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Critically ill patients frequently require analgesic and sedative medications to manage pain, agitation, and the stress associated with their condition. The onset of Acute Kidney Injury (AKI) can complicate the pharmacokinetics of these drugs, requiring careful dose adjustments to prevent adverse effects. Additionally, Kidney Replacement Therapy (KRT) may further influence drug metabolism and clearance. As renal dysfunction may alter the elimination of these medications, a comprehensive understanding of their pharmacologic profiles and the impact of KRT is essential for optimizing pain and sedation management in critically ill patients. In particular, this review explores the challenges and strategies involved in dosing analgesic and sedative drugs in critically ill patients with AKI undergoing various KRT modalities, including intermittent hemodialysis (IHD), continuous kidney replacement therapy (CKRT), and prolonged intermittent kidney replacement therapy (PIKRT). Moreover, this narrative review is aimed at summarizing existing evidence on pharmacokinetic alterations, clearance rates and eventual dose adjustments in critically ill patients with AKI undergoing various KRT modalities. Special emphasis is placed on the effects of different KRT modalities on drug elimination and associated therapeutic implications, seeking to provide healthcare professionals with evidence-based guidelines for the safe and effective administration of analgesics and sedatives in this complex, high-risk patient population.

ABSTRACT Background Critically ill patients with severe acute kidney injury (AKI) requiring kidney replacement therapy (KRT) have a grim prognosis. Recently, multiple studies focused on the impact of KRT initiation time [i.e., accelerated versus watchful waiting KRT initiation (WWS-KRT)] on patient outcomes. We aim to review the results of all related clinical trials. Methods In this systematic review, we searched all relevant randomized clinical trials from January 2000 to April 2021. We assessed the impacts of accelerated versus WWS-KRT on KRT dependence, KRT-free days, mortality and adverse events, including hypotension, infection, arrhythmia and bleeding. We rated the certainty of evidence according to Cochrane methods and the GRADE approach. Results A total of 4932 critically ill patients with AKI from 10 randomized clinical trials were included in this analysis. The overall 28-day mortality rate was 38.5%. The 28-day KRT-dependence rate was 13.0%. The overall incident of KRT in the accelerated group was 97.4% and 62.8% in the WWS-KRT group. KRT in the accelerated group started 36.7 h earlier than the WWS-KRT group. The two groups had similar risks of 28-day [pooled log odds ratio (OR) 1.001, P = 0.982] and 90-day (OR 0.999, P = 0.991) mortality rates. The accelerated group had a significantly higher risk of 90-day KRT dependence (OR 1.589, P = 0.007), hypotension (OR 1.687, P < 0.001) and infection (OR 1.38, P = 0.04) compared with the WWS-KRT group. Conclusions This meta-analysis revealed that accelerated KRT leads to a higher probability of 90-day KRT dependence and dialysis-related complications without any impact on mortality rate when compared with WWS-KRT. Therefore, we suggest the WWS-KRT strategy for critically ill patients. Graphical Abstract Graphical Abstract

BackgroundKidney replacement therapy (KRT) is frequently used in critically ill children. The objective of this study is to investigate if the requirement for hemodialysis (HD) is an independent risk factor for mortality in mechanically ventilated childrenMethodsIn this retrospective cohort study, we analyzed the 2012 and 2016 Kids Inpatient Database and used a weighted sample to obtain a national outcome estimate. For our analysis, we included children aged one month to 17 years who were mechanically ventilated; we then compared the demographics, comorbidities, and mortality rates of those patients who had undergone HD with those who did not. Statistical analysis was performed using the chi-squared test and regression models. The patients were matched 1:2 with a correlative propensity score using age, weekend admission, elective admission, gender, hospital region, income quartiles, race, presence of kidney failure, bone marrow transplantation (BMT), cardiac surgery, trauma, and All Patients Refined Diagnosis Related Groups (APR-DRG) severity score. The mortality rate was compared between the matched groups.ResultsOut of 100,289 mechanically ventilated children, 1393 (1.4%) underwent HD. The mortality rate was 32.5% in the HD group, compared with 8.8% in the control group (p < 0.05). Factors that were associated with higher mortality in HD patients included severe sepsis, BMT, cardiopulmonary resuscitation (CPR), and extracorporeal membrane oxygenation therapy (ECMO). After propensity score–matched analysis, HD was still significantly associated with a higher risk of mortality (31.9% vs. 22.0%, p < 0.05)ConclusionsThe requirement for HD in mechanically ventilated children is associated with higher mortality.

