Characteristics and Outcomes of Children and Young Adults With Sepsis Requiring Continuous Renal Replacement Therapy: A Comparative Analysis From the Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK).

OBJECTIVES: Pediatric sepsis-associated acute kidney injury (AKI) often requires continuous renal replacement therapy (CRRT), but limited data exist regarding patient characteristics and outcomes. We aimed to describe these features, including the impact of possible dialytrauma (i.e., vasoactive requirement, negative fluid balance) on outcomes, and contrast them to nonseptic patients in an international cohort of children and young adults receiving CRRT. DESIGN: A secondary analysis of Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK), an international, multicenter, retrospective study. SETTING: Neonatal, cardiac and PICUs at 34 centers in nine countries from January 1, 2015, to December 31, 2021. PATIENTS: Patients 0-25 years old requiring CRRT for AKI and/or fluid overload. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 1016 patients, 446 (44%) had sepsis at CRRT initiation and 650 (64%) experienced Major Adverse Kidney Events at 90 days (MAKE-90) (defined as a composite of death, renal replacement therapy [RRT] dependence, or > 25% decline in estimated glomerular filtration rate from baseline at 90 d from CRRT initiation). Septic patients were less likely to liberate from CRRT by 28 days (30% vs. 38%; p < 0.001) and had higher rates of MAKE-90 (70% vs. 61%; p = 0.002) and higher mortality (47% vs. 31%; p < 0.001) than nonseptic patients; however, septic survivors were less likely to be RRT dependent at 90 days (10% vs. 18%; p = 0.011). On multivariable regression, pre-CRRT vasoactive requirement, time to negative fluid balance, and median daily fluid balance over the first week of CRRT were not associated with MAKE-90; however, increasing duration of vasoactive requirement was independently associated with increased odds of MAKE-90 (adjusted OR [aOR], 1.16; 95% CI, 1.05-1.28) and mortality (aOR, 1.20; 95% CI, 1.1-1.32) for each additional day of support. CONCLUSIONS: Septic children requiring CRRT have different clinical characteristics and outcomes compared with those without sepsis, including higher rates of mortality and MAKE-90. Increasing duration of vasoactive support during the first week of CRRT, a surrogate of potential dialytrauma, appears to be associated with these outcomes.

Global structures, practices, and tools for provision of hemodialysis.

BACKGROUND: Hemodialysis (HD) is the most commonly utilized modality for kidney replacement therapy worldwide. This study assesses the organizational structures, availability, accessibility, affordability and quality of HD care worldwide. METHODS: This cross-sectional study relied on desk research data as well as survey data from stakeholders (clinicians, policymakers and patient advocates) from countries affiliated with the International Society of Nephrology from July to September 2022. RESULTS: Overall, 167 countries or jurisdictions participated in the survey. In-center HD was available in 98% of countries with a median global prevalence of 322.7 [interquartile range (IQR) 76.3-648.8] per million population (pmp), ranging from 12.2 (IQR 3.9-103.0) pmp in Africa to 1575 (IQR 282.2-2106.8) pmp in North and East Asia. Overall, home HD was available in 30% of countries, mostly in countries of Western Europe (82%). In 74% of countries, more than half of people with kidney failure were able to access HD. HD centers increased with increasing country income levels from 0.31 pmp in low-income countries to 9.31 pmp in high-income countries. Overall, the annual cost of in-center HD was US$19 380.3 (IQR 11 817.6-38 005.4), and was highest in North America and the Caribbean (US$39 825.9) and lowest in South Asia (US$4310.2). In 19% of countries, HD services could not be accessed by children. CONCLUSIONS: This study shows significant variations that have remained consistent over the years in availability, access and affordability of HD across countries with severe limitations in lower-resourced countries.

A Pilot and Feasibility Study of Continuous Cardiac Output and Blood Pressure Monitoring during Intermittent Hemodialysis.

