Patterns of Multiple Organ Dysfunction and Renal Recovery in Critically Ill Children and Young Adults Receiving Continuous Renal Replacement Therapy.

OBJECTIVES: Acute kidney injury requiring dialysis (AKI-D) commonly occurs in the setting of multiple organ dysfunction syndrome (MODS). Continuous renal replacement therapy (CRRT) is the modality of choice for AKI-D. Mid-term outcomes of pediatric AKI-D supported with CRRT are unknown. We aimed to describe the pattern and impact of organ dysfunction on renal outcomes in critically ill children and young adults with AKI-D. DESIGN: Retrospective cohort. SETTING: Two large quarternary care pediatric hospitals. PATIENTS: Patients 26 y old or younger who received CRRT from 2014 to 2020, excluding patients with chronic kidney disease. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Organ dysfunction was assessed using the Pediatric Logistic Organ Dysfunction-2 (PELOD-2) score. MODS was defined as greater than or equal to two organ dysfunctions. The primary outcome was major adverse kidney events at 30 days (MAKE30) (decrease in estimated glomerular filtration rate greater than or equal to 25% from baseline, need for renal replacement therapy, and death). Three hundred seventy-three patients, 50% female, with a median age of 84 mo (interquartile range [IQR] 16-172) were analyzed. PELOD-2 increased from 6 (IQR 3-9) to 9 (IQR 7-12) between ICU admission and CRRT initiation. Ninety-seven percent of patients developed MODS at CRRT start and 266 patients (71%) had MAKE30. Acute kidney injury (adjusted odds ratio [aOR] 3.55 [IQR 2.13-5.90]), neurologic (aOR 2.07 [IQR 1.15-3.74]), hematologic/oncologic dysfunction (aOR 2.27 [IQR 1.32-3.91]) at CRRT start, and progressive MODS (aOR 1.11 [IQR 1.03-1.19]) were independently associated with MAKE30. CONCLUSIONS: Ninety percent of critically ill children and young adults with AKI-D develop MODS by the start of CRRT. Lack of renal recovery is associated with specific extrarenal organ dysfunction and progressive multiple organ dysfunction. Currently available extrarenal organ support strategies, such as therapeutic plasma exchange lung-protective ventilation, and other modifiable risk factors, should be incorporated into clinical trial design when investigating renal recovery.

Preexisting Diabetes Mellitus and All-Cause Mortality in Adult Patients With Sepsis: A Population-Based Cohort Study.

OBJECTIVES: We assessed the association of preexisting diabetes mellitus with all-cause mortality and organ support receipt in adult patients with sepsis. DESIGN: Population-based cohort study. SETTING: Ontario, Canada (2008-2019). POPULATION: Adult patients (18 yr old or older) with a first sepsis-related hospitalization episode. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The main exposure of interest was preexisting diabetes (either type 1 or 2). The primary outcome was all-cause mortality by 90 days; secondary outcomes included receipt of invasive mechanical ventilation and new renal replacement therapy. We report adjusted (for baseline characteristics using standardization) risk ratios (RRs) alongside 95% CIs. A main secondary analysis evaluated the potential mediation by prior metformin use of the association between preexisting diabetes and all-cause mortality following sepsis. Overall, 503,455 adults with a first sepsis-related hospitalization episode were included; 36% had preexisting diabetes. Mean age was 73 years, and 54% of the cohort were females. Preexisting diabetes was associated with a lower adjusted risk of all-cause mortality at 90 days (RR, 0.81; 95% CI, 0.80-0.82). Preexisting diabetes was associated with an increased risk of new renal replacement therapy (RR, 1.53; 95% CI, 1.46-1.60) but not invasive mechanical ventilation (RR, 1.03; 95% CI, 1.00-1.05). Overall, 21% (95% CI, 19-28) of the association between preexisting diabetes and reduced risk of all-cause mortality was mediated by prior metformin use. CONCLUSIONS: Preexisting diabetes is associated with a lower risk of all-cause mortality and higher risk of new renal replacement therapy among adult patients with sepsis. Future studies should evaluate the underlying mechanisms of these associations.

