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1.  Acute Kidney Injury and Mortality following Ventricular Assist Device Implantation 
American journal of nephrology  2014;39(3):195-203.
Background
Ventricular assist devices (VADs) are increasingly common and their surgical implantation predisposes patients to an increased risk of acute kidney injury (AKI). We sought to evaluate the incidence, risk factors, short and long term all cause mortality of patients with AKI following VAD implantation.
Methods
We identified all patients who underwent VAD implantation at the University of Chicago from January 1, 2008 to January 31, 2012. We evaluated the incidence of AKI, defined as a ≥50% increase in serum creatinine over the first 7 post-operative days (RIFLE Risk-Creatinine). A logistic regression model was used to identify risk factors for development of AKI and a cox proportional hazards model was used to examine factors associated with 30-day and 365-day all cause mortality.
Results
157 eligible patients had VAD implantations with 44 (28%) developing post-implantation AKI. In a multivariate analysis only diabetes mellitus [OR=2.25 (1.03-4.94), P=0.04] was identified as a significant predictor of postoperative AKI. Using a multivariable model censored for heart transplantation, only AKI [HR= 3.01(1.15-7.92), P=0.03] and cardiopulmonary bypass time [HR =1.01(1.001-1.02), P= 0.02] were independent predictors of 30-day mortality. Pre-operative Body Mass Index [HR=0.95(0.90-0.99), P=0.03], pre-operative diabetes mellitus [HR=1.89 (1.07-3.35), P=0.03] and post-implantation AKI [HR=1.85 (1.06-3.21); P=0.03] independently predicted 365-day mortality.
Conclusion
AKI is common following VAD implantation and is an independent predictor of 30-day and 1-year all cause mortality.
doi:10.1159/000358495
PMCID: PMC4000722  PMID: 24556808
Acute Kidney Injury; Cardiac Surgery; Mortality; Ventricular Assist Device; RIFLE
2.  Preoperative angiotensin-converting enzyme inhibitors and angiotensin receptor blocker use and acute kidney injury in patients undergoing cardiac surgery 
Nephrology Dialysis Transplantation  2013;28(11):2787-2799.
Background
Using either an angiotensin-converting enzyme inhibitor (ACEi) or an angiotensin receptor blocker (ARB) the morning of surgery may lead to ‘functional’ postoperative acute kidney injury (AKI), measured by an abrupt increase in serum creatinine. Whether the same is true for ‘structural’ AKI, measured with new urinary biomarkers, is unknown.
Methods
The TRIBE-AKI study was a prospective cohort study of 1594 adults undergoing cardiac surgery at six hospitals between July 2007 and December 2010. We classified the degree of exposure to ACEi/ARB into three categories: ‘none’ (no exposure prior to surgery), ‘held’ (on chronic ACEi/ARB but held on the morning of surgery) or ‘continued’ (on chronic ACEi/ARB and taken the morning of surgery). The co-primary outcomes were ‘functional’ AKI based upon changes in pre- to postoperative serum creatinine, and ‘structural AKI’, based upon peak postoperative levels of four urinary biomarkers of kidney injury.
Results
Across the three levels (none, held and continued) of ACEi/ARB exposure there was a graded increase in functional AKI, as defined by AKI stage 1 or worse; (31, 34 and 42%, P for trend 0.03) and by percentage change in serum creatinine from pre- to postoperative (25, 26 and 30%, P for trend 0.03). In contrast, there were no differences in structural AKI across the strata of ACEi/ARB exposure, as assessed by four structural AKI biomarkers (neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, interleukin-18 or liver-fatty acid-binding protein).
Conclusions
Preoperative ACEi/ARB usage was associated with functional but not structural acute kidney injury. As AKI from ACEi/ARB in this setting is unclear, interventional studies testing different strategies of perioperative ACEi/ARB use are warranted.
doi:10.1093/ndt/gft405
PMCID: PMC3811062  PMID: 24081864
acute renal failure; biomarkers; serum creatinine
3.  Chemical Analog-to-Digital Signal Conversion Based on Robust Threshold Chemistry and Its Evaluation in the Context of Microfluidics-Based Quantitative Assays 
Journal of the American Chemical Society  2013;135(39):10.1021/ja4062882.