INTRODUCTION: Hypotension is common during intermittent hemodialysis (IHD) and may be due to a decreased cardiac index (CI). However, no study has simultaneously and continuously measured CI and mean arterial pressure (MAP) to understand the prevalence, severity, and duration of CI decreases or relate them to MAP, blood volume (BV), and net ultrafiltration (NUF) rate. METHODS: In a prospective, pilot and feasibility investigation, we studied 10 chronic IHD patients. We used the ClearSight System™ to continuously monitor CI and MAP; the CRIT-LINE®IV monitor to detect BV changes and collected data on NUF rate. RESULTS: Device tolerance and compliance were 100%. All patients experienced at least ≥1 episode of severe CI decrease (>25% from baseline), with a median duration of 24 min (IQR 6-87) and of 68 min [14-106] for moderate decreases (>15% but ≤25% from baseline). Eight patients experienced a low CI state (<2.2 L/min/m2). The lowest CI was 0.9 L/min/m2 with a concomitant MAP of 94 mm Hg. When the fall in CI was severe, MAP increased in 58% of cases and remained stable in 28%. Overall, CI decreased by -0.55 L/min/m2 when BV decrease was moderate versus mild (p < 0.001) and by -0.8 L/min/m2 when NUF rate was high versus low (p < 0.001). CONCLUSION: Continuous CI monitoring is feasible in IHD and shows frequent moderate-severe CI decreases, sometimes to low CI state levels. Such decreases are typically associated with markers of decreased intravascular volume status but not with a decrease in MAP, implying marked vasoconstriction.

Relative Blood Volume Monitoring during Continuous Renal Replacement Therapy: A Prospective Observational Study.

INTRODUCTION: Hematocrit monitoring during continuous renal replacement therapy (CRRT) allows the continuous estimation of relative blood volume (RBV). This may enable early detection of intravascular volume depletion prior to clinical sequelae. We aimed to investigate the feasibility of extended RBV monitoring and its epidemiology during usual CRRT management by clinicians unaware of RBV. Moreover, we studied the association between changes in RBV and net ultrafiltration (NUF) rates. METHODS: In a cohort of adult intensive care unit patients receiving CRRT, we continuously monitored hematocrit and RBV using a pre-filter noninvasive optical sensor. We analyzed temporal changes in RBV and investigated the association between RBV change and NUF rates, using the classification of NUF rates into low, moderate, or high based on predefined cut-offs. RESULTS: We obtained >60,000 minute-by-minute measurements in >1,000 CRRT hours in 36 patients. The median RBV change was negative (decrease) in 69% of patients and the median peak change in RBV was -9.3% (interquartile range: -3.9% to -14.3%). Moreover, the median RBV decreased from baseline by >5% in 40.2% of measurements and by >10% in 20.6% of measurements. Finally, RBV decreased significantly more when patients received a high NUF rate (>1.75 mL/kg/h) compared to low or moderate NUF rates (5.32% vs. 1.93% or 1.97%, p < 0.001). CONCLUSION: Continuous hematocrit and RBV monitoring during CRRT was feasible. RBV decreased significantly during CRRT, and decreases were greater with higher NUF rates. RBV monitoring may help optimize NUF management and prevent the occurrence of intravascular volume depletion.

Recommendations for clinical trial design in acute kidney injury from the 31st acute disease quality initiative consensus conference. A consensus statement.

