Dan Negoianu

Automated, electronic alerts for acute kidney injury: a single-blind, parallel-group, randomised controlled trial

BACKGROUND Acute kidney injury often goes unrecognised in its early stages when effective treatment options might be available. We aimed to determine whether an automated electronic alert for acute kidney injury would reduce the severity of such injury and improve clinical outcomes in patients in hospital. METHODS In this investigator-masked, parallel-group, randomised controlled trial, patients were recruited from the hospital of the University of Pennsylvania in Philadelphia, PA, USA. Eligible participants were adults aged 18 years or older who were in hospital with stage 1 or greater acute kidney injury as defined by Kidney Disease Improving Global Outcomes creatinine-based criteria. Exclusion criteria were initial hospital creatinine 4·0 mg/dL (to convert to μmol/L, multiply by 88·4) or greater, fewer than two creatinine values measured, inability to determine the covering provider, admission to hospice or the observation unit, previous randomisation, or end-stage renal disease. Patients were randomly assigned (1:1) via a computer-generated sequence to receive an acute kidney injury alert (a text-based alert sent to the covering provider and unit pharmacist indicating new acute kidney injury) or usual care, stratified by medical versus surgical admission and intensive care unit versus non-intensive care unit location in blocks of 4-8 participants. The primary outcome was a composite of relative maximum change in creatinine, dialysis, and death at 7 days after randomisation. All analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01862419. FINDINGS Between Sept 17, 2013, and April 14, 2014, 23,664 patients were screened. 1201 eligible participants were assigned to the acute kidney injury alert group and 1192 were assigned to the usual care group. Composite relative maximum change in creatinine, dialysis, and death at 7 days did not differ between the alert group and the usual care group (p=0·88), or within any of the four randomisation strata (all p>0·05). At 7 days after randomisation, median maximum relative change in creatinine concentrations was 0·0% (IQR 0·0-18·4) in the alert group and 0·6% (0·0-17·5) in the usual care group (p=0·81); 87 (7·2%) patients in the alert group and 70 (5·9%) patients in usual care group had received dialysis (odds ratio 1·25 [95% CI 0·90-1·74]; p=0·18); and 71 (5·9%) patients in the alert group and 61 (5·1%) patients in the usual care group had died (1·16 [0·81-1·68]; p=0·40). INTERPRETATION An electronic alert system for acute kidney injury did not improve clinical outcomes among patients in hospital. FUNDING Penn Center for Healthcare Improvement and Patient Safety.

Just Add Water

“Just add water” is the modern chime turning various prepared foods into family dinner; however, is it good advice for people at the table as well? In this issue of JASN , Berl[1][1] describes how solute intake affects the kidneys handling of water. What of the converse: How does intake of

False-Positive Rate of AKI Using Consensus Creatinine–Based Criteria

BACKGROUND AND OBJECTIVES Use of small changes in serum creatinine to diagnose AKI allows for earlier detection but may increase diagnostic false-positive rates because of inherent laboratory and biologic variabilities of creatinine. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We examined serum creatinine measurement characteristics in a prospective observational clinical reference cohort of 2267 adult patients with AKI by Kidney Disease Improving Global Outcomes creatinine criteria and used these data to create a simulation cohort to model AKI false-positive rates. We simulated up to seven successive blood draws on an equal population of hypothetical patients with unchanging true serum creatinine values. Error terms generated from laboratory and biologic variabilities were added to each simulated patients true serum creatinine value to obtain the simulated measured serum creatinine for each blood draw. We determined the proportion of patients who would be erroneously diagnosed with AKI by Kidney Disease Improving Global Outcomes creatinine criteria. RESULTS Within the clinical cohort, 75.0% of patients received four serum creatinine draws within at least one 48-hour period during hospitalization. After four simulated creatinine measurements that accounted for laboratory variability calculated from assay characteristics and 4.4% of biologic variability determined from the clinical cohort and publicly available data, the overall false-positive rate for AKI diagnosis was 8.0% (interquartile range =7.9%-8.1%), whereas patients with true serum creatinine ≥1.5 mg/dl (representing 21% of the clinical cohort) had a false-positive AKI diagnosis rate of 30.5% (interquartile range =30.1%-30.9%) versus 2.0% (interquartile range =1.9%-2.1%) in patients with true serum creatinine values <1.5 mg/dl (P<0.001). CONCLUSIONS Use of small serum creatinine changes to diagnose AKI is limited by high false-positive rates caused by inherent variability of serum creatinine at higher baseline values, potentially misclassifying patients with CKD in AKI studies.

