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SEE PDF] Timing of initiation Early CRRT initiation may not improve outcomes, and the definition of “early” varies between studies [3,4,5]. [...]clinical judgement guides CRRT initiation. [...]we prescribe regional citrate anticoagulation. [...]modality selection is based on local expertise. A high NUF rate in CRRT may be harmful [12], although optimal values are not yet established. Because fluid overload is common and undesirable, we regularly reassess fluid status and adjust NUF rate accordingly.

In patients receiving continuous renal replacement therapy (CRRT) for acute kidney injury (AKI), excessive net ultrafiltration (NUF) rates >1.75 mL/kg/h have been associated with increased mortality, delayed AKI recovery and complications of hemodynamic instability. There is limited information on fluid removal practices and NUF rates in AKI patients treated with intermittent hemodialysis (IHD). We conducted a retrospective study of AKI patients who underwent IHD at our center between 2020 and 2023. The primary outcome was NUF rate, assessed as body weight-scaled, body surfaces area-scaled and unadjusted values. Secondary outcomes included mortality and measures of renal recovery at 90 days (estimated glomerular filtration rate [eGFR], major adverse kidney events [MAKE], IHD dependence and days to liberation from IHD). We studied 74 patients (median age 62 years [IQR 46-71], median baseline eGFR 81 mL/min/1.73 m [IQR 71-96]). The median NUF rate was 5.61 mL/kg/h (weight scaled), 228 mL/h/m (BSA-scaled), and 462 mL/h (unadjusted). Higher fluid removal rates were observed in patients with better baseline kidney function, while older age, diabetes and hypertension were associated with lower rates. No significant differences in AKI recovery, dialysis dependence, or change in renal function at 90 days were observed between high and low NUF groups. By 90 days, 45 patients (60.8%) had developed a MAKE. Among AKI patients, median NUF rates during IHD was higher than reported for CRRT and influenced by comorbidity and pre-morbid eGFR. At 90 days, MAKE was common, two thirds of patients had  > 25% eGFR reduction, and one in 12 had died.

To determine the diagnostic yield and clinical impact of exome sequencing (ES) in patients with suspected monogenic kidney disease. We performed clinically accredited singleton ES in a prospectively ascertained cohort of 204 patients assessed in multidisciplinary renal genetics clinics at four tertiary hospitals in Melbourne, Australia. ES identified a molecular diagnosis in 80 (39%) patients, encompassing 35 distinct genetic disorders. Younger age at presentation was independently associated with an ES diagnosis (p < 0.001). Of those diagnosed, 31/80 (39%) had a change in their clinical diagnosis. ES diagnosis was considered to have contributed to management in 47/80 (59%), including negating the need for diagnostic renal biopsy in 10/80 (13%), changing surveillance in 35/80 (44%), and changing the treatment plan in 16/80 (20%). In cases with no change to management in the proband, the ES result had implications for the management of family members in 26/33 (79%). Cascade testing was subsequently offered to 40/80 families (50%). In this pragmatic pediatric and adult cohort with suspected monogenic kidney disease, ES had high diagnostic and clinical utility. Our findings, including predictors of positive diagnosis, can be used to guide clinical practice and health service design.

Background How sex and gender are considered in randomized controlled trials (RCTs) in critical care nephrology is unclear. We aimed to perform a meta-epidemiologic study to describe the representation, sex and gender reporting, and sex- and gender-based analyses (SGBA) in high-impact RCTs in critical care nephrology. Methods We searched the Web of Science Core Collection for critical care nephrology papers from 2000 to 2024. We included trials published in high-impact journals in general medicine, pediatrics, critical care, and nephrology. The main outcome was the proportion of female/woman participants enrolled and the association with trial characteristics, findings, and women authorship. We estimated the participation-to-prevalence ratio (PPR) to evaluate the representativeness of females within identified RCTs and selected case-mix and disease populations. Sex and gender reporting and SGBA were investigated. Results A total of 117 RCTs, including 106,057 participants, were included. Sex (54.7%), gender (26.5%), both (2.6%), or none (16.2%) terminology were used for reporting. Male/female (82.1%), men/women (11.1%), both (4.3%), boys/girls (0.9%) and none (1.7%) were used as descriptors. Of the 115 RCTs with available sex/gender data, the median proportion of female/women participants was 35.4% (interquartile range (IQR) 31.2%–40.8%). Pediatric age group and process of care as an intervention were independently associated with the proportion of female/women participants. The median PPR was 0.89 (IQR 0.8–1.06), except in major surgery, for which PPR was 0.67 (IQR 0.29–0.73). Twelve (10.9%) and 49 (41.9%) studies used sex and/or gender as inclusion and exclusion criteria, respectively; 5 (4.3%) studies used sex/gender-stratified randomization; and 35 (29.9%) studies performed SGBA. RCTs with pregnancy, lactation, or women of childbearing age as exclusion criteria had a lower enrollment of female/women participants than RCTs that did not (33.6% vs. 36.8%, P  = 0.04). Exclusion criteria of pregnancy, lactation, or childbearing age were considered strongly justified, potentially justified, and poorly justified in 36.1%, 14.9%, and 48.9%, respectively. There were no changes in the representation of females/women and SGBA across identified RCTs over the search range. Conclusions Females/women are less frequently represented in critical care nephrology RCTs. Significant gaps exist in sex- and gender-specific eligibility criteria, reporting, and analysis.