PURPOSE: Novel interventions for the prevention or treatment of acute kidney injury (AKI) are currently lacking. To facilitate the evaluation and adoption of new treatments, the use of the most appropriate design and endpoints for clinical trials in AKI is critical and yet there is little consensus regarding these issues. We aimed to develop recommendations on endpoints and trial design for studies of AKI prevention and treatment interventions based on existing data and expert consensus. METHODS: At the 31st Acute Disease Quality Initiative (ADQI) meeting, international experts in critical care, nephrology, involving adults and pediatrics, biostatistics and people with lived experience (PWLE) were assembled. We focused on four main areas: (1) patient enrichment strategies, (2) prevention and attenuation studies, (3) treatment studies, and (4) innovative trial designs of studies other than traditional (parallel arm or cluster) randomized controlled trials. Using a modified Delphi process, recommendations and consensus statements were developed based on existing data, with > 90% agreement among panel members required for final adoption. RESULTS: The panel developed 12 consensus statements for clinical trial endpoints, application of enrichment strategies where appropriate, and inclusion of PWLE to inform trial designs. Innovative trial designs were also considered. CONCLUSION: The current lack of specific therapy for prevention or treatment of AKI demands refinement of future clinical trial design. Here we report the consensus findings of the 31st ADQI group meeting which has attempted to address these issues including the use of predictive and prognostic enrichment strategies to enable appropriate patient selection.

Dialysis Outcomes Across Countries and Regions: A Global Perspective From the International Society of Nephrology Global Kidney Health Atlas Study.

Introduction: Kidney failure treated with hemodialysis (HD), or peritoneal dialysis (PD) is a major global health problem that is associated with increased risks of death and hospitalization. This study aimed to compare the incidence and causes of death and hospitalization during the first year of HD or PD among countries. Methods: The third iteration of the International Society of Nephrology Global Kidney Health Atlas (ISN-GKHA) was conducted between June and September 2022. For this analysis, data were obtained from the cross-sectional survey of key stakeholders from ISN-affiliated countries. Results: A total of 167 countries participated in the survey (response rate 87.4%). In 48% and 58% of countries, 1% to 10% of people treated with HD and PD died within the first year, respectively, with cardiovascular disease being the main cause. Access-related infections or treatment withdrawal owing to cost were important causes of death in low-income countries (LICs). In most countries, <30% and <20% of patients with HD and PD, respectively, required hospitalization during the first year. A greater proportion of patients with HD and PD in LICs were hospitalized in the first year than those in high-income countries (HICs). Access-related infection and cardiovascular disease were the commonest causes of hospitalization among patients with HD, whereas PD-related infection was the commonest cause in patients with PD. Conclusion: There is significant heterogeneity in the incidence and causes of death and hospitalization in patients with kidney failure treated with dialysis. These findings highlight opportunities to improve care, especially in LICs where infectious and social factors are strong contributors to adverse outcomes.

Greater haemodialysis exposure ('quotidian haemodialysis') has different mortality associations by patient age group.

Background: Worldwide, most people requiring kidney replacement therapy receive haemodialysis (HD) three times per week. Greater HD time and/or frequency may improve survival, but implementation requires understanding potential benefits across the range of patients. Methods: Using data from the Australia and New Zealand Dialysis and Transplant Registry, we assessed whether quotidian HD (defined as >3 sessions/week and/or >5 h/session) was associated with reduced mortality in adult patients. The primary outcome of all-cause mortality was analysed by a time-varying Cox proportional hazards model with quotidian HD as the exposure of interest. Results: Of 24 138 people who received HD between 2011 and 2019, 2632 (10.9%) received quotidian HD at some stage. These patients were younger, more likely male and more likely to receive HD at home. Overall, quotidian versus standard HD was associated with a decreased risk for all-cause mortality {crude hazard ratio [HR] 0.50 [95% confidence interval (CI) 0.45-0.56]}, but an interaction between quotidian HD and age was identified (P = .005). Stratified by age groups and splitting follow-up time where proportional hazards were violated, the corresponding HR compared with standard HD was 2.43 (95% CI 1.56-3.79) for people >75 years of age in the first year of quotidian HD, 1.52 (95% CI 0.89-2.58) for 1-3 years and 0.95 (95% CI 0.51-1.78) for ≥3 years. There was no significant survival advantage in younger people. Conclusions: Although quotidian HD conferred survival benefit in crude analyses, people ≥75 years of age had greater mortality with quotidian HD than standard HD. The mortality benefit in younger people was attenuated when adjusted for known confounders.

Hemoadsorption: Consensus report of the 30th Acute Disease Quality Initiative workgroup.