In this paper, we describe a nonlinear threshold chemistry based on enzymatic inhibition and demonstrate how it can be coupled with microfluidics to convert a chemical concentration (analog input) into patterns of ON or OFF reaction outcomes (chemical digital readout). Quantification of small changes in concentration is needed in a number of assays, such as that for cystatin C, where a 1.5-fold increase in concentration may indicate the presence of acute kidney injury or the progression of chronic kidney disease. We developed an analog-to-digital chemical signal conversion that gives visual readout and applied it to an assay for cystatin C as a model target. The threshold chemistry is based on enzymatic inhibition and gives sharper responses with tighter inhibition. The chemistry described here uses acetylcholinesterase (AChE) and produces an unambiguous color change when the input is above a pre-determined threshold concentration. An input gives a pattern of ON/OFF responses when subjected to a monotonic sequence of threshold concentrations, revealing the input concentration at the point of transition from OFF to ON outcomes. We demonstrated that this threshold chemistry can detect a 1.30–fold increase in concentration at 22 °C, and that it is robust to experimental fluctuations: it provided the same output despite changes in temperature (22–34 °C) and readout time (10-fold range). We applied this threshold chemistry to diagnostics by coupling it with a traditional sandwich immunoassay for serum cystatin C. Because one quantitative measurement comprises several assays, each with its own threshold concentration, we used a microfluidic SlipChip device to process 12 assays in parallel, detecting a 1.5-fold increase (0.64 mg/L (49 nM) to 0.96 mg/L (74 nM)) of cystatin C in serum. We also demonstrated applicability to analysis of patient serum samples and the ability to image results using a cell phone camera. This work indicates that combining developments in nonlinear chemistries with microfluidics may lead to the development of user-friendly diagnostic assays with simple readouts.
doi:10.1021/ja4062882
PMCID: PMC3860884  PMID: 24060606
4.  Adjudication of etiology of acute kidney injury: experience from the TRIBE-AKI multi-center study 
BMC Nephrology  2014;15:105.
Background
Adjudication 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)).
Methods
We 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.
Results
There 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.
Conclusion
The 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 registration
Clinicaltrials.gov: NCT00774137
doi:10.1186/1471-2369-15-105
PMCID: PMC4091753  PMID: 24996668
Acute kidney injury; Acute tubular necrosis; Cardio-thoracic surgery; Adjudication
5.  The Effects of Heart Failure on Renal Function 
Cardiology clinics  2010;28(3):453-465.
Summary
Heart-kidney interactions have been increasingly recognized by clinicians and researchers involved in the study and treatment of heart failure and kidney disease. A classification system has been developed to categorize the different manifestations of cardiac and renal dysfunction. Recent work has highlighted the significant negative prognostic effect of worsening renal function on outcomes for individuals with heart failure. The etiology of the concomitant cardiac and renal dysfunction remains unclear; however, increasing evidence supports alternatives to the established theory of underfilling, including effects of venous congestion and changes in intra-abdominal pressure. Conventional therapy focuses on blockade of the renin-angiotensin-aldosterone system with expanding use of direct renin and aldosterone antagonists. Novel therapeutic interventions using extracorporeal therapy and antagonists of the adenosine pathway show promise and require further investigation.
doi:10.1016/j.ccl.2010.04.004
PMCID: PMC2904358  PMID: 20621250
Cardiorenal; decompensated heart failure; acute kidney injury; management; prognosis
6.  Urinary Cystatin C and Acute Kidney Injury After Cardiac Surgery 
Background
Acute Kidney Injury (AKI) is common following cardiac surgery and is associated with adverse patient outcomes. Urinary cystatin C (CysC) is a biomarker of proximal tubule function and may rise earlier in AKI than serum creatinine.
