Assessing the role of Chemokine (C-C motif) ligand 14 in AKI: a European consensus meeting.

BACKGROUND: Urinary Chemokine (C-C motif) ligand 14 (CCL14) is a biomarker associated with persistent severe acute kidney injury (AKI). There is limited data to support the implementation of this AKI biomarker to guide therapeutic actions. METHODS: Sixteen AKI experts with clinical CCL14 experience participated in a Delphi-based method to reach consensus on when and how to potentially use CCL14. Consensus was defined as ≥ 80% agreement (participants answered with 'Yes', or three to four points on a five-point Likert Scale). RESULTS: Key consensus areas for CCL14 test implementation were: identifying challenges and mitigations, developing a comprehensive protocol and pairing it with a treatment plan, and defining the target population. The majority agreed that CCL14 results can help to prioritize AKI management decisions. CCL14 levels above the high cutoff (> 13 ng/mL) significantly changed the level of concern for modifying the AKI treatment plan (p < 0.001). The highest level of concern to modify the treatment plan was for discussions on renal replacement therapy (RRT) initiation for CCL14 levels > 13 ng/mL. The level of concern for discussion on RRT initiation between High and Low, and between Medium and Low CCL14 levels, showed significant differences. CONCLUSION: Real world urinary CCL14 use appears to provide improved care options to patients at risk for persistent severe AKI. Experts believe there is a role for CCL14 in AKI management and it may potentially reduce AKI-disease burden. There is, however, an urgent need for evidence on treatment decisions and adjustments based on CCL14 results.

Initial renal replacement therapy (RRT) modality associates with 90-day postdischarge RRT dependence in critically ill AKI survivors.

PURPOSE: Real-world comparison of RRT modality on RRT dependence at 90 days postdischarge among ICU patients discharged alive after RRT for acute kidney injury (AKI). METHODS: Using claims-linked to US hospital discharge data (Premier PINC AI Healthcare Database [PHD]), we compared continuous renal replacement therapy (CRRT) vs. intermittent hemodialysis (IHD) for AKI in adult ICU patients discharged alive from January 1, 2018 to June 30, 2021. RRT dependence at 90 days postdischarge was defined as ≥2 RRT treatments in the last 8 days. Between-group differences were balanced using inverse probability treatment weighting (IPTW). RESULTS: Of 34,804 patients, 3804 patients (from 382 hospitals) had claims coverage for days 83-90 postdischarge. Compared to IHD-treated patients (n = 2740), CRRT-treated patients (n = 1064) were younger; had more admission to large teaching hospitals, surgery, sepsis, shock, mechanical ventilation, but lower prevalence of comorbidities (p < 0.05 for all). Compared to IHD-treated patients, CRRT-treated patients had lower RRT dependence at hospital discharge (26.5% vs. 29.8%, p = 0.04) and lower RRT dependence at 90 days postdischarge (4.9% vs. 7.4% p = 0.006) with weighted adjusted OR (95% CI): 0.68 (0.47-0.97), p = 0.03. Results persisted in sensitivity analyses including patients who died during days 1-90 postdischarge (n = 112) or excluding patients from hospitals with IHD patients only (n = 335), or when excluding patients who switched RRT modalities (n = 451). CONCLUSIONS: Adjusted for potential confounders, the odds of RRT dependence at 90 days postdischarge among survivors of RRT for AKI was 30% lower for those treated first with CRRT vs. IHD, overall and in several sensitivity analyses. SUMMARY: Critically ill patients in intensive care units (ICU) may develop acute kidney injury (AKI) that requires renal replacement therapy (RRT) to temporarily replace the injured kidney function of cleaning the blood. Two main types of RRT in the ICU are called continuous renal replacement therapy (CRRT), which is performed almost continuously, i.e., for >18 h per day, and intermittent hemodialysis (IHD), which is a more rapid RRT that is usually completed in a little bit over 6 h, several times per week. The slower CRRT may be gentler on the kidneys and is more likely to be used in the sickest patients, who may not be able to tolerate IHD. We conducted a data-analysis study to evaluate whether long-term effects on kidney function (assessed by ongoing need for RRT, i.e., RRT dependence) differ depending on use of CRRT vs. IHD. In a very large US linked hospital-discharge/claims database we found that among ICU patients discharge alive after RRT for AKI, fewer CRRT-treated patients had RRT dependence at hospital discharge (26.5% vs. 29.8%, p = 0.04) and at 90 days after discharge (4.9% vs. 7.4% p = 0.006). In adjusted models, RRT dependence at 90 days postdischarge was >30% lower for CRRT than IHD-treated patients. These results from a non-randomized study suggest that among survivors of RRT for AKI, CRRT may result in less RRT dependence 90 days after hospital discharge.