Predictive performance of two types of urinary biomarkers for renal non-recovery in sepsis-associated acute kidney injury: a prospective observational study.

BACKGROUND AND PURPOSE: Renal non-recovery is known to have negative prognostic implications in patients suffering from acute kidney injury (AKI). Nevertheless, the identification of biomarkers for predicting renal non-recovery in sepsis-associated AKI (SA-AKI) within clinical settings remains unresolved. This study aims to evaluate and compare the predictive ability for renal non-recovery, use of kidney replacement therapy (KRT) in the Intensive Care Unit (ICU), and 30-day mortality after SA-AKI by two urinary biomarkers, namely C-C motif chemokine ligand 14 (CCL14) and [TIMP-2]•[IGFBP7]. METHODS: We prospectively screened adult patients who met the criteria for AKI stage 2-3 and Sepsis-3.0 in two ICUs from January 2019 to May 2022. Patients who developed new-onset SA-AKI after ICU admission were enrolled and urinary biomarkers including [TIMP-2]•[IGFBP7] and CCL14 were detected at the time of SA-AKI diagnosis. The primary endpoint was non-recovery from SA-AKI within 7 days. The secondary endpoints were the use of KRT in the ICU and 30-day mortality after SA-AKI. The individual discriminative ability of [TIMP-2]•[IGFBP7] and CCL14 to predict renal non-recovery were evaluated by the area under receiver operating characteristics curve (AUC). RESULTS: 141 patients with stage 2-3 SA-AKI were finally included, among whom 54 (38.3%) experienced renal non-recovery. Urinary CCL14 exhibited a higher predictive capability for renal non-recovery compared to [TIMP-2]•[IGFBP7], with CCL14 showing an AUC of 0.901, versus an AUC of 0.730 for [TIMP-2]•[IGFBP7] (P = 0.001). Urinary CCL14 and [TIMP-2]•[IGFBP7] demonstrated a moderate predictive value for the need for KRT in ICU, with AUC values of 0.794 and 0.725, respectively; The AUC of [TIMP-2]•[IGFBP7] combined with CCL14 reached up to 0.816. Urinary CCL14 and [TIMP-2]•[IGFBP7] exhibited poor predictive power for 30-day mortality, with respective AUC values of 0.623 and 0.593. CONCLUSION: Urinary CCL14 had excellent predictive value for renal non-recovery in SA-AKI patients. For predicting the use of KRT in the ICU, the predictive capability of urinary [TIMP-2]•[IGFBP7] or CCL14 was fair. However, a combination of [TIMP-2]•[IGFBP7] and CCL14 showed good predictive ability for the use of KRT.

Predicting chronic kidney disease progression with artificial intelligence.

BACKGROUND: The use of tools that allow estimation of the probability of progression of chronic kidney disease (CKD) to advanced stages has not yet achieved significant practical importance in clinical setting. This study aimed to develop and validate a machine learning-based model for predicting the need for renal replacement therapy (RRT) and disease progression for patients with stage 3-5 CKD. METHODS: This was a retrospective, closed cohort, observational study. Patients with CKD affiliated with a private insurer with five-year follow-up data were selected. Demographic, clinical, and laboratory variables were included, and the models were developed based on machine learning methods. The outcomes were CKD progression, a significant decrease in the estimated glomerular filtration rate (eGFR), and the need for RRT. RESULTS: Three prediction models were developed-Model 1 (risk at 4.5 years, n = 1446) with a F1 of 0.82, 0.53, and 0.55 for RRT, stage progression, and reduction in the eGFR, respectively,- Model 2 (time- to-event, n = 2143) with a C-index of 0.89, 0.67, and 0.67 for RRT, stage progression, reduction in the eGFR, respectively, and Model 3 (reduced Model 2) with C-index = 0.68, 0.68 and 0.88, for RRT, stage progression, reduction in the eGFR, respectively. CONCLUSION: The time-to-event model performed well in predicting the three outcomes of CKD progression at five years. This model can be useful for predicting the onset and time of occurrence of the outcomes of interest in the population with established CKD.

Strategies for prevention and treatment of SARS-COV-2 infection in patients with chronic kidney disease: Literature review.

