Cary S. Passik

Performance of kidney injury molecule-1 and liver fatty acid-binding protein and combined biomarkers of AKI after cardiac surgery.

BACKGROUND AND OBJECTIVES AKI is common and novel biomarkers may help provide earlier diagnosis and prognosis of AKI in the postoperative period. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This was a prospective, multicenter cohort study involving 1219 adults and 311 children consecutively enrolled at eight academic medical centers. Performance of two urine biomarkers, kidney injury molecule-1 (KIM-1) and liver fatty acid-binding protein (L-FABP), alone or in combination with other injury biomarkers during the perioperative period was evaluated. AKI was defined as doubling of serum creatinine or need for acute dialysis. RESULTS KIM-1 peaked 2 days after surgery in adults and 1 day after surgery in children, whereas L-FABP peaked within 6 hours after surgery in both age groups. In multivariable analyses, the highest quintile of the first postoperative KIM-1 level was associated with AKI compared with the lowest quintile in adults, whereas the first postoperative L-FABP was not associated with AKI. Both KIM-1 and L-FABP were not significantly associated with AKI in adults or children after adjusting for other kidney injury biomarkers (neutrophil gelatinase-associated lipocalin and IL-18). The highest area under the curves achievable for discrimination for AKI were 0.78 in adults using urine KIM-1 from 6 to 12 hours, urine IL-18 from day 2, and plasma neutrophil gelatinase-associated lipocalin from day 2 and 0.78 in children using urine IL-18 from 0 to 6 hours and urine L-FABP from day 2. CONCLUSIONS Postoperative elevations of KIM-1 associate with AKI and adverse outcmes in adults but were not independent of other AKI biomarkers. A panel of multiple biomarkers provided moderate discrimination for AKI.

Serum Cystatin C– Versus Creatinine-Based Definitions of Acute Kidney Injury Following Cardiac Surgery: A Prospective Cohort Study

BACKGROUND The primary aim of this study was to compare the sensitivity and rapidity of acute kidney injury (AKI) detection by cystatin C level relative to creatinine level after cardiac surgery. STUDY DESIGN Prospective cohort study. SETTINGS & PARTICIPANTS 1,150 high-risk adult cardiac surgery patients in the TRIBE-AKI (Translational Research Investigating Biomarker Endpoints for Acute Kidney Injury) Consortium. PREDICTOR Changes in serum creatinine and cystatin C levels. OUTCOME Postsurgical incidence of AKI. MEASUREMENTS Serum creatinine and cystatin C were measured at the preoperative visit and daily on postoperative days 1-5. To allow comparisons between changes in creatinine and cystatin C levels, AKI end points were defined by the relative increases in each marker from baseline (25%, 50%, and 100%) and the incidence of AKI was compared based on each marker. Secondary aims were to compare clinical outcomes among patients defined as having AKI by cystatin C and/or creatinine levels. RESULTS Overall, serum creatinine level detected more cases of AKI than cystatin C level: 35% developed a ≥25% increase in serum creatinine level, whereas only 23% had a ≥25% increase in cystatin C level (P < 0.001). Creatinine level also had higher proportions meeting the 50% (14% and 8%; P < 0.001) and 100% (4% and 2%; P = 0.005) thresholds for AKI diagnosis. Clinical outcomes generally were not statistically different for AKI cases detected by creatinine or cystatin C level. However, for each AKI threshold, patients with AKI confirmed by both markers had a significantly higher risk of the combined mortality/dialysis outcome compared with patients with AKI detected by creatinine level alone (P = 0.002). LIMITATIONS There were few adverse clinical outcomes, limiting our ability to detect differences in outcomes between subgroups of patients based on their definitions of AKI. CONCLUSIONS In this large multicenter study, we found that cystatin C level was less sensitive for AKI detection than creatinine level. However, confirmation by cystatin C level appeared to identify a subset of patients with AKI with a substantially higher risk of adverse outcomes.

Preoperative Serum Brain Natriuretic Peptide and Risk of Acute Kidney Injury After Cardiac Surgery

Background— Acute kidney injury (AKI) after cardiac surgery is associated with poor outcomes and is difficult to predict. We conducted a prospective study to evaluate whether preoperative brain natriuretic peptide (BNP) levels predict postoperative AKI among patients undergoing cardiac surgery. Methods and Results— The Translational Research Investigating Biomarker Endpoints in Acute Kidney Injury (TRIBE-AKI) study enrolled 1139 adults undergoing cardiac surgery at 6 hospitals from 2007 to 2009 who were selected for high AKI risk. Preoperative BNP was categorized into quintiles. AKI was common with the use of Acute Kidney Injury Network definitions; at least mild AKI was a ≥0.3-mg/dL or 50% rise in creatinine (n=407, 36%), and severe AKI was either a doubling of creatinine or the requirement of acute renal replacement therapy (n=58, 5.1%). In analyses adjusted for preoperative characteristics, preoperative BNP was a strong and independent predictor of mild and severe AKI. Compared with the lowest BNP quintile, the highest quintile had significantly higher risk of at least mild AKI (risk ratio, 1.87; 95% confidence interval, 1.40–2.49) and severe AKI (risk ratio, 3.17; 95% confidence interval, 1.06–9.48). After adjustment for clinical predictors, the addition of BNP improved the area under the curve to predict at least mild AKI (0.67–0.69; P=0.02) and severe AKI (0.73–0.75; P=0.11). Compared with clinical parameters alone, BNP modestly improved risk prediction of AKI cases into lower and higher risk (continuous net reclassification index; at least mild AKI: risk ratio, 0.183; 95% confidence interval, 0.061–0.314; severe AKI: risk ratio, 0.231; 95% confidence interval, 0.067–0.506). Conclusions— Preoperative BNP level is associated with postoperative AKI in high-risk patients undergoing cardiac surgery. If confirmed in other types of patients and surgeries, preoperative BNP may be a valuable component of future efforts to improve preoperative risk stratification and discrimination among surgical candidates. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00774137.