Exploring the Cost-Utility of a Biomarker Predicting Persistent Severe Acute Kidney Injury: The Case of C-C Motif Chemokine Ligand 14 (CCL14).

Background: Approximately 24% of hospitalized stage 2-3 acute kidney injury (AKI) patients will develop persistent severe AKI (PS-AKI), defined as KDIGO stage 3 AKI lasting ≥3 days or with death in ≤3 days or stage 2 or 3 AKI with dialysis in ≤3 days, leading to worse outcomes and higher costs. There is currently no consensus on an intervention that effectively reverts the course of AKI and prevents PS-AKI in the population with stage 2-3 AKI. This study explores the cost-utility of biomarkers predicting PS-AKI, under the assumption that such intervention exists by comparing C-C motif chemokine ligand 14 (CCL14) to hospital standard of care (SOC) alone. Methods: The analysis combined a 90-day decision tree using CCL14 operating characteristics to predict PS-AKI and clinical outcomes in 66-year-old patients, and a Markov cohort estimating lifetime costs and quality-adjusted life years (QALYs). Cost and QALYs from admission, 30-day readmission, intensive care, dialysis, and death were compared. Clinical and cost inputs were informed by a large retrospective cohort of US hospitals in the PINC AI Healthcare Database. Inputs and assumptions were challenged in deterministic and probabilistic sensitivity analyses. Two-way analyses were used to explore the efficacy and costs of an intervention preventing PS-AKI. Results: Depending on selected costs and early intervention efficacy, CCL14-directed care led to lower costs and more QALYs (dominating) or was cost-effective at the $50,000/QALY threshold. Assuming the intervention would avoid 10% of PS-AKI complications in AKI stage 2-3 patients identified as true positive resulted in 0.066 additional QALYs and $486 reduced costs. Results were robust to substantial parameter variation. Conclusion: The analysis suggests that in the presence of an efficacious intervention preventing PS-AKI, identifying people at risk using CCL14 in addition to SOC is likely to represent a cost-effective use of resources.

Predictions of Serum Phosphate Concentration during Continuous Renal Replacement Therapy Using a Steady-State Mass Balance Model.

INTRODUCTION: Hypophosphatemia is common during continuous renal replacement therapy (CRRT), but serum phosphate levels can potentially be maintained during treatment by either intravenous phosphate supplementation or addition of phosphate to renal replacement therapy (RRT) solutions. METHODS: We developed a steady-state phosphate mass balance model to assess the effects of CRRT dose on serum phosphate concentration when using both phosphate-free and phosphate-containing RRT solutions, with emphasis on low CRRT doses. RESULTS: The model predicted that measurements of serum phosphate concentration prior to (initial) and during CRRT (final) together with clinical data on CRRT dose, treatment duration, and phosphate supplementation can determine model patient parameters, that is, both the initial generation rate and clearance of phosphate prior to CRRT. Model parameters were then calculated from average patient data reported in several previous publications with a standard or high CRRT dose. Using representative model parameters for typical patients, predictions were then made of the effect of low CRRT dose on the change in serum phosphate levels after implementation of CRRT. The model predicted that CRRT at a low dose using phosphate-free RRT solutions will limit, but not eliminate, the incidence of hypophosphatemia. Further, the model predicted that CRRT at a low dose will have virtually no influence on the incidence of hyperphosphatemia when using phosphate-containing RRT solutions. CONCLUSIONS: This report identifies the clinical measurements to be used with the proposed model for individualizing the CRRT dose and RRT phosphate concentration to maintain serum phosphate concentrations in a desired range.

Clinical Research With Large Language Models Generated Writing-Clinical Research with AI-assisted Writing (CRAW) Study.

IMPORTANCE: The scientific community debates Generative Pre-trained Transformer (GPT)-3.5's article quality, authorship merit, originality, and ethical use in scientific writing. OBJECTIVES: Assess GPT-3.5's ability to craft the background section of critical care clinical research questions compared to medical researchers with H-indices of 22 and 13. DESIGN: Observational cross-sectional study. SETTING: Researchers from 20 countries from six continents evaluated the backgrounds. PARTICIPANTS: Researchers with a Scopus index greater than 1 were included. MAIN OUTCOMES AND MEASURES: In this study, we generated a background section of a critical care clinical research question on "acute kidney injury in sepsis" using three different methods: researcher with H-index greater than 20, researcher with H-index greater than 10, and GPT-3.5. The three background sections were presented in a blinded survey to researchers with an H-index range between 1 and 96. First, the researchers evaluated the main components of the background using a 5-point Likert scale. Second, they were asked to identify which background was written by humans only or with large language model-generated tools. RESULTS: A total of 80 researchers completed the survey. The median H-index was 3 (interquartile range, 1-7.25) and most (36%) researchers were from the Critical Care specialty. When compared with researchers with an H-index of 22 and 13, GPT-3.5 was marked high on the Likert scale ranking on main background components (median 4.5 vs. 3.82 vs. 3.6 vs. 4.5, respectively; p < 0.001). The sensitivity and specificity to detect researchers writing versus GPT-3.5 writing were poor, 22.4% and 57.6%, respectively. CONCLUSIONS AND RELEVANCE: GPT-3.5 could create background research content indistinguishable from the writing of a medical researcher. It was marked higher compared with medical researchers with an H-index of 22 and 13 in writing the background section of a critical care clinical research question.

