Advances in Neonatal Acute Kidney Injury.

In this state-of-the-art review, we highlight the major advances over the last 5 years in neonatal acute kidney injury (AKI). Large multicenter studies reveal that neonatal AKI is common and independently associated with increased morbidity and mortality. The natural course of neonatal AKI, along with the risk factors, mitigation strategies, and the role of AKI on short- and long-term outcomes, is becoming clearer. Specific progress has been made in identifying potential preventive strategies for AKI, such as the use of caffeine in premature neonates, theophylline in neonates with hypoxic-ischemic encephalopathy, and nephrotoxic medication monitoring programs. New evidence highlights the importance of the kidney in "crosstalk" between other organs and how AKI likely plays a critical role in other organ development and injury, such as intraventricular hemorrhage and lung disease. New technology has resulted in advancement in prevention and improvements in the current management in neonates with severe AKI. With specific continuous renal replacement therapy machines designed for neonates, this therapy is now available and is being used with increasing frequency in NICUs. Moving forward, biomarkers, such as urinary neutrophil gelatinase-associated lipocalin, and other new technologies, such as monitoring of renal tissue oxygenation and nephron counting, will likely play an increased role in identification of AKI and those most vulnerable for chronic kidney disease. Future research needs to be focused on determining the optimal follow-up strategy for neonates with a history of AKI to detect chronic kidney disease.

Management of acute metabolic acidosis in the ICU: sodium bicarbonate and renal replacement therapy.

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2021. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2021 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from https://link.springer.com/bookseries/8901 .

Registry on extracorporeal multiple organ support with the advanced organ support (ADVOS) system: 2-year interim analysis.

ABSTRACT: The objective of this registry is to collect data on real-life treatment conditions for patients for whom multiple organ dialysis with Advanced Organ Support (ADVOS) albumin hemodialysis is indicated.This registry was performed under routine conditions and without any study-specific intervention, diagnostic procedures, or assessments. Data on clinical laboratory tests, health status, liver function, vital signs, and examinations were collected (DRKS-ID: DRKS00017068). Mortality rates 28 and 90 days after the first ADVOS treatment, adverse events and ADVOS treatment parameters, including treatment abortions, were documented.This analysis was performed 2 years after the first patient was included on January 18, 2017. As of February 20, 2019, 4 clinical sites in Germany participated and enrolled 118 patients with a median age of 60 (IQR: 45, 69) of whom 70 were male (59.3%). Patients had a median SOFA Score of 14 (IQR: 11, 16) and a predicted mortality of 80%. The median number of failing organs was 3 (IQR: 2, 4).Four hundred twenty nine ADVOS treatments sessions were performed with a median duration of 17 hours (IQR: 6, 23). A 5.8% of the ADVOS sessions (25 of 429) were aborted due to device related errors, while 14.5% (62 of 429) were stopped for other reasons. Seventy nine adverse events were documented, 13 of them device related (all clotting, and all recovered without sequels).A significant reduction in serum creatinine (1.5 vs 1.2 mg/dl), blood urea nitrogen (24 vs 17 mg/dl) and bilirubin (6.9 vs 6.5 mg/dl) was observed following the first ADVOS treatment session. Blood pH, bicarbonate (HCO3-) and base excess returned to the physiological range, while partial pressure of carbon dioxide (pCO2) remained unchanged. At the time of the analysis, 28- and 90-day mortality were 60% and 65%, respectively, compared to an expected ICU-mortality rate of 80%. SOFA score was an independent predictor for outcome in a multivariable logistic regression analysis.The reported data show a high quality and completion of all participating centers. Data interpretation must be cautious due to the small number of patients, and the nature of the registry, without a control group. However, the data presented here show an improvement of expected mortality rates. Minor clotting events similar to other dialysis therapies occurred during the treatments.

The haemodynamic effects of oXiris haemofilter in septic shock patients requiring renal support: A single-centre experience.

