Kidney replacement therapy: trends in incidence, treatment, and outcomes of myocardial infarction and stroke in a nationwide Scottish study.

BACKGROUND AND AIMS: Patients with kidney failure have a higher risk of cardiovascular disease compared with the general population. Whilst temporal trends of myocardial infarction and stroke are declining in the general population, these have not been evaluated in patients with kidney failure. This study aimed to describe national trends in the incidence, treatment, and outcomes of myocardial infarction and stroke in patients with kidney failure (i.e. on dialysis or with a kidney transplant) over a 20-year period, stratified by age and sex. METHODS: In this retrospective national data linkage study, all patients with kidney failure in Scotland (UK) receiving kidney replacement therapy between January 1996 and December 2016 were linked to national hospitalization, prescribing, and death records. The primary outcomes were the incidence of myocardial infarction and stroke, and subsequent cardiovascular death. Generalized additive models were constructed to estimate age-standardized, sex-stratified incidence rates and trends in cardiovascular and all-cause death. RESULTS: Amongst 16 050 patients with kidney failure [52 (SD 15) years; 41.5% women], there were 1992 [66 (SD 12) years; 34.8% women] and 996 [65 (SD 13) years; 45.1% women] incident myocardial infarctions and strokes, respectively, between January 1996 and December 2016. During this period, the age-standardized incidence of myocardial infarction per 100 000 decreased in men {from 4376 [95% confidence interval (CI) 3998-4785] to 1835 (95% CI 1692-1988)} and women [from 3268 (95% CI 2982-3593) to 1369 (95% CI 1257-1491)]. Similarly, the age-standardized incidence of stroke per 100 000 also decreased in men [from 1978 (95% CI 1795-2175) to 799 (95% CI 729-875)] and women [from 2234 (95% CI 2031-2468) to 903 (95% CI 824-990)]. Compared with the general population, the incidence of myocardial infarction was four- to eight-fold higher in patients with kidney failure, whilst for stroke it was two- to four-fold higher. The use of evidence-based cardioprotective treatment increased over the study period, and the predicted probability of cardiovascular death within 1 year of myocardial infarction for a 66-year-old patient with kidney failure (mean age of the cohort) fell in men (76.6% to 38.6%) and women (76.8% to 38.8%), and also decreased in both sexes following stroke (men, from 63.5% to 41.4%; women, from 67.6% to 45.8%). CONCLUSIONS: The incidence of myocardial infarction and stroke has halved in patients with kidney failure over the past 20 years but remains significantly higher than in the general population. Despite improvements in treatment and outcomes, the prognosis of these patients following myocardial infarction and stroke remains poor.

How to use meropenem in pediatric patients undergoing CKRT? Integrated meropenem pharmacokinetic model for critically ill children.

Standard dosing could fail to achieve adequate systemic concentrations in ICU children or may lead to toxicity in children with acute kidney injury. The population pharmacokinetic analysis was used to simultaneously analyze all available data (plasma, prefilter, postfilter, effluent, and urine concentrations) and provide the pharmacokinetic characteristics of meropenem. The probability of target fT > MIC attainment, avoiding toxic levels, during the entire dosing interval was estimated by simulation of different intermittent and continuous infusions in the studied population. A total of 16 critically ill children treated with meropenem were included, with 7 of them undergoing continuous kidney replacement therapy (CKRT). Only 33% of children without CKRT achieved 90% of the time when the free drug concentration exceeded the minimum inhibitory concentration (%fT > MIC) for an MIC of 2 mg/L. In dose simulations, only continuous infusions (60-120 mg/kg in a 24-h infusion) reached the objective in patients <30 kg. In patients undergoing CKRT, the currently used schedule (40 mg/kg/12 h from day 2 in a short infusion of 30 min) was clearly insufficient in patients <30 kg. Keeping the dose to 40 mg/kg q8h without applying renal adjustment and extended infusions (40 mg/kg in 3- or 4-h infusion every 12 h) was sufficient to reach 90% fT > MIC (>2 mg/L) in patients >10 kg. In patients <10 kg, only continuous infusions reached the objective. In patients >30 kg, 60 mg/kg in a 24-h infusion is sufficient and avoids toxicity. This population model could help with an individualized dosing approach that needs to be adopted in critically ill pediatric patients. Critically ill patients subjected to or not to CKRT may benefit from the administration of meropenem in an extended or continuous infusion.

Low-Dose Continuous Kidney Replacement Therapy and Mortality in Critically Ill Patients With Acute Kidney Injury: A Retrospective Cohort Study.

