Our shared responsibility: the urgent necessity of global environmentally sustainable kidney care.

In response to Earth's accelerating climate crisis, we, an international group of nephrologists, call on our global community to unite and align kidney care in accordance with United Nation's 26th Conference of the Parties health sector principles. We announce a global and inclusive initiative, "GREEN-K": Global Environmental Evolution in Nephrology and Kidney Care, with a vision of "sustainable kidney care for a healthy planet and healthy kidneys" and mission to "promote and support environmentally sustainable and resilient kidney care globally through advocacy, education, and collaboration." A patient-centric approach that permits climate change mitigation and adaptation is proposed. Multi-stakeholder GREEN-K action and focus areas will include education, sustainable clinical care, and advances toward environmentally sustainable innovations, procurement, and infrastructure. Mindful of the disproportionately high climate impact of kidney therapies, we welcome the opportunity to work together in shared accountability to patients and Earth's natural systems.

Mitochondrial Haplogroup and the Risk of Acute Kidney Injury Following Cardiac Bypass Surgery.

Although mitochondrial dysfunction plays a key role in the pathophysiology of acute kidney injury (AKI), the influence of mitochondrial genetic variability in this process remains unclear. We explored the association between the risk of post-cardiac bypass AKI and mitochondrial haplotype - inherited mitochondrial genomic variations of potentially functional significance. Our single-centre study recruited consecutive patients prior to surgery. Exclusions included stage 5 CKD, non-Caucasian race and subsequent off-pump surgery. Haplogroup analysis allowed characterisation of the study population using the common mutations and by phylogenetic supergroup (WXI and HV). Chi-square tests for association allowed the identification of potential predictors of AKI for use in logistic regression analysis. AKI occurred in 12.8% of the study population (n = 881; male 69.6%, non-diabetic 78.5%, median (interquartile range) age 68.0 (61.0-75.0) years). The haplogroup profile comprised H (42.7%), J (12.1%), T (10.9%), U (14.4%) and K (7.6%). Although the regression model was statistically significant (χ2 = 95.483, p < 0.0005), neither the phylogenetic supergroups nor any individual haplogroup was a significant contributor. We found no significant association between common European haplogroups and the risk of post-cardiac bypass AKI. However, given the major role of mitochondrial dysfunction in AKI, there is a need to replicate our findings in other cohorts and with other aetiologies of AKI.

Computerized clinical decision support for the early recognition and management of acute kidney injury: a qualitative evaluation of end-user experience.

BACKGROUND: Although the efficacy of computerized clinical decision support (CCDS) for acute kidney injury (AKI) remains unclear, the wider literature includes examples of limited acceptability and equivocal benefit. Our single-centre study aimed to identify factors promoting or inhibiting use of in-patient AKI CCDS. METHODS: Targeting medical users, CCDS triggered with a serum creatinine rise of ≥25 µmol/L/day and linked to guidance and test ordering. User experience was evaluated through retrospective interviews, conducted and analysed according to Normalization Process Theory. Initial pilot ward experience allowed tool refinement. Assessments continued following CCDS activation across all adult, non-critical care wards. RESULTS: Thematic saturation was achieved with 24 interviews. The alert was accepted as a potentially useful prompt to early clinical re-assessment by many trainees. Senior staff were more sceptical, tending to view it as a hindrance. 'Pop-ups' and mandated engagement before alert dismissal were universally unpopular due to workflow disruption. Users were driven to close out of the alert as soon as possible to review historical creatinines and to continue with the intended workflow. CONCLUSIONS: Our study revealed themes similar to those previously described in non-AKI settings. Systems intruding on workflow, particularly involving complex interactions, may be unsustainable even if there has been a positive impact on care. The optimal balance between intrusion and clinical benefit of AKI CCDS requires further evaluation.

Fluids for continuous renal replacement therapy--an evaluation of microbial integrity.