Excessive pro-inflammatory and anti-inflammatory cytokines are mediators for haemodynamic alterations, metabolic acidosis, and multi-organ failure in sepsis. Recently, oXiris® haemofilter (Baxter, IL, USA) has been introduced as a novel haemofilter to mitigate inflammatory response during sepsis-associated acute kidney injury requiring renal replacement therapy. In the present case series, the researchers retrospectively reviewed critically ill patients with septic shock with the use of at least one oXiris haemofilter during continuous renal replacement therapy between June 2015 and December 2017. The timing for oXiris initiation was at the nephrologists' discretion. The impact of oXiris haemofilter was evaluated on mean arterial pressure, vasopressor dosage, Sequential Organ Failure Assessment score, lactate and base excess during 72 h after treatment. Thirty-five patients were enrolled in the study. An improvement of haemodynamic status was found, shown by increased mean arterial pressure by 6.1% (p = 0.35), decreased norepinephrine dose by 45.9% (p = 0.02), inotropic score by 26.4% (p = 0.02) and vasopressor dependency index by 40.5% (p = 0.01). Cardiovascular Sequential Organ Failure Assessment scores significantly decreased over 72 h (p = 0.02). Blood lactate levels and base excess also showed statistically significant improvements. The median filter lifetime was 23 (interquartile range = 14-36) hours. The intensive care unit mortality was 82.9%. Treatment with oXiris was safe and well-tolerated with no device-related adverse events. In conclusion, continuous renal replacement therapy with oXiris haemofilter is safe and may improve haemodynamic parameters in septic patients with severe renal dysfunction. Nonetheless, these findings were drawn from a retrospective analysis without a control group, and therefore cannot be generalised. Randomised controlled trials are warranted to confirm these findings.

Management of Acute Kidney Injury in Coronavirus Disease 2019.

Acute kidney injury is a common complication in hospitalized patients with coronavirus disease 2019. Similar to acute kidney injury associated with other conditions such as sepsis and cardiac surgery, morbidity and mortality are much higher in patients with coronavirus disease 2019 who develop acute kidney injury, especially in the intensive care unit. Management of coronavirus disease 2019-associated acute kidney injury with kidney replacement therapy should follow existing recommendations regarding modality, dose, and timing of initiation. However, patients with coronavirus disease 2019 are very hypercoagulable, and close vigilance to anticoagulation strategies is necessary to prevent circuit clotting. During situations of acute surge, where demand for kidney replacement therapy outweighs supplies, conservative measures have to be implemented to safely delay kidney replacement therapy. A collaborative effort and careful planning is needed to conserve dialysis supplies, to ensure that treatment can be safely delivered to every patient who will benefit for kidney replacement therapy.

Comparison of different anticoagulation strategies for renal replacement therapy in critically ill patients with COVID-19: a cohort study.

BACKGROUND: Critically ill coronavirus disease 2019 (COVID-19) patients have a high risk of acute kidney injury (AKI) that requires renal replacement therapy (RRT). A state of hypercoagulability reduces circuit life spans. To maintain circuit patency and therapeutic efficiency, an optimized anticoagulation strategy is needed. This study investigates whether alternative anticoagulation strategies for RRT during COVID-19 are superior to administration of unfractionated heparin (UFH). METHODS: Retrospective cohort study on 71 critically ill COVID-19 patients (≥18 years), admitted to intensive care units at a tertiary health care facility in the southwestern part of Germany between February 26 and May 21, 2020. We collected data on the disease course, AKI, RRT, and thromboembolic events. Four different anticoagulatory regimens were administered. Anticoagulation during continuous veno-venous hemodialysis (CVVHD) was performed with UFH or citrate. Anticoagulation during sustained low-efficiency daily dialysis (SLEDD) was performed with UFH, argatroban, or low molecular weight heparin (LMWH). Primary outcome is the effect of the anticoagulation regimen on mean treatment times of RRT. RESULTS: In patients receiving CVVHD, mean treatment time in the UFH group was 21.3 h (SEM: ±5.6 h), in the citrate group 45.6 h (SEM: ±2.7 h). Citrate anticoagulation significantly prolonged treatment times by 24.4 h (P = .001). In patients receiving SLEDD, mean treatment time with UFH was 8.1 h (SEM: ±1.3 h), with argatroban 8.0 h (SEM: ±0.9 h), and with LMWH 11.8 h (SEM: ±0.5 h). LMWH significantly prolonged treatment times by 3.7 h (P = .008) and 3.8 h (P = .002), respectively. CONCLUSIONS: UFH fails to prevent early clotting events in the dialysis circuit during COVID-19. For patients, who do not require effective systemic anticoagulation, regional citrate dialysis is the most effective strategy. For patients, who require effective systemic anticoagulation, the usage of LMWH results in the longest circuit life spans. The proposed anticoagulatory strategies are safe, can easily be monitored, and allow an individualized treatment.

