0.95). These groups also had higher rates of 28- and 90-day mortality and fewer ICU-free and hospital-free days. Thrombocytopenia at CRRT initiation was also associated with renal nonrecovery, although the clinical effect was small. CONCLUSIONS: Platelet nadir <100 × 103/µL and platelet decrease by >50% following CRRT initiation were both associated with lower rates of renal recovery. Further research is needed to evaluate mechanisms-linking platelet changes and renal nonrecovery in CRRT.

An Initiative to Improve 30-Day Readmission Rates Using a Transitions-of-Care Clinic Among a Mixed Urban and Rural Veteran Population.

BACKGROUND/OBJECTIVE: Hospital readmissions in the United States, especially in patients at high-risk, cost more than $17 billion annually. Although care transitions is an important area of research, data are limited regarding its efficacy, especially among rural patients. In this study, we describe a novel transitions-of-care clinic (TOCC) to reduce 30-day readmissions in a Veterans Health Administration setting that serves a high proportion of rural veterans. METHODS: In this quality improvement initiative we conducted a pre-post study evaluating clinical outcomes in adult patients at high risk for 30-day readmission (Care Assessment Needs score > 85) discharged from the Iowa City Veterans Affairs (ICVA) Health Care System from 2017 to 2020. The ICVA serves 184,000 veterans across 50 counties in eastern Iowa, western Illinois, and northern Missouri, with more than 60% of these patients residing in rural areas. We implemented a multidisciplinary TOCC to provide in-person or virtual follow-up to high-risk veterans after hospital discharge. The main purpose of this study was to assess how TOCC follow-up impacted the monthly 30-day patient readmission rate. RESULTS: The TOCC resulted in a 19.2% relative reduction in 30-day readmission rates in the 12-month postimplementation period compared to the preimplementation period (9.2% vs 11.4%, P = .04). Virtual visits were more popular than in-person visits among both urban and rural veterans. There was no difference in outcomes between these two follow-up options, and both groups had reduced readmission rates compared to non-TOCC follow-up. CONCLUSIONS: A multidisciplinary TOCC within the ICVA featuring both virtual and in-person visits reduced the 30-day readmission rate. This reduction was particularly notable among patients with congestive heart failure.

The Association of Platelet Decrease Following Continuous Renal Replacement Therapy Initiation and Increased Rates of Secondary Infections.

OBJECTIVES: Thrombocytopenia is common in critically ill patients treated with continuous renal replacement therapy and decreases in platelets following continuous renal replacement therapy initiation have been associated with increased mortality. Platelets play a role in innate and adaptive immunity, making it plausible that decreases in platelets following continuous renal replacement therapy initiation predispose patients to development of infection. Our objective was to determine if greater decreases in platelets following continuous renal replacement therapy correlate with increased rates of secondary infection. DESIGN: Retrospectivecohort analysis. SETTING: This study uses a continuous renal replacement therapy database from Mayo Clinic (Rochester, MN), a tertiary academic center. PARTICIPANTS: Adult patients who survived until ICU discharge and were on continuous renal replacement therapy for less than 30 days were included. A subgroup analysis was also performed in patients with thrombocytopenia (platelets < 100 × 103/µL) at continuous renal replacement therapy initiation. MEASUREMENTS AND MAIN RESULTS: The primary predictor variable was a decrease in platelets from precontinuous renal replacement therapy levels of greater than 40% or less than or equal to 40%, although multiple cut points were analyzed. The primary outcome was infection after ICU discharge, and secondary endpoints included post-ICU septic shock and post-ICU mortality. Univariable, multivariable, and propensity-adjusted analyses were used to determine associations between the predictor variable and the outcomes. RESULTS: Among 797 eligible patients, 253 had thrombocytopenia at continuous renal replacement therapy initiation. A greater than 40% decrease in platelets after continuous renal replacement therapy initiation was associated in the multivariable-adjusted models with increased odds of post-ICU infection in the full cohort (odds ratio, 1.49; CI, 1.02-2.16) and in the thrombocytopenia cohort (odds ratio, 2.63; CI, 1.35-5.15) cohorts. CONCLUSIONS: Platelet count drop by greater than 40% following continuous renal replacement therapy initiation is associated with an increased risk of secondary infection, particularly in patients with thrombocytopenia at the time of continuous renal replacement therapy initiation. Further research is needed to evaluate the impact of both continuous renal replacement therapy and platelet loss on subsequent infection risk.

Stage 1 acute kidney injury is independently associated with infection following cardiac surgery.

OBJECTIVES: Severe acute kidney injury (AKI) is a known risk factor for infection and mortality. However, whether stage 1 AKI is a risk factor for infection has not been evaluated in adults. We hypothesized that stage 1 AKI following cardiac surgery would independently associate with infection and mortality. METHODS: In this retrospective propensity score-matched study, we evaluated 1620 adult patients who underwent nonemergent cardiac surgery at the University of Colorado Hospital from 2011 to 2017. Patients who developed stage 1 AKI by Kidney Disease Improving Global Outcomes creatinine criteria within 72 hours of surgery were matched to patients who did not develop AKI. The primary outcome was an infection, defined as a new surgical-site infection, positive blood or urine culture, or development of pneumonia. Secondary outcomes included in-hospital mortality, stroke, and intensive care unit (ICU) and hospital length of stay (LOS). RESULTS: Stage 1 AKI occurred in 293 patients (18.3%). Infection occurred in 20.9% of patients with stage 1 AKI compared with 8.1% in the no-AKI group (P < .001). In propensity-score matched analysis, stage 1 AKI independently associated with increased infection (odds ratio [OR]; 2.24, 95% confidence interval [CI], 1.37-3.17), ICU LOS (OR, 2.38; 95% CI, 1.71-3.31), and hospital LOS (OR, 1.30; 95% CI, 1.17-1.45). CONCLUSIONS: Stage 1 AKI is independently associated with postoperative infection, ICU LOS, and hospital LOS. Treatment strategies focused on prevention, early recognition, and optimal medical management of AKI may decrease significant postoperative morbidity.