RATIONALE & OBJECTIVE: Continuous kidney replacement therapy (CKRT) is preferred when available for hemodynamically unstable acute kidney injury (AKI) patients in the intensive care unit (ICU). The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend a delivered CKRT dose of 20-25mL/kg/h; however, in Japan the doses are typically below this recommendation due to government health insurance system restrictions. This study investigated the association between mortality and dose of CKRT. STUDY DESIGN: Single-center retrospective cohort study. SETTING & PARTICIPANTS: Critically ill patients with AKI treated with CKRT at a tertiary Japanese university hospital between January 1, 2012, and December 31, 2021. EXPOSURE: Delivered CKRT doses below or above the median. OUTCOME: 90-day mortality after CKRT initiation. ANALYTICAL APPROACH: Multivariable Cox regression analysis and Kaplan-Meier analysis. RESULTS: The study population consisted of 494 patients. The median age was 72 years, and 309 patients (62.6%) were men. Acute tubular injury was the leading cause of AKI, accounting for 81.8%. The median delivered CKRT dose was 13.2mL/kg/h. Among the study participants, 456 (92.3%) received delivered CKRT doses below 20mL/kg/h, and 204 (41.3%) died within 90 days after CKRT initiation. Multivariable Cox regression analysis revealed increased mortality in the below-median group (HR, 1.73 [95% CI, 1.19-2.51], P=0.004). Additionally, a significant, inverse, nonlinear association between 90-day mortality and delivered CKRT dose was observed using delivered CKRT dose as a continuous variable. LIMITATIONS: Single-center, retrospective, observational study. CONCLUSIONS: A lower delivered CKRT dose was independently associated with higher 90-day mortality among critically ill patients who mostly received dosing below the current KDIGO recommendations. PLAIN-LANGUAGE SUMMARY: The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend delivering a continuous kidney replacement therapy (CKRT) dose of 20-25mL/kg/h. However, it is not clear if it is safe to use delivered CKRT doses below this recommendation. In this study, over 90% of the patients received CKRT with a delivered dose below the KDIGO recommendation. We divided these patients into 2 groups based on the median delivered CKRT dose. Our findings show that a delivered CKRT dose below the median was associated with increased risk of death within 90 days. These findings show that a lower delivered CKRT dose was independently associated with higher 90-day mortality among critically ill patients who mostly received dosing below current KDIGO recommendations.

Continuous Kidney Replacement Therapy and Survival in Children and Young Adults: Findings From the Multinational WE-ROCK Collaborative.

RATIONALE & OBJECTIVE: There are limited studies describing the epidemiology and outcomes in children and young adults receiving continuous kidney replacement therapy (CKRT). We aimed to describe associations between patient characteristics, CKRT prescription, and survival. STUDY DESIGN: Retrospective multicenter cohort study. SETTING & PARTICIPANTS: 980 patients aged from birth to 25 years who received CKRT between 2015 and 2021 at 1 of 32 centers in 7 countries participating in WE-ROCK (Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Diseases). EXPOSURE: CKRT for acute kidney injury or volume overload. OUTCOMES: Death before intensive care unit (ICU) discharge. ANALYTICAL APPROACH: Descriptive statistics. RESULTS: Median age was 8.8 years (IQR, 1.6-15.0), and median weight was 26.8 (IQR, 11.6-55.0) kg. CKRT was initiated a median of 2 (IQR, 1-6) days after ICU admission and lasted a median of 6 (IQR, 3-14) days. The most common CKRT modality was continuous venovenous hemodiafiltration. Citrate anticoagulation was used in 62%, and the internal jugular vein was the most common catheter placement location (66%). 629 participants (64.1%) survived at least until ICU discharge. CKRT dose, filter type, and anticoagulation were similar in those who did and did not survive to ICU discharge. There were apparent practice variations by institutional ICU size. LIMITATIONS: Retrospective design; limited representation from centers outside the United States. CONCLUSIONS: In this study of children and young adults receiving CKRT, approximately two thirds survived at least until ICU discharge. Although variations in dialysis mode and dose, catheter size and location, and anticoagulation were observed, survival was not detected to be associated with these parameters. PLAIN-LANGUAGE SUMMARY: In this large contemporary epidemiological study of children and young adults receiving continuous kidney replacement therapy in the intensive care unit, we observed that two thirds of patients survived at least until ICU discharge. However, patients with comorbidities appeared to have worse outcomes. Compared with previously published reports on continuous kidney replacement therapy practice, we observed greater use of continuous venovenous hemodiafiltration with regional citrate anticoagulation.

Patients' Perspectives on Health-Related Social Needs and Recommendations for Interventions: A Qualitative Study.

