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Item Admission plasma uromodulin and the risk of acute kidney injury in hospitalized patients with cirrhosis: a pilot study(American Physiological Society, 2019-10-01) Patidar, Kavish R.; Garimella, Pranav S.; Macedo, Etienne; Slaven, James E.; Ghabril, Marwan S.; Weber, Regina E.; Anderson, Melissa; Orman, Eric S.; Nephew, Lauren D.; Desai, Archita P.; Chalasani, Naga; El-Achkar, Tarek M.; Medicine, School of MedicineAcute kidney injury (AKI) is a common complication in hospitalized patients with cirrhosis. Uromodulin, a protein uniquely produced by the kidney and released both in the urine and circulation, has been shown to regulate AKI and is linked to tubular reserve. Although low levels of urine uromodulin are associated with AKI after cardiac surgery, it is unclear whether circulating uromodulin can stratify the risk of AKI, particularly in a susceptible population such as hospitalized patients with cirrhosis. Thus, we investigated whether plasma uromodulin measured at the time of admission is associated with subsequent hospital-acquired AKI (defined by a rise in serum creatinine >0.3mg/dL within 48 h or ≥ 1.5 times baseline) in patients with cirrhosis. A total of 98 patients [mean age 54 yr, Model for Endstage Liver Disease Sodium (MELD-Na) score 19, and baseline creatinine of 0.95 mg/dL] were included, of which 13% (n = 13) developed AKI. Median uromodulin levels were significantly lower in patients who developed AKI compared with patients who did not (9.30 vs. 13.35 ng/mL, P = 0.02). After adjusting for age, sex, diabetes, hypertension, albumin, and MELD-Na score as covariates on multivariable logistic regression, uromodulin was independently associated with AKI [odd ratios of 1.19 (95% confidence interval 1.02, 1.37; P = 0.02)]. Lower uromodulin levels on admission are associated with increased odds of subsequent AKI in hospitalized patients with cirrhosis. Further studies are needed to better understand the role of uromodulin in the pathogenesis and as a predictive biomarker of AKI in this population. NEW & NOTEWORTHY In this study, we found that admission plasma uromodulin levels are significantly lower in patients who developed subsequent acute kidney injury (AKI) during their hospital stay compared with patients who did not. Additionally, uromodulin is independently associated with AKI development after adjusting for clinically relevant parameters such as age, sex, diabetes, hypertension, severity of cirrhosis, and kidney function. To our knowledge, this is the first study linking plasma uromodulin with AKI development in patients with cirrhosis.Item Changing epidemiology and outcomes of acute kidney injury in hospitalized patients with cirrhosis - a US population-based study(Elsevier, 2020-11) Desai, Archita P.; Knapp, Shannon M.; Orman, Eric S.; Ghabril, Marwan S.; Nephew, Lauren D.; Anderson, Melissa; Ginès, Pere; Chalasani, Naga P.; Patidar, Kavish R.; Medicine, School of MedicineBackground & aims: Acute kidney injury (AKI) is a significant clinical event in cirrhosis yet contemporary population-based studies on the impact of AKI on hospitalized cirrhotics are lacking. We aimed to characterize longitudinal trends in incidence, healthcare burden and outcomes of hospitalized cirrhotics with and without AKI using a nationally representative dataset. Methods: Using the 2004-2016 National Inpatient Sample (NIS), admissions for cirrhosis with and without AKI were identified using ICD-9 and ICD-10 codes. Regression analysis was used to analyze the trends in hospitalizations, costs, length of stay and inpatient mortality. Descriptive statistics, simple and multivariable logistic regression were used to assess associations between individual characteristics, comorbidities, and cirrhosis complications with AKI and death. Results: In over 3.6 million admissions for cirrhosis, 22% had AKI. AKI admissions were more costly (median $13,127 [IQR $7,367-$24,891] vs. $8,079 [IQR $4,956-$13,693]) and longer (median 6 [IQR 3-11] days vs. 4 [IQR 2-7] days). Over time, AKI prevalence doubled from 15% in 2004 to 30% in 2016. CKD was independently and strongly associated with AKI (adjusted odds ratio 3.75; 95% CI 3.72-3.77). Importantly, AKI admissions were 3.75 times more likely to result in death (adjusted odds ratio 3.75; 95% CI 3.71-3.79) and