COVID-19 has proven to be particularly aggressive in patients with chronic kidney disease (CKD). The lower immune response rate and the greater susceptibility to progress to severe forms of the disease have contributed to this phenomenon, which has persisted in the post-vaccination era of the pandemic. Paradoxically, CKD has been excluded from most clinical trials of the main therapeutic tools developed against SARS-CoV-2. However, experience in the use of these drugs has been accumulating in different stages of CKD, supporting their use with guarantees of efficacy and safety. The objective of this review is to gather all treatment indications for COVID-19 in the different phases of the disease, tailored to CKD in its various stages, including renal replacement therapy.

Serum Nostrin-A risk factor of death, kidney replacement therapy and acute kidney disease in acute kidney injury.

BACKGROUND: The prediction of Acute Kidney Injury (AKI)-related outcomes remains challenging. Persistent kidney excretory dysfunction for longer than 7 days has been defined as Acute Kidney Disease (AKD). In this study, we prospectively quantified serum Nostrin, an essential regulator of endothelial NO metabolism, in hospitalized patients with AKI. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In-hospital subjects with AKI of various etiology were identified through the in-hospital AKI alert system of the Brandenburg University Hospital. Serum Nostrin, and serum NGAL and KIM-1 were measured within a maximum of 48 hours from the timepoint of initial diagnosis of AKI. The following endpoints were defined: in-hospital death, need of kidney replacement therapy (KRT), recovery of kidney function (ROKF) until discharge. RESULTS: AKI patients had significantly higher serum Nostrin levels compared to Controls. The level of serum Nostrin increased significantly with the severity of AKI. Within the group of AKI patients (n = 150) the in-hospital mortality was 16.7%, KRT was performed in 39.3%, no ROKF occurred in 28%. Patients who required KRT had significantly higher levels of serum Nostrin compared to patients who did not require KRT. Significantly higher levels of serum Nostrin were also detected in AKI patients without ROKF compared to patients with ROKF. In addition, low serum Nostrin levels at the timepoint of AKI diagnosis were predictive of in-hospital survival. For comparison, the serum concentrations of NGAL and KIM-1 were determined in parallel to the Nostrin concentrations and the results confirm the prognostic properties of serum Nostrin in AKI. CONCLUSIONS: The current study suggests serum Nostrin as novel biomarker of AKI-associated mortality, KRT and Acute Kidney Disease.

Risk factors and outcomes in patients who switched from peritoneal dialysis to physician-oriented or patient-oriented kidney replacement therapy.

BACKGROUND: We aimed to compare the cardiovascular events and mortality in patients who underwent either physician-oriented or patient-oriented kidney replacement therapy (KRT) conversion due to discontinuation of peritoneal dialysis (PD). METHODS: Patients with end-stage kidney disease who were receiving PD and required a switch to an alternative KRT were included. They were divided into physician-oriented group or patient-oriented group based on the decision-making process. Logistic regression analysis was used to explore the influencing factors related to KRT conversion in PD patients. The association of physician-oriented or patient-oriented KRT conversion with outcomes after the conversion was assessed by using Cox proportional hazards models. RESULTS: A total of 257 PD patients were included in the study. The median age at catheterization was 35 years. 69.6% of the participants were male. The median duration of PD was 20 months. 162 participants had patient-oriented KRT conversion, while 95 had physician-oriented KRT conversion. Younger patients, those with higher education levels, higher income, and no diabetes were more likely to have patient-oriented KRT conversion. Over a median follow-up of 39 months, 40 patients experienced cardiovascular events and 16 patients died. Physician-oriented KRT conversion increased nearly 3.8-fold and 4.0-fold risk of cardiovascular events and death, respectively. After adjusting for confounders, physician-oriented KRT conversion remained about a 3-fold risk of cardiovascular events. CONCLUSION: Compared to patient-oriented KRT conversion, PD patients who underwent physician-oriented conversion had higher risks of cardiovascular events and all-cause mortality. Factors included age at catheterization, education level, annual household income, and history of diabetes mellitus.

Cardiogenic shock and chronic kidney disease: Dangerous liaisons.