Several studies have suggested that patients with kidney failure may benefit from high-dose hemodiafiltration as compared with standard hemodialysis. However, given the limitations of the various published studies, additional data are needed. We conducted a pragmatic, multinational, randomized, controlled trial involving patients with kidney failure who had received high-flux hemodialysis for at least 3 months. All the patients were deemed to be candidates for a convection volume of at least 23 liters per session (as required for high-dose hemodiafiltration) and were able to complete patient-reported outcome assessments. The patients were assigned to receive high-dose hemodiafiltration or continuation of conventional high-flux hemodialysis. The primary outcome was death from any cause. Key secondary outcomes were cause-specific death, a composite of fatal or nonfatal cardiovascular events, kidney transplantation, and recurrent all-cause or infection-related hospitalizations. A total of 1360 patients underwent randomization: 683 to receive high-dose hemodiafiltration and 677 to receive high-flux hemodialysis. The median follow-up was 30 months (interquartile range, 27 to 38). The mean convection volume during the trial in the hemodiafiltration group was 25.3 liters per session. Death from any cause occurred in 118 patients (17.3%) in the hemodiafiltration group and in 148 patients (21.9%) in the hemodialysis group (hazard ratio, 0.77; 95% confidence interval, 0.65 to 0.93). In patients with kidney failure resulting in kidney-replacement therapy, the use of high-dose hemodiafiltration resulted in a lower risk of death from any cause than conventional high-flux hemodialysis. (Funded by the European Commission Research and Innovation; CONVINCE Dutch Trial Register number, NTR7138.).

Background Limited quantitative data suggests that patients who have chronic kidney disease without kidney replacement therapy (CKD without KRT) may present with psychosocial needs just as patients who have acute kidney injury and are treated by dialysis (AKI stage 3D) do. This systematic review aims to synthesise qualitative research on patients’ experiences of CKD without KRT to provide further insight into patients’ experience of the healthcare they receive and simultaneously, their psychosocial needs, to inform the development of appropriate psychological interventions. Methods The review followed ENTREQ guidelines. PubMed/MEDLINE, PsycINFO, EMBASE and CINAHL were searched in July and August 2021. Qualitative studies in English on the experiences of CKD without KRT care were included in the review. Thematic synthesis was conducted on the findings of the included studies. Results The search identified 231 articles for screening. Eight studies met the inclusion criteria, and one was excluded at the quality assessment stage. The final seven articles [ n  = 130 patients] were analysed. Five themes on psychosocial needs were developed: addressing patients’ CKD-related educational needs, supporting the patient’s relationships, honouring the patient’s need for control, adjusting to change, and recognising fear of disease and treatment. Discussion This review highlights the range of psychosocial needs of patients who have CKD without KRT. There are numerous intervention options that clinicians may develop that could benefit patients and address multiple needs, such as group educational programmes. Graphical abstract

Xenotransplantation offers a potential solution to the organ shortage crisis. A 62-year-old hemodialysis-dependent man with long-standing diabetes, advanced vasculopathy, and marked dialysis-access challenges received a gene-edited porcine kidney with 69 genomic edits, including deletion of three glycan antigens, inactivation of porcine endogenous retroviruses, and insertion of seven human transgenes. The xenograft functioned immediately. The patient’s creatinine levels decreased promptly and progressively, and dialysis was no longer needed. After a T-cell–mediated rejection episode on day 8, intensified immunosuppression reversed rejection. Despite sustained kidney function, the patient died from unexpected, sudden cardiac causes on day 52; autopsy revealed severe coronary artery disease and ventricular scarring without evident xenograft rejection. (Funded by Massachusetts General Hospital and eGenesis.) This report describes the transplantation of a gene-edited porcine kidney in a hemodialysis-dependent man with long-standing diabetes, advanced vasculopathy, and marked dialysis-access challenges.