RATIONALE & OBJECTIVE: People with low socioeconomic status are disproportionately affected by kidney failure, and their adverse outcomes may stem from unmet health-related social needs. This study explored hemodialysis patient perspectives on health-related social needs and recommendations for intervention. STUDY DESIGN: Qualitative study using semistructured interviews. SETTINGS & PARTICIPANTS: Thirty-two people with low socioeconomic status receiving hemodialysis at 3 hemodialysis facilities in Austin, Texas. ANALYTICAL APPROACH: Interviews were analyzed for themes and subthemes using the constant comparative method. RESULTS: Seven themes and 21 subthemes (in parentheses) were identified: (1) kidney failure was unexpected (never thought it would happen to me; do not understand dialysis); (2) providers fail patients (doctors did not act; doctors do not care); (3) dialysis is detrimental (life is not the same; dialysis is all you do; dialysis causes emotional distress; dialysis makes you feel sick); (4) powerlessness (dependent on others; cannot do anything about my situation); (5) financial resource strain (dialysis makes you poor and keeps you poor; disability checks are not enough; food programs exist but are inconsistent; eat whatever food is available; not enough affordable housing; unstable housing affects health and well-being); (6) motivation to keep going (faith, support system, will to live); and (7) interventions should promote self-efficacy (navigation of community resources, support groups). LIMITATIONS: Limited quantitative data such as on dialysis vintage, and limited geographic representation. CONCLUSIONS: Dialysis exacerbates financial resource strain, and health-related social needs exacerbate dialysis-related stress. The participants made recommendations to address social needs with an emphasis on increasing support and community resources for this population. PLAIN-LANGUAGE SUMMARY: People receiving dialysis often experience health-related social needs, such as food and housing needs, but little is known about how these impact patients' health and well-being or how to best address them. We interviewed people receiving dialysis about how health-related social needs affect them and what they think dialysis facilities can do to help them address those needs. The participants reported that they often lose their independence after starting dialysis and health-related social needs are common, exacerbate their stress and emotional distress, and reduce their sense of well-being. Dialysis facilities may be able to enhance the experience of these patients by facilitating connections with local resources and providing opportunities for patients to support one another.

Mortality Rates and a Clinical Predictive Model for the Elderly on Maintenance Hemodialysis: A Large Observational Cohort Study of 17,354 Asian Patients.

INTRODUCTION: Mortality following hemodialysis initiation may influence the decision to initiate hemodialysis in elderly patients. Our objective is to demonstrate mortality following hemodialysis initiation in elderly patients (≥70 years) and to derive a prediction risk score based on clinical and laboratory indicators to determine risk of all-cause mortality in patients aged ≥80 years. METHODS: We identified elderly patients (≥70 years) who initiated maintenance hemodialysis between January 2005 and December 2016 using data from the Thai Renal Replacement Therapy (TRT) registry. The mortality rate was determined based on age categories. A predictive risk score for all-cause mortality was created for 4,451 patients aged ≥80 years by using demographics, laboratory values, and interview-based parameters. Using a flexible parametric survival analysis, we predicted mortality 3 months, 6 months, 1 year, 5 years, and 10 years after hemodialysis initiation. RESULTS: 17,354 patients (≥70 years) were included, mean age 76.9 ± 5.1 years, 46.5% male, and 6,309 (36.4%) died. Patients aged <80 years had a median survival time of 110.6 months. A 9-point risk score was developed to predict mortality in patients aged ≥80 years: age >85 years, male, body mass index <18.5 kg/m2, hemoglobin <10.0 g/dL, albumin <3.5 g/dL, substantial assistance required in daily living (1 point each), and Karnofsky Performance Status (KPS) score <50 (3 points). C-statistic of 0.797 indicated high model discrimination. Internal validation demonstrated good agreement between observed and anticipated mortalities. CONCLUSIONS: Hemodialysis is appropriate for patients aged 70-80 years. A risk score for mortality in patients aged ≥80 years has been developed. The score is based on seven readily obtainable and evaluable clinical characteristics.

Albuminuria predicts kidney events in IgA nephropathy.

BACKGROUND & HYPOTHESIS: KDIGO recommends proteinuria <1 g/d as a treatment target in patients with immunoglobulin A nephropathy (IgAN) because of high-risk of progression to kidney failure. However, long-term kidney outcomes in patients with low-grade proteinuria remain insufficiently studied. METHODS: We enrolled patients with biopsy-proven primary IgAN from the Swedish Renal Registry and analyzed associations between urine albumin-to-creatinine ratio (uACR, in categories < 0.3, ≥0.3-0.5, ≥0.5-1.0, ≥1.0-1.5, ≥1.5-2.0 and ≥ 2.0 g/g) and the occurrence of major adverse kidney events (MAKE, a composite of kidney replacement therapy [KRT] and > 30% decline in eGFR). We also explored the risk of kidney events associated with change in uACR within a year. RESULTS: We included 1269 IgAN patients (74% men, median 53 years, mean eGFR 33 mL/min/1.73m², median uACR 0.7 g/g). Over median follow-up of 5.5 [2.8;9.2] years, 667 MAKE and 517 KRT events occurred, and 528 patients experienced > 30% eGFR decline. Compared with uACR < 0.3 g/g, any higher uACR category was strongly and incrementally associated with the risk of MAKE (adjusted HR ranging from 1.56 [95%CI 1.14-2.14] if uACR 0.3-0.5 g/g to 4.53 [3.36-6.11] if uACR ≥ 2.0 g/g), KRT (HR ranging from 1.39 to 4.65), and eGFR decline > 30% (HR ranging from 1.76 to 3.47). In 785 patients who had repeated uACR measurements within a year, and compared with stable uACR, the risk of kidney events was lower if uACR decreased by 2-fold (HR ranging from 0.47 to 0.49), and higher if uACR increased by 2-fold (HR from 1.18 to 2.56), irrespective of baseline uACR. CONCLUSIONS: There is substantial risk of adverse kidney outcomes among patients with IgAN and uACR between 0.3 and 1.0 g/g, a population currently considered at low-risk of CKD progression. Reduction in uACR is associated with better kidney outcomes, irrespective of baseline uACR.