PURPOSE: We have previously demonstrated widespread microbial contamination in the dialysis and replacement fluid circuits of bicarbonate-buffered, continuous renal replacement therapies (CRRTs). It is not known whether different CRRT fluids have an impact on bacterial activity. METHODS: In this study the in vitro growth and biofilm formation associated with seven strains of bacteria (Burkholderia cepacia, Escherichia coli, Staphylococcus aureus, Stenotrophomonas maltophilia, Pseudomonas aeruginosa, Pseudomonas fluorescens, and Staphylococcus epidermidis) in five CRRT fluids (Prismocitrate, Monosol S, Accusol 35, tri-sodium citrate and Ci-Ca K2) were studied. The fluids were each inoculated with light and heavy concentrations of each of the bacterial strains and incubated at 22 or 37°C for up to 72 h with and without bacterial growth medium. Bacterial growth was assessed by spectrophotometry. Biofilm formation was assessed by a standard microtiter plate assay. RESULTS: Unsupplemented fluids did not support bacterial growth or biofilm formation after 72 h incubation. When supplemented with bacterial growth medium, some fluids, in particular Accusol 35, Ci-Ca K2, and tri-sodium citrate, had an inhibitory effect on bacterial growth, although none suppressed growths across the panel of tested organisms. CONCLUSIONS: Different CRRT fluids have different impacts on bacterial growth and biofilm formation, but all remain susceptible to extrinsic contamination.

Anti-neutrophil cytoplasmic antibody (ANCA) associated small-vessel vasculitis in a patient with diabetic nephropathy and autoimmune polyendocrinopathy syndrome (APS) Type 2: a case report.

We present a 42-year-old woman with pre-existing autoimmune polyendocrinopathy syndrome (APS) Type 2 and chronic kidney disease due to Type 1 diabetic nephropathy, who developed a rapid deterioration in renal function due to perinuclear anti-neutrophil cytoplasmic antibody (pANCA)-associated vasculitis. Although possibly a chance occurrence, ANCA have been detected more frequently in patients with a history of certain autoimmune diseases. Such an association may simply reflect an underlying tendency to immune system dysfunction in these patients and the finding of positive ANCA serology does not reliably herald the development of ANCA-associated vasculitis. However, our case illustrates that positive ANCA serology in such circumstances is not always a benign phenomenon and should still be interpreted within the clinical context. Moreover, clinicians managing patients with pre-existing autoimmune disease should maintain a low threshold for appropriate assessment should such patients develop evidence suggestive of vasculitis.

Microbial control in renal support for acute kidney injury.

Renal support offers a lifeline for our patients with acute kidney injury but the decision to start it requires a careful evaluation of both its benefits and its risks. Among the latter must be included the threat from microorganisms. The hazards associated with vascular access are real, accepted but also reducible. We discuss the nature of the problem and measures that might reduce the risk. We also discuss a different potential hazard--that of bacterial contamination of the fluids used in our renal therapies. Although a well-established fact of chronic hemodialysis practice, its scale and relevance in acute renal support has only just started to be defined.

A microbiological survey of bicarbonate-based replacement circuits in continuous veno-venous hemofiltration.

OBJECTIVE: The potential for clinically significant transfer of pyrogen-inducing material in dialysate and substitution fluids is well recognized in the setting of chronic hemodialysis and hemodiafiltration and has led to the establishment of strict standards for microbiological purity. Preliminary evidence has indicated the potential for fluid contamination in continuous renal replacement therapy, and although the scale of the problem in contemporary, industry-standard equipment is unclear. We aimed to define the microbial integrity of modern continuous veno-venous hemofiltration (CVVH) replacement fluid circuitry. DESIGN: Twenty-four CVVH replacement fluid circuits (mean lifespan, 34.2 hours; range, 4-86) were studied at completion of therapy. SETTING: The integrated critical care unit and cardiothoracic intensive care unit of the Freeman Hospital, Newcastle upon Tyne, United Kingdom, between January and August 2007. SUBJECTS: Patients with renal failure receiving treatment with CVVH. INTERVENTIONS: Nil. MEASUREMENTS: Culture and endotoxin assays of replacement fluid, culture of endoluminal swabs, and electron microscopy of harvested tubing. MAIN RESULTS: Of the 24 replacement fluid cultures, nine (mean lifespan 32.8 hours, range 5-79) breached European Pharmacopoeia standards for ultrapure water (<0.1 colony-forming units/mL). One of 24 endotoxin measurements breached European Pharmacopoeia standards (<0.03 endotoxin units/mL). Internal tubing cultures were negative, but electron microscopy revealed 13 of the 24 collected tubing samples to be contaminated with biofilm. Only seven of the 24 studied circuits proved to be free from microbial contamination. CONCLUSIONS: We have confirmed frequent breaches of microbial integrity in industry-standard, bicarbonate-based CVVH, indicating the potential for added risk to the vulnerable, critically ill patient. These findings are of particular concern given the need for systemic infusion of replacement fluid. Measures to reduce the levels of contamination and their impact are discussed.