The COVID-19 nephrology compendium: AKI, CKD, ESKD and transplantation.

The pandemic of coronavirus disease 2019 (CoVID-19) has been an unprecedented period. The disease afflicts multiple organ systems, with acute kidney injury (AKI) a major complication in seriously ill patients. The incidence of AKI in patients with CoVID-19 is variable across numerous international studies, but the high incidence of AKI and its associated worse outcomes in the critical care setting are a consistent finding. A multitude of patterns and mechanisms of AKI have been elucidated, and novel strategies to address shortage of renal replacement therapy equipment have been implemented. The disease also has had consequences on longitudinal management of patients with chronic kidney disease and end stage kidney disease. Kidney transplant recipients may be especially susceptible to CoVID-19 as a result of immunosuppression, with preliminary studies demonstrating high mortality rates. Increased surveillance of disease with low threshold for testing and adjustment of immunosuppression regimen during acute periods of illness have been recommended.

Perspectives in Individualizing Solutions for Dialysis Access.

The vascular access is the lifeline for the hemodialysis patient. Previous national vascular access guidelines have emphasized placement of arteriovenous fistulas in most hemodialysis patients. However, the new Kidney Disease Outcomes Quality Initiative guidelines for vascular access, soon to be published, will focus on a patient's end-stage kidney disease "life plan" and take a patient "first" approach. One of the major themes of the new Kidney Disease Outcomes Quality Initiative guidelines is selecting the "right access, for the right patient, at the right time, for the right reason". Given the availability of new advances in biomedical technologies, techniques, and devices in the vascular access field, this shift to a more patient-centered vascular access approach presents unique opportunities to individualize the solutions and care for patients requiring a dialysis vascular access. This review article will address 3 potential areas where there is an unmet need to individualize solutions for dialysis vascular access care: (1) biological approaches to improve vascular access selection and selection of therapies, (2) vascular access care for the post-transplant patient, and (3) vascular access disparities in race, gender, and the elderly patient.

Continuous kidney replacement therapy in critically ill neonates and infants: a retrospective analysis of clinical results with a dedicated device.

BACKGROUND: Providing extracorporeal renal support to neonates and infants involves a number of technical and clinical issues, possibly discouraging early utilization. This report aims to describe a multicenter experience of continuous kidney replacement therapy (CKRT) delivery to small infants using a device specifically designed for this age group. METHODS: A retrospective cohort analysis of all patients treated with the Carpediem™ machine (Bellco-Medtronic, Mirandola, Italy) in 6 centers between June 2013 and December 2016. RESULTS: Twenty-six neonates and small infants received 165 CKRT sessions in convective modality. Median age at neonatal intensive care unit admission 1 day (IQR 1-11), median body weight 2.9 kg (IQR 2.2-3.6). Median circuit duration 14 h (IQR 10-22), with delivered/prescribed time ratio of 84%. CKRT was conducted using 4 Fr (27%), 5 Fr (35%), 6.5 Fr (11%), and 7 Fr (3%) vascular access, and with umbilical and peripheral accesses (11% each) allowing overall median blood flow of 4.5 ml/kg/min (IQR 3.4-6) and median effluent flow rate 35 ml/kg/h (IQR 28-42). Circuits were primed with normal saline in 58% of treatments, colloids in 31%, and packed red blood cells in 11%. No serious adverse events directly related to machine application were reported by any center. Twenty-five (96%) patients survived their CKRT course and 13 patients (50%) survived to ICU discharge. CONCLUSIONS: CKRT in neonates was easy to initiate and conduct when performed with small central vascular accesses coupled with this device. A dedicated technology for infant CKRT delivery enables patients to be safely treated avoiding technical complications. Graphical abstract.

Toward Patient-Centered Innovation: A Conceptual Framework for Patient-Reported Outcome Measures for Transformative Kidney Replacement Devices.