BACKGROUND: Chronic kidney disease (CKD) is one of the leading causes of death worldwide, closely interrelated with cardiovascular diseases, ultimately leading to the failure of both organs - the so-called "cardiorenal syndrome". Despite this burden, data related to cardiogenic shock outcomes in CKD patients are scarce. METHODS: FRENSHOCK (NCT02703038) was a prospective registry involving 772 patients with cardiogenic shock from 49 centres. One-year outcomes (rehospitalization, death, heart transplantation, ventricular assist device) were analysed according to history of CKD at admission and were adjusted on independent predictive factors. RESULTS: CKD was present in 164 of 771 patients (21.3%) with cardiogenic shock; these patients were older (72.7 vs. 63.9years) and had more comorbidities than those without CKD. CKD was associated with a higher rate of all-cause mortality at 1month (36.6% vs. 23.2%; hazard ratio 1.39, 95% confidence interval 1.01-1.9; P=0.04) and 1year (62.8% vs. 40.5%, hazard ratio 1.39, 95% confidence interval 1.09-1.77; P<0.01). Patients with CKD were less likely to be treated with norepinephrine/epinephrine or undergo invasive ventilation or receive mechanical circulatory support, but were more likely to receive renal replacement therapy (RRT). RRT was associated with a higher risk of all-cause death at 1month and 1year regardless of baseline CKD status. CONCLUSIONS: Cardiogenic shock and CKD are frequent "cross-talking" conditions with limited therapeutic options, resulting in higher rates of death at 1month and 1year. RRT is a strong predictor of death, regardless of preexisting CKD. Multidisciplinary teams involving cardiac and kidney physicians are required to provide integrated care for patients with failure of both organs.

Clinical characteristics and prognosis of patients with COVID-19 on mechanical ventilation undergoing continuous renal replacement therapy.

BACKGROUND: The coronavirus disease (COVID-19) pandemic has significantly strained global healthcare, particularly in the management of patients requiring mechanical ventilation (MV) and continuous renal replacement therapy (CRRT). This study investigated the characteristics and prognoses of these patients. METHODS: This multicenter retrospective cohort study gathered data from patients with COVID-19 across 26 medical centers. Logistic analysis was used to identify the factors associated with CRRT implementation. RESULTS: Of the 640 patients with COVID-19 who required MV, 123 (19.2%) underwent CRRT. Compared to the non-CRRT group, the CRRT group was older and exhibited higher sequential organ failure assessment scores. The incidence of hypertension, diabetes, cardiovascular disease, chronic neurological disease, and chronic kidney disease was also higher in the CRRT group. Moreover, the CRRT group had higher intensive care unit (ICU) (75.6% vs. 26.9%, p < 0.001) and in-hospital (79.7% vs. 29.6%, p < 0.001) mortality rates. CRRT implementation was identified as an independent risk factor for both ICU mortality (hazard ratio [HR]:1.833, 95% confidence interval [CI]:1.342-2.505, p < 0.001) and in-hospital mortality (HR: 2.228, 95% CI: 1.648-3.014, p < 0.001). Refractory respiratory failure (n = 99, 19.1%) was the most common cause of death in the non-CRRT death group, and shock with multi-organ failure (n = 50, 40.7%) was the most common cause of death in the CRRT death group. Shock with multi-organ failure and cardiac death were significantly more common in the CRRT death group, compared to non-CRRT death group. CONCLUSION: This study indicates that CRRT is associated with higher ICU and in-hospital mortality rates in patients with COVID-19 who require MV. Notably, the primary cause of death in the CRRT group was shock with multi-organ failure, emphasizing the severe clinical course for these patients, while refractory respiratory failure was most common in non-CRRT patients.

Intraoperative renal replacement therapy during liver transplantation in children: Safety, efficacy and impact on survival.

