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Online hemodiafiltration (HDF) has been increasingly used for improved clearance of middle molecular weight toxins. The impact of this mode of clearance is unknown in critically ill patients. We aimed to determine whether the use of HDF in acute kidney injury (AKI) is associated with lower mortality and improved kidney recovery up to 90 days after initiation of therapy.Single-center retrospective cohort study using data from 2017 to 2020 of adults with AKI who initiated intermittent renal replacement therapy (IRRT) in the intensive care unit (ICU), using either hemodialysis (HD) or HDF depending on the maintenance status of the water system without regards for patient characteristics. We assessed association with patient-events and session-events using time-dependent Cox models and general estimating equations models, respectively.We included 182 adults with AKI for whom 848 IRRT sessions were performed in the ICU. The 90-day mortality rate was 43 of 182 (24.6%). There was no significant association with the use of HDF and mortality (adjusted hazard ratio [aHR]: 0.85 (0.43; 1.67)The use of HDF in the setting of AKI was not associated with a differential risk of mortality or kidney recovery.

In patients with respiratory failure, loop diuretics remain the cornerstone of the treatment to maintain fluid balance, but resistance is common.To determine the efficacy and safety of common diuretic combinations in critically ill patients with respiratory failure.We searched MEDLINE, Embase, Cochrane Library and PROSPERO for studies reporting the effects of a combination of a loop diuretic with another class of diuretic. A meta-analysis using mean differences (MD) with 95% confidence interval (CI) was performed for the 24-h fluid balance (primary outcome) and the 24-h urine output, while descriptive statistics were used for safety events.Nine studies totalling 440 patients from a total of 6510 citations were included. When compared to loop diuretics alone, the addition of a second diuretic is associated with an improved negative fluid balance at 24 h [MD: -1.06 L (95%CI: -1.46; -0.65)], driven by the combination of a thiazide plus furosemide [MD: -1.25 L (95%CI: -1.68; -0.82)], while no difference was observed with the combination of a loop-diuretic plus acetazolamide [MD: -0.40 L (95%CI: -0.96; 0.16)] or spironolactone [MD: -0.65 L (95%CI: -1.66; 0.36)]. Heterogeneity was high and the report of clinical and safety endpoints varied across studies.Based on limited evidence, the addition of a second diuretic to a loop diuretic may promote diuresis and negative fluid balance in patients with respiratory failure, but only when using a thiazide. Further larger trials to evaluate the safety and efficacy of such interventions in patients with respiratory failure are required.

BACKGROUND: Mortality of patients who are critically ill with AKI initiated on RRT is very high. Identifying modifiable and unmodifiable clinical variables at dialysis start that are associated with hospital survival can help, not only in prognostication, but also in clinical triaging. METHODS: A retrospective observational study was conducted on patients with AKI-D who were initiated on RRT in the medical and surgical intensive care units (ICUs) of a high-acuity academic medical center from January 2010 through December 2015. We excluded patients with suspected poisoning, ESKD, stage 5 CKD not on dialysis, or patients with AKI-D initiated on RRT outside of the ICU setting. The primary outcome was in-hospital mortality. RESULTS: Of the 416 patients who were critically ill with AKI-D admitted to the medical (38%), surgical (41%), and cardiac (21%) ICUs, with nearly 75% on artificial organ support, the mean age 62.1±14.8 years, mean SOFA score was 11.8±4.3, dialysis was initiated using continuous RRT in 261 (63%) and intermittent hemodialysis in 155 (37%) patients. Incidence of survival to hospital discharge was 48%. Using multivariable logistic regression with stepwise backward elimination, a prognostic model was created that included the variables age, CKD, COPD, admission, and within 24 hours of the start SOFA score, refractory hyperkalemia and uremic encephalopathy as dialysis indications, BUN >100 mg/dl, serum creatinine, serum lactate, serum albumin, CRRT as initial modality, severe volume overload, and abdominal surgery. The model exhibited good calibration (goodness of fit test, P=0.83) and excellent discrimination (optimism-corrected C statistic 0.93). CONCLUSIONS: In this single-center, diverse, critically ill AKI-D population, a novel prognostic model that combined widely used ICU scores, clinical and biochemical data at dialysis start, and dialysis indication and modality, robustly predicted short-term survival. External validation is needed to prove the generalizability of the study findings.