Adsorption-based extracorporeal therapies have been subject to technical developments and clinical application for close to five decades. More recently, new technological developments in membrane and sorbent manipulation have made it possible to deliver more biocompatible extracorporeal adsorption therapies to patients with a variety of conditions. There are several key rationales based on physicochemical principles and clinical considerations that justify the application and investigation of such therapies as evidenced by multiple ex-vivo, experimental, and clinical observations. Accordingly, unspecific adsorptive extracorporeal therapies have now been applied to the treatment of a wide array of conditions from poisoning to drug overdoses, to inflammatory states and sepsis, and acute or chronic liver and kidney failure. In response to the rapidly expanding knowledge base and increased clinical evidence, we convened an Acute Disease Quality Initiative (ADQI) consensus conference dedicated to such treatment. The data show that hemoadsorption has clinically acceptable short-term biocompatibility and safety, technical feasibility, and experimental demonstration of specified target molecule removal. Pilot studies demonstrate potentially beneficial effects on physiology and larger studies of endotoxin-based hemoadsorption have identified possible target phenotypes for larger randomized controlled trials (RCTs). Moreover, in a variety of endogenous and exogenous intoxications, removal of target molecules has been confirmed in vivo. However, some studies have raised concerns about harm or failed to deliver benefits. Thus, despite many achievements, modern hemoadsorption remains a novel and experimental intervention with limited data, and a large research agenda.

Capacity for the management of kidney failure in the International Society of Nephrology Oceania and South East Asia (OSEA) region: report from the 2023 ISN Global Kidney Health Atlas (ISN-GKHA).

The International Society of Nephrology (ISN) region of Oceania and South East Asia (OSEA) is a mix of high- and low-income countries, with diversity in population demographics and densities. Three iterations of the ISN-Global Kidney Health Atlas (GKHA) have been conducted, aiming to deliver in-depth assessments of global kidney care across the spectrum from early detection of CKD to treatment of kidney failure. This paper reports the findings of the latest ISN-GKHA in relation to kidney-care capacity in the OSEA region. Among the 30 countries and territories in OSEA, 19 (63%) participated in the ISN-GKHA, representing over 97% of the region's population. The overall prevalence of treated kidney failure in the OSEA region was 1203 per million population (pmp), 45% higher than the global median of 823 pmp. In contrast, kidney replacement therapy (KRT) in the OSEA region was less available than the global median (chronic hemodialysis, 89% OSEA region vs. 98% globally; peritoneal dialysis, 72% vs. 79%; kidney transplantation, 61% vs. 70%). Only 56% of countries could provide access to dialysis to at least half of people with incident kidney failure, lower than the global median of 74% of countries with available dialysis services. Inequalities in access to KRT were present across the OSEA region, with widespread availability and low out-of-pocket costs in high-income countries and limited availability, often coupled with large out-of-pocket costs, in middle- and low-income countries. Workforce limitations were observed across the OSEA region, especially in lower-middle-income countries. Extensive collaborative work within the OSEA region and globally will help close the noted gaps in kidney-care provision.

Renin Levels and Angiotensin II Responsiveness in Vasopressor-Dependent Hypotension.