BACKGROUND: Intraoperative Continuous Renal Replacement Therapy (iCRRT) can prevent life-threatening complications, facilitate fluid management, and maintain metabolic homeostasis during liver transplantation (LT) in adults. There is a paucity of data in pediatric LT. We evaluated the safety, efficacy, and impact on survival of iCRRT in pediatric LT. METHODS: We conducted a retrospective cohort study of all children requiring CRRT pre-OLT at a quaternary children's hospital from 2014 to 2022. Demographic characteristics, intraoperative events, and post-LT outcomes were compared between those who received iCRRT and those who did not. RESULTS: Out of 306 patients who received LT, 30 (10%) were supported with CRRT at least 24 h prior to LT, of which 11 (36%) received iCRRT. The two cohorts were similar in demographics, diagnosis of liver disease, and severity of illness. The iCRRT patients experienced massive blood loss and increased transfusion requirements. There was no difference in intraoperative metabolic balance. One-year post-LT mortality rates were similar. CONCLUSION: ICRRT is safe in critically ill children with pre-LT renal dysfunction. It optimizes fluid and blood product resuscitation while maintaining metabolic homeostasis. Candidates need to be carefully chosen for this highly resource-intensive therapy to benefit this fragile population.

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

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

Renal Replacement Therapy in Cirrhosis: A Contemporary Review.

Acute kidney injury is a common complication of decompensated cirrhosis, frequently requires hospitalization, and carries a high short-term mortality. This population experiences several characteristic types of acute kidney injury: hypovolemic-mediated (prerenal), ischemic/nephrotoxic-mediated (acute-tubular necrosis), and hepatorenal syndrome. Prerenal acute kidney injury is treated with volume resuscitation. Acute-tubular necrosis is treated by optimizing perfusion pressure and discontinuing the offending agent. Hepatorenal syndrome, a unique physiology of decreased effective arterial circulation leading to renal vasoconstriction and ultimately acute kidney injury, is treated with plasma expansion with albumin and splanchnic vasoconstrictors such as terlipressin or norepinephrine. Common acute stressors such as bleeding, infection, and volume depletion often contribute to multifactorial acute kidney injury. Even with optimal medical management, many clinicians are faced with the challenge of initiating renal replacement therapy in these patients. This article reviews the epidemiology, indications, and complex considerations of renal replacement therapy for acute kidney injury in decompensated cirrhosis.

Intraoperative central venous pressure during cardiopulmonary bypass is an alternative indicator for early prediction of acute kidney injury in adult cardiac surgery.

BACKGROUND: The relationship between venous congestion in cardiopulmonary bypass (CPB) and acute kidney injury (AKI) in cardiac surgery has not utterly substantiated. This study aimed at investigate the relationship between CVP in CPB and the occurrence of AKI. METHODS: We retrospectively reviewed 2048 consecutive patients with cardiovascular disease undergoing cardiac procedure with CPB from January 2018 to December 2022. We used the median CVP value obtained during CPB for our analysis and patients were grouped according to this parameter. The primary outcomes were AKI and renal replacement therapy(RRT). Multivariable logistic regression was used to explore the association between CVP and AKI. RESULTS: A total of 2048 patients were enrolled in our study and divided into high CVP group (CVP ≥ 6.5 mmHg) and low CVP group (CVP < 6.5 mmHg) according to the median CVP value. Patients in high CVP group had the high AKI and RRT rate when compared to the low CVPgroup[(367/912,40.24%)vs.(408/1136,35.92%),P = 0.045;(16/912,1.75%vs.9/1136;0.79%), P = 0.049]. Multivariate logistic regression analysis displayed CVP played an indispensable part in development of renal failure in surgical. CONCLUSIONS: Elevated CVP(≥ 6.5mmH2OmmHg) in CPB during cardiac operation is associated with an increased risk of AKI in cardiovascular surgery patients. Clinical attention should be paid to the potential role of CVP in predicting the occurrence of AKI.

Primary and specialist care interaction and referral patterns for individuals with chronic kidney disease: a narrative review.

