Chirag R Parikh

Yale University, New Haven, Connecticut, United States

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Publications (239)1487.62 Total impact

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    ABSTRACT: Reviewing the literature in many fields on proposed risk models reveals problems with the way many risk models are developed. Furthermore, papers reporting new risk models do not always provide sufficient information to allow readers to assess the merits of the model. In this review, we discuss sources of bias that can arise in risk model development. We focus on two biases that can be introduced during data analysis. These two sources of bias are sometimes conflated in the literature and we recommend the terms resubstitution bias and model-selection bias to delineate them. We also propose the RiGoR reporting standard to improve transparency and clarity of published papers proposing new risk models.
    12/2015; 3(1):2. DOI:10.1186/s40364-014-0027-7
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    ABSTRACT: Given growth in kidney transplant waitlists and discard rates, donor kidney acceptance is an important problem. We used network analysis to examine whether organ procurement organization (OPO) network centrality affects discard and outcomes. We identified 106,160 deceased donor kidneys recovered for transplant from 2000 to 2010 in Scientific Registry of Transplant Recipients. We constructed the transplant network by year with each OPO representing a node and each kidney-sharing relationship between OPOs representing a directed tie between nodes. Primary exposures were the number of different OPOs to which an OPO has given a kidney or from which an OPO has received a kidney in year preceding procurement year. Primary outcomes were discard, cold-ischemia time, delayed graft function, and 1-year graft loss. We used multivariable regression, restricting analysis to the 50% of OPOs with highest discard and stratifying remaining OPOs by kidney volume. Models controlled for kidney donor risk index, waitlist time, and kidney pumping. An increase in one additional OPO to which a kidney was given by a procuring OPO in a year was associated with 1.4% lower likelihood of discard for a given kidney (odds ratio, 0.986; 95% confidence interval, 0.974-0.998) among OPOs procuring high kidney volume, but 2% higher likelihood of discard (odds ratio, 1.021; 95% confidence interval, 1.006-1.037) among OPOs procuring low kidney volume, with mixed associations with recipient outcomes. Our study highlights the value of network analysis in revealing how broader kidney sharing is associated with levels of organ acceptance. We conclude interventions to promote broader inter-OPO sharing could be developed to reduce discard for a subset of OPOs.
    Transplantation 06/2015; DOI:10.1097/TP.0000000000000773 · 3.78 Impact Factor
  • Sarah C Huen, Chirag R Parikh
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    ABSTRACT: AKI is a common hospital complication. There are no effective treatments to minimize kidney injury or limit associated morbidity and mortality. Currently, serum creatinine and urine output remain the gold standard used clinically in the diagnosis of AKI. Several novel biomarkers can diagnose AKI earlier than elevations of serum creatinine and changes in urine output. Recent long term observational studies have elucidated a sub-group of patients who have positive biomarkers of AKI but do not meet criteria for AKI by serum creatinine or urine output, termed subclinical AKI. These patients with subclinical AKI have increased risk of both short and long-term mortality. In this review we will highlight the implications of what these patients may represent and the need for better phenotyping of AKI by etiology, severity of injury and ability to recover. We will discuss two AKI biomarkers, NGAL and BRP-39/YKL-40, that exemplify the need to characterize the complexity of the biologic meaning behind the biomarker, beyond elevated levels reporting on tissue injury. Ultimately, careful phenotyping of AKI will lead to identification of therapeutic targets and appropriate patient populations for clinical trials. Copyright © 2014, American Journal of Physiology - Renal Physiology.