Critical clinical forms of COVID-19 infection often include Acute Kidney Injury (AKI), requiring kidney replacement therapy (KRT) in up to 20% of patients, further worsening the outcome of the disease. No specific medical therapies are available for the treatment of COVID-19, while supportive care remains the standard treatment with the control of systemic inflammation playing a pivotal role, avoiding the disease progression and improving organ function. Extracorporeal blood purification (EBP) has been proposed for cytokines removal in sepsis and could be beneficial in COVID-19, preventing the cytokines release syndrome (CRS) and providing Extra-corporeal organ support (ECOS) in critical patients. Different EBP procedures for COVID-19 patients have been proposed including hemoperfusion (HP) on sorbent, continuous kidney replacement therapy (CRRT) with adsorbing capacity, or the use of high cut-off (HCO) membranes. Depending on the local experience, the multidisciplinary capabilities, the hardware, and the available devices, EBP can be combined sequentially or in parallel. The purpose of this paper is to illustrate how to perform EBPs, providing practical support to extracorporeal therapies in COVID-19 patients with AKI.

Background The occurrence of Kidney Failure with Replacement Therapy (KFRT) amongst Irish Travellers has not been well described. This study aims to determine the burden of KFRT amongst the Irish Traveller population and identify determinants of health amongst this cohort which may differ from the general population in Ireland. Methods This retrospective cohort study included self-identifying Irish Travellers with KFRT registered in the National Kidney Disease Clinical Patient Management System between 1995 and 2022. KFRT was defined as Chronic Kidney Disease stage 5 (CKD G5) treated by dialysis or CKD G1–G5 after transplantation. The primary outcome measure was the prevalence of KFRT in Irish Travellers. Secondary exploratory outcomes included age at diagnosis, family history, biopsy diagnosis, kidney replacement therapy (KRT) modality, time to initiation of KRT, primary vascular access used, and time to receive a kidney transplant. Results Four of six Irish hospital groups participated in the study. A total of 38 patients were identified as Irish Travellers with KFRT, with a crude prevalence rate of KFRT of 0.12% (CI 0.084–0.161, 95%) or 11.9 per 10,000 Irish Travellers. The mean age for diagnosis of kidney disease was 43 (SD, 20.8) and at commencement of KRT was 45 (SD, 20.9) years. A biopsy-proven diagnosis was provided in 24%. Twenty-two per cent was diagnosed with polycystic kidney disease or congenital anomalies of the kidney and urinary tract. The predominant modality for KRT was haemodialysis (89%), with central venous catheters being the most common initial vascular access (79%). Kidney transplants occurred in 45% of those studied, with a mean waiting time of 1.96 (SD, 1.6) years. Conclusions The Irish Traveller community have similar prevalence of KFRT when compared to the national prevalence, with a short time interval from diagnosis to commencement of KRT. They are less likely to avail of home therapies but have comparable wait times to the national waiting time to receive a kidney transplant.

Estimating equations for the glomerular filtration rate — EKFC eGFRcr (creatinine) and EKFC eGFRcys (cystatin C) — were tested. EKFC eGFRcys was unbiased and accurate, irrespective of the inclusion of race or sex.

Background Continuous kidney replacement therapy (CKRT) is often used for acute kidney injury (AKI) or fluid overload (FO) in children ≤ 10 kg. Intensive care unit (ICU) mortality in children ≤ 10 kg reported by the prospective pediatric CRRT (ppCRRT, 2001–2003) registry was 57%. We aimed to evaluate characteristics associated with ICU mortality using a contemporary registry. Methods The Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK) registry is a retrospective, multinational, observational study of children and young adults aged 0–25 years receiving CKRT (2015–2021) for AKI or FO. This analysis included patients ≤ 10 kg at hospital admission. Primary and secondary outcomes: ICU mortality and major adverse kidney events at 90 days (MAKE-90) defined as death, persistent kidney dysfunction, or dialysis within 90 days, respectively. Results A total of 210 patients were included (median age 0.53 years (IQR, 0.1, 0.9)). ICU mortality was 46.5%. MAKE-90 occurred in 150/207 (72%). CKRT was initiated at a median 3 days (IQR 1, 9) after ICU admission and lasted a median 6 days (IQR 3, 16). On multivariable analysis, pediatric logistic organ dysfunction score (PELOD-2) at CKRT initiation was associated with increased odds of ICU mortality (aOR 2.64, 95% CI 1.68–4.16), and increased odds of MAKE-90 (aOR 2.2, 95% CI 1.31–3.69). Absence of comorbidity was associated with lower MAKE-90 (aOR 0.29, 95%CI 0.13–0.65). Conclusions We report on a contemporary cohort of children ≤ 10 kg treated with CKRT for acute kidney injury and/or fluid overload. ICU mortality is decreased compared to ppCRRT. The extended risk of death and morbidity at 90 days highlights the importance of close follow-up. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information