BACKGROUND: Timely referral of individuals with chronic kidney disease from primary care to secondary care is evidenced to improve patient outcomes, especially for those whose disease progresses to kidney failure requiring kidney replacement therapy. A shortage of specialist nephrology services plus no consistent criteria for referral and reporting leads to referral pattern variability in the management of individuals with chronic kidney disease. OBJECTIVE: The objective of this review was to explore the referral patterns of individuals with chronic kidney disease from primary care to specialist nephrology services. It focused on the primary-specialist care interface, optimal timing of referral to nephrology services, adequacy of preparation for kidney replacement therapy, and the role of clinical criteria vs. risk-based prediction tools in guiding the referral process. METHODS: A narrative review was utilised to summarise the literature, with the intent of providing a broad-based understanding of the referral patterns for patients with chronic kidney disease in order to guide clinical practice decisions. The review identified original English language qualitative, quantitative, or mixed methods publications as well as systematic reviews and meta-analyses available in PubMed and Google Scholar from their inception to 24 March 2023. RESULTS: Thirteen papers met the criteria for detailed review. We grouped the findings into three main themes: (1) Outcomes of the timing of referral to nephrology services, (2) Adequacy of preparation for kidney replacement therapy, and (3) Comparison of clinical criteria vs. risk-based prediction tools. The review demonstrated that regardless of the time frame used to define early vs. late referral in relation to the start of kidney replacement therapy, better outcomes are evidenced in patients referred early. CONCLUSIONS: This review informs the patterns and timing of referral for pre-dialysis specialist care to mitigate adverse outcomes for individuals with chronic kidney disease requiring dialysis. Enhancing current risk prediction equations will enable primary care clinicians to accurately predict the risk of clinically important outcomes and provide much-needed guidance on the timing of referral between primary care and specialist nephrology services.

Arteriovenous Access for Hemodialysis: A Review.

Importance: Hemodialysis requires reliable vascular access to the patient's blood circulation, such as an arteriovenous access in the form of an autogenous arteriovenous fistula or nonautogenous arteriovenous graft. This Review addresses key issues associated with the construction and maintenance of hemodialysis arteriovenous access. Observations: All patients with kidney failure should have an individualized strategy (known as Patient Life-Plan, Access Needs, or PLAN) for kidney replacement therapy and dialysis access, including contingency plans for access failure. Patients should be referred for hemodialysis access when their estimated glomerular filtration rate progressively decreases to 15 to 20 mL/min, or when their peritoneal dialysis, kidney transplant, or current vascular access is failing. Patients with chronic kidney disease should limit or avoid vascular procedures that may complicate future arteriovenous access, such as antecubital venipuncture or peripheral insertion of central catheters. Autogenous arteriovenous fistulas require 3 to 6 months to mature, whereas standard arteriovenous grafts can be used 2 to 4 weeks after being established, and "early-cannulation" grafts can be used within 24 to 72 hours of creation. The prime pathologic lesion of flow-related complications of arteriovenous access is intimal hyperplasia within the arteriovenous access that can lead to stenosis, maturation failure (33%-62% at 6 months), or poor patency (60%-63% at 2 years) and suboptimal dialysis. Nonflow complications such as access-related hand ischemia ("steal syndrome"; 1%-8% of patients) and arteriovenous access infection require timely identification and treatment. An arteriovenous access at high risk of hemorrhaging is a surgical emergency. Conclusions and Relevance: The selection, creation, and maintenance of arteriovenous access for hemodialysis vascular access is critical for patients with kidney failure. Generalist clinicians play an important role in protecting current and future arteriovenous access; identifying arteriovenous access complications such as infection, steal syndrome, and high-output cardiac failure; and making timely referrals to facilitate arteriovenous access creation and treatment of arteriovenous access complications.

People with genetic kidney diseases on kidney replacement therapy have different clinical outcomes compared to people with other kidney diseases.

Despite increasing awareness of genetic kidney disease prevalence, there is limited population-level information about long term outcomes of people with genetic kidney disease receiving kidney replacement therapy. This analysis included people who commenced kidney replacement therapy between 1989 and 2020 as recorded in the Australian and New Zealand Dialysis and Transplant registry. Genetic kidney diseases were subclassified as majority and minority monogenic. Non-genetic kidney diseases were included as the comparator group. Primary outcome measures were 10-year mortality and 10-year graft failure. Cox proportional hazard regression were used to calculate unadjusted and adjusted hazard ratios (AHRs) for primary outcomes. There were 59,231 people in the dialysis subgroup and 21,860 people in the transplant subgroup. People on dialysis with genetic kidney diseases had reduced 10-year mortality risk (majority monogenic AHR: 0.70, 95% CI 0.66-0.76; minority monogenic AHR 0.86, 95% CI 0.80-0.92). This reduced 10-year mortality risk continued after kidney transplantation (majority monogenic AHR: 0.82, 95% CI 0.71-0.93; minority monogenic AHR 0.80, 95% CI 0.68-0.95). Majority monogenic genetic kidney diseases were associated with reduced 10-year graft failure compared to minority monogenic genetic kidney diseases and other kidney diseases (majority monogenic AHR 0.69, 95% CI 0.59-0.79). This binational registry analysis identified that people with genetic kidney disease have different mortality and graft failure risks compared to people with other kidney diseases.