    AJP Renal Physiology 06/2015; DOI:10.1152/ajprenal.00682.2014 · 4.42 Impact Factor
  • PLoS ONE 06/2015; 10(6):e0129619. DOI:10.1371/journal.pone.0129619 · 3.53 Impact Factor
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    ABSTRACT: APOL1 genotype is associated with advanced kidney disease in African Americans, but the pathogenic mechanisms are unclear. Here, associations of APOL1 genotype with urine biomarkers of glomerular and tubular injury and kidney function decline were evaluated. Observational study. 431 human immunodeficiency virus (HIV)-infected African American women enrolled in Women's Interagency HIV Study (WIHS). APOL1 genotype. Albumin-creatinine ratio (ACR), 4 tubular injury biomarkers (interleukin 18 [IL-18], kidney injury molecule 1 [KIM-1], neutrophil gelatinase-associated lipocalin [NGAL], and α1-microglobulin [A1M]), and kidney function estimated using the CKD-EPI cystatin C equation. Participants were genotyped for APOL1 single-nucleotide polymorphisms rs73885319 (G1 allele) and rs71785313 (G2 allele). Urine biomarkers were measured using stored samples from 1999-2000. Cystatin C was measured using serum collected at baseline and 4- and 8-year follow-ups. At baseline, ACRs were higher among 47 women with 2 APOL1 risk alleles versus 384 women with 0/1 risk allele (median, 24 vs 11mg/g; P<0.001). Compared with women with 0/1 risk allele, women with 2 risk alleles had 104% higher ACRs (95% CI, 29-223mg/g) and 2-fold greater risk of ACR>30 (95% CI, 1.17-3.44) mg/g after multivariable adjustment. APOL1 genotype showed little association with urine IL-18:Cr ratio, KIM-1:Cr ratio, and NGAL:Cr ratio (estimates of -5% [95% CI, -24% to 18%], -20% [95% CI, -36% to -1%], and 10% [95% CI, -26% to 64%], respectively) or detectable urine A1M (prevalence ratio, 1.13; 95% CI, 0.65-1.97) in adjusted analyses. Compared with women with 0/1 allele, women with 2 risk alleles had faster eGFR decline, by 1.2 (95% CI, 0.2 to 2.2) mL/min/1.73m(2) per year, and 1.7- and 3.4-fold greater rates of incident chronic kidney disease (95% CI, 1.1 to 2.5) and 10% annual eGFR decline (95% CI, 1.7 to 6.7), respectively, with minimal attenuation after adjustment for glomerular and tubular injury biomarker levels. Results may not be generalizable to men. Among HIV-infected African American women, APOL1-associated kidney injury appears to localize to the glomerulus, rather than the tubules. Published by Elsevier Inc.
    American Journal of Kidney Diseases 04/2015; 65(6). DOI:10.1053/j.ajkd.2015.02.329 · 5.76 Impact Factor
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    ABSTRACT: Children undergoing cardiac surgery may exhibit a pronounced inflammatory response to cardiopulmonary bypass (CPB). Inflammation is recognized as an important pathophysiologic process leading to acute kidney injury (AKI). The aim of this study was to evaluate the association of the inflammatory cytokines interleukin (IL)-6 and IL-10 with AKI and other adverse outcomes in children after CPB surgery. This is a sub-study of the Translational Research Investigating Biomarker Endpoints in AKI (TRIBE-AKI) cohort, including 106 children ranging in age from 1 month to 18 years undergoing CPB. Plasma IL-6 and IL-10 concentrations were measured preoperatively and postoperatively [day 1 (within 6 h after surgery) and day 3]. Stage 2/3 AKI, defined by at least a doubling of the baseline serum creatinine concentration or dialysis, was diagnosed in 24 (23 %) patients. The preoperative IL-6 concentration was significantly higher in patients with stage 2/3 AKI [median 2.6 pg/mL, interquartile range (IQR) 2.6 0.6-4.9 pg/mL] than in those without stage 2/3 AKI (median 0.6 pg/mL, IQR 0.6-2.2 pg/mL) (p = 0.03). After adjustment for clinical and demographic variables, the highest preoperative IL-6 tertile was associated with a sixfold increased risk for stage 2/3 AKI compared with the lowest tertile (adjusted odds ratio 6.41, 95 % confidence interval 1.16-35.35). IL-6 and IL-10 levels increased significantly after surgery, peaking postoperatively on day 1. First postoperative IL-6 and IL-10 measurements did not significantly differ between patients with stage 2/3 AKI and those without stage 2/3 AKI. The elevated IL-6 level on day 3 was associated with longer hospital stay (p = 0.0001). Preoperative plasma IL-6 concentration is associated with the development of stage 2/3 AKI and may be prognostic of resource utilization.