presence of AKI increased risk of mortality in key subgroups of cirrhosis, such as those with infections and portal hypertension-related complications. Conclusions: The prevalence of AKI is significantly increased among hospitalized cirrhotics. AKI substantially increases the healthcare burden associated with cirrhosis. Despite advances in cirrhosis care, a significant gap remains in outcomes between cirrhotics with and without AKI, suggesting that AKI continues to represent a major clinical challenge.Item Development and Validation of a Model to Predict Acute Kidney Injury in Hospitalized Patients With Cirrhosis(Wolters Kluwer, 2019-09) Patidar, Kavish R.; Xu, Chenjia; Shamseddeen, Hani; Cheng, Yao-Wen; Ghabril, Marwan S.; Mukthinuthalapati, V.V. Pavan K.; Fricker, Zachary P.; Akinyeye, Samuel; Nephew, Lauren D.; Desai, Archita P.; Anderson, Melissa; El-Achkar, Tarek M.; Chalasani, Naga P.; Orman, Eric S.; Medicine, School of MedicineOBJECTIVES: Acute kidney injury (AKI) is a common complication in hospitalized patients with cirrhosis which contributes to morbidity and mortality. Improved prediction of AKI in this population is needed for prevention and early intervention. We developed a model to identify hospitalized patients at risk for AKI. METHODS: Admission data from a prospective cohort of hospitalized patients with cirrhosis without AKI on admission (n = 397) was used for derivation. AKI development in the first week of admission was captured. Independent predictors of AKI on multivariate logistic regression were used to develop the prediction model. External validation was performed on a separate multicenter cohort (n = 308). RESULTS: In the derivation cohort, the mean age was 57 years, the Model for End-Stage Liver Disease score was 17, and 59 patients (15%) developed AKI after a median of 4 days. Admission creatinine (OR: 2.38 per 1 mg/dL increase [95% CI: 1.47-3.85]), international normalized ratio (OR: 1.92 per 1 unit increase [95% CI: 1.92-3.10]), and white blood cell count (OR: 1.09 per 1 × 10/L increase [95% CI: 1.04-1.15]) were independently associated with AKI. These variables were used to develop a prediction model (area underneath the receiver operator curve: 0.77 [95% CI: 0.70-0.83]). In the validation cohort (mean age of 53 years, Model for End-Stage Liver Disease score of 16, and AKI development of 13%), the area underneath the receiver operator curve for the model was 0.70 (95% CI: 0.61-0.78). DISCUSSION: A model consisting of admission creatinine, international normalized ratio, and white blood cell count can identify patients with cirrhosis at risk for in-hospital AKI development. On further validation, our model can be used to apply novel interventions to reduce the incidence of AKI among patients with cirrhosis who are hospitalized.Item High Moral Distress in Clinicians Involved in the Care of Undocumented Immigrants Needing Dialysis in the United States(Mary Ann Liebert, Inc., 2021-07-15) Jawed, Areeba; Moe, Sharon M.; Anderson, Melissa; Slaven, James E.; Wocial, Lucia De.; Saeed, Fahad; Torke, Alexia M.; Medicine, School of MedicinePurpose: To understand clinicians' perspectives on dialysis care of undocumented immigrants. Methods: A 21-item Internet-based survey using Survey Monkey® was sent to 765 physicians and nurses at a safety-net hospital located in Indianapolis, IN. Moral distress thermometer score was used to assess moral distress (MD). Participants were asked to rate their MD regarding five ethically challenging clinical situations: (1) frail patients with multiple comorbidities and poor quality of life, (2) patients with dementia, (3) a noncompliant patient with frequent emergency room (ER) visits, (4) violent patients with potential harm to others, and (5) undocumented immigrants receiving emergent dialysis only. Key Results: There were 299 of 775 participants (38.5% response rate) who completed the survey; 49.5% were physicians. Nearly half (48%) reported severe MD and 33% reported none to mild. In adjusted ordered logistic regression, females had significantly higher odds of MD (odds ratio [OR]=2.12, CI 1.03-4.33), and nurses had lower MD than fellows/residents (OR=0.14, CI 0.03-0.63). Over 70% of respondents attributed their distress to suffering of patients due to inadequate dialysis and tension between what is considered ethical and the law