Economic Analysis of Renal Replacement Therapy Modality in Acute Kidney Injury Patients With Fluid Overload.

Acute kidney injury (AKI) and fluid overload (FO) are among the top reasons to initiate intermittent hemodialysis (IHD) or continuous renal replacement therapy (CRRT). Prior research suggests CRRT provides more precise volume control, but whether CRRT is cost-effective remains unclear. We assessed the cost-effectiveness of CRRT for volume control compared with IHD from a U.S. healthcare payer perspective. DESIGN: Decision analytical model comparing health outcomes and healthcare costs of CRRT versus IHD initiation for AKI patients with FO. The model had an inpatient phase (over 90-d) followed by post-discharge phase (over lifetime). The 90-day phase had three health states: FO, fluid control, and death. After 90 days, surviving patients entered the lifetime phase with four health states: dialysis independent (DI), dialysis dependent (DD), renal transplantation, and death. Model parameters were informed by current literature. Sensitivity analyses were performed to evaluate results robustness to parametric uncertainty. SETTING: ICU. PATIENTS OR SUBJECTS: AKI patients with FO. INTERVENTIONS: IHD or CRRT. MEASUREMENTS AND MAIN RESULTS: The 90-day horizon revealed better outcomes for patients initiated on CRRT (survival: CRRT 59.2% vs IHD 57.5% and DD rate among survivors: CRRT 5.5% vs IHD 6.9%). Healthcare cost was 2.7% (+$2,836) higher for CRRT. Over lifetime, initial CRRT was associated with +0.313 life years (LYs) and +0.187 quality-adjusted life years (QALYs) compared with initial IHD. Even though important savings were observed for initial CRRT with a lower rate of DD among survivors (-$13,437), it did not fully offset the incremental cost of CRRT (+$1,956) and DI survival (+$12,830). The incremental cost-per-QALY gained with CRRT over IRRT was +$10,429/QALY. Results were robust to sensitivity analyses. CONCLUSIONS: Our analysis provides an economic rationale for CRRT as the initial modality of choice in AKI patients with FO who require renal replacement therapy. Our finding needs to be confirmed in future research.

Clinical Outcomes of Persistent Severe Acute Kidney Injury among Patients with Kidney Disease Improving Global Outcomes Stage 2 or 3 Acute Kidney Injury.

INTRODUCTION: The burden of persistent (≥3 days) severe AKI (PS-AKI) is poorly described among inpatients with stage 2-3 AKI in the ward or ICU. Quantification could motivate targeted interventions to decrease duration of AKI in these high-risk patients. METHODS: This retrospective cohort study included adult patients discharged from January 1, 2017, to December 31, 2019, from US hospitals in the PINC AI Healthcare Database. Patients with KDIGO stage 2 or 3 AKI, length of stay ≥3 days, ≥3 serum creatinine measures, and no history of renal transplant, dialysis, or stage 5 chronic kidney disease were included. Patients were classified as PS-AKI (stage 3 AKI lasting ≥3 days or with death in ≤3 days, or stage 2 or 3 AKI with dialysis in ≤3 days) or not PS-AKI (NPS-AKI) (stage 3 AKI for ≤2 days, or stage 2 AKI without dialysis in ≤3 days). Outcomes during index (initial) hospitalization were PS-AKI incidence, ICU use, and in-hospital mortality, and during 30 days post-discharge were readmissions, in-hospital mortality, dialysis, and "new" dialysis (dialysis among patients without dialysis during index hospitalization). For index outcomes, we used a sensitivity definition, PS-AKISens, that excluded patients who met PS-AKI criteria by dialysis/death in ≤3 days of AKI onset. Multivariable-adjusted logistic regression quantified differences between PS-AKI and NPS-AKI, overall, and separately for ICU and non-ICU patients. RESULTS: Among 126,528 inpatients with stage 2 or 3 AKI, PS-AKI developed in 24.4% (30,916), with 39% of PS-AKI occurring in non-ICU patients. With NPS-AKI as the reference group, adjusted odds ratios (aORs) (95% CI) for PS-AKI and for PS-AKISens were 2.15 (2.09-2.21) and 1.28 (1.24-1.32) for ICU use and 4.58 (4.41-4.75) and 1.79 (1.70-1.89) for in-hospital mortality during index hospitalization. For outcomes during 30 days post-discharge, aORs for PS-AKI versus NPS-AKI were 1.07 (1.02-1.11) for readmissions, 1.33 (1.18-1.49) for in-hospital mortality, 15.66 (13.87-17.67) for dialysis, and 6.80 (5.84-7.93) for new dialysis. Despite higher mortality among ICU patients, aORs for outcomes during index and 30 days post-discharge were similar for ICU and non-ICU patients. CONCLUSION: In and out of the ICU, PS-AKI frequently affected inpatients with stage 2 or 3 AKI and was independently associated with worse clinical outcomes during index hospitalization and during 30 days post-discharge. These results suggest that interventions to prevent persistence of severe AKI may reduce adverse clinical outcomes among patients with stage 2 or 3 AKI in or out of the ICU.

