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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). 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. 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. Among critically patients with severe AKI requiring CKRT, use of pre-filter CVVH resulted in significantly shorter filter life compared to CVVHD. 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.

Severe acute kidney injury (AKI) is associated with subsequent infection. Whether AKI followed by a return to baseline creatinine is associated with incident infection is unknown. We hypothesized that risk of both short and long term infection would be higher among patients with AKI and return to baseline creatinine than in propensity score matched peers without AKI in the year following a non-infectious hospital admission. Retrospective, propensity score matched cohort study. We identified 494 patients who were hospitalized between January 1, 1999 and December 31, 2009 and had AKI followed by return to baseline creatinine. These were propensity score matched to controls without AKI. The predictor variable was AKI defined by International Classification of Diseases, Ninth Revision (ICD-9) codes and by the Kidney Disease Improving Global Outcomes definition, with return to baseline creatinine defined as a decrease in serum creatinine level to within 10% of the baseline value within 7 days of hospital discharge. The outcome variable was incident infection defined by ICD-9 code within 1 year of hospital discharge. AKI followed by return to baseline creatinine was associated with a 4.5-fold increased odds ratio for infection (odds ratio 4.53 [95% CI, 2.43-8.45]; p<0.0001) within 30 days following discharge. The association between AKI and subsequent infection remained significant at 31-60 days and 91 to 365 days but not during 61-90 days following discharge. Among patients from an integrated health care delivery system, non-infectious AKI followed by return to baseline creatinine was associated with an increased odds ratio for infection in the year following discharge.

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

Acute kidney injury (AKI) occurs at high rates among agricultural workers (12-33%) in tropical environments. Because of the remote locations affected, traditional laboratory services are often unavailable. In this study we compare point of care (POC) creatinine values to standardized laboratory values, and examine the effect of POC testing on the interpretation of AKI rates under tropical field conditions. Blood samples were collected from 104 sugarcane workers from two time points in January 2018 as a derivation cohort, and from 105 workers from February to April 2017 as a validation cohort. Finger stick and venipuncture samples were drawn at the end of a worker's shift to measure creatinine. Laboratory samples were tested in Guatemala City, Guatemala, in duplicate using the Jaffe Generation 2 method. An adjustment factor to improve agreement with serum creatinine was statistically derived and validated, and then used to determine impact on observed rates of acute kidney injury based on across shift changes in creatinine. POC creatinine and serum creatinine measures showed that POC consistently overestimated the creatinine by an average of 22% (95% CI: 19.8%, 24.7%) and the disagreement appeared greater at higher values of serum creatinine. An adjustment factor of 0.7775 was applied, which led to significantly greater agreement between the two measures. Rates of AKI in the two combined groups fell from 72% before adjustment to 57% afterwards. POC testing under tropical field conditions routinely overestimates creatinine compared to laboratory testing, which leads to overestimation of rates of acute kidney injury. The application of an adjustment factor significantly improved the accuracy of the POC value.

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 [ 13 C 6 ]-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.

Early diagnosis of muscle wasting in critically ill patients with acute kidney injury requiring continuous kidney replacement therapy (AKI-CKRT) may improve outcomes timely rehabilitation and nutrition. Muscle ultrasound (MUS) has recently gained traction for assessing muscle atrophy in the intensive care unit (ICU) but requires training to achieve reproducibility. We evaluated the inter-rater reliability of MUS in patients with AKI-CKRT performed by multidisciplinary raters including nephrologists. Two blinded independent raters used portable ultrasound to acquire images of the rectus femoris (RF). All raters were clinicians routinely caring for patients with CKRT in the ICU and were initially novices in MUS. They underwent three two-hour teleconference training sessions in MUS led by an experienced physiotherapist. Inter-rater reliability was evaluated with intraclass correlation coefficients (ICCs) [95% confidence interval] using a two-way random-effects model. We analyzed 54 MUS images (27 pairs) from nine patients at baseline (  = 16), day 3 (  = 6), day 7 (  = 8), ICU discharge (  = 10), hospital discharge (  = 10), and 1-3 months after discharge (  = 4). The mean (±standard deviation) values of RF thickness, cross-sectional area, and echointensity were 1.7 ± 1.4 cm, 4.6 ± 2.7 cm , and 84.0 ± 17.7 AU, respectively. Reliability was excellent for RF thickness (ICC = 0.96 [0.91-0.98],  < 0.001) and cross-sectional area (ICC = 0.92 [0.83-0.96],  < 0.001) but poor for echointensity (ICC = 0.41 [0.04-0.68],  < 0.05). These results demonstrate reliable assessment of muscle size in patients with AKI-CKRT using ultrasound performed by multidisciplinary novice sonographers trained teleconference, suggesting that this methodology may be useful in future studies of muscle wasting in patients with AKI-CKRT.

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.

IntroductionAcute 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 analysisThis 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 disseminationWe 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 numberNCT05287204.

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. 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. 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. 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. POC testing can be more accessible in resource-limited settings. The selection of the appropriate device will depend on the use-case.

Background Ensuring that patients, especially those in underserved areas, have access to specialized nephrology care is essential to addressing the increasing burden of chronic kidney disease. To address this, we developed the Telenephrology Dashboard for the 150,000 Veterans served by the Iowa City Veterans Affairs Health Care System (ICVAHCS). Our goal was to optimize the dashboard as a comprehensive and practical tool for end-users in order to monitor kidney health and facilitate remote nephrology consultations. Methods The optimization process adhered to the Human-Centered Design (HCD) framework, encompassing five stages: Empathize, Define, Ideate, Prototype and Test. Research team members spent 10 h observing nephrologists during remote consultations and supplemented these observations with semi-structured interviews with clinicians to gain insights into existing workflows and challenges. A rapid ideation workshop was then held to propose innovative solutions that balanced technical needs with user preferences. Subsequent prototyping and testing helped refine and evaluate the proposed designs, identifying key areas for improvement. Results The iterative design process identified three critical needs: (1) improved clarity in visual data representation, (2) enhanced data accuracy, and (3) a balance between standardized features and customization options. Five dashboard prototypes were created, tested, and iteratively refined into a final version. The completed Telenephrology Dashboard includes five core features: (1) graphical representation of kidney function trends, (2) tables summarizing key lab data, (3) functionality to examine specific events in detail, (4) customizable views tailored to user workflows, and (5) integration of predictive kidney disease progression models. Conclusion The Telenephrology Dashboard was developed using a Human-Centered Design approach to improve remote nephrology consultations. Future efforts will focus on evaluating its impact on user satisfaction, referring clinician satisfaction, access to nephrology care, and patient care outcomes. Clinical trial number Not applicable, as this is not a clinical trial.