Aquapheresis Versus Intravenous Diuretics and Hospitalizations for Heart Failure

OBJECTIVES The AVOID-HF (Aquapheresis versus Intravenous Diuretics and Hospitalization for Heart Failure) trial tested the hypothesis that patients hospitalized for HF treated with adjustable ultrafiltration (AUF) would have a longer time to first HF event within 90 days after hospital discharge than those receiving adjustable intravenous loop diuretics (ALD). BACKGROUND Congestion in hospitalized heart failure (HF) patients portends unfavorable outcomes. METHODS The AVOID-HF trial, designed as a multicenter, 1-to-1 randomized study of 810 hospitalized HF patients, was terminated unilaterally and prematurely by the sponsor (Baxter Healthcare, Deerfield, Illinois) after enrollment of 224 patients (27.5%). Aquadex FlexFlow System (Baxter Healthcare) was used for AUF. A Clinical Events Committee, blinded to the randomized treatment, adjudicated whether 90-day events were due to HF. RESULTS A total of 110 patients were randomized to AUF and 114 to ALD. Baseline characteristics were similar. Estimated days to first HF event for the AUF and ALD group were, respectively, 62 and 34 (p = 0.106). At 30 days, compared with the ALD group, the AUF group had fewer HF and cardiovascular events. Renal function changes were similar. More AUF patients experienced an adverse effect of special interest (p = 0.018) and a serious study product-related adverse event (p = 0.026). The 90-day mortality was similar. CONCLUSIONS Compared with the ALD group, the AUF group trended toward a longer time to first HF event within 90 days and fewer HF and cardiovascular events. More patients in the AUF group experienced special interest or serious product-related adverse event. Due to the trials untimely termination, additional AUF investigation is warranted.

Extracorporeal Ultrafiltration for Fluid Overload in Heart Failure: Current Status and Prospects for Further Research.

More than 1 million heart failure hospitalizations occur annually, and congestion is the predominant cause. Rehospitalizations for recurrent congestion portend poor outcomes independently of age and renal function. Persistent congestion trumps serum creatinine increases in predicting adverse heart failure outcomes. No decongestive pharmacological therapy has reduced these harmful consequences. Simplified ultrafiltration devices permit fluid removal in lower-acuity hospital settings, but with conflicting results regarding safety and efficacy. Ultrafiltration performed at fixed rates after onset of therapy-induced increased serum creatinine was not superior to standard care and resulted in more complications. In contrast, compared with diuretic agents, some data suggest that adjustment of ultrafiltration rates to patients’ vital signs and renal function may be associated with more effective decongestion and fewer heart failure events. Essential aspects of ultrafiltration remain poorly defined. Further research is urgently needed, given the burden of congestion and data suggesting sustained benefits of early and adjustable ultrafiltration.

Should Nephrology Training Programs Continue to Train Fellows in the Placement of Temporary Hemodialysis Catheters

Wong J: Is bigger better? A retrospective analysis of native renal biopsies with 16 Gauge versus 18 Gauge automatic needles. Nephrology (Carlton) 18:525–530, 2013 19. Roth R, Parikh S, Makey D, Foster J, Rozenblit G, Satoskar A, Nadasdy G, Von VJ, Hebert L, Rovin BH, Nadasdy T, Brodsky SV: When size matters: diagnostic value of kidney biopsy according to the gauge of the biopsy needle. Am J Nephrol 37:249–254, 2013 20. Yushkov Y, Selck FW: An approach to needle biopsy technique to improve glomerulus yield. Transplant Proc 40:1051–1053, 2008

Accuracy of Acid-Base Diagnoses Using the Central Venous Blood Gas in the Medical Intensive Care Unit