Incidence and outcomes of kidney replacement therapy for end-stage kidney disease due to primary glomerular disease in Europe: findings from the ERA Registry.

BACKGROUND: Primary glomerular disease (PGD) is a major cause of end-stage kidney disease (ESKD) leading to kidney replacement therapy (KRT). We aimed to describe incidence (trends) in individuals starting KRT for ESKD due to PGD and to examine their survival and causes of death. METHODS: We used data from the European Renal Association (ERA) Registry on 69 854 patients who started KRT for ESKD due to PGD between 2000 and 2019. ERA primary renal disease codes were used to define six PGD subgroups. We examined age and sex standardized incidence, trend of the incidence and survival. RESULTS: The standardized incidence of KRT for ESKD due to PGD was 16.6 per million population (pmp), ranging from 8.6 pmp in Serbia to 20.0 pmp in France. Immunoglobulin A nephropathy (IgAN) and focal segmental glomerulosclerosis (FSGS) had the highest incidences, of 4.6 pmp and 2.6 pmp, respectively. Histologically non-examined PGDs represented over 50% of cases in Serbia, Bosnia and Herzegovina, and Romania and were also common in Greece, Estonia, Belgium and Sweden. The incidence declined from 18.6 pmp in 2000 to 14.5 pmp in 2013, after which it stabilized. All PGD subgroups had 5-year survival probabilities above 50%, with crescentic glomerulonephritis having the highest risk of death [adjusted hazard ratio 1.8 (95% confidence interval 1.6-1.9)] compared with IgAN. Cardiovascular disease was the most common cause of death (33.9%). CONCLUSION: The incidence of KRT for ESKD due to PGD showed large differences between countries and was highest and increasing for IgAN and FSGS. Lack of kidney biopsy facilities in some countries may have affected accurate assignment of the cause of ESKD. The recognition of the incidence and outcomes of KRT among different PGD subgroups may contribute to a more individualized patient care approach.

A comparison of the epidemiology of kidney replacement therapy between Europe and the United States: 2021 data of the ERA Registry and the USRDS.

BACKGROUND: This paper compares the most recent data on the incidence and prevalence of kidney replacement therapy (KRT), kidney transplantation rates, and mortality on KRT from Europe to those from the United States (US), including comparisons of treatment modalities (haemodialysis (HD), peritoneal dialysis (PD), and kidney transplantation (KTx)). METHODS: Data were derived from the annual reports of the European Renal Association (ERA) Registry and the United States Renal Data System (USRDS). The European data include information from national and regional renal registries providing the ERA Registry with individual patient data. Additional analyses were performed to present results for all participating European countries together. RESULTS: In 2021, the KRT incidence in the US (409.7 per million population (pmp)) was almost 3-fold higher than in Europe (144.4 pmp). Despite the substantial difference in KRT incidence, approximately the same proportion of patients initiated HD (Europe: 82%, US: 84%), PD (14%; 13%, respectively), or underwent pre-emptive KTx (4%; 3%, respectively). The KRT prevalence in the US (2436.1 pmp) was 2-fold higher than in Europe (1187.8 pmp). Within Europe, approximately half of all prevalent patients were living with a functioning graft (47%), while in the US, this was one third (32%). The number of kidney transplantations performed was almost twice as high in the US (77.0 pmp) compared to Europe (41.6 pmp). The mortality of patients receiving KRT was 1.6-fold higher in the US (157.3 per 1000 patient years) compared to Europe (98.7 per 1000 patient years). CONCLUSIONS: The US had a much higher KRT incidence, prevalence, and mortality compared to Europe, and despite a higher kidney transplantation rate, a lower proportion of prevalent patients with a functioning graft.

Global Kidney Health priorities - Perspectives from the ISN-GKHA.