Early versus delayed initiation of renal replacement therapy in cardiac-surgery associated acute kidney injury: an economic perspective.

BACKGROUND: Timing for renal replacement therapy (RRT) initiation for cardiac-surgery associated acute kidney surgery (CSA-AKI) is subject to debate. Evidence suggests earlier initiation leads to shorter length of stay (LoS). We investigated differences in healthcare costs associated with timing of RRT initiation in CSA-AKI. METHODS: A cost-consequences model compared costs of Early (<24 h) vs. Delayed (>24 h) RRT initiation. Data were from the ELAIN trial in Germany, and the HiDenIC database, a US multi-hospital database. Resource utilization was determined by RRT duration, ICU, and hospital LoS. All resources were costed from a US healthcare perspective. Extensive sensitivity analyses (SA) were conducted, notably regarding the proportion of patients not initiated on RRT with the Delayed strategy. RESULTS: Early RRT initiation exhibited cost savings compared to Delayed RRT initiation. With ELAIN data, savings reached -$122,188 (ranging from -$157,707 to -$74,763 in the SA). Findings were confirmed with HiDenIC data; Early RRT initiation showed savings of -$77,303 (ranging from -$108,971 to -$47,012 in the SA). CONCLUSIONS: Our costing model indicates that Early RRT initiation for CSA-AKI may result in appreciable cost savings. Delaying RRT, in the setting of CSA-AKI, may lead to longer LoS and increased healthcare costs.

Cost-effectiveness of the TherMax blood warmer during continuous renal replacement therapy.

Hypothermia is a common adverse event during continuous renal replacement therapy (CRRT), affecting multiple organ systems and increasing risk of poor health outcomes among patients with acute kidney injury (AKI) undergoing CRRT. TheraMax blood warmers are the next generation of extracorporeal blood warmers which reduce risk of hypothermia during CRRT. The purpose of this study is to elucidate the potential health economic impacts of avoiding CRRT-induced hypothermia by using the novel TherMax blood warming device. This study compares health care costs associated with use of the new TherMax blood warmer unit integrated with the PrisMax system compared to CRRT with a standalone blood warming device to avoid hypothermia in continuous renal replacement therapy (CRRT). An economic model was developed in which relevant health states for each intervention were normothermia, hypothermia, discharge, and death. Clinical inputs and costs were obtained from a combination of retrospective chart review and publicly available summary estimates. The proportion of AKI patients treated with CRRT who became hypothermic (<36°C) during CRRT treatment was 34.5% in the TherMax group compared to 71.9% in the 'standalone warmer' group. Given the 78.7-year average life expectancy in the US and the assumed average patient age at discharge/death of 65.4 years, the total life-years gained by avoiding mortality related to hypothermia was 9.0 in the TherMax group compared to 8.0 in the 'standalone warmer' group. Cost per life-year gained was $8,615 in the TherMax group versus $10,115 in the 'standalone warmer' group for a difference of -$1,501 favoring TherMax. The incremental cost-effectiveness ratio was negative, indicating superior cost-effectiveness for TherMax versus 'standalone warmer'. The TherMax blood warming device used with the PrisMax system is associated with lower risk of hypothermia, which our model indicates leads to lower costs, lower risk of mortality due to hypothermia, and superior cost-effectiveness.

Modeling acid-base balance during continuous kidney replacement therapy.