Study Design
Prospective cohort study
Settings & Participants
The TRIBE AKI (Translational Research Investigating Biomarker Endpoints in AKI) Consortium prospectively enrolled 1,203 adults and 299 children at 8 institutions from 2007–2009.
Index Test
Urinary CysC (mg/L) within the first 12 hours after surgery
Outcome
Serum Creatinine based AKI was defined as AKI Network stage 1 (Mild AKI) as well as a doubling of serum creatinine from the pre-operative value or the need for dialysis during hospitalization (Severe AKI).
Other Measurements
Analyses were adjusted for characteristics used clinically for AKI risk stratification including age, sex, race, eGFR, diabetes, hypertension, heart failure, non-elective surgery, cardiac catheterization within 72 hours, type of surgery, myocardial infarction, and cardiopulmonary bypass time greater than 120 minutes.
Results
Urinary CysC measured in the early post-operative period (0–6 and 6–12 hours postoperatively) correlated with both mild and severe AKI in adults and children. However after analyses were adjusted for other factors the effect was attenuated for both forms of AKI in both cohorts.
Limitations
Limited numbers of patients with severe AKI and short-term dialysis
Conclusions
Urinary CysC values are not significantly associated with the development of AKI following cardiac surgery in adults and children.
doi:10.1053/j.ajkd.2012.12.006
PMCID: PMC3627833  PMID: 23332602
Acute kidney injury Biomarkers; Cystatin C; Dialysis; Peri-operative
7.  Human miRNome Profiling Identifies MicroRNAs Differentially Present in the Urine after Kidney Injury 
Clinical chemistry  2013;59(12):10.1373/clinchem.2013.210245.
BACKGROUND
Extracellular microRNAs (miRNAs) have been proposed as potentially robust and stable biomarkers of various disease conditions. The primary objective of this study was to identify miRNAs differentially occurring in the urine that could serve as potential biomarkers of acute kidney injury (AKI), because traditional AKI markers have limitations with respect to sensitivity, specificity, and timeliness of diagnosis.
METHODS
We profiled 1809 miRNAs in pooled urine samples from 6 patients with AKI and from 6 healthy controls. We measured the 378 stably detectable miRNAs in the 12 samples individually and selected the top 7 miRNAs that were most different in the urine of patients with AKI compared with the non-AKI control individuals. These miRNAs were assessed in a larger cohort of patients with AKI (n = 98:71 AKI patients in the intensive care unit (ICU) and 27 kidney transplantation patients with biopsy-proven tubular injury) and patients without AKI (n = 97: 74 healthy volunteers and 23 ICU patients without AKI).
RESULTS
We identified 4 miRNAs capable of significantly differentiating patients with AKI from individuals without AKI: miR-21 (P = 0.0005), miR-200c (P < 0.0001), miR-423 (P = 0.001), and miR-4640 (P = 0.0355). The combined cross-validated area under the ROC curve for these 4 miRNAs was 0.91. The imprecision with respect to miRNA isolation and reverse transcription efficiency was <9% across 224 samples.
CONCLUSIONS
In this study we determined the entire miRNome of human urine and identified a panel of miRNAs that are both detectable noninvasively and diagnostically sensitive indicators of kidney damage.
doi:10.1373/clinchem.2013.210245
PMCID: PMC3870155  PMID: 24153252
8.  Implementation of Novel Biomarkers in the Diagnosis, Prognosis, and Management of Acute Kidney Injury: Executive Summary from the Tenth Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) 
Contributions to nephrology  2013;182:10.1159/000349962.