Kidney diseases have become a global epidemic with significant public health impact. Chronic kidney disease (CKD) is set to become the fifth largest cause of death by 2040, with major impacts on low-resource countries. This review is based on recent report of the International Society of Nephrology Global Kidney Health Atlas (ISN-GKHA) that uncovered gaps in key vehicles of kidney care delivery assessed using World Health Organization building blocks for health systems (financing, services delivery, workforce, access to essential medicines, health information systems, and leadership/governance). High-income countries had more centres for kidney replacement therapies (KRT), higher KRT access, higher allocation of public funds to KRT, larger workforce, more health information systems, and higher government recognition of CKD and KRT as health priorities than low-income nations. Evidence identified from the current ISN-GKHA initiative should serve as template for generating and advancing policies and partnerships to address the global burden of kidney disease. The results provide opportunities for kidney health policymakers, nephrology leaders, and organizations to initiate consultations to identify strategies for improving care delivery and access in equitable, and resource-sensitive manners. Policies to increase use of public funding for kidney care, lower cost of KRT, and increase workforce should be high-priority in low-resource nations, while strategies that expand access to kidney care and maintain current status of care should be prioritized in high-income countries. In all countries, the perspectives of people with CKD should be exhaustively explored to identify core kidney care priorities.

Adult outcomes of childhood kidney replacement therapy in Europe from 2008 to 2019: an ERA Registry study.

BACKGROUND AND HYPOTHESIS: Young adults starting kidney replacement therapy (KRT) during childhood and reaching their 18th birthday (i.e. adult survivors of childhood KRT) form a challenging population of interest to nephrologists treating adults, as during this period there will be a transition to adult renal centres. Nonetheless, few studies have focused on the epidemiology of KRT in this group. We aimed to provide an update on these patients' characteristics, treatment history, graft and patient survival, to report their 5-year prognosis, and expected remaining lifetime. METHODS: Data on KRT patients reaching their 18th birthday in 2008-2019 were collected from 21 European countries/regions providing individual patient data to the European Renal Association (ERA) Registry. Patient characteristics and treatment trajectories were examined before and after turning 18 years. Kaplan-Meier and Cox proportional hazards regression were used for patient and graft survival analyses. RESULTS: In total, 2944 patients were included. The proportion of adult survivors initiating KRT at a very young age (0-4 years), and undergoing pre-emptive kidney transplantation increased. Unadjusted 5-year patient survival was 96.9% (95% CI: 96.2-97.5). Dialysis patients had a higher risk of death than kidney transplant recipients (adjusted hazard ratio 5.44 (95% CI: 3.34-8.86)). Between ages 18 and 23 years, about 21% of the adult survivors lost their kidney transplant and 34% of the dialysis patients continued this treatment. Compared with the general population, life expectancy for eighteen-year-old kidney transplant and dialysis patients was 17 and 40 years shorter, respectively. CONCLUSION: Life expectancy of 18-year-old kidney transplant recipients was lower compared with the general population. Yet, having a functioning kidney graft at age 18 years resulted in better outcomes than being on dialysis. Nevertheless, between ages 18 and 23 years, about one-fifth of the kidney grafts failed and one-third of the patients remained on dialysis.

Acute kidney injury after out-of-hospital cardiac arrest.

BACKGROUND: Acute kidney injury (AKI) is a significant risk factor associated with reduced survival following out-of-hospital cardiac arrest (OHCA). Whether the severity of AKI simply serves as a surrogate measure of worse peri-arrest conditions, or represents an additional risk to long-term survival remains unclear. METHODS: This is a sub-study derived from a randomized trial in which 789 comatose adult OHCA patients with presumed cardiac cause and sustained return of spontaneous circulation (ROSC) were enrolled. Patients without prior dialysis dependent kidney disease and surviving at least 48 h were included (N = 759). AKI was defined by the kidney disease: improving global outcome (KDIGO) classification, and patients were divided into groups based on the development of AKI and the need for continuous kidney replacement therapy (CKRT), thus establishing three groups of patients-No AKI, AKI no CKRT, and AKI CKRT. Primary outcome was overall survival within 365 days after OHCA according to AKI group. Adjusted Cox proportional hazard models were used to assess overall survival within 365 days according to the three groups. RESULTS: In the whole population, median age was 64 (54-73) years, 80% male, 90% of patients presented with shockable rhythm, and time to ROSC was median 18 (12-26) min. A total of 254 (33.5%) patients developed AKI according to the KDIGO definition, with 77 requiring CKRT and 177 without need for CKRT. AKI CKRT patients had longer time-to-ROSC and worse metabolic derangement at hospital admission. Overall survival within 365 days from OHCA decreased with the severity of kidney injury. Adjusted Cox regression analysis found that AKI, both with and without CKRT, was significantly associated with reduced overall survival up until 365 days, with comparable hazard ratios relative to no AKI (HR 1.75, 95% CI 1.13-2.70 vs. HR 1.76, 95% CI 1.30-2.39). CONCLUSIONS: In comatose patients who had been resuscitated after OHCA, patients developing AKI, with or without initiation of CKRT, had a worse 1-year overall survival compared to non-AKI patients. This association remains statistically significant after adjusting for other peri-arrest risk factors. TRIAL REGISTRATION: The BOX trial is registered at ClinicalTrials.gov: NCT03141099.