The humoral immune response to the BNT 162B2 vaccine in pediatrics on renal replacement therapy.

INTRODUCTION: Since the start of the COVID-19 pandemic, data published on the immunogenicity of the SARS-CoV-2 BNT 162B2 vaccine in pediatric patients receiving renal replacement therapy are scant. Our primary objective is to study this population's humoral immune response to the COVID-19 vaccine. METHODS: Pediatric kidney transplant recipients (PKTRs) and hemodialysis recipients (HR) at our center who received two doses of the SARS-CoV-2 BNT 162B2 vaccine were included. Transplant and HR who had PCR-positive COVID-19 infections during the study, regardless of their vaccine status, were also included. SARS-CoV-2 anti-spike protein (S1/S2) IgG was measured after the second dose of the vaccine and after any PCR-positive COVID-19 infection as routine clinical practice. Data on demographics, induction, maintenance immunosuppressants, type of transplant, and posttransplant or dialysis duration were included. RESULTS: Of the 61 patients included, 19 were dialysis recipients who received two doses of vaccine without subsequent infection (HV), and 42 were kidney transplant recipients. All dialysis patients and 33 (78.6%) transplant recipients received two doses of the SARS-CoV-2 BNT 162b2 vaccine. A total of 33.3% (11/33) of the transplant recipients who received vaccination developed COVID-19 infection (KTH) at a median time of 13 days after the second dose of vaccine. Nine transplant patients had pure COVID-19 infection without vaccination (KTI). The seroconversion rate in the HV group was 94.7% (18/19) compared to 50% (11/22) in the kidney transplant vaccine recipients who did not develop subsequent COVID-19 infection (KTV) (p < .001). The median S1/S2 IgG titers for the HV group were 400 AU/mL versus 15 AU/mL in the KTV group (p < .0001). There was no significant difference in the duration of the test from the second dose of the vaccine between HV and KTV (55 vs. 33.5 days, p = .095). The KTH had higher titers than KTV group (370 vs. 15 p < .0001). The median duration of the test after vaccination in the vaccine group and those with hybrid immunity was similar (35 vs. 33.5 days, p = .2).There were no clear predictors for seroconversion in the PKTRs. Natural infection alone was as good as the vaccine in eliciting humoral immune response. CONCLUSION: The humoral immune response to two doses of the SARS-CoV-2 BNT 162B2 vaccine in PKTRs without subsequent COVID-19 infection is suboptimal compared to that in hemodialysis recipients and in PKTRs with hybrid immunity from both infection and vaccination.

Personalizing renal replacement therapy initiation in the intensive care unit: a reinforcement learning-based strategy with external validation on the AKIKI randomized controlled trials.

OBJECTIVE: The timely initiation of renal replacement therapy (RRT) for acute kidney injury (AKI) requires sequential decision-making tailored to individuals' evolving characteristics. To learn and validate optimal strategies for RRT initiation, we used reinforcement learning on clinical data from routine care and randomized controlled trials. MATERIALS AND METHODS: We used the MIMIC-III database for development and AKIKI trials for validation. Participants were adult ICU patients with severe AKI receiving mechanical ventilation or catecholamine infusion. We used a doubly robust estimator to learn when to start RRT after the occurrence of severe AKI for three days in a row. We developed a "crude strategy" maximizing the population-level hospital-free days at day 60 (HFD60) and a "stringent strategy" recommending RRT when there is significant evidence of benefit for an individual. For validation, we evaluated the causal effects of implementing our learned strategies versus following current best practices on HFD60. RESULTS: We included 3748 patients in the development set and 1068 in the validation set. Through external validation, the crude and stringent strategies yielded an average difference of 13.7 [95% CI -5.3 to 35.7] and 14.9 [95% CI -3.2 to 39.2] HFD60, respectively, compared to current best practices. The stringent strategy led to initiating RRT within 3 days in 14% of patients versus 38% under best practices. DISCUSSION: Implementing our strategies could improve the average number of days that ICU patients spend alive and outside the hospital while sparing RRT for many. CONCLUSION: We developed and validated a practical and interpretable dynamic decision support system for RRT initiation in the ICU.

