Browsing by Subject "acute kidney injury"

Now showing 1 - 10 of 18
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    1-year mortality following contrast-induced nephropathy
    (2013) Mitchell, Alice M; Jones, Alan E; Tumlin, James A; Kline, Jeffrey A.
    Objective: The aim of this study was to determine the 1-year mortality risk subsequent to Contrast-Induced Nephropathy (CIN) following CECT imaging, relative to other well-recognized predictors of mortality. Methods: We followed a prospective, consecutive cohort of ambulatory patients who received intravenous contrast for CECT for the outcome of death from any cause within 1 year. In a multivariate analysis, we compared CIN with other predictors of mortality: active malignancy, coronary artery disease (CAD), congestive heart failure (CHF) and age ≥70 years. Anticipating that terminal cancers would account for the majority of deaths in this population, we also analyzed the subset of patients without an active malignancy at the time of enrollment. Results: We followed 633 patients and 46 died (7%, 95%CI: 5-9%) within 1 year. The incidence of CIN was 11% (95%CI: 8-14%). Active malignancy (HR 9.2, 95%CI: 5.1-16.8), CIN (HR 2.4, 95%CI: 1.3-4.6), CHF (HR 2.1, 95%CI: 1.0-4.2), CAD (HR 2.2, 95%CI: 1.0-5.5) and age ≥70 years (HR 1.8, 95%CI: 1.0-3.8) were significant predictors of all-cause mortality. Among patients without active malignancies, the mortality rate was 4% (25/580, 95%CI: 3-6%) and CIN (HR 4.0, 95%CI: 1.7-9.6) and age ≥70 years (HR 3.7, 95%CI: 1.4-9.7) were significantly associated with death, whereas CAD (HR 2.5, 95%CI: 0.8-7.7) and CHF (HR 1.8, 95%CI: 0.6-5.3) were not. Conclusions: The development of CIN following CECT is associated with an increased likelihood of death at 1 year among patients with and without active malignancies, comparable to CAD, CHF and advanced age.
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    Beyond Biomarkers: Machine Learning in Diagnosing Acute Kidney Injury
    (Mayo Clinic, 2019-05) Molitoris, Bruce A.; Medicine, School of Medicine
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    The case for capillary rarefaction in the AKI to CKD progression: insights from multiple injury models
    (American Physiological Society, 2019-11) Basile, David P.; Anatomy and Cell Biology, School of Medicine
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    Cytokine-induced F-actin reorganization in endothelial cells involves RhoA activation
    (2009-03) Campos, Silvia B; Ashworth, Sharon L; Wean, Sarah; Hosford, Melanie; Sandoval, Ruben M; Hallett, Mark A; Atkinson, Simon J; Molitoris, Bruce A
    Acute ischemic kidney injury results in marked increases in local and systemic cytokine levels. IL-1α, IL-6, and TNF-α orchestrate various inflammatory reactions influencing endothelial permeability by altering cell-to-cell and cell-to-extracellular matrix attachments. To explore the role of actin and the regulatory proteins RhoA and cofilin in this process, microvascular endothelial cells (MS1) were exposed to individual cytokines or a cytokine cocktail. Within minutes, a marked, time-dependent redistribution of the actin cytoskeleton occurred with the formation of long, dense F-actin basal stress fibers. The concentration of F-actin, normalized to nuclear staining, significantly increased compared with untreated cells (up 20%, P ≤ 0.05). Western blot analysis of MS1 lysates incubated with the cytokine cocktail for 4 h showed an increase in phosphorylated/inactive cofilin (up 25 ± 15%, P ≤ 0.05) and RhoA activation (up to 227 ± 26% increase, P ≤ 0.05) compared with untreated cells. Decreasing RhoA levels using small interfering RNA blocked the effect of cytokines on stress fiber organization. Treatment with Y-27632, an inhibitor of the RhoA effector p160-ROCK, decreased levels of phosphorylated cofilin and reduced stress fiber fluorescence by 22%. In cells treated with Y-27632 followed by treatment with the cytokine cocktail, stress fiber levels were similar to control cells and cofilin phosphorylation was 55% of control levels. Taken together, these studies demonstrate cytokine stimulation of RhoA, which in turn leads to cofilin phosphorylation and formation of numerous basal actin stress fibers. These results suggest cytokines signal through the Rho-ROCK pathway, but also through another pathway to affect actin dynamics.