Standard vs. carbone dioxide adapted kidney replacement therapy in hypercapnic ARDS patients: a randomized controlled pilot trial (BigBIC).

BACKGROUND: Current continuous kidney replacement therapy (CKRT) protocols ignore physiological renal compensation for hypercapnia. This study aimed to explore feasibility, safety, and clinical benefits of pCO2-adapted CKRT for hypercapnic acute respiratory distress syndrome (ARDS) patients with indication for CKRT. METHODS: We enrolled mechanically ventilated hypercapnic ARDS patients (pCO2 > 7.33 kPa) receiving regional citrate anticoagulation (RCA) based CKRT in a prospective, randomized-controlled pilot-study across five intensive care units at the Charité-Universitätsmedizin Berlin, Germany. Patients were randomly assigned 1:1 to the control group with bicarbonate targeted to 24 mmol/l or pCO2-adapted-CKRT with target bicarbonate corresponding to physiological renal compensation. Study duration was six days. Primary outcome was bicarbonate after 72 h. Secondary endpoints included safety and clinical endpoints. Endpoints were assessed in all patients receiving treatment. RESULTS: From September 2021 to May 2023 40 patients (80% male) were enrolled. 19 patients were randomized to the control group, 21 patients were randomized to pCO2-adapted-CKRT. Five patients were excluded before receiving treatment: three in the control group (consent withdrawal, lack of inclusion criteria fulfillment (n = 2)) and two in the intervention group (lack of inclusion criteria fulfillment, sudden unexpected death) and were therefore not included in the analysis. Median plasma bicarbonate 72 h after randomization was significantly higher in the intervention group (30.70 mmol/l (IQR 29.48; 31.93)) than in the control group (26.40 mmol/l (IQR 25.63; 26.88); p < 0.0001). More patients in the intervention group received lung protective ventilation defined as tidal volume < 8 ml/kg predicted body weight. Thirty-day mortality was 10/16 (63%) in the control group vs. 8/19 (42%) in the intervention group (p = 0.26). CONCLUSION: Tailoring CKRT to physiological renal compensation of respiratory acidosis appears feasible and safe with the potential to improve patient care in hypercapnic ARDS. TRIAL REGISTRATION: The trial was registered in the German Clinical Trials Register (DRKS00026177) on September 9, 2021 and is now closed.

Assessing the predictive value of elevated postoperative syndecan-1 levels for progressive acute kidney injury and kidney replacement therapy necessity in adult cardiac surgery patients.

BACKGROUND: The development of acute kidney injury (AKI) post-cardiac surgery significantly increases patient morbidity and healthcare costs. Prior researches have established Syndecan-1 (SDC-1) as a potential biomarker for endothelial injury and subsequent acute kidney injury development. This study assessed whether postoperative SDC-1 levels could further predict AKI requiring kidney replacement therapy (AKI-KRT) and AKI progression. METHODS: In this prospective study, 122 adult cardiac surgery patients, who underwent valve or coronary artery bypass grafting (CABG) or a combination thereof and developed AKI within 48 h post-operation from May to September 2021, were monitored for the progression to stage 2-3 AKI or the need for KRT. We analyzed the predictive value of postoperative serum SDC-1 levels in relation to multiple endpoints. RESULTS: In the study population, 110 patients (90.2%) underwent cardiopulmonary bypass, of which thirty received CABG or combined surgery. Fifteen patients (12.3%) required KRT, and thirty-eight (31.1%) developed progressive AKI, underscoring the severe AKI incidence. Multivariate logistic regression indicated that elevated SDC-1 levels were independent risk factors for progressive AKI (OR = 1.006) and AKI-KRT (OR = 1.011). The AUROC for SDC-1 levels in predicting AKI-KRT and AKI progression was 0.892 and 0.73, respectively, outperforming the inflammatory cytokines. Linear regression revealed a positive correlation between SDC-1 levels and both hospital (ß = 0.014, p = 0.022) and ICU stays (ß = 0.013, p < 0.001). CONCLUSION: Elevated postoperative SDC-1 levels significantly predict AKI progression and AKI-KRT in patients following cardiac surgery. The study's findings support incorporating SDC-1 level monitoring into post-surgical care to improve early detection and intervention for severe AKI.

Impact of Using Blood Warmer During Continuous Kidney Replacement Therapy in Patients With Acute Kidney Injury.