Clinical studies have suggested that use of bicarbonate-containing substitution and dialysis fluids during continuous kidney replacement therapy may result in excessive increases in the carbon dioxide concentration of blood; however, the technical parameters governing such changes are unclear. The current work used a mathematical model of acid-base chemistry of blood to predict its composition within and exiting the extracorporeal circuit during continuous veno-venous hemofiltration (CVVH) and continuous veno-venous hemodiafiltration (CVVHDF). Model predictions showed that a total substitution fluid infusion rate of 2 L/h (33% predilution) with a bicarbonate concentration of 32 mEq/L during CVVH at a blood flow rate of 200 mL/min resulted in only modest increases in plasma bicarbonate concentration by 2.0 mEq/L and partial pressure of dissolved carbon dioxide by 4.4 mmHg in blood exiting the extracorporeal circuit. The relative increase in bicarbonate concentration (9.7%) was similar to that in partial pressure of dissolved carbon dioxide (8.2%), resulting in no significant change in plasma pH in the blood exiting the CVVH circuit. The changes in plasma acid-base levels were larger with a higher infusion rate of substitution fluid but smaller with a higher blood flow rate or use of substitution fluid with a lower bicarbonate concentration (22 mEq/L). Under comparable flow conditions and substitution fluid composition, model predicted changes in acid-base levels during CVVHDF were similar, but smaller, than those during CVVH. The described mathematical model can predict the effect of operating conditions on acid-base balance within and exiting the extracorporeal circuit during continuous kidney replacement therapy.

Targeting arterial partial pressure of carbon dioxide in acute respiratory distress syndrome patients using extracorporeal carbon dioxide removal.

BACKGROUND: A retrospective analysis of SUPERNOVA trial data showed that reductions in tidal volume to ultraprotective levels without significant increases in arterial partial pressure of carbon dioxide (PaCO2 ) for critically ill, mechanically ventilated patients with acute respiratory distress syndrome (ARDS) depends on the rate of extracorporeal carbon dioxide removal (ECCO2 R). METHODS: We used a whole-body mathematical model of acid-base balance to quantify the effect of altering carbon dioxide (CO2 ) removal rates using different ECCO2 R devices to achieve target PaCO2 levels in ARDS patients. Specifically, we predicted the effect of using a new, larger surface area PrismaLung+ device instead of the original PrismaLung device on the results from two multicenter clinical studies in critically ill, mechanically ventilated ARDS patients. RESULTS: After calibrating model parameters to the clinical study data using the PrismaLung device, model predictions determined optimal extracorporeal blood flow rates for the PrismaLung+ and mechanical ventilation frequencies to obtain target PaCO2 levels of 45 and 50 mm Hg in mild and moderate ARDS patients treated at a tidal volume of 3.98 ml/kg predicted body weight (PW). Comparable model predictions showed that reductions in tidal volumes below 6 ml/kg PBW may be difficult for acidotic highly severe ARDS patients with acute kidney injury and high CO2 production rates using a PrismaLung+ device in-series with a continuous venovenous hemofiltration device. CONCLUSIONS: The described model provides guidance on achieving target PaCO2 levels in mechanically ventilated ARDS patients using protective and ultraprotective tidal volumes when increasing CO2 removal rates from ECCO2 R devices.

Modeling acid-base balance for in-series extracorporeal carbon dioxide removal and continuous venovenous hemofiltration devices.

Patients with acute respiratory distress syndrome and acute kidney injury (AKI) treated by kidney replacement therapy may also require treatment with extracorporeal carbon dioxide removal (ECCO2 R) devices to permit protective or ultraprotective mechanical ventilation. We developed a mathematical model of acid-base balance during extracorporeal therapy using ECCO2 R and continuous venovenous hemofiltration (CVVH) devices applied in series for the treatment of mechanically ventilated AKI patients. Published data from clinical studies of mechanically ventilated AKI patients treated by CVVH at known infusion rates of substitution fluid without ECCO2 R were used to adjust the model parameters to fit plasma levels of arterial partial pressure of carbon dioxide (PaCO2 ), arterial plasma bicarbonate concentration ([HCO3 ]), and plasma pH (as well as certain other unmeasured physiological variables). The effects of applying ECCO2 R at an unchanged and a reduced tidal volume on PaCO2 , [HCO3 ] and plasma pH were then simulated assuming carbon dioxide removal rates from the ECCO2 R device measured in the clinical studies. Agreement of such model predictions with clinical data was good whether the ECCO2 R device was positioned proximal or distal to the CVVH device in the extracorporeal circuit. Although carbon dioxide removal rates from the ECCO2 R device measured in one previous clinical study were higher when it was placed proximal to the CVVH device, suggesting that such in-series positioning was optimal, the current mathematical model demonstrates that proximal positioning of the ECCO2 R device also results in lower bicarbonate (and, therefore, total carbon dioxide) removal from the distal CVVH device. Thus, the removal of total carbon dioxide by such extracorporeal circuits is relatively independent of the position of the in-series devices. It is concluded that the described mathematical model has quantitative accuracy; these results suggest that the overall acid-base balance when using ECCO2 R and CVVH devices in a single extracorporeal circuit will be similar, independent of their in-series position.