Background In critically ill patients receiving kidney replacement therapy (KRT), high ultrafiltration rates and persistent fluid accumulation are associated with adverse outcomes. The purpose of this international survey was to evaluate current practices and evidence gaps related to fluid removal with KRT in critically ill patients. Methods This was a multinational, web-based survey distributed by 7 networks comprising nephrologists and intensivists. Physicians involved in the care of critically ill patients were invited to complete a 39 question survey about fluid-management practices on KRT. The survey was distributed from September 2021 to December 2021. Results There were 757 respondents from 96 countries (response rate of 65%). Most respondents practiced adult medicine (89%) and worked in an academic center (69%). The majority (91%) reported aiming for a 0.5 to 2 L negative fluid balance per day when fluid removal is indicated, although there was important variability in what respondents considered a safe maximal target. Intensivists were more likely than nephrologists to use adjunct volume status assessment methods (i.e. ultrasound, hemodynamic markers, intra-abdominal pressure) while nephrologists were more likely to deploy co-interventions aimed at improving tolerance to fluid removal (i.e. osmotic agents, low-temperature dialysate). There was a broad consensus that rapid decongestion should be prioritized when fluid accumulation is present, but the prevention of hypotension was also reported as a competing priority. A majority (77%) agreed that performing trials that compare fluid management strategies would be ethical and clinically relevant. Conclusions We have identified multiple areas of variability in current practice of fluid management for patients receiving KRT. The majority of nephrologists and intensivists agreed that several knowledge gaps related to fluid removal strategies should be investigated in future randomized controlled trials.

Introduction: In critically ill patients requiring intermittent renal replacement therapy (RRT), the benefits of convective versus diffusive clearance remain uncertain. We conducted a systematic review and meta-analysis to determine the safety, clinical efficacy, and clearance efficiency of hemofiltration (HF) and hemodiafiltration (HDF) compared to hemodialysis (HD) in patients with acute kidney injury (AKI) receiving intermittent RRT. Method: We searched Medline, Embase, Cochrane Library, and PROSPERO. We included clinical trials and observational studies that reported the use of intermittent HF or HDF in adult patients with AKI. The following outcomes were included: mortality, renal recovery, clearance efficacy, intradialytic hemodynamic stability, circuit loss, and inflammation modulation. Results: A total of 3,169 studies were retrieved and screened. Four randomized controlled trials and 4 observational studies were included (n: 615 patients). Compared with conventional HD, intermittent convective therapies had no effect on in-hospital mortality (relative risk, 1.23; 95% confidence interval (CI), 0.76–1.99), renal recovery at 30 days (RR, 0.98; 95% CI, 0.82–1.16), time-to-renal recovery (mean difference [MD], 0.77; 95% CI, −6.56 to 8.10), and number of dialysis sessions until renal recovery (MD, −1.34; 95% CI, −3.39 to 0.72). The overall quality of included studies was low, and dialysis parameters were suboptimal for all included studies. Conclusion: This meta-analysis suggests that there is no significant difference in short-term mortality and renal recovery in patients with severe AKI when treated with intermittent HF or HDF compared to conventional HD. This systematic review emphasizes the need for further trials evaluating optimal convective parameters in AKI patients treated with intermittent dialysis.