Detection of acute kidney injury is undergoing a dynamic revolution of biomarker technology allowing greater, earlier, and more accurate determination of diagnosis, prognosis, and with powerful implication for management. Biomarkers can be broadly considered as any measurable biologic entity or process that allows differentiation between normal function and injury or disease. The ADQI (Acute Dialysis Quality Initiative) had its Ninth Consensus Conference dedicated to synthesis and formulation of the existing literature on biomarkers for the detection of acute kidney injury in a variety of settings. In the papers that accompany this summary, ADQI workgroups fully develop key concepts from a summary of the literature in the domains of early diagnosis, differential diagnosis, prognosis and management, and concurrent physiologic and imaging measures.
doi:10.1159/000349962
PMCID: PMC3856225  PMID: 23689652
9.  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 AKI detection by cystatin C relative to creatinine following cardiac surgery.
Study Design
Prospective cohort study
Settings and 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
Outcome
Post-surgical 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, AKI endpoints were defined by the relative increases in each marker from baseline (25, 50 and 100%) and the incidence of AKI was compared based upon each marker. Secondary aims were to compare clinical outcomes among patients defined as having AKI by cystatin C and/or creatinine.
Results
Overall, serum creatinine detected more cases of AKI than cystatin C: 35% developed a ≥25% increase in serum creatinine, whereas only 23% had ≥25% increase in cystatin C (p < 0.001). Creatinine 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 were generally not statistically different for AKI cases detected by creatinine or cystatin C. However, for each AKI threshold, patients with AKI confirmed by both markers had significantly higher risk of the combined mortality/dialysis outcome compared with patients with AKI detected by creatinine alone (p=0.002).
Limitations
There were few adverse clinical outcomes, limiting our ability to detect differences in outcomes between subgroups of patients based upon their definitions of AKI.
Conclusion
In this large multicenter study, we found that cystatin C was less sensitive for AKI detection compared with creatinine. However, confirmation by cystatin C appeared to identify a subset of AKI patients with substantially higher risk of adverse outcomes.
doi:10.1053/j.ajkd.2012.06.002
PMCID: PMC3496012  PMID: 22809763
10.  Development and Standardization of a Furosemide Stress Test to Predict the Severity of Acute Kidney Injury 
Critical Care  2013;17(5):R207.
Introduction
In the setting of early acute kidney injury (AKI), no test has been shown to definitively predict the progression to more severe stages.
Methods
We investigated the ability of a furosemide stress test (FST) (one-time dose of 1.0 or 1.5 mg/kg depending on prior furosemide-exposure) to predict the development of AKIN Stage-III in 2 cohorts of critically ill subjects with early AKI. Cohort 1 was a retrospective cohort who received a FST in the setting of AKI in critically ill patients as part of Southern AKI Network. Cohort 2 was a prospective multicenter group of critically ill patients who received their FST in the setting of early AKI.
Results
We studied 77 subjects; 23 from cohort 1 and 54 from cohort 2; 25 (32.4%) met the primary endpoint of progression to AKIN-III. Subjects with progressive AKI had significantly lower urine output following FST in each of the first 6 hours (p<0.001). The area under the receiver operator characteristic curves for the total urine output over the first 2 hours following FST to predict progression to AKIN-III was 0.87 (p = 0.001). The ideal-cutoff for predicting AKI progression during the first 2 hours following FST was a urine volume of less than 200mls(100ml/hr) with a sensitivity of 87.1% and specificity 84.1%.
Conclusions
The FST in subjects with early AKI serves as a novel assessment of tubular function with robust predictive capacity to identify those patients with severe and progressive AKI. Future studies to validate these findings are warranted.
doi:10.1186/cc13015
PMCID: PMC4057505  PMID: 24053972
11.  Pre-Operative Serum Brain Natriuretic Peptide and Risk of Acute Kidney Injury after Cardiac Surgery 
Circulation  2012;125(11):1347-1355.
Background
Acute kidney injury (AKI) following cardiac surgery is associated with poor outcomes and is difficult to predict. We conducted a prospective study to evaluate whether pre-operative brain natriuretic peptide (BNP) levels predict postoperative AKI among patients undergoing cardiac surgery.