Background: Acid-base disturbances are frequent in critically ill patients. Arterial blood gas (ABG) is the gold standard in the diagnosis of these disturbances, but it is invasive with potential hazards. For patients with a central venous catheter, venous blood gas (VBG) sampling may be an alternative, less-invasive diagnostic tool. However, the accuracy of a central VBG-based acid-base disorder diagnosis compared to an ABG is unknown. The primary objective of this study was to assess the accuracy of a central VBG-based acid-base disorder diagnosis compared to the “gold standard” ABG in critically ill patients. Methods: This was a study of adult patients in a medical intensive care unit that had simultaneously drawn ABG and central VBG samples. Expert acid-base diagnosticians, all nephrologists, diagnosed the acid-base disorder(s) in each blood gas sample. The central VBG diagnostic accuracy was assessed with percent agreement, sensitivity, and specificity compared to the ABG-based diagnosis. Results: The study involved 23 participants. Overall, the central VBG had 100% sensitivity for metabolic acidosis, metabolic alkalosis, and respiratory acidosis, and lower sensitivity (71%) for respiratory alkalosis, and high percent agreement, ranging from 75 to 94%. VBG-based diagnoses in vasopressor-dependent patients (n = 13, 56.5%) performed similarly to the entire sample. Conclusions: In critically ill adult patients, central VBG may be used to detect and diagnose acid-base disturbances with reasonable diagnostic accuracy, even in shock states, compared to the ABG. This study supports the use of central VBG for diagnosis of acid-base disturbances in critically ill patients.

An Interactive Ambulatory Nephrology Curriculum for Internal Medicine Interns: Design, Implementation, and Participant Feedback

While diminishing nephrology fellow recruitment is a known issue, more work is needed to evaluate possible interventions to reverse this trend. We designed and implemented a curriculum to increase exposure to ambulatory nephrology among internal medicine interns. The curriculum focused on key aspects of outpatient nephrology practice, including supervised clinic visits, formal themed didactic content, and an online interactive forum with assigned evidence-based readings and small-group responses to relevant cases. We obtained postcourse surveys from all participating interns. Of the 43 interns who took part in the first year of the ambulatory nephrology curriculum, 100% reported a positive didactic experience and 91% reported a positive interactive online experience. 77% reported an improvement in their familiarity with clinical nephrology practice (median 2-point increase in familiarity score on a 7-point scale, P<0.001 by signed rank testing). Qualitative feedback included praise for the high-yield topics covered by the lectures and energizing teachers. In conclusion, we successfully implemented an ambulatory nephrology curriculum using a framework that integrated formal didactics, interactive online learning, and key clinical components of outpatient nephrology care. Future investigation will evaluate whether early implementation of this curriculum is associated with increased pursuit of nephrology as a career.

How much is enough? The impact of frequent hemodialysis.