Individuals with dialysis-dependent kidney failure experience considerable disease- and treatment-related decline in functional status and overall well-being. Despite these experiences, there have been few substantive technological advances in KRT in decades. As such, new federal initiatives seek to accelerate innovation. Historically, integration of patient perspectives into KRT product development has been limited. However, the US Food and Drug Administration recognizes the importance of incorporating patient perspectives into the total product life cycle (i.e., from product conception to postmarket surveillance) and encourages the consideration of patient-reported outcomes in regulatory-focused clinical trials when appropriate. Recognizing the significance of identifying patient-reported outcome measures (PROMs) that capture contemporary patient priorities, the Kidney Health Initiative, a public-private partnership between the American Society of Nephrology and US Food and Drug Administration, convened a workgroup to (1) develop a conceptual framework for a health-related quality of life PROM; (2) identify and map existing PROMs to the conceptual framework, prioritizing them on the basis of their supporting evidence for use in the regulatory environment; and (3) describe next steps for identifying PROMs for use in regulatory clinical trials of transformative KRT devices. This paper summarizes the proposed health-related quality-of-life PROM conceptual framework, maps and prioritizes PROMs, and identifies gaps and future needs to advance the development of rigorous, meaningful PROMS for use in clinical trials of transformative KRT devices.

Renal Replacement Knowledge and Preferences for African Americans With Chronic Kidney Disease.

BACKGROUND: Renal replacement therapies (RRT) other than in-centre haemodialyses are underutilised by African Americans with end-stage renal disease (ESRD) even though they are associated with reduced costs, morbidity and mortality as well as improved quality of life for patients. OBJECTIVES: To understand African American patients' knowledge of RRT options and how patient, provider and system-factors contribute to knowledge and preferences. Participants' interviews were conducted at the University of Chicago Medical Center with African American patients with chronic kidney disease (CKD). The final analysis included 28 interviews; 22 patients had CKD not yet on dialysis or having received a transplant, while 6 had reached ESRD and were receiving treatment for kidney failure. Approach Transcripts were uploaded into NVivo8 for coding. Thematic analysis was used for data interpretation. RESULTS: Four themes were identified: (1) limited knowledge of home modalities and deceased donor options, (2) CKD patients gave little thought to choosing RRT options, (3) CKD patients relied on doctors for treatment decisions, and (4) while patients reported knowledge of living kidney donation transplants (LKDT), it did not translate to receiving an LKDT. CONCLUSION: African Americans face significant knowledge and access barriers when deciding on their RRT treatment. Even patients with advanced CKD were still in the early stages of RRT selection. Understanding the knowledge gaps and barriers patients face will inform our subsequent intervention to educate and motivate patients to increase CKD self-care and improve communication between patients, their families and their providers about different RRT treatments.

Terapias de reemplazo renal en insuficiencia renal aguda / Renal replacement therapies in acute renal failure