Methods and Results
The TRIBE-AKI Consortium enrolled 1,139 adults undergoing cardiac surgery at six hospitals from 2007–2009, who were selected for high AKI risk. Pre-operative BNP was categorized into quintiles. AKI was common using Acute Kidney Injury Network definitions; at least mild AKI was a ≥0.3mg/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 pre-operative characteristics, pre-operative 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 [RR] 1.87; 1.40–2.49) and severe AKI (RR 3.17; 1.06–9.48). After adjustment for clinical predictors, addition of BNP improved the area under the curve to predict at least mild AKI (0.67 to 0.69, p=0.02) and severe AKI (0.73 to 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 0.183; 0.061, 0.314; severe AKI 0.231; 0.067, 0.506).
Conclusions
Pre-operative BNP level is associated with post-operative AKI in high-risk patients undergoing cardiac surgery. If confirmed in other types of patients and surgeries, pre-operative BNP may be a valuable component of future efforts to improve pre-operative risk stratification and discrimination among surgical candidates.
doi:10.1161/CIRCULATIONAHA.111.029686
PMCID: PMC3312808  PMID: 22322531
brain natriuretic peptide; cardiac surgery; acute renal failure; creatinine
12.  Autologous Creatinine Clearance in a Case of Necrotizing Fasciitis and Anuria 
American Journal of Nephrology  2012;35(3):225-229.
Necrotizing fasciitis can present with concomitant acute kidney injury. The etiology of acute kidney injury is often multifactorial; potential sources include volume depletion, abdominal compartment syndrome, rhabdomyolysis, and acute tubular necrosis (which may be related to hemodynamic instability, medications, or sepsis/infection). Kidney injury, defined via changes in serum creatinine, portends increased morbidity and mortality. Thus, it is crucial to accurately diagnose and assess the severity of kidney injury. We present the case of a patient with necrotizing fasciitis who endured 31 consecutive days of complete anuria. His serum creatinine decreased over this interval without the use of extracorporeal hemofiltration or dialysis. The explanation for this novel phenomenon lies in massive daily sero-sanguineous discharge and insensible losses with subsequent volume resuscitation. The patient's own convective clearance was substantial enough to maintain a modest creatinine clearance of 15 ml/min during sustained anuria. Our case emphasizes the importance of employing the creatinine, estimated glomerular filtration rate, and urine output portions of the Acute Kidney Injury Network (AKIN) or Risk Injury Failure Loss End stage (RIFLE) criteria in assessing the severity of kidney injury. It further reinforces the imperfection in using serum creatinine as a primary measure of glomerular filtration rate.
doi:10.1159/000336309
PMCID: PMC3711005  PMID: 22343604
Necrotizing soft tissue infection; Fasciitis; Acute renal failure; Burn; Debridement
13.  Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury 
Critical Care  2013;17(1):R25.
Introduction
Acute kidney injury (AKI) can evolve quickly and clinical measures of function often fail to detect AKI at a time when interventions are likely to provide benefit. Identifying early markers of kidney damage has been difficult due to the complex nature of human AKI, in which multiple etiologies exist. The objective of this study was to identify and validate novel biomarkers of AKI.
Methods
We performed two multicenter observational studies in critically ill patients at risk for AKI - discovery and validation. The top two markers from discovery were validated in a second study (Sapphire) and compared to a number of previously described biomarkers. In the discovery phase, we enrolled 522 adults in three distinct cohorts including patients with sepsis, shock, major surgery, and trauma and examined over 300 markers. In the Sapphire validation study, we enrolled 744 adult subjects with critical illness and without evidence of AKI at enrollment; the final analysis cohort was a heterogeneous sample of 728 critically ill patients. The primary endpoint was moderate to severe AKI (KDIGO stage 2 to 3) within 12 hours of sample collection.