Dosing intermittent haemodialysis in the intensive care unit patient with acute renal failure--estimation of urea removal and evidence for the regional blood flow model.

BACKGROUND: Blood-side dosing methods may overestimate urea removal in comparison to dialysate-side measurements during intermittent HD (IHD) for acute renal failure (ARF). The present study sought to quantify this mass balance error (MBE) and explore potential explanatory factors. METHODS: Prospective, formal, blood-side urea kinetic modelling was performed in serial sessions (n = 42) in 18 intensive care unit ARF patients. Three blood-side estimates of urea removal were calculated and these were compared to urea removal derived from fractional dialysate sampling and use of an on-line urea monitor. We also examined urea rebound in these patients, as expressed by the intercompartmental urea clearance (Kc), and in a subset of patients examined the relation of Kc to cardiac output and systemic vascular resistance (SVR). RESULTS: The mean % MBE (MBE = blood - dialysate-estimated urea removal) was about 9% using conventional two-pool modelling based on a 60-min post-dialysis blood urea nitrogen (BUN) with or without the use of one or more intra-dialytic BUN values. The extent of MBE could not be explained by the clinical or dialytic variables that were measured. Part of the MBE error was due to overestimation of the intradialytic BUN profile, because model-independent profiling of intra-dialytic BUN values to compute urea removal reduced the MBE to approximately 6%. The log Kc was correlated with cardiac output and showed trends towards an inverse correlation with SVR. CONCLUSIONS: Classical, two-pool, blood-side UKM produces a modest overestimate of urea removal in IHD for critically ill ARF patients. The source of this small, residual MBE is unknown. The amount of urea rebound, as reflected by Kc, varied among patients and associated with cardiac output and SVR, as predicted by the regional blood flow model.

Direct dialysis quantification: investigation of the impact of dialysate preservation techniques on solute assays.

AIMS: Urease-producing microorganisms may lower urea nitrogen (UN) during dialysate-side dosing. We investigated the impact of 3 proven preservatives (acetic acid, ceftazidime, thimerosal) on UN concentration, and the concentrations of creatinine (CR) and beta2-microglobulin (beta2M). METHODS: The UN, CR and beta2M concentrations were assayed in 3 separate aliquots from 20 spent dialysate samples (ceftazidime, 125 mg/l, or 1% thimerosal, 1 ml/l, vs. control). The beta2M concentration was assayed in 10 further spent dialysate collections (concentrated glacial acetic acid, 5 ml/l, vs. control). Solute concentrations were compared with the concordance correlation coefficient (rc). RESULTS: Ceftazidime and thimerosal had little effect on the concentrations of UN and CR (rc >0.97). For the beta2M concentration, agreement remained good (rc >0.96) for ceftazidime and thimerosal (although the former tended to lower concentrations) but acetic acid was less optimal (rc = 0.893). CONCLUSIONS: Ceftazidime and thimerosal may be used as dialysate preservatives without affecting the UN or CR concentrations. Thimerosal is to be preferred when studying beta2M. Acetic acid produces unacceptable inaccuracy when measuring beta2M.