OBJECTIVES: The relationship between renin levels, exposure to renin-angiotensin system (RAS) inhibitors, angiotensin II (ANGII) responsiveness, and outcome in patients with vasopressor-dependent vasodilatory hypotension is unknown. DESIGN: We conducted a single-center prospective observational study to explore whether recent RAS inhibitor exposure affected baseline renin levels, whether baseline renin levels predicted ANGII responsiveness, and whether renin levels at 24 hours were associated with clinical outcomes. SETTING: An academic ICU in Melbourne, VIC, Australia. PATIENTS: Forty critically ill adults who received ANGII as the primary agent for vasopressor-dependent vasodilatory hypotension who were included in the Acute Renal effects of Angiotensin II Management in Shock study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: After multivariable adjustment, recent exposure to a RAS inhibitor was independently associated with a relative increase in baseline renin levels by 198% (95% CI, 36-552%). The peak amount of ANGII required to achieve target mean arterial pressure was independently associated with baseline renin level (increase by 46% per ten-fold increase; 95% CI, 8-98%). Higher renin levels at 24 hours after ANGII initiation were independently associated with fewer days alive and free of continuous renal replacement therapy (CRRT) (-7 d per ten-fold increase; 95% CI, -12 to -1). CONCLUSIONS: In patients with vasopressor-dependent vasodilatory hypotension, recent RAS inhibitor exposure was associated with higher baseline renin levels. Such higher renin levels were then associated with decreased ANGII responsiveness. Higher renin levels at 24 hours despite ANGII infusion were associated with fewer days alive and CRRT-free. These preliminary findings emphasize the importance of the RAS and the role of renin as a biomarker in patients with vasopressor-dependent vasodilatory hypotension.

Factors associated with successful liberation from continuous renal replacement therapy in children and young adults: analysis of the worldwide exploration of renal replacement outcomes collaborative in Kidney Disease Registry.

PURPOSE: Continuous renal replacement therapy (CRRT) is used for supportive management of acute kidney injury (AKI) and disorders of fluid balance (FB). Little is known about the predictors of successful liberation in children and young adults. We aimed to identify the factors associated with successful CRRT liberation. METHODS: The Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease study is an international multicenter retrospective study (32 centers, 7 nations) conducted from 2015 to 2021 in children and young adults (aged 0-25 years) treated with CRRT for AKI or FB disorders. Patients with previous dialysis dependence, tandem extracorporeal membrane oxygenation use, died within the first 72 h of CRRT initiation, and those who never had liberation attempted were excluded. Patients were categorized based on first liberation attempt: reinstituted (resumption of any dialysis within 72 h) vs. success (no receipt of dialysis for ≥ 72 h). Multivariable logistic regression was used to identify factors associated with successful CRRT liberation. RESULTS: A total of 622 patients were included: 287 (46%) had CRRT reinstituted and 335 (54%) were successfully liberated. After adjusting for sepsis at admission and illness severity parameters, several factors were associated with successful liberation, including higher VIS (vasoactive-inotropic score) at CRRT initiation (odds ratio [OR] 1.35 [1.12-1.63]), higher PELOD-2 (pediatric logistic organ dysfunction-2) score at CRRT initiation (OR 1.71 [1.24-2.35]), higher urine output prior to CRRT initiation (OR 1.15 [1.001-1.32]), and shorter CRRT duration (OR 0.19 [0.12-0.28]). CONCLUSIONS: Inability to liberate from CRRT was common in this multinational retrospective study. Modifiable and non-modifiable factors were associated with successful liberation. These results may inform the design of future clinical trials to optimize likelihood of CRRT liberation success.

Major Adverse Kidney Events in Pediatric Continuous Kidney Replacement Therapy.