Results
Moderate to severe AKI occurred in 14% of Sapphire subjects. The two top biomarkers from discovery were validated. Urine insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2), both inducers of G1 cell cycle arrest, a key mechanism implicated in AKI, together demonstrated an AUC of 0.80 (0.76 and 0.79 alone). Urine [TIMP-2]·[IGFBP7] was significantly superior to all previously described markers of AKI (P <0.002), none of which achieved an AUC >0.72. Furthermore, [TIMP-2]·[IGFBP7] significantly improved risk stratification when added to a nine-variable clinical model when analyzed using Cox proportional hazards model, generalized estimating equation, integrated discrimination improvement or net reclassification improvement. Finally, in sensitivity analyses [TIMP-2]·[IGFBP7] remained significant and superior to all other markers regardless of changes in reference creatinine method.
Conclusions
Two novel markers for AKI have been identified and validated in independent multicenter cohorts. Both markers are superior to existing markers, provide additional information over clinical variables and add mechanistic insight into AKI.
Trial registration
ClinicalTrials.gov number NCT01209169.
doi:10.1186/cc12503
PMCID: PMC4057242  PMID: 23388612
14.  Presurgical Serum Cystatin C and Risk of Acute Kidney Injury After Cardiac Surgery 
Background
Acute kidney injury (AKI) following cardiac surgery is associated with poor outcomes, but is challenging to predict from information available prior to surgery.
Study Design
Prospective cohort study
Setting & Participants
The TRIBE-AKI Consortium enrolled 1,147 adults undergoing cardiac surgery at six hospitals from 2007–2009; participants were selected for high AKI risk.
Predictors
Pre-surgical cystatin C, creatinine, and creatinine-based estimated glomerular filtration rate (eGFR) were categorized into quintiles and grouped as ‘Best’ (quintiles 1–2), ‘Intermediate’ (quintiles 3–4), and ‘Worst’ (quintile 5) kidney function.
Outcomes
The primary outcome was AKI Network (Acute Kidney Injury Network) Stage 1 or higher; ≥0.3mg/dL or 50% rise in creatinine.
Measurements
Analyses were adjusted for characteristics used clinically for pre-surgical risk stratification.
Results
The average age and kidney function were: 71±10 years (mean ± standard deviation), serum creatinine 1.1±0.3 mg/dL, eGFR-Cr, 74±9 mL/min/1.73m2, and cystatin C, 0.9 ±0.3 mg/L. A total of 407 (36%) participants developed AKI during hospitalization. Adjusted odds ratios for intermediate and worst kidney function by cystatin C were 1.9 (95% CI, 1.4–2.7) and 4.8 (95% CI, 2.9–7.7) compared with 1.2 (95% CI, 0.9–1.7) and 1.8 (95% CI, 1.2–2.6) for creatinine and 1.0 (95% CI, 0.7–1.4) and 1.7 (95% CI, 1.1–2.3) for eGFR-Cr categories, respectively. After adjustment for clinical predictors, the C statistic to predict AKI was 0.70 without kidney markers, 0.69 with creatinine, and 0.72 with cystatin C. Cystatin C also substantially improved AKI risk classification compared to creatinine, based on a net reclassification index of 0.21 (p<0.001).
Limitations
The ability of these kidney biomarkers to predict risk for dialysis-requiring AKI or death could not be reliably assessed in our study due to a small number of patients with either outcome.
Conclusions
Pre-surgical cystatin C is better than creatinine or creatinine-based eGFR at forecasting the risk of AKI after cardiac surgery.
doi:10.1053/j.ajkd.2011.03.015
PMCID: PMC3159705  PMID: 21601336
acute renal failure; creatinine; prognosis
15.  Urine Cystatin C as a Biomarker of Proximal Tubular Function Immediately after Kidney Transplantation 
American Journal of Nephrology  2011;33(5):407-413.
Background/Aims
Clinical methods to predict allograft function soon after kidney transplantation are ineffective.
Methods
We analyzed urine cystatin C (CyC) in a prospective multicenter observational cohort study of deceased-donor kidney transplants to determine its peritransplant excretion pattern, utility for predicting delayed graft function (DGF) and association with 3-month graft function. Serial urine samples were collected for 2 days following transplant and analyzed blindly for CyC. We defined DGF as any hemodialysis in the first week after transplant, slow graft function (SGF) as a serum creatinine reduction <70% by the first week and immediate graft function (IGF) as a reduction ≥70%.