Clinical evaluation of the Prismaflex™ HF 20 set and Prismaflex™ system 7.10 for acute continuous kidney replacement therapy (CKRT) in children.

BACKGROUND: Continuous kidney replacement therapy (CKRT) is a common modality for treatment of severe acute kidney injury (AKI) in children. Adult technologies routinely utilized to provide this therapy have a large extracorporeal volume. The Prismaflex™ HF20 filter set has a relatively low extracorporeal blood volume of 60 mL, which provides technological benefit for smaller children compared with current filter sets available in the USA. METHODS: We conducted a multicenter, open-label single group study to evaluate whether the Prismaflex™ HF20 filter set delivers efficacious and safe CKRT to support patients with AKI, fluid overload, or both in pediatric patients weighing ≥ 8 to 20 kg. RESULTS: Twenty-three patients were enrolled between April 24, 2016 and April 8, 2018. The mean reduction in blood urea nitrogen from baseline to 24 h was 58.12 ± 20.08% (95% CI, - 68.45 and - 47.79 (p = 0.0008)). Median cumulative normalized effluent rate at 24 h was 60.8 mL/kg/h (25.9, 83.7). None of the patients participating in the study suffered a serious adverse event; thus, no obvious safety concerns were noted. CONCLUSIONS: We suggest that the Prismaflex HF20™ filter set used in conjunction with the Prismaflex™ System Software Version 7.10 or 7.20 is a suitable alternative to larger filter sets for use in pediatric patients weighing less than 20 kg. Graphical abstract.

[Ajuste de fármacos y nutrición en terapias de reemplazo renal continuo].

Del 6 al 23% de los pacientes con lesión renal aguda (LRA) en unidades de cuidados intensivos (UCI) requieren apoyo renal, siendo la terapia continua una modalidad de alta frecuencia de uso en el paciente críticamente enfermo. Si bien el objetivo general de las terapias de reemplazo renal continuo (TRRC) es restablecer el equilibrio hídrico y ácido-base, junto con la eliminación de toxinas urémicas e inflamatorias relacionadas con la pérdida de depuración renal y la disfunción multiorgánica; reconocemos como efecto colateral la depuración (K) no deseado de moléculas y sustancias deseadas en la recuperación del paciente crítico, como pueden ser antimicrobianos y nutrientes. La sepsis es la causa más frecuente de LRA en la UCI y en este contexto la terapia antimicrobiana adecuadamente seleccionada y a la dosis correcta es la médica terapéutica más importante. De la misma manera, es indispensable garantizar el adecuado apoyo nutricional en este grupo poblacional. Proponemos en esta revisión una aproximación teórica y práctica para seleccionar el tratamiento farmacológico de antimicrobianos y el apoyo nutricional en el paciente en TRRC.Six to 23% of patients with acute kidney injury (AKI) in intensive care units (ICU) require renal support. Continuous renal replacement therapies (CRRT) have become the modality of choice in critical care. Although the aim of CRRT is to restore the water and acid-base balance, together with the removal of uremic and inflammatory toxins related to the loss of renal clearance and multi-organ dysfunction; we recognize as a side effect the unwanted clearance of molecules and substances desired for the recovery of the critically ill patient such as antimicrobials and nutrients. Sepsis is the most frequent cause of AKI in the ICU and, in this context, the appropriate selection of antimicrobial therapy, and at the correct dose, is one of the most important decisions; it is also essential to guarantee the adequate nutritional support in this population. We propose in this review a theoretical and practical approach to address the pharmacological management of antimicrobials and nutritional support in the patient in CRRT.