Importance: Continuous kidney replacement therapy (CKRT) is increasingly used in youths with critical illness, but little is known about longer-term outcomes, such as persistent kidney dysfunction, continued need for dialysis, or death. Objective: To characterize the incidence and risk factors, including liberation patterns, associated with major adverse kidney events 90 days after CKRT initiation (MAKE-90) in children, adolescents, and young adults. Design, Setting, and Participants: This international, multicenter cohort study was conducted among patients aged 0 to 25 years from The Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK) registry treated with CKRT for acute kidney injury or fluid overload from 2015 to 2021. Exclusion criteria were dialysis dependence, concurrent extracorporeal membrane oxygenation use, or receipt of CKRT for a different indication. Data were analyzed from May 2 to December 14, 2023. Exposure: Patient clinical characteristics and CKRT parameters were assessed. CKRT liberation was classified as successful, reinstituted, or not attempted. Successful liberation was defined as the first attempt at CKRT liberation resulting in 72 hours or more without return to dialysis within 28 days of CKRT initiation. Main Outcomes and Measures: MAKE-90, including death or persistent kidney dysfunction (dialysis dependence or ≥25% decline in estimated glomerular filtration rate from baseline), were assessed. Results: Among 969 patients treated with CKRT (529 males [54.6%]; median [IQR] age, 8.8 [1.7-15.0] years), 630 patients (65.0%) developed MAKE-90. On multivariable analysis, cardiac comorbidity (adjusted odds ratio [aOR], 1.60; 95% CI, 1.08-2.37), longer duration of intensive care unit admission before CKRT initiation (aOR for 6 days vs 1 day, 1.07; 95% CI, 1.02-1.13), and liberation pattern were associated with MAKE-90. In this analysis, patients who successfully liberated from CKRT within 28 days had lower odds of MAKE-90 compared with patients in whom liberation was attempted and failed (aOR, 0.32; 95% CI, 0.22-0.48) and patients without a liberation attempt (aOR, 0.02; 95% CI, 0.01-0.04). Conclusions and Relevance: In this study, MAKE-90 occurred in almost two-thirds of the population and patient-level risk factors associated with MAKE-90 included cardiac comorbidity, time to CKRT initiation, and liberation patterns. These findings highlight the high incidence of adverse outcomes in this population and suggest that future prospective studies are needed to better understand liberation patterns and practices.

An update on the global disparities in kidney disease burden and care across world countries and regions.

BACKGROUND: Since 2015, the International Society of Nephrology (ISN) Global Kidney Health Atlas (ISN-GKHA) has spearheaded multinational efforts to understand the status and capacity of countries to provide optimal kidney care, particularly in low-resource settings. In this iteration of the ISN-GKHA, we sought to extend previous findings by assessing availability, accessibility, quality, and affordability of medicines, kidney replacement therapy (KRT), and conservative kidney management (CKM). METHODS: A consistent approach was used to obtain country-level data on kidney care capacity during three phases of data collection in 2016, 2018, and 2022. The current report includes a detailed literature review of published reports, databases, and registries to obtain information on the burden of chronic kidney disease and estimate the incidence and prevalence of treated kidney failure. Findings were triangulated with data from a multinational survey of opinion leaders based on the WHO's building blocks for health systems (ie, health financing, service delivery, access to essential medicines and health technology, health information systems, workforce, and governance). Country-level data were stratified by the ISN geographical regions and World Bank income groups and reported as counts and percentages, with global, regional, and income level estimates presented as medians with interquartile ranges. FINDINGS: The literature review used information on prevalence of chronic kidney disease from 161 countries. The global median prevalence of chronic kidney disease was 9·5% (IQR 5·9-11·7) with the highest prevalence in Eastern and Central Europe (12·8%, 11·9-14·1). For the survey analysis, responses received covered 167 (87%) of 191 countries, representing 97·4% (7·700 billion of 7·903 billion) of the world population. Chronic haemodialysis was available in 162 (98%) of 165 countries, chronic peritoneal dialysis in 130 (79%), and kidney transplantation in 116 (70%). However, 121 (74%) of 164 countries were able to provide KRT to more than 50% of people with kidney failure. Children did not have access to haemodialysis in 12 (19%) of 62 countries, peritoneal dialysis in three (6%) countries, or kidney transplantation in three (6%) countries. CKM (non-dialysis management of people with kidney failure chosen through shared decision making) was available in 87 (53%) of 165 countries. The annual median costs of KRT were: US$19 380 per person for haemodialysis, $18 959 for peritoneal dialysis, and $26 903 for the first year of kidney transplantation. Overall, 74 (45%) of 166 countries allocated public funding to provide free haemodialysis at the point of delivery; use of this funding scheme increased with country income level. The median global prevalence of nephrologists was 11·8 per million population (IQR 1·8-24·8) with an 80-fold difference between low-income and high-income countries. Differing degrees of health workforce shortages were reported across regions and country income levels. A quarter of countries had a national chronic kidney disease-specific strategy (41 [25%] of 162) and chronic kidney disease was recognised as a health priority in 78 (48%) of 162 countries. INTERPRETATION: This study provides new information about the global burden of kidney disease and its treatment. Countries in low-resource settings have substantially diminished capacity for kidney care delivery. These findings have major policy implications for achieving equitable access to kidney care. FUNDING: International Society of Nephrology.