CONTEXTO CLÍNICO: La insuficiencia renal aguda o injuria renal aguda (IRA) es la disminución abrupta y muchas veces reversible de la función renal. Se caracteriza por disminución de la tasa de filtración glomerular (TFG), produciendo el incremento de la urea nitrogenada en sangre, la creatinina sérica y otros produtos metabólicos. En pacientes hospitalizados, especialmente en cuidados intensivos y con IRA de origen renal las indicaciones más importantes de terapia de reemplazo renal son uremia, azoemia progresiva, disturbio electrolítico, sobrecarga de volumen, acidosis metabólica, oliguria y desbalance electrolítico. La incidencia y prevalencia de esta patología no es conocida en el mundo, algunas series de casos reportan una tasa de incidencia de IRA del 21,6% con tasas de mortalidad cercanas al 50 % em adultos.23 En Argentina su incidencia se ha elevado en los últimos años, pasando de 2.000 a 15.000 pacientes por millón de habitantes al año, trayendo con ello el aumento de uso de la TRR como terapia ideal en el manejo de las complicaciones de la IRA. TECNOLOGÍA: El término terapia de reemplazo renal se refiere a las terapias que purifican la sangre en forma extracorpórea, sustituyendo la función renal. La depuración (diálisis) se realiza a través de la circulación de la sangre por una membrana (filtro) de distintas características en contracorriente a un líquido de diálisis (de características semejantes al plasma sanguíneo) o filtración a través de filtros de alta permeabilidad (convección). OBJETIVO: El objetivo del presente informe es evaluar la evidencia disponible acerca de la eficacia, seguridad y aspectos relacionados a las políticas de cobertura del uso de terapias de reemplazo renal (terapias de reemplazo continuas versus terapia de reemplazo intermitente en la insuficiencia renal aguda. MÉTODOS: Se realizó una búsqueda en las principales bases de datos bibliográficas, en buscadores genéricos de internet, y financiadores de salud. Se priorizó la inclusión de revisiones sistemáticas (RS), ensayos clínicos controlados aleatorizados (ECAs), evaluaciones de tecnologías sanitarias (ETS), evaluaciones económicas, guías de práctica clínica (GPC) y políticas de cobertura de diferentes sistemas de salud. CONCLUSIONES: Evidencia de moderada calidad sugiere que las terapias de reemplazo renal continuas versus las terapias de reemplazo renal intermitentes son similares, clínicamente en pacientes adultos con insuficiencia renal aguda. Las mismas no difieren en la mortalidad intrahospitalaria global, en la mortalidad en unidades de terapia intensiva, y tampoco en el número de pacientes que sobreviven sin necesidad de reemplazo renal posterior. Además, no mostraron diferencias en la mejoría de la inestabilidad hemodinámica o episodios de hipotensión arterial. Las terapias continuas mostraron mayor riesgo eventos adversos leves (coagulación de filtros con los que se realizan los procedimientos, trombocitopenia). No se encontraron estudios que comparen las terapias continuas entre si. Las guías de práctica clínica argentinas, estadounidenses y europeas relevadas recomiendan que la modalidad de reemplazo de función renal debe basarse en el estado clínico del paciente, la experiencia del equipo médico y enfermería, la disponibilidad de medios de la institución, así como regulaciones locales y de seguridad social. Todos los pacientes con insuficiencia renal aguda deben dializar con máquinas que tengan control de ultrafiltración. Las terapias continuas y las intermitentes son complementarias y no excluyentes entre sí. Los distintos consensos de expertos sugieren las terapias continuas en pacientes con inestabilidad hemodinamica y/o edema cerebral, acidosis metabólica persistente, o necesidad de realizar balance hídrico negativo profuso. Dada la heterogeneidad en los costos locales de las diferentes modalidades y variantes, es variable el impacto económico y la posible costo-efectividad de las terapias de reemplazo renal continuas.

The Artificial Kidney Initiation in Kidney Injury 2 (AKIKI2): study protocol for a randomized controlled trial.

BACKGROUND: The Artificial Kidney Initiation in Kidney Injury (AKIKI) trial showed that a delayed renal replacement therapy (RRT) strategy for severe acute kidney injury (AKI) in critically ill patients was safe and associated with major reduction in RRT initiation compared with an early strategy. The five criteria which mandated RRT initiation in the delayed arm were: severe hyperkalemia, severe acidosis, acute pulmonary edema due to fluid overload resulting in severe hypoxemia, serum urea concentration > 40 mmol/l and oliguria/anuria > 72 h. However, duration of anuria/oliguria and level of blood urea are still criteria open to debate. The objective of the study is to compare the delayed strategy used in AKIKI (now termed "standard") with another in which RRT is further delayed for a longer period (termed "delayed strategy"). METHODS/DESIGN: This is a prospective, multicenter, open-label, two-arm randomized trial. The study is composed of two stages (observational and randomization stages). At any time, the occurrence of a potentially severe condition (severe hyperkalemia, severe metabolic or mixed acidosis, acute pulmonary edema due to fluid overload resulting in severe hypoxemia) suggests immediate RRT initiation. Patients receiving (or who have received) intravenously administered catecholamines and/or invasive mechanical ventilation and presenting with AKI stage 3 of the KDIGO classification and with no potentially severe condition are included in the observational stage. Patients presenting a serum urea concentration > 40 mmol/l and/or an oliguria/anuria for more than 72 h are randomly allocated to a standard (RRT is initiated within 12 h) or a delayed RRT strategy (RRT is initiated only if an above-mentioned potentially severe condition occurs or if the serum urea concentration reaches 50 mmol/l). The primary outcome will be the number of RRT-free days at day 28. One interim analysis is planned. It is expected to include 810 patients in the observational stage and to randomize 270 subjects. DISCUSSION: The AKIKI2 study should improve the knowledge of RRT initiation criteria in critically ill patients. The potential reduction in RRT use allowed by a delayed RRT strategy might be associated with less invasive care and decreased costs. Enrollment is ongoing. Inclusions are expected to be completed by November 2019. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03396757. Registered on 11 January 2018.