PURPOSE: We investigated the impact of blood warmer use on hypotensive episodes in patients with acute kidney injury (AKI) receiving continuous kidney replacement therapy (CKRT). MATERIALS AND METHODS: We included patients with AKI undergoing CKRT between January 1, 2012, and January 1, 2021, at a tertiary academic hospital. Hypotensive episodes were defined as mean arterial pressure (MAP) <60 mm Hg or a decrease in MAP by ≥10 mm Hg, systolic blood pressure (SBP) < 90 mm Hg or a decrease in SBP by ≥20 mm Hg, or increased vasopressor requirement. These were analyzed by Poisson regression with repeated-measures analysis of variance using generalized estimation equation. RESULTS: There were 669 patients with AKI that required CKRT. Use of blood warmer on first day of CKRT was in 324 (48%) patients. Incidence rate ratio of hypotensive episodes during the first 24-h of CKRT in patients where a blood warmer was used was 1.06 (95% confidence interval [CI]: 0.98-1.13) compared to those where blood warmer was not used. This did not change in adjusted model. Overall, the within-subject effect of temperature on hypotensive episodes showed that higher temperature was associated with fewer episodes (0.94, 95% CI: 0.9-0.99 per 10 degrees increase, P = .007). CONCLUSION: Blood rewarming was not associated with hypotensive episodes during CKRT.

Medication patterns and dosing guidance in pediatric patients supported with intermittent hemodialysis or continuous kidney replacement therapy.

BACKGROUND: Hemodialysis is a life-saving technology used during periods of acute or chronic kidney failure to remove toxins, and maintain fluid, electrolyte and metabolic balance. While this technology plays an important role for pediatric patients with kidney dysfunction, it can alter the pharmacokinetic behavior of medications placing patients at risk for suboptimal dosing and drug toxicity. The ability to directly translate pharmacokinetic alterations into dosing recommendations has thus far been limited and dosing guidance specific to pediatric hemodialysis patients is rare. Despite differences in dialysis prescription and patient populations, intermittent (iHD) and continuous kidney replacement therapy (CKRT) patients are often pooled together. In order to develop evidence-based dosing guidelines, it is important to first prioritize drugs for study in each modality. METHODS: Here we aim to identify priority drugs in two hemodialysis modalities, through: 1) Identification of hospitalized, pediatric patients who received CKRT or intermittent hemodialysis (iHD) using a machine learning-based predictive model based on medications; 2) Identification of medication administration patterns in these patient cohorts; and 3) Identification of the most commonly prescribed drugs that lack published dosing guidance. RESULTS: Notable differences were found in the pattern of medications and drug dosing guidance between iHD and CKRT patients. Antibiotics, diuretics and sedatives were more common in CKRT patients. Out of the 50 most commonly administered medications in the two modalities, only 34% and 28% had dosing guidance present for iHD and CKRT, respectively. CONCLUSIONS: Our results add to the understanding of the differences between iHD and CKRT patient populations by identifying commonly used medications that lack dosing guidance for each hemodialysis modality, helping to pinpoint priority medications for further study. Overall, this study provides an overview of the current limitations in medication use in this at-risk population, and provides a framework for future studies by identifying commonly used medications in pediatric CKRT and iHD patients.

Association of continuous kidney replacement therapy timing and mortality in critically ill children.

BACKGROUND: Acute kidney injury (AKI) is a common complication of critical illness and associated with high morbidity and mortality. Optimal timing of continuous kidney replacement therapy (CKRT) in children is unknown. We aimed to measure the association between timing of initiation and mortality. METHODS: This is a single-center retrospective cohort study of pediatric patients receiving CKRT from 2013 to 2019. The primary exposure, time to CKRT initiation, was measured from onset of stage 3 AKI during hospitalization (defined using Kidney Disease: Improving Global Outcomes creatinine and urine output criteria) and analyzed as both a continuous and categorical variable. The primary outcome was ICU mortality. RESULTS: Ninety-nine patients met criteria for analysis. Overall mortality was 39% (39/99). Median time from stage 3 AKI onset to CKRT initiation was 1.5 days in survivors and 5.5 days in nonsurvivors (p < 0.001). In multivariable analysis, increased time to CKRT initiation was independently associated with mortality [OR 1.02 per hour (95% CI 1.01-1.04), p < 0.001]. Longer time to CKRT initiation was associated with higher odds of mortality in ascending time intervals. Patients started on CKRT > 2 days compared to < 2 days after stage 3 AKI onset had higher mortality (65% vs. 5%, p < 0.001), longer median ICU length of stay (25 vs. 12 d, p < 0.001), longer median CKRT duration (11 vs. 5 d, p < 0.001), and fewer AKI-free days (0 vs. 14 d, p < 0.001). CONCLUSIONS: Longer time to initiation of CKRT after development of severe AKI is independently associated with mortality. Consideration of early CKRT in this high-risk population may be a strategy to reduce mortality and improve recovery of kidney function. However, there remains significant heterogeneity in the definition of early versus late initiation and the optimal timing of CKRT remains unknown.