Estructura poblacional y distribución espacial del roble negro (Colombobalanus excelsa, Fagaceae), especie endémica, en fragmentos de bosque andino colombiano / Population structure and spatial distribution of black oak (Colombobalanus excelsa, Fagaceae), endemic species, in Colombian Andean forest fragments

Resumen Los bosques andinos en Colombia son reconocidos por su alta biodiversidad y endemismo, sin embargo han experimentado un severo proceso de fragmentación debido a procesos antrópicos. Como resultado de esto, muchas especies vulnerables han sido particularmente afectadas. Este es el caso del roble negro (Colombobalanus excelsa (Lozano, Hern. Cam., & Henao) Nixon & Crepet), especie endémica y poco estudiada de los Andes colombianos, cuya distribución está restringida a cuatro localidades en el país, una de ellas el sector suroriental del departamento del Huila. Con el fin de estudiar las poblaciones de roble negro en la Serrania de Peñas Blancas (Huila), localidad más sur de distribución; en 2006 se establecieron 16 parcelas de 50 x 20 m (1.6 ha) en fragmentos de bosque, donde se determinó la estructura etaria y la distribución espacial de esta especie. En total se registraron 1 228 individuos de roble negro entre adultos, juveniles y plántulas; los cuáles presentaron patrones de distribución Gamma y Weibull. Con estos resultados se pudo confirmar que la mayoría de los individuos se encuentran en las primeras clases diamétricas. Asimismo, sus poblaciones presentaron un patrón de distribución agregado debido al proceso de extracción de madera. Estos resultados indican que las poblaciones de roble negro se encuentran en una fase de recuperación despúes de una fuerte intervención antrópica. El conocimiento del actual estado de los bosques de roble negro, puede contribuir para el diseño de efectivos planes de conservacion de la especie en Colombia.

Abstract The Colombian Andean forests are recognized for its great biodiversity and endemism; however, they have undergone a severe process of fragmentation due to anthropic factors. As a result, many vulnerable species have been especially affected. That is the case of the black oak (Colombobalanus excelsa (Lozano, Hern. Cam., & Henao) Nixon & Crepet), an endemic and poorly studied species of the Colombian Andes, which has a distribution restricted to only four areas in the country, one of which is the Southeastern Huila region. To examine black oak populations in Serranía Peñas Blancas (Huila), in 2006 we studied the age structure and spatial distribution in plots of 50 x 20 m (1.6 ha) in forest fragments, in southern distribution. In total, 1 228 black oak species were registered among saplings, juvenile and adults, and they have distribution patterns Gamma and Weibull. These results confirm that the majority of the individuals are in the first diametric class. Also, these populations show an added distribution pattern due to the wood extraction process. These results indicate that black oak populations are in a recovery phase after forceful anthropic intervention. Knowing the current status of black oak forests can contribute to the design of effective conservation plans of this species in Colombia. Rev. Biol. Trop. 66(2): 486-494. Epub 2018 June 01.

Candida haemulonii: causa infrecuente de peritonitis asociada a diálisis peritoneal / Candida haemulonii: an infrequent cause of dialysis related peritonitis

La peritonitis fúngica es la responsable del 3 a 6% de los casos de peritonitis asociada a diálisis. Es causa importante de morbimortalidad y de falla de la técnica. El microorganismo aislado con mayor frecuencia es la Candida albicans. Sin embargo, en los últimos años la incidencia de nuevos casos asociados a Candida no albicans y otros hongos, ha aumentado. De estas especies patógenas, Candida haemulonii es causal de infecciones humanas, siendo inusual en pacientes en diálisis, encontrándose un caso reportado en la literatura de peritonitis asociado a diálisis. C. haemulonii supone ciertos retos diagnósticos ya que es un complejo de tres especies que requieren métodos moleculares de laboratorio para su diferenciación. Adicionalmente, tiene un perfil de multirresistencia a los antimicóticos que constituye para el clínico, un reto en el oportuno tratamiento de estos pacientes. A continuación, se describe un caso de peritonitis asociado a diálisis peritoneal por C. haemulonii.

Fungal peritonitis represents 3 to 6% of peritonitis in dialysis patients. It is an important cause of morbidity, mortality and technique failure. The most frequently isolated microorganism is Candida albicans; however, in recent years there are an increasing number of cases of non Candida albicans and other fungal peritonitis. Candida haemulonii causes human infections, but it is unusual in dialysis patients. There is one reported case of peritonitis in a dialysis patient. C. haemulonii generates certain diagnostic and therapeutic challenges because it is a complex of three species that can only be differentiated by specialized molecular methods and additionally, has a multidrug resistance profile. We describe the case of a dialysis patient with C. haemulonii peritonitis.

Combination of biomarkers for diagnosis of acute kidney injury after cardiopulmonary bypass.