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    DNA damage response protects against progressive kidney disease
    (American Society for Clinical Investigation, 2019-10) Molitoris, Bruce A.; Medicine, School of Medicine
    he pathophysiology of cellular injury and repair has been extensively studied in acute kidney injury (AKI) for more than 70 years. Although a great deal of knowledge has been generated, a debate over the importance of repairing damaged cells versus replacing them by proliferation remains. In this issue of the JCI, Kishi et al. demonstrate that following kidney epithelial cell injury, DNA repair, rather than cell proliferation, plays the central role in recovery and longevity by minimizing apoptosis, G2/M cell-cycle arrest, and subsequent fibrosis. This has important therapeutic implications and highlights the need for more sensitive techniques to evaluate functional, structural, and molecular recovery following injury.
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    Empagliflozin and incidence of events consistent with acute kidney injury: Pooled safety analysis in >15 000 individuals
    (Wiley, 2022) Agarwal, Rajiv; Hauske, Sibylle Jenny; Wheeler, David C.; Doi, Kent; Elsaesser, Amelie; Ritter, Ivana; Steubl, Dominik; Wanner, Christoph; Medicine, School of Medicine
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    Evidence-based development of a nephrotoxic medication list to screen for acute kidney injury risk in hospitalized children
    (Oxford, 2019-10-30) Goswami, Elizabeth; Ogden, Richard K.; Bennett, William E, Jr.; Goldstein, Stuart L; Hackbarth, Richard; Somers, Michael J G; Yonekawa, Karyn; Misurac, Jason; Pediatrics, School of Medicine
    Purpose Medications are commonly associated with acute kidney injury (AKI). However, in both clinical practice and research, consideration of specific medications as nephrotoxic varies widely. The Nephrotoxic Injury Negated by Just-in-time Action quality improvement collaborative was formed to focus on prevention or reduction of nephrotoxic medication-associated AKI in noncritically ill hospitalized children. However, there were discrepancies among institutions as to which medications should be considered nephrotoxic. The collaborative convened a Nephrotoxic Medication (NTMx) Subcommittee to develop a consensus for the classification of nephrotoxic medications. Summary The NTMx Subcommittee initially included pediatric nephrologists, a pharmacist, and a pediatric intensivist. The committee reviewed NTMx lists from the collaborative and identified changes from the initial NTMx list. The NTMx Subcommittee conducted a literature review of the disputed medications and assigned an evidence grade based on the reported association with nephrotoxicity and the quality of the data. The association between medication exposure and AKI was also determined using administrative data from the Pediatric Health Information Systems database. The NTMx Subcommittee then came to a majority consensus regarding which medications should be included on the list. The subcommittee’s recommendations were presented to the larger collaborative for approval, and consensus was achieved. The list continues to be reviewed and updated annually. Conclusion Formation of a multicenter quality-improvement initiative exposed current limitations as to which medications are considered nephrotoxic in clinical and research settings and presented an opportunity to approach this problem using an evidence-based process. A consensus definition of nephrotoxic-medication exposure was achieved.
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    Fluid Resuscitation and Progression to Renal Replacement Therapy in Patients With COVID-19
    (Elsevier, 2022-02) Holt, Daniel B.; Lardaro, Thomas; Wang, Alfred Z.; Musey, Paul I.; Trigonis, Russell; Bucca, Antonino; Croft, Alexander; Glober, Nancy; Peterson, Kelli; Schaffer, Jason T.; Hunter, Benton R.; Medicine, School of Medicine
    Background Coronavirus disease 2019 (COVID-19) is associated with respiratory symptoms and renal effects. Data regarding fluid resuscitation and kidney injury in COVID-19 are lacking, and understanding this relationship is critical. Objectives To determine if there is an association between fluid volume administered in 24 h and development of renal failure in COVID-19 patients. Methods Retrospective chart review; 14 hospitals in Indiana. Included patients were adults admitted between March 11, 2020 and April 13, 2020 with a positive test for severe acute respiratory syndrome coronavirus 2 within 3 days of admission. Patients requiring renal replacement therapy prior to admission were excluded. Volumes and types of resuscitative intravenous fluids in the first 24 h were obtained with demographics, medical history, and other objective data. The primary outcome was initiation of renal replacement therapy. Logistic regression modeling was utilized in creating multivariate models for determining factors associated with the primary outcome. Results The fluid volume received in the first 24 h after hospital admission was associated with initiation of renal replacement therapy in two different multivariate logistic regression models. An odds ratio of 1.42 (95% confidence interval 1.01–1.99) was observed when adjusting for age, heart failure, obesity, creatinine, bicarbonate, and total fluid volume. An odds ratio of 1.45 (95% confidence interval 1.02–2.05) was observed when variables significant in univariate analysis were adjusted for. Conclusions Each liter of intravenous fluid administered to patients with COVID-19 in the first 24 h of presentation was independently associated with an increased risk for initiation of renal replacement therapy, supporting judicious fluid administration in patients with this disease.