The ability to prolong life with hemodialysis (HD) treatments has been tarnished by frustration and disappointment with the exceedingly high mortality rate of patients with end-stage renal disease (ESRD) (1). Attempts at improving outcomes via interventions such as anemia treatment, high-flux dialyzers, and moderate increases in urea clearance have all failed to provide convincing declines in mortality (2–4). Kidney transplantation is the only therapy that seems to have had a palpable impact on mortality (5)—although only for those patients without medical contraindications and with the staying power towait years for a cadaver kidney if no living donor is available. The prospect of improving survival through frequent hemodialysis (FHD) has generated significant interest and some debate. Given the alarming death rate among ESRD patients, how much evidence will be needed before we popularize this option? The benefits of FHD can be viewed frommany different perspectives. FHD impacts quality of life, as it appears to improve disease-related symptoms and allow greater control over daily schedule and diet (6,7). Additionally, FHD may decrease the cost of dialysis care: most FHD is carried out in the home, and home HD appears to be less costly than conventional in-center HD (8). Finally, FHD is associated with improvements in multiple risk factors believed to contribute to risk of death, including: hypertension, left ventricular hypertrophy (LVH), and hyperphosphatemia (9). FHD may therefore be a way to increase patients’ quantity of life as well as quality of life. In addition to the multiple different perspectives regarding the potential benefits of FHD, there are also multiple different schedules that can be used to deliver it. Nocturnal hemodialysis (NHD) generally consists of five to six overnight treatments per week of at least 6 hours duration. Short-daily HD (SDHD) consists of 2–3 hour daytime treatments, 5–6 days ⁄week. Generally, less urea clearance and less treatment time is provided by SDHD than NHD, so the benefits of NHD may be different than those of SDHD. However, there are currently no useful data comparingdifferentFHDschedules.Of note, home HD can provide the same thrice-weekly schedule used for in-center HD. This might impart cost savings compared with in-center HD, but one would not expect the same physiological benefits ofNHDor SDHD.Conversely, in-center HD can be provided more frequently than the usual thrice-weekly schedule, but is limited by economic and scheduling constraints. Finally, the group in Tassin, France, provides patients thrice-weekly in-center treatments that are 8 hours long (10). Historically, these patients have had very low mortality rates. However, there has been only sporadic pursuit of this approach in North America. Clearly, the wide variety of potential schedules and the multiple possible study outcomes complicate the interpretation of the literature on FHD. In the first published randomized clinical trial (RCT) of NHD, Culleton et al. (11) randomized 52 subjects to either begin NHD or to remain on ‘‘conventional’’ HD (CHD) three times per week. One subject in the NHD group refused all further participation after randomization and was dropped from the study. All other subjects were analyzed in an intention-to-treat fashion. The two groups appeared well-matched at baseline, and they were followed for 6 months. Change in left ventricular (LV) mass on cardiac magnetic resonance imaging (MRI) was the primary outcome. LV mass was assessed only in the 44 subjects who did not have a contraindication to MRI. Average LV mass decreased 13.8 g in the NHD group and increased 1.5 g in the CHD group. The difference in change in average LV mass between the two groups was therefore )15.3 g (95% CI )29.6 to )1.0 g; p < 0.05). The difference in change of LV mass index (LVMI) was also statistically significant ()7.1 g ⁄m; 95% CI )16.2 to )0.1 g ⁄m; p < 0.05). While there was no significant difference in the change in blood pressure between the two groups, there was a significant difference in discontinuation of antihypertensive medications: 16 of 26 subjects randomized to NHD discontinued all antihypertensive medications, while only three of 25 subjects randomized to CHD did so (p < 0.001). There was also a significant difference in change in serum phosphate ()1.5 mg ⁄dl; 95% CI )2.5 to )0.5 mg ⁄dl; p < 0.01) and in difference in change of calcium–phosphate product ()13.6 g ⁄dl; 95% CI Address correspondence to: Jeffrey S. Berns, MD, RenalElectrolyte and Hypertension Division, Renal Fellowship Training Program Director, University of Pennsylvania School of Medicine, Hospital of the University of Pennsylvania, 3400 Spruce Street; 1 Founders Pavilion, Philadelphia, PA 19104, or e-mail: jeffrey.berns@uphs.upenn.edu. Seminars in Dialysis—Vol 21, No 2 (March–April) 2008 pp. 192–195 DOI: 10.1111/j.1525-139X.2007.00411.x

An Unusual yet “Mg”nificent Indication for Hemodialysis

Hypermagnesemia is an uncommon electrolyte abnormality, due to the fact that magnesium toxicity is only seen in the setting of a massive exposure to exogenous magnesium, often in the setting of renal insufficiency. Here, we report a case of severe hypermagnesemia that resulted in complete paralysis that was secondary to Renacidin administration, a rarely used agent used for intra‐renal pelvic or intra‐vesicular instillation dissolution of struvite stones. The patient also had concurrent acute kidney injury (AKI). The patients magnesium was as high as 16.7 mg/dL, and he initially received hemodialysis followed by continuous venovenous hemodialysis. These therapies resulted in a rapid reduction in magnesium levels and eventual resolution of the muscular weakness. The case discussion highlights several key aspects of magnesium homeostasis, the limited mechanistic understanding of Renacidin‐induced hypermagnesemia, and the role of renal replacement therapies in the treatment of hypermagnesemia.