Prescribing an equilibrated intermittent hemodialysis dose in intensive care unit acute renal failure.

BACKGROUND: Prospective, formal, blood-side, urea kinetic modeling (UKM) has yet to be applied in intermittent hemodialysis for acute renal failure (ARF). Methods for prescribing a target, equilibrated Kt/V (eKt/V) are described for this setting. METHODS: Serial sessions (N= 108) were studied in 28 intensive care unit ARF patients. eKt/V was derived using delayed posthemodialyis urea samples and formal, double-pool UKM (eKt/Vref), and by applying the Daugirdas-Schneditz venous rate equation to pre- and posthemodialysis samples (eKt/Vrate). Individual components of prescribed and delivered dose were compared. Prescribed eKt/V values were determined using in vivo dialyzer clearance estimates and anthropometric (Watson and adjusted Chertow) and modeled urea volumes. RESULTS: eKt/Vref (mean +/- SD = 0.91 +/- 0.26) was well-approximated by eKt/Vrate (0.92 +/- 0.25), R= 0.92. Modeled V exceeded Watson V by 25%+/- 29% (P < 0.001) and Adjusted Chertow V by 18%+/- 28% (P < 0.001), although the degree of overestimation diminished over time. This difference was influenced by access recirculation (AR) and use of saline flushes. The median % difference between Vdprate and Watson V was reduced to 1% after adjusting for AR for the 22 sessions with < or =1 saline flush. The median coefficients of variation for serial determinations of Adjusted Chertow V, modeled V, urea generation rate, and eKt/Vref were 2.7%, 12.2%, 30.1%, and 16.4%, respectively. Because of comparatively higher modeled urea Vs, delivered eKt/Vref was lower than prescribed eKt/V, based on Watson V or Adjusted Chertow V, by 0.13 and 0.08 Kt/V units. The median absolute errors of prescribed eKt/V vs. delivered therapy (eKt/Vref) were not large and were similar in prescriptions based on the Adjusted Chertow V (0.127) vs. those based on various double-pool modeled urea volumes (approximately 0.127). CONCLUSION: Equilibrated Kt/V can be derived using formal, double-pool UKM in intensive care unit ARF patients, with the venous rate equation providing a practical alternative. A target eKt/V can be prescribed to within a median absolute error of less than 0.14 Kt/V units using practical prescription algorithms. The causes of the increased apparent volume of urea distribution appear to be multifactorial and deserve further investigation.

Dialyzer fiber bundle volume and kinetics of solute removal in continuous venovenous hemodialysis.

The relationship between dialyzer fiber bundle volume (FBV), dialyzer life span, and small-solute clearance has yet to be clearly defined in continuous venovenous hemodialysis (CVVHD). This study sought to define this relationship using novel ultrasound dilution technology. We studied 55 sessions in 31 intensive care unit patients on CVVHD therapy. A session was defined as the life span of a single dialyzer. The following variables were assessed every 6 hours throughout each session, starting within 1 hour of initiation of that session: FBV, access recirculation, extracorporeal blood flow rate, effluent (EUN) to blood urea nitrogen (BUN) concentration ratio, effluent creatinine to blood creatinine concentration ratio, and urea nitrogen and creatinine clearances. Data were analyzed using random-effects linear models to estimate trends. Several dialysis-related and solute-removal parameters were analyzed for association with each other. Systemic or dialysis circuit heparin was administered in 28 of 55 sessions. One hundred seventy sets of FBV, 101 sets of urea clearance, and 102 sets of creatinine clearance measurements were performed. There was a declining trend for FBV (0.8 mL/h), heart rate (0.25 beats/min/h), and measured blood flow (0.33 mL/min/h; P < 0.05). Apart from dialysate inflow rate (P = 0.044), there was no significant correlation with EUN-BUN ratio. Session duration was associated with dialysis access site; the femoral access provided longer dialysis sessions than subclavian and internal jugular accesses (P = 0.029). We conclude that small-solute removal remains stable over the course of our CVVHD system life spans despite significant loss of hemodialyzer FBV.