allows or forbids; 78% believed the patients' quality of life to be worse than those who receive routine hemodialysis. Among nephrologists, caring for these patients led to MD levels like that of dealing with a violent dialysis patient. Conclusions: Emergent-only dialysis causes significant MD in clinicians. Legal and fiscal policies need to be balanced with the ethical and moral commitments of providers for ensuring standard of care to all.Item Hospital-Acquired Versus Community-Acquired Acute Kidney Injury in Patients with Cirrhosis: A Prospective Study(Wolters Kluwer, 2020-09) Patidar, Kavish R.; Shamseddeen, Hani; Xu, Chenjia; Ghabril, Marwan S.; Nephew, Lauren D.; Desai, Archita P.; Anderson, Melissa; El-Achkar, Tarek M.; Ginès, Pere; Chalasani, Naga P.; Orman, Eric S.; Medicine, School of MedicineIntroduction: In patients with cirrhosis, differences between acute kidney injury (AKI) at the time of hospital admission (community-acquired) and AKI occurring during hospitalization (hospital-acquired) have not been explored. We aimed to compare patients with hospital-acquired AKI (H-AKI) and community-acquired AKI (C-AKI) in a large, prospective study. Methods: Hospitalized patients with cirrhosis were enrolled (N = 519) and were followed for 90 days after discharge for mortality. The primary outcome was mortality within 90 days; secondary outcomes were the development of de novo chronic kidney disease (CKD)/progression of CKD after 90 days. Cox proportional hazards and logistic regressions were used to determine the independent association of either AKI for primary and secondary outcomes, respectively. Results: H-AKI occurred in 10%, and C-AKI occurred in 25%. In multivariable Cox models adjusting for significant confounders, only patients with C-AKI had a higher risk for mortality adjusting for model for end-stage liver disease-Na: (hazard ratio 1.64, 95% confidence interval [CI] 1.04-2.57, P = 0.033) and adjusting for acute on chronic liver failure: (hazard ratio 2.44, 95% CI 1.63-3.65, P < 0.001). In univariable analysis, community-acquired-AKI, but not hospital-acquired-AKI, was associated with de novo CKD/progression of CKD (odds ratio 2.13, 95% CI 1.09-4.14, P = 0.027), but in multivariable analysis, C-AKI was not independently associated with de novo CKD/progression of CKD. However, when AKI was dichotomized by stage, C-AKI stage 3 was independently associated with de novo CKD/progression of CKD (odds ratio 4.79, 95% CI 1.11-20.57, P = 0.035). Discussion: Compared with H-AKI, C-AKI is associated with increased mortality and de novo CKD/progression of CKD in patients with cirrhosis. Patients with C-AKI may benefit from frequent monitoring after discharge to improve outcomes.Item Karnofsky performance status predicts outcomes in candidates for simultaneous liver-kidney transplant(Wiley, 2021-02) Shamseddeen, Hani; Pike, Francis; Ghabril, Marwan; Patidar, Kavish R.; Desai, Archita P.; Nephew, Lauren; Anderson, Melissa; Kubal, Chandrashekhar; Chalasani, Naga; Orman, Eric S.; Medicine, School of MedicineKarnofsky performance status (KPS), a measure of physical frailty, predicts pre-transplant and post-transplant outcomes in liver transplantation, but has not been assessed in simultaneous liver–kidney transplantation (SLKT). We examined the association between KPS and outcomes in SLKT waitlist registrants and recipients (2005-2018) in the UNOS database. KPS was categorized into A (able to work), B (able to provide self-care), and C (unable to provide self-care). Cox regression and competing risk analysis were used to assess the association between KPS groups and outcomes. A total of 10,785 patients were waitlisted (KPS: 19% A, 46% B, 35% C), and 5,516 underwent SLKT (12% A, 36% B, 52% C). One-year waitlist mortality was 17%, 22%, and 32% for KPS A, B, and C, respectively. In adjusted competing risk regression, KPS C was associated with increased waitlist mortality (SHR 1.15, 95%CI 1.04-1.28). One-year post-transplant survival was 92%, 91%, and 87% for KPS A, B, and C, respectively. In adjusted Cox regression, KPS C was associated with increased post-transplant mortality (HR 1.32, 95%CI 1.08-1.61). It was also associated with increased liver and kidney graft losses and with hospital length of stay. Frailty, as assessed by KPS, is associated with poor outcomes in SLKT pre- and post-transplant.