Fluid assessment, fluid balance, and fluid overload in sick children: a report from the Pediatric Acute Disease Quality Initiative (ADQI) conference.

BACKGROUND: The impact of disorders of fluid balance, including the pathologic state of fluid overload in sick children has become increasingly apparent. With this understanding, there has been a shift from application of absolute thresholds of fluid accumulation to an appreciation of the intricacies of fluid balance, including the impact of timing, trajectory, and disease pathophysiology. METHODS: The 26th Acute Disease Quality Initiative was the first to be exclusively dedicated to pediatric and neonatal acute kidney injury (pADQI). As part of the consensus panel, a multidisciplinary working group dedicated to fluid balance, fluid accumulation, and fluid overload was created. Through a search, review, and appraisal of the literature, summative consensus statements, along with identification of knowledge gaps and recommendations for clinical practice and research were developed. CONCLUSIONS: The 26th pADQI conference proposed harmonized terminology for fluid balance and for describing a pathologic state of fluid overload for clinical practice and research. Recommendations include that the terms daily fluid balance, cumulative fluid balance, and percent cumulative fluid balance be utilized to describe the fluid status of sick children. The term fluid overload is to be preserved for describing a pathologic state of positive fluid balance associated with adverse events. Several recommendations for research were proposed including focused validation of the definition of fluid balance, fluid overload, and proposed methodologic approaches and endpoints for clinical trials.

School attendance and sport participation amongst children with chronic kidney disease: a cross-sectional analysis from the Kids with CKD (KCAD) study.

BACKGROUND: School attendance and life participation, particularly sport, is a high priority for children with chronic kidney disease (CKD). This study is aimed at assessing the association between CKD stage, sports participation, and school absences in children with CKD. METHODS: Using data from the binational Kids with CKD study (ages 6-18 years, n = 377), we performed multivariable regression to evaluate the association between CKD stage, school absences, and sports participation. RESULTS: Overall, 62% of participants played sport with the most frequent sport activities engaged in being swimming (17%) and soccer (17%). Compared to children with CKD 1-2, the incidence rate ratios (IRR) (95% CI) for sports participation amongst children with CKD 3-5, dialysis, or transplant were 0.84 (0.64-1.09), 0.59 (0.39-0.90), and 0.75 (0.58-0.96), respectively. The median (IQR) days of school absences within a four-week period were 1 day (0-1), with children on dialysis reporting the highest number of school absences (9 days (5-15)), followed by transplant recipients (2 days (1-7)), children with CKD 3-5 (1 day (0-3)), and with CKD 1-2 (1 day (0-3)). Duration of CKD modified the association between CKD stage and school absences, with children with a transplant experiencing a higher number of missed school days with increasing duration of CKD, but not in children with CKD 1-5 or on dialysis (p-interaction < 0.01). CONCLUSIONS: Children receiving dialysis and with a kidney transplant had greater school absences and played fewer sports compared to children with CKD stages 1-2. Innovative strategies to improve school attendance and sport participation are needed to improve life participation of children with CKD.

Factors influencing circuit lifetime in paediatric continuous kidney replacement therapies - results from the EurAKId registry.

BACKGROUND: Continuous kidney replacement therapy (CKRT) has recently become the preferred kidney replacement modality for children with acute kidney injury (AKI). We hypothesise that CKRT technical parameters and treatment settings in addition to the clinical characteristics of patients may influence the circuit lifetime in children. METHODS: The study involved children included in the EurAKId registry (NCT02960867), who underwent CKRT treatment. We analysed patient characteristics and CKRT parameters. The primary end point was mean circuit lifetime (MCL). Secondary end points were number of elective circuit changes and occurrence of dialysis-related complications. RESULTS: The analysis was composed of 247 children who underwent 37,562 h of CKRT (median 78, IQR 37-165 h per patient). A total of 1357 circuits were utilised (3, IQR 2-6 per patient). MCL was longer in regional citrate anticoagulation (RCA), compared to heparin (HA) and no anticoagulation (NA) (42, IQR 32-58 h; 24, IQR 14-34 h; 18, IQR 12-24 h, respectively, p < 0.001). RCA was associated with longer MCL regardless of the patient's age or dialyser surface. In multivariate analysis, MCL correlated with dialyser surface area (beta = 0.14, p = 0.016), left internal jugular vein vascular access site (beta = -0.37, p = 0.027), and the use of HA (beta = -0.14, p = 0.038) or NA (beta = -0.37, p < 0.001) vs. RCA. RCA was associated with the highest ratio of elective circuit changes and the lowest incidence of complications. CONCLUSION: Anticoagulation modality, dialyser surface, and vascular access site influence MCL. RCA should be considered when choosing first-line anticoagulation for CKRT in children. Further efforts should focus on developing guidelines and clinical practice recommendations for paediatric CKRT.