Novel acute kidney injury (AKI) biomarkers offer promise of earlier diagnosis and risk stratification, but have yet to find widespread clinical application. We measured urinary α and π glutathione S-transferases (α-GST and π-GST), urinary l-type fatty acid-binding protein (l-FABP), urinary neutrophil gelatinase-associated lipocalin (NGAL), urinary hepcidin and serum cystatin c (CysC) before surgery, post-operatively and at 24 h after surgery in 93 high risk patient undergoing cardiopulmonary bypass (CPB) and assessed the ability of these biomarkers alone and in combination to predict RIFLE-R defined AKI in the first 5 post-operative days. Twenty-five patients developed AKI. π-GST (ROCAUC = 0.75), lower urine Hepcidin:Creatine ratio at 24 h (0.77), greater urine NGAL:Cr ratio post-op (0.73) and greater serum CysC at 24 h (0.72) best predicted AKI. Linear combinations with significant improvement in AUC were: Hepcidin:Cr 24 h + post-operative π-GST (AUC = 0.86, p = 0.01), Hepcidin:Cr 24 h + NGAL:Cr post-op (0.84, p = 0.03) and CysC 24 h + post-operative π-GST (0.83, p = 0.03), notably these significant biomarkers combinations all involved a tubular injury and a glomerular filtration biomarker. Despite statistical significance in receiver-operator characteristic (ROC) analysis, when assessed by ability to define patients to two groups at high and low risk of AKI, combinations failed to significantly improve classification of risk compared to the best single biomarkers. In an alternative approach using Classification and Regression Tree (CART) analysis a model involving NGAL:Cr measurement post-op followed by Hepcidin:Cr at 24 h was developed which identified high, intermediate and low risk groups for AKI. Regression tree analysis has the potential produce models with greater clinical utility than single combined scores.

Evaluation of a teaching strategy based on integration of clinical subjects, virtual autopsy, pathology museum, and digital microscopy for medical students.

BACKGROUND: Learning pathology is fundamental for a successful medical practice. In recent years, medical education has undergone a profound transformation toward the development of an integrated curriculum incorporating both basic science and clinical material. Simultaneously, there has been a shift from a magisterial teaching approach to one centered around problem-based learning. Now-a-days, informatics tools are expected to help better implement these strategies. AIM: We applied and evaluated a new teaching method based on an active combination of clinical problems, gross pathology, histopathology, and autopsy pathology, all given through informatics tools, to teach a group of medical students at the Universidad de Santander, Colombia. DESIGN: Ninety-four medical students were followed in two consecutive semesters. Students were randomized to receive teaching either through traditional methodology or through the new integrated approach. RESULTS: There was no significant difference between the intervention group and the control group at baseline. At the end of the study, the scores in the intervention group were significantly higher compared to the control group (3.91/5.0 vs. 3.33/5.0, P = 0.0008). Students and tutors endorsed the benefits of the integrated approach. Participants were very satisfied with this training approach and rated the program an 8.7 out of 10, on average. CONCLUSION: This study confirms that an integrated curriculum utilizing informatics systems provides an excellent opportunity to associate pathology with clinical medicine early in training of medical students. This can be possible with the use of virtual microscopy and digital imaging.

Valoración preanestésica en el paciente con enfermedad renal crónica (énfasis en riesgo cardiovascular) / Pre-anesthesia evaluation in patients with chronic renal disease (emphasis on cardiovascular risk)

Periodo perioperatorio La enfermedad renal crónica es un problema de salud pública mundial. En varias ocasiones los pacientes son llevados a cirugías relacionadas con su diálisis con operaciones propias de sus comorbilidades. El propósito de la valoración preanestésica es asesorar el riesgo de eventos cardiovasculares e iniciar las intervenciones que puedan influir en su morbimor-talidad. El presente artículo describe datos epidemiológicos relevantes de la enfermedad renal crónica, así como su riesgo cardiovascular, y nos orienta en su valoración clínica, ayudas diagnósticas y estrategias para reducir el riesgo quirúrgico. La presente revisión narrativa de la literatura fue desarrollada con artículos escritos en inglés y español, limitados a los últimos 10 años, información referenciada en textos guía y bases de datos primarias (como Pubmed-Embase-Lilacs), complementada con artículos referenciados de la anterior búsqueda.

Chronic renal disease is a public health problem worldwide. Several times these patients will undergo surgical procedures related to dialysis or surgeries related to their co-morbidities. The purpose of the pre-anesthesia evaluation is to assess the risk of cardiovascular events and initiate interventions that may influence morbidity and mortality. This article Anesthesia describes the relevant epidemiological data of chronic kidney disease and its cardiovascular Perioperative Period risk and provides a guide on clinical assessment, diagnostic tools and strategies to reduce surgical risk. This narrative literature review is based on articles written in both English and Spanish limited to the last 10 years, information frombasic textbooks and primary databases (i.e., PUBMED - EMBASE - LILACS), supported by articles referenced in the above-mentioned search.