Renal replacement therapies (RRT) are commonly used in critically ill patients to achieve solute clearance, maintain acid-base status, and remove fluid excess. The last two decades have seen the emergence of large randomized control trials bringing new evidence regarding how RRT should now be managed in the ICU. RRT is considered a vital supportive care and needs to be adequately prescribed and delivered. This chapter first summarizes the basic principles and characteristics of the three major RTT modalities: intermittent hemodialysis (IHD), prolonged intermittent RRT (PIRRT), and continuous RRT (CRRT). Then, the large body of literature regarding indications for initiation (early vs late), choice of modality (intermittent vs continuous and diffusion vs convection), dosing (intensive vs less-intensive), and anticoagulation alternatives is reviewed to guide clinical decision-making. Recent evidence in the optimal timing of discontinuing RRT is reported. Finally, troubleshooting scenarios frequently seen in clinics and requiring an adapted RRT prescription are also discussed.

Background: Recent studies have identified the combination of vancomycin with piperacillin-tazobactam (VPT) to be associated with increased nephrotoxicity. Multiple, large cohort studies have found this widely used combination to have a higher risk of nephrotoxicity than other regimens in a variety of populations. Summary: This review summarizes the epidemiology and clinical features of VPT-associated acute kidney injury (AKI). Potential mechanisms involved in the pathogenesis of this phenomenon are also discussed. Key Message: VPT-associated nephrotoxicity is a recently recognized clinical entity. Clinical strategies to minimize the risk of toxicity in this setting include antimicrobial stewardship, monitoring of kidney function, and emerging data supporting the potential role for novel biomarkers in predicting and managing AKI.

Purpose of review To describe recent advances in the development of therapeutic agents for acute kidney injury (AKI). Recent findings Traditional care for AKI is mostly supportive. At present, no specific therapy has been developed to prevent or treat AKI. However, based on a better understanding of the pathophysiology of AKI, various potential compounds have been recently identified and tested. A variety of pathways has been targeted, including oxidative and mitochondrial stress, cellular metabolism and repair, inflammation, apoptosis and hemodynamics. Many of these potential agents are currently ongoing early-phase clinical trials, and the purpose of this review is to provide a summary of those with the most potential. Summary Despite the lack of therapies specifically approved for AKI, many interesting potential agents are entering clinical trials, with the potential to transform the care of patients with AKI.

Background An increased risk of acute kidney injury (AKI) with the widely prescribed piperacillin-tazobactam(PTZ)-vancomycin combination in hospitalized patients has recently been reported, but evidence in ICU patients remain uncertain. This study evaluates the association between the exposure of various broad-spectrum antibiotic regimens with Pseudomonas and/or methicillin-resistance Staphylococcus aureus (MRSA) coverage and the risk of AKI in critically ill patients. Methods and findings A retrospective cohort study based on the publicly available MIMIC-III database reporting hospitalization data from ICU patients from a large academic medical center between 2001 and 2012. Adult patients receiving an anti-pseudomonal or an anti-MRSA agent in the ICU for more than 24-hours were included. Non-PTZ anti-pseudomonal agents were compared to PTZ; non-vancomycin agents covering MRSA were compared to vancomycin; and their combinations were compared to the PTZ-vancomycin combination. The primary outcome was defined as new or worsening AKI within 7 days of the antibiotic exposure using an adjusted binomial generalized estimating equation. Overall, 18 510 admissions from 15 673 individual patients, cumulating 169 966 days of antibiotherapy were included. When compared to PTZ, exposure to another anti-pseudomonal agent was associated with lower AKI risk (OR, 0.85; 95% CI, 0.80–0.91; p < .001). When compared to vancomycin, exposure to another anti-MRSA was also associated with lower AKI risk (OR, 0.71; 95% CI, 0.64–0.80; p < .001). Finally, when compared to the PTZ-vancomycin combination, exposure to another regimen with a similar coverage was associated with an even lower risk (OR, 0.63; 95% CI; 0.54–0.73; p < .001). A sensitivity analysis of patients with high illness severity showed similar results. Conclusions These results suggest that the risk of AKI in ICU patients requiring antibiotherapy may be partially mitigated by the choice of antibiotics administered. Further clinical trials are required to confirm these findings.