Venous congestion in septic shock quantified with point-of-care ultrasound: a pilot prospective multicentre cohort study.

PURPOSE: Venous congestion is a pathophysiologic state that can result in organ dysfunction, particularly acute kidney injury (AKI). We sought to evaluate the feasibility of performing a definitive observational study to determine the impact of venous congestion quantified using point-of-care ultrasound (POCUS) in patients with septic shock. METHODS: We conducted a prospective observational feasibility study at two intensive care units (ICUs). We recruited adult patients with septic shock within 12 hr of ICU admission. Using the validated Venous Excess Ultrasound Score (VEXUS), we quantified venous congestion on day 1 and day 3 of ICU admission. The primary feasibility outcome was successful completion rate of the two VEXUS scores. We performed a survival analysis to quantify the hazard of renal replacement therapy (RRT). RESULTS: We enrolled 75 patients from January 2022 to January 2023. The success rate of completion for VEXUS scans was 94.5% (95% confidence interval [CI], 89.5 to 97.6). Severe venous congestion was present in 19% (14/75) of patients on ICU admission day 1 and in 16% (10/61) of patients on day 3. Venous congestion on ICU admission may be associated with a higher risk of requiring RRT (unadjusted hazard ratio, 3.35; 95% CI, 0.94 to 11.88; P = 0.06). CONCLUSIONS: It is feasible to conduct a definitive observational study exploring the association between venous congestion quantified with POCUS and clinical outcomes in patients with septic shock. We hypothesize that venous congestion may be associated with an increased hazard of receiving RRT.

RéSUMé: OBJECTIF: La congestion veineuse est un état physiopathologique qui peut entraîner un dysfonctionnement des organes, en particulier une insuffisance rénale aiguë (IRA). Nous avons cherché à évaluer la faisabilité de la réalisation d'une étude observationnelle définitive pour déterminer l'impact de la congestion veineuse quantifiée à l'aide de l'échographie ciblée (POCUS) chez des patient·es en choc septique. MéTHODE: Nous avons réalisé une étude de faisabilité observationnelle prospective dans deux unités de soins intensifs (USI). Nous avons recruté des patient·es adultes souffrant d'un choc septique dans les 12 heures suivant leur admission aux soins intensifs. À l'aide du score VEXUS (score d'échographie de l'excès veineux) validé, nous avons quantifié la congestion veineuse au jour 1 et au jour 3 de leur admission aux soins intensifs. Le principal critère de faisabilité était le taux de réussite des deux scores VEXUS. Nous avons réalisé une analyse de survie pour quantifier le risque de thérapie de substitution rénale (TSR). RéSULTATS: Nous avons recruté 75 patient·es de janvier 2022 à janvier 2023. Le taux de réussite des scores VEXUS était de 94,5 % (intervalle de confiance [IC] à 95 %, 89,5 à 97,6). Une congestion veineuse sévère était présente chez 19 % (14/75) des patient·es au jour 1 d'admission aux soins intensifs et chez 16 % (10/61) des patient·es au jour 3. La congestion veineuse lors de l'admission aux soins intensifs peut être associée à un risque plus élevé de nécessiter une TSR (rapport de risque non ajusté, 3,35; IC 95 %, 0,94 à 11,88; P = 0,06). CONCLUSION: Il est possible de mener une étude observationnelle définitive explorant l'association entre la congestion veineuse quantifiée par POCUS et les devenirs cliniques chez les patient·es en choc septique. Nous émettons l'hypothèse que la congestion veineuse peut être associée à un risque accru de recevoir une thérapie de substitution rénale.