Results
Of 91 recipients, 33 had DGF, 34 had SGF and 24 had IGF. Urine CyC/urine creatinine was highest in DGF for all time-points. The area under the curve (95% CI) for predicting DGF at 6 h was 0.69 (0.57–0.81) for urine CyC, 0.74 (0.62–0.86) for urine CyC/urine creatinine and 0.60 (0.45–0.75) for percent change in urine CyC. On the first postoperative day, urine CyC/urine creatinine and percent change in urine CyC were associated with 3-month graft function.
Conclusion
Urine CyC on the day after transplant differs between degrees of perioperative graft function and modestly corresponds with 3-month function.
doi:10.1159/000326753
PMCID: PMC3100377  PMID: 21494031
Transplantation; Biomarkers; Ischemia/reperfusion; Outcomes
16.  Mechanical Ventilation and the Kidney 
Blood Purification  2009;29(1):52-68.
Acute lung injury (ALI) and acute kidney injury (AKI) are complications often encountered in the setting of critical illness. Both forms of end-organ injury commonly occur in similar settings of systemic inflammatory response syndrome, shock, and evolving multiple organ dysfunction. Recent elucidation of the pathobiology of critical illness has led to a more basic mechanistic understanding of the complex interplay between injured organs in patients with multiple organ dysfunction syndrome; this has been aptly called ‘the slippery slope of critical illness’ [Kidney Int Suppl 1998;66:S25–S33]. Distant organ effects of apparently isolated injuries to the lungs, gut, and kidneys have all been discovered in recent years. In this article, we will review the harmful bidirectional interaction between ALI and AKI, which appears to be a common clinical syndrome with routine clinical implications. We will review the current understanding of lung-kidney interactions from both perspectives, including the renal effects of ALI and mechanical ventilation, and the pulmonary sequelae of AKI. In this review of the emerging evidence of deleterious bidirectional organ cross talk between lung and kidney, we will focus on the role of ventilator-induced kidney injury in the pathogenesis of AKI in patients with ALI.
doi:10.1159/000259585
PMCID: PMC2914396  PMID: 19923815
Acute kidney injury; Critical care nephrology; Acute lung injury; Mechanical ventilation; Cytokines
17.  Urinary cystatin C as an early biomarker of acute kidney injury following adult cardiothoracic surgery 
Kidney international  2008;74(8):1059-1069.
There is a need to develop early biomarkers of acute kidney injury following cardiac surgery, where morbidity and mortality are increased by its presence. Plasma cystatin C (CyC) and plasma and urine Neutrophil Gelatinase Associated Lipocalin (NGAL) have been shown to detect kidney injury earlier than changes in plasma creatinine in critically ill patients. In order to determine the utility of urinary CyC levels as a measure of kidney injury, we prospectively collected plasma and urine from 72 adults undergoing elective cardiac surgery for analysis. Acute kidney injury was defined as a 25% or greater increase in plasma creatinine or renal replacement therapy within the first 72 hours following surgery. Plasma CyC and NGAL were not useful predictors of acute kidney injury within the first 6 hours following surgery. In contrast, both urinary CyC and NGAL were elevated in the 34 patients who later developed acute kidney injury, compared to those with no injury. The urinary NGAL at the time of ICU arrival and the urinary CyC level 6 hours after ICU admission were most useful for predicting acute kidney injury. A composite time point consisting of the maximum urinary CyC achieved in the first 6 hours following surgery outperformed all individual time points. Our study suggests that urinary CyC and NGAL are superior to conventional and novel plasma markers in the early diagnosis of acute kidney injury following adult cardiac surgery.
doi:10.1038/ki.2008.341
PMCID: PMC2745082  PMID: 18650797
cystatin C; acute kidney injury; biomarker; cardiac surgery; Neutrophil Gelatinase Associated Lipocalin

Results 1-17 (17)