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    Human adipose stromal cell therapy improves survival and reduces renal inflammation and capillary rarefaction in acute kidney injury
    (Wiley, 2017-07) Collett, Jason A.; Traktuev, Dmitry O.; Mehrotra, Purvi; Crone, Allison; Merfeld-Clauss, Stephanie; March, Keith L.; Basile, David P.; Department of Cellular and Integrative Physiology, School of Medicine
    Damage to endothelial cells contributes to acute kidney injury (AKI) by causing impaired perfusion, while the permanent loss of the capillary network following AKI has been suggested to promote chronic kidney disease. Therefore, strategies to protect renal vasculature may impact both short-term recovery and long-term functional preservation post-AKI. Human adipose stromal cells (hASCs) possess pro-angiogenic and anti-inflammatory properties and therefore have been tested as a therapeutic agent to treat ischaemic conditions. This study evaluated hASC potential to facilitate recovery from AKI with specific attention to capillary preservation and inflammation. Male Sprague Dawley rats were subjected to bilateral ischaemia/reperfusion and allowed to recover for either two or seven days. At the time of reperfusion, hASCs or vehicle was injected into the suprarenal abdominal aorta. hASC-treated rats had significantly greater survival compared to vehicle-treated rats (88.7% versus 69.3%). hASC treatment showed hastened recovery as demonstrated by lower creatinine levels at 48 hrs, while tubular damage was significantly reduced at 48 hrs. hASC treatment resulted in a significant decrease in total T cell and Th17 cell infiltration into injured kidneys at 2 days post-AKI, but an increase in accumulation of regulatory T cells. By day 7, hASC-treated rats showed significantly attenuated capillary rarefaction in the cortex (15% versus 5%) and outer medulla (36% versus 18%) compared to vehicle-treated rats as well as reduced accumulation of interstitial alpha-smooth muscle actin-positive myofibroblasts. These results suggest for the first time that hASCs improve recovery from I/R-induced injury by mechanisms that contribute to decrease in inflammation and preservation of peritubular capillaries.
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    Intraoperative hypotension is associated with persistent acute kidney disease after noncardiac surgery: a multicentre cohort study
    (Elsevier, 2022) Shaw, Andrew D.; Khanna, Ashish K.; Smischney, Nathan J.; Shenoy, Apeksha V.; Boero, Isabel J.; Bershad, Michael; Hwang, Seungyoung; Chen, Qinyu; Stapelfeldt , Wolf H.; Anesthesia, School of Medicine
    Background: Whilst intraoperative hypotension is associated with postoperative acute kidney injury (AKI), the link between intraoperative hypotension and acute kidney disease (AKD), defined as continuing renal dysfunction for up to 3 months after exposure, has not yet been studied. Methods: We conducted a retrospective multicentre cohort study using data from noncardiac, non-obstetric surgery extracted from a US electronic health records database. Primary outcome was the association between intraoperative hypotension, at three MAP thresholds (≤75, ≤65, and ≤55 mm Hg), and the following two AKD subtypes: (i) persistent (initial AKI incidence within 7 days of surgery, with continuation between 8 and 90 days post-surgery) and (ii) delayed (renal impairment without AKI within 7 days, with AKI occurring between 8 and 90 days post-surgery). Secondary outcomes included healthcare resource utilisation for patients with either AKD subtype or no AKD. Results: A total of 112 912 surgeries qualified for the study. We observed a rate of 2.2% for delayed AKD and 0.6% for persistent AKD. Intraoperative hypotension was significantly associated with persistent AKD at MAP ≤55 mm Hg (hazard ratio 1.1; 95% confidence interval: 1.38–1.22; P<0.004). However, IOH was not significantly associated with delayed AKD across any of the MAP thresholds. Patients with delayed or persistent AKD had higher healthcare resource utilisation across both hospital and intensive care admissions, compared with patients with no AKD. Conclusions: Intraoperative hypotension is associated with persistent but not delayed acute kidney disease. Both types of acute kidney disease appear to be associated with increased healthcare utilisation. Correction of intraoperative hypotension is a potential opportunity to decrease postoperative kidney injury and associated costs.