Adjudication of etiology of acute kidney injury: experience from the TRIBE-AKI multi-center study

BackgroundAdjudication of patient outcomes is a common practice in medical research and clinical trials. However minimal data exists on the adjudication process in the setting of Acute Kidney Injury (AKI) as well as the ability to judge different etiologies (e.g. Acute Tubular Necrosis (ATN), Pre-renal Azotemia (PRA)).MethodsWe enrolled 475 consecutive patients undergoing cardiac surgery at four sites of the Translational Research Investigating Biomarker Endpoints in AKI (TRIBE-AKI) study. Three expert nephrologists performed independent chart review, utilizing clinical variables and retrospective case report forms with pre intra and post-operative data, and then adjudicated all cases of AKI (n = 67). AKI was defined as a > 50% increase in serum creatinine for baseline (RIFLE Risk). We examined the patterns of AKI diagnoses made by the adjudication panel as well as association of these diagnoses with pre and postoperative kidney injury biomarkers.ResultsThere was poor agreement across the panel of reviewers with their adjudicated diagnoses being independent of each other (Fleiss’ Kappa = 0.046). Based on the agreement of the two out of three reviewers, ATN was the adjudicated diagnosis in 41 cases (61%) while PRA occurred in 13 (19%). Neither serum creatinine or any other biomarker of AKI (urine or serum), was associated with an adjudicated diagnosis of ATN within the first 24 post-operative hours.ConclusionThe etiology of AKI after cardiac surgery is probably multi-factorial and pure forms of AKI etiologies, such as ATN and PRA may not exist. Biomarkers did not appear to correlate with the adjudicated etiology of AKI; however the lack of agreement among the adjudicators impacted these results.Trial registrationClinicaltrials.gov: NCT00774137

Early bioprosthetic mitral valve “pseudostenosis” after complete preservation of the native mitral apparatus

An advantage of bioprosthetic mitral valve replacement in patients with normal sinus rhythm is avoidance of the need for long-term anticoagulation. Bioprosthetic valve thrombosis is a rare complication, supporting this approach. This case report represents an example of porcine mitral valve stenosis, likely secondary to thrombosis, in which all of the native mitral valve apparatus was left intact. This was successfully treated with standard anticoagulation therapy. This complication should be considered in patients in whom retention of the mitral valve apparatus has been performed. Such patients may benefit from long-term anticoagulation treatment to obviate this event.

A Simpler Solution to the Old Problem of Frozen Leads

Pacemaker generator replacement is usually a straightforward and simple procedure. However, it is occasionally complicated by entrapment of the lead in the header. Solutions to this problem have been described previously. We describe a simpler and safer technique to solve this old problem.

Interleukin-8 and Tumor Necrosis Factor Predict Acute Kidney Injury After Pediatric Cardiac Surgery

BACKGROUND Inflammation is a key component of both acute kidney injury (AKI) and response to cardiopulmonary bypass. Because AKI poses risks to children after cardiac surgery, we investigated the value of inflammatory biomarkers interleukin-8 (IL-8) and tumor necrosis factor alpha (TNFα) for predicting AKI and other complications. METHODS We enrolled 412 children between the ages of 1 month and 18 years undergoing cardiopulmonary bypass for cardiac surgery. We collected blood both preoperatively and postoperatively (within 6 hours post-surgery) and measured plasma IL-8 and TNFα. RESULTS IL-8 and TNFα did not predict AKI in children <2 years, but were strongly associated with AKI in children ≥2 years. There were significant associations between biomarker levels and age (<2 or ≥2 years). In children ≥2 years, patients in the highest tertile of preoperative IL-8 and postoperative TNFα had 4.9-fold (95% CI: 1.8-13.2) and 3.3-fold (95% CI: 1.2-9.0) higher odds of AKI compared with those in the lowest tertile. Children <2 years with higher biomarker levels also had higher odds of AKI, but the difference was not significant. We also found that postoperative TNFα levels were significantly higher in patients with longer hospital stays, and that both postoperative IL-8 and TNFα levels were significantly higher in patients with longer ventilation lengths. There was no evidence that biomarker levels mediated the association between AKI and length of ventilation; they appear to be independent predictors. CONCLUSIONS Preoperative IL-8 and postoperative TNFα are significantly associated with higher odds of AKI and greater lengths of hospital stays and ventilator use in children 2 years and older.

An Unusual Cause of Dyspnea

Sialadenoma papilliferum is a tumor of salivary gland origin. It is believed that sialadenoma papilliferum is a benign lesion usually known to occur in the hard palate, retromolar fat pads, lips, and parotid glands. Its origin in the bronchial tree is an extremely rare occurrence. We report only the fourth known case of bronchial sialadenoma papilliferum and the first to originate in the trachea. The patient underwent successful resection of the lesion, with complete relief of his dyspnea.