Prophylactic laxative bowel regimens may prevent constipation in enterally-fed critically ill patients. However, their use may also increase diarrhea. We performed a systematic review to: 1. Explore the epidemiology of constipation and/or diarrhea in critically ill patients; and 2. Appraise trials evaluating prophylactic laxative bowel regimens. We searched MEDLINE, Embase, and CINAHL for publications that reported constipation or diarrhea in critically ill adult patients and/or prophylactic laxative bowel regimens. The proportion of critically ill patients experiencing constipation was reported between 20% and 83% and the proportion experiencing diarrhea was reported between 3.3% and 78%. Six studies of prophylactic laxative bowel regimens were identified but only 3 randomised controlled trials were identified, and these were subjected to meta-analysis. Compared with placebo, a prophylactic laxative bowel regimen increased the risk of diarrhea (RR 1.58, 95% CI 1.22 to 2.04) but did not reduce the risk of constipation (RR 0.39, 95% CI 0.14 to 1.05), and did not affect the duration of mechanical ventilation, duration of ICU admission, or mortality. Constipation and diarrhea occur frequently in the critically ill but data evaluating prophylactic laxative bowel regimens in such patients are sparse and do not support their use. •There is wide variation in the taxonomy used to define constipation and diarrhea.•Constipation and diarrhea appear to occur frequently in the critically ill and may be associated with unfavourable outcomes.•There are limited data evaluating prophylactic laxative bowel regimens.•Current evidence does not support the use of prophylactic laxative bowel regimens.

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

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

Human natural killer (NK) cells are key functional players in kidney transplant rejection. However, the respective contributions of the two functionally distinct human NK cell subsets (CD56 cytokine-producing vs. CD56 cytotoxic effector) in episodes of allograft rejection remain uncertain, with current immunohistochemical methods unable to differentiate these discrete populations. We report the outcomes of an innovative multi-color flow cytometric-based approach to unequivocally define and evaluate NK cell subsets in human kidney allograft rejection. We extracted renal lymphocytes from human kidney transplant biopsies. NK cell subsets were identified, enumerated, and phenotyped by multi-color flow cytometry. Dissociation supernatants were harvested and levels of soluble proteins were determined using a multiplex bead-based assay. Results were correlated with the histopathological patterns in biopsies-no rejection, borderline cellular rejection, T cell-mediated rejection (TCMR), and antibody-mediated rejection (AMR). Absolute numbers of only CD56 NK cells were significantly elevated in TCMR biopsies. In contrast, both CD56 and CD56 NK cell numbers were significantly increased in biopsies with histopathological evidence of AMR. Notably, expression of the activation marker CD69 was only significantly elevated on CD56 NK cells in AMR biopsies compared with no rejection biopsies, indicative of a pathogenic phenotype for this cytotoxic NK cell subset. In line with this, we detected significantly elevated levels of cytotoxic effector molecules (perforin, granzyme A, and granulysin) in the dissociation supernatants of biopsies with a histopathological pattern of AMR. Our results indicate that human NK cell subsets are differentially recruited and activated during distinct types of rejection, suggestive of specialized functional roles.

Acute kidney injury (AKI) survivors are at increased risk of major adverse kidney events (MAKEs), including chronic kidney disease (CKD), end-stage kidney disease (ESKD) and death. High-risk AKI patients may benefit from specialist follow-up, but factors associated with increased risk have not been reported. We conducted a retrospective study of AKI patients admitted to a single centre between 2012 and 2016 who had a baseline estimated glomerular filtration rate (eGFR) >30 mL/min/1.73 m and were alive and independent of renal replacement therapy (RRT) at 30 days following discharge. AKI was identified using International Classification of Diseases, Tenth Revision codes and staged according to the Kidney Disease: Improving Global Outcomes criteria. Patients were excluded if they were kidney transplant recipients or if AKI was attributed to intrinsic kidney disease. We performed Cox regression models to examine MAKEs in the first year, defined as the composite of CKD (sustained 25% drop in eGFR), ESKD (requirement for chronic RRT or sustained eGFR <15 mL/min/1.73 m ) or death. We examined secondary outcomes (CKD, ESKD and death) using Cox and competing risk regression analyses. We studied 2101 patients (mean ± SD age 69 ± 15 years, baseline eGFR 72 ± 23 mL/min/1.73 m ). Of these, 767 patients (37%) developed at least one MAKE (429 patients developed CKD, 21 patients developed ESKD, 375 patients died). MAKEs occurred more frequently with older age [hazard ratio (HR) 1.16 per decade, 95% confidence interval (CI) 1.10-1.24], greater severity of AKI (Stage 2 HR 1.38, 95% CI 1.16-1.64; Stage 3 HR 1.62, 95% CI 1.31-2.01), higher serum creatinine at discharge (HR 1.04 per 10 µmol/L, 95% CI 1.03-1.06), chronic heart failure (HR 1.41, 95% CI 1.19-1.67), liver disease (HR 1.68, 95% CI 1.39-2.03) and malignancy (non-metastatic HR 1.44, 95% CI 1.14-1.82; metastatic HR 2.26, 95% CI 1.80-2.83). Traditional risk factors (e.g. diabetes and cardiovascular disease) had limited predictive value. More than a third of AKI patients develop MAKEs within the first year. Clinical variables available at the time of discharge can help identify patients at increased risk of such events.

Even if such data had been available, our small sample size would have limited the statistical power to detect meaningful associations. [...]although a subgroup analysis would have been valuable, our sample size of 10 patients precluded any meaningful stratification. In future research, if subgroup analyses demonstrate that patients with impaired cardiac reserve or other comorbidities are more prone to significant and clinically relevant CI declines, these populations could be considered a target for prospective studies evaluating strategies to mitigate CI reductions during IHD.