Haematocrit monitoring and blood volume estimation during continuous renal replacement therapy.

BACKGROUND: Continuous haemoglobin, venous blood oxygen saturation, and haematocrit (Hct) monitoring is currently not applied during continuous renal replacement therapy (CRRT). Such Hct monitoring enables estimation of changes in blood volume as percentage change (ΔBV%) from therapy start time and is incorporated into intermittent haemodialysis machines but not CRRT machines despite its potential to optimise fluid management in CRRT patients. METHODS: To overcome this problem, we used a standalone monitor (CRIT-LINE®IV, Fresenius Medical Care, Concord, USA) with an associated in-line blood chamber (CRIT-LINE®IV Blood Chamber, Fresenius Medical Care, Concord, USA) and designed our own adaptor connection piece (TekMed and Morriset, Melbourne and Brisbane, Australia) to allow these readings at the vascular access outflow and recorded data for estimated Hct and derived ΔBV% during CRRT. RESULTS: We report on this technique with an illustrative case example and 12 h of CRRT data on the fluid loss rate prescribed, hourly net patient fluid loss (range: 0-308 mL/h), mean arterial pressure, norepinephrine dose (range: 5-14 mcg/min), estimated continuous Hct and ΔBV%, and the otherwise undetected diagnosis of an approximate 15 % decrease in blood volume during the CRRT. CONCLUSION: We have described a technical CRRT circuit modification that can facilitate a previously unavailable assessment of fluid shifts during CRRT. Further application in clinical trials is now possible.

Cardiac Output Changes during Renal Replacement Therapy: A Scoping Review.

INTRODUCTION: Renal replacement therapy (RRT) is associated with hypotension. However, its impact on cardiac output (CO) is less understood. We aimed to describe current knowledge of CO monitoring and changes during RRT. METHODS: We searched MEDLINE, Embase, and Cochrane from January 1, 2000, to January 31, 2023, using Covidence for studies of intermittent hemodialysis (IHD) and continuous RRT (CRRT) with at least three CO measurements during treatment. Two independent reviewers screened citations, and a third resolved disagreements. The findings did not allow meta-analysis and are presented descriptively. RESULTS: We screened 3,285 articles and included 48 (37 during IHD, nine during CRRT, and two during both). Non-invasive devices (electrical conductivity techniques and finger cuff pulse contour) were the most common CO measurement techniques (21 studies). The median baseline cardiac index in IHD studies was 3 L/min/m2 (95% CI, 2.7-3.39). Among the 88 patient cohorts studied, a decrease in CO occurred in 63 (72%). In 16 cohorts, the decrease was severe (>25%). Changes in blood pressure (BP) were not concordant in extent or direction with changes in CO. The decrease in CO correlated weakly with ultrafiltration rate (r = -0.3, p = 0.05) and strongly with changes in systemic vascular resistance (SVR) (r = -0.6, p < 0.001). CONCLUSION: There are limited data on CO changes during RRT. However, a decrease in CO appeared common and was marked in 1 of 5 patient cohorts. Such decreases often occurred without BP changes and were associated with increased SVR.

Exploring the norepinephrine to angiotensin II conversion ratio in patients with vasodilatory hypotension: A post-hoc analysis of the ARAMIS trial.