PURPOSE To investigate various diuretic strategies to alleviate loop-diuretics resistance in critically ill patients. MATERIALS AND METHOD ICU adults requiring more than 1 mg/kg/day of furosemide, from the MIMIC-III database. Four diuretic strategies were investigated: incremental dose of loop diuretics, continuous infusion, combinations with a second class of diuretics and administration of intravenous albumin. A generalized estimating equation was used to investigate the associations between these strategies and endpoints. The primary outcome was the 24-h urine output and secondary endpoints included fluid balance, weight change, electrolyte and acid-base abnormalities, kidney replacement therapy initiation, and mortality. RESULTS A total of 7645 ICU stays from 6358 patients were included. After adjustment, the use of continuous loop-diuretic infusion was associated with a higher 24-h urine output (β: 732, 95% CI:669-795, p < 0.001), lower 24-h fluid balance (p < 0.001) and greater weight loss at 48-h (p < 0.001). Thiazide- and carbonic anhydrase inhibitor combinations were both associated with higher urine output (p < 0.001) and weight loss at 48-h (p < 0.01), while intravenous albumin was associated with fluid gain (p < 0.001). Risks of electrolyte and metabolic disturbances varied across diuretic strategies. CONCLUSIONS Continuous loop-diuretic infusion and thiazide- or acetazolamide-loop diuretic combinations increased urine output significantly, leading to a negative fluid balance and weight loss.

Background Acute kidney injury (AKI) is common in hospitalized patients and is associated with high morbidity and mortality. The Dublin Acute Biomarker Group Evaluation study is a prospective cohort study of critically ill patients (n = 717). We hypothesized that novel urinary biomarkers would predict progression of AKI and associated outcomes. Methods The primary (diagnostic) analysis assessed the ability of biomarkers levels at the time of early Stage 1 or 2 AKI to predict progression to higher AKI stage, renal replacement therapy (RRT) or death within 7 days of intensive care unit admission. In the secondary (prognostic) analysis, we investigated the association between biomarker levels and RRT or death within 30 days. Results In total, 186 patients had an AKI within 7 days of admission. In the primary (diagnostic) analysis, 8 of the 14 biomarkers were independently associated with progression. The best predictors were cystatin C [adjusted odds ratio (aOR) 5.2; 95% confidence interval (CI) 1.3–23.6], interleukin-18 (IL-18; aOR 5.1; 95% CI 1.8–15.7), albumin (aOR 4.9; 95% CI 1.5–18.3) and neutrophil gelatinase-associated lipocalin (NGAL; aOR 4.6; 95% CI 1.4–17.9). Receiver-operating characteristics and net reclassification index analyses similarly demonstrated improved prediction by these biomarkers. In the secondary (prognostic) analysis of Stages 1–3 AKI cases, IL-18, NGAL, albumin and monocyte chemotactic protein-1 were also independently associated with RRT or death within 30 days. Conclusions Among 14 novel urinary biomarkers assessed, cystatin C, IL-18, albumin and NGAL were the best predictors of Stages 1–2 AKI progression. These biomarkers, after further validation, may have utility to inform diagnostic and prognostic assessment and guide management of AKI in critically ill patients.

Introduction: The use of novel kidney injury biomarkers has been shown to improve diagnostic assessment and prognostic prediction in various populations with acute kidney injury (AKI), but their use in a standard clinical practice have been rarely reported. Methods: We reported the clinical implementation of neutrophil gelatinase-associated lipocalin (NGAL) measurement for routine AKI diagnostic workup of patients receiving nephrology consultation in a tertiary academic centre. Specific focus was made on the diagnostic performance to discriminate functional (“pre-renal”) from intra-renal AKI and to predict AKI progression. Results: Forty-five urine NGAL (uNGAL) and 25 plasma NGAL (pNGAL) samples in the first 50 consecutive patients were analysed. KDIGO Stage 1, 2, 3 AKI, and renal replacement therapy occurred in 10%, 40%, 50%, and 24% of cases, respectively. The uNGAL was lower in patients with transient AKI (p = 0.016), while pNGAL did not discriminate transient (264 [100–373] ng/mL) from persistent AKI (415 [220–816] ng/mL) (p = 0.137). The median uNGAL level was 63 (35–1,123) ng/mL for functional/pre-renal AKI and 451 (177–1,315) ng/mL for intra-renal AKI (p = 0.043), while the pNGAL was 264 (114–468) and 415 (230–816) ng/mL (p = 0.235), respectively. Conclusion: NGAL, as part of the routine workup, is useful for diagnostic and prognostic assessment of new-onset AKI in clinical practice. Interpretation of an increased NGAL level should be clinically evaluated in its clinical context, particularly considering concomitant infection (urinary or systemic). Clinical adoption of emerging AKI biomarkers as diagnostic tests in clinical practice should be further encouraged.