    Pediatric Nephrology 04/2015; DOI:10.1007/s00467-015-3088-4 · 2.88 Impact Factor
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    ABSTRACT: Inflammation has an integral role in the pathophysiology of AKI. We investigated the associations of two biomarkers of inflammation, plasma IL-6 and IL-10, with AKI and mortality in adults undergoing cardiac surgery. Patients were enrolled at six academic centers (n=960). AKI was defined as a ≥50% or ≥0.3-mg/dl increase in serum creatinine from baseline. Pre- and postoperative IL-6 and IL-10 concentrations were categorized into tertiles and evaluated for associations with outcomes of in-hospital AKI or postdischarge all-cause mortality at a median of 3 years after surgery. Preoperative concentrations of IL-6 and IL-10 were not significantly associated with AKI or mortality. Elevated first postoperative IL-6 concentration was significantly associated with higher risk of AKI, and the risk increased in a dose-dependent manner (second tertile adjusted odds ratio [OR], 1.61 [95% confidence interval (95% CI), 1.10 to 2.36]; third tertile adjusted OR, 2.13 [95% CI, 1.45 to 3.13]). First postoperative IL-6 concentration was not associated with risk of mortality; however, the second tertile of peak IL-6 concentration was significantly associated with lower risk of mortality (adjusted hazard ratio, 0.75 [95% CI, 0.57 to 0.99]). Elevated first postoperative IL-10 concentration was significantly associated with higher risk of AKI (adjusted OR, 1.57 [95% CI, 1.04 to 2.38]) and lower risk of mortality (adjusted HR, 0.72 [95% CI, 0.56 to 0.93]). There was a significant interaction between the concentration of neutrophil gelatinase-associated lipocalin, an established AKI biomarker, and the association of IL-10 concentration with mortality (P=0.01). These findings suggest plasma IL-6 and IL-10 may serve as biomarkers for perioperative outcomes. Copyright © 2015 by the American Society of Nephrology.
    Journal of the American Society of Nephrology 04/2015; DOI:10.1681/ASN.2014080764 · 9.47 Impact Factor
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    ABSTRACT: Research has identified improved biomarkers of acute kidney injury (AKI). Cystatin C (CysC) is a better glomerular filtration rate marker than serum creatinine (SCr) and may improve AKI definition. To determine if defining clinical AKI by increases in CysC vs SCr alters associations with biomarkers and clinical outcomes. Three-center prospective cohort study of intensive care units in New Haven, Connecticut, Cincinnati, Ohio, and Montreal, Quebec, Canada. Participants were 287 patients 18 years or younger without preoperative AKI or end-stage renal disease who were undergoing cardiac surgery. The study dates were July 1, 2007, through December 31, 2009. For biomarker vs clinical AKI associations, the exposures were first postoperative (0-6 hours after surgery) urine interleukin 18, neutrophil gelatinase-associated lipocalin, kidney injury molecule 1, and liver fatty acid-binding protein. For clinical AKI outcome associations, the exposure was Kidney Disease: Improving Global Outcomes AKI definition (based on SCr or CysC). Clinical AKI, length of stay, and length of mechanical ventilation. We determined areas under the receiver operating characteristic curve and odds ratios for first postoperative biomarkers to predict AKI. The SCr-defined vs CysC-defined AKI incidence differed substantially (43.6% vs 20.6%). Percentage agreement was 71% (κ = 0.38); stage 2 or worse AKI percentage agreement was 95%. Interleukin 18 and kidney injury molecule 1 discriminated for CysC-defined AKI better than for SCr-defined AKI. For interleukin 18 and kidney injury molecule 1, the areas under the receiver operating characteristic curve were 0.74 and 0.65, respectively, for CysC-defined AKI, and 0.66 and 0.58, respectively, for SCr-defined AKI. Fifth (vs first) quintile concentrations of both biomarkers were more strongly associated with CysC-defined AKI. For interleukin 18 and kidney injury molecule 1, the odds ratios were 16.19 (95% CI, 3.55-73.93) and 6.93 (95% CI, 1.88-25.59), respectively, for CysC-defined AKI vs 6.60 (95% CI, 2.76-15.76) and 2.04 (95% CI, 0.94-4.38), respectively, for SCr-defined AKI. Neutrophil gelatinase-associated lipocalin and liver fatty acid-binding protein associations with both definitions were similar. The CysC definitions and SCr definitions were similarly associated with clinical outcomes of resource use. Compared with the SCr-based definition, the CysC-based definition is more strongly associated with urine interleukin 18 and kidney injury molecule 1 in children undergoing cardiac surgery. Consideration should be made for defining AKI based on CysC in clinical care and future studies.
    04/2015; 169(6). DOI:10.1001/jamapediatrics.2015.54
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    ABSTRACT: Acute kidney injury (AKI) is a common complication after cardiac surgery and is associated with worse outcomes. Since heart fatty acid binding protein (H-FABP) is a myocardial protein that detects cardiac injury, we sought to determine whether plasma H-FABP was associated with AKI in the TRIBE-AKI cohort; a multi-center cohort of 1219 patients at high risk for AKI who underwent cardiac surgery. The primary outcomes of interest were any AKI (Acute Kidney Injury Network (AKIN) stage