PURPOSE: Angiotensin II is approved for catecholamine-refractory vasodilatory shock but the conversion dose ratio from norepinephrine to angiotensin II remains unclear. METHODS: We conducted a post-hoc analysis of the Acute Renal effects of Angiotensin II Management in Shock (ARAMIS) trial involving patients with vasodilatory hypotension. We determined the norepinephrine equivalent dose immediately prior to angiotensin II initiation and calculated the conversion dose ratio between norepinephrine and angiotensin II. We performed subgroup analyses based on recent exposure to angiotensin receptor blockers (ARBs) and renin levels at baseline. RESULTS: In 37 patients, the median conversion dose ratio between norepinephrine equivalent and angiotensin II was to 10:1 for norepinephrine bitartrate (5:1 for norepinephrine base). The conversion ratio was not affected by the baseline renin, with a median ratio of 10 (7-21) in the high renin group versus 12 (5-22) in the low renin group. Finally, exposure to ARBs prior admission appeared to diminish the conversion ratio with a median ratio of 7 (4-13) in ARB patients vs. 12 (7-22) in non-ARB patients. CONCLUSIONS: The norepinephrine to angiotensin II conversion dose ratio is 10:1 in a vasodilatory hypotension population. These findings can guide clinicians and researchers in the use, dosing, and study of angiotensin II in critical care.

Adults are just big kids: pediatric considerations for adult critical care nephrology.

PURPOSE OF REVIEW: In recent years, there has been growing attention to pediatric kidney health, especially pediatric acute kidney injury (AKI). However, there has been limited focus on the role of pediatric AKI on adult kidney health, specifically considerations for the critical care physician. RECENT FINDINGS: We summarize what is known in the field of pediatric AKI to inform adult medical care including factors throughout the early life course, including perinatal, neonatal, and pediatric exposures that impact survivor care later in adulthood. SUMMARY: The number of pediatric AKI survivors continues to increase, leading to a higher burden of chronic kidney disease and other long-term co-morbidities later in life. Adult medical providers should consider pediatric history and illnesses to inform the care they provide. Such knowledge may help internists, nephrologists, and intensivists alike to improve risk stratification, including a lower threshold for monitoring for AKI and kidney dysfunction in their patients.

Sepsis-associated acute kidney injury in the intensive care unit: incidence, patient characteristics, timing, trajectory, treatment, and associated outcomes. A multicenter, observational study.

PURPOSE: The Acute Disease Quality Initiative (ADQI) Workgroup recently released a consensus definition of sepsis-associated acute kidney injury (SA-AKI), combining Sepsis-3 and Kidney Disease Improving Global Outcomes (KDIGO) AKI criteria. This study aims to describe the epidemiology of SA-AKI. METHODS: This is a retrospective cohort study carried out in 12 intensive care units (ICUs) from 2015 to 2021. We studied the incidence, patient characteristics, timing, trajectory, treatment, and associated outcomes of SA-AKI based on the ADQI definition. RESULTS: Out of 84,528 admissions, 13,451 met the SA-AKI criteria with its incidence peaking at 18% in 2021. SA-AKI patients were typically admitted from home via the emergency department (ED) with a median time to SA-AKI diagnosis of 1 day (interquartile range (IQR) 1-1) from ICU admission. At diagnosis, most SA-AKI patients (54%) had a stage 1 AKI, mostly due to the low urinary output (UO) criterion only (65%). Compared to diagnosis by creatinine alone, or by both UO and creatinine criteria, patients diagnosed by UO alone had lower renal replacement therapy (RRT) requirements (2.8% vs 18% vs 50%; p < 0.001), which was consistent across all stages of AKI. SA-AKI hospital mortality was 18% and SA-AKI was independently associated with increased mortality. In SA-AKI, diagnosis by low UO only, compared to creatinine alone or to both UO and creatinine criteria, carried an odds ratio of 0.34 (95% confidence interval (CI) 0.32-0.36) for mortality. CONCLUSION: SA-AKI occurs in 1 in 6 ICU patients, is diagnosed on day 1 and carries significant morbidity and mortality risk with patients mostly admitted from home via the ED. However, most SA-AKI is stage 1 and mostly due to low UO, which carries much lower risk than diagnosis by other criteria.