The aim of this study was to determine whether kidney transplantations performed after previous non-renal solid organ transplants are associated with worse graft survival when there are repeated HLA mismatches (RMM) with the previous donor(s). We performed a retrospective cohort study using data from the Scientific Registry of Transplant Recipients. Our cohort comprised 6, 624 kidney transplantations performed between January 1st 1990 and January 1st, 2015. All patients had previously received one or more non-renal solid organ transplants. RMM were observed in 35.3% of kidney transplantations and 3, 012 grafts were lost over a median follow-up of 5.4 years. In multivariate Cox regression analyses, we found no association between overall graft survival and either RMM in class 1 (hazard ratio (HR): 0.97, 95% confidence interval (CI) 0.89-1.07) or class 2 (HR: 0.95, 95% CI 0.85- 1.06). Results were similar for the associations between RMM, death-censored graft survival and patient survival. Our results suggest that the presence of RMM with previous donor(s) does not have an important impact on allograft survival in kidney transplant recipients who have previously received a non-renal solid organ transplant. This article is protected by copyright. All rights reserved.

Henoch-Schonlein purpura is a relatively common pediatric vasculitis. Very few cases of Henoch-Schonlein purpura during pregnancy have been described. Henoch-Schonlein purpura is variable in its presentation, from completely benign to possibly catastrophic complications. This rarely encountered condition in adults can also be a recurrence of a previous childhood disease. We present a case of a pregnant 40-year-old woman with Henoch-Schonlein purpura, resulting in a viable birth with no fetal complications. Her presentation is discussed in detail and a general presentation of Henoch-Schonlein purpura is explored, with particular attention to its rare onset during pregnancy.

Supplemental digital content is available in the text., Background The poor prognosis classically associated with Banff grade 2 acute cell-mediated rejection (CMR) may be due to unrecognized antibody-mediated damage. We thus performed a systematic review of the literature to determine the rate of response to treatment in kidney transplant recipients with pure CMR, stratified by Banff class. Methods In addition to a manual search, databases interrogated included Excerpta Medica Database (EMBASE), Medical Literature Analysis and Retrieval System Online (MEDLINE), Evidence-Based Medicine (EBM) databases, Central, PubMed and CINAHL. Studies providing functional and/or histological response rates to the treatment of CMR rejection by Banff class (1997 or more recent) were included. Results Among the 746 articles identified, 5 articles were included in the final review. Two studies excluded some, and 2 excluded all features of antibody-mediated rejection, while providing data on functional recovery. The absence of functional recovery was reported in 4% of borderline, 15% for Banff grade 1A and IB pooled, 0% to 25% of Banff grade 1B alone, 11% to 20% of Banff grade 2A, and 38% of Banff grade 2B rejections. Conclusions The rate of functional recovery of pure Banff IIA CMR overlapped with that of Banff grade 1 CMR, whereas Banff grade 2B showed worse prognosis. There was important heterogeneity in the definition of response to treatment and paucity of data describing the histological response to treatment stratified by Banff class. There is a pressing need to standardize outcome metrics for the reversibility of rejection in kidney transplant recipients in order to design high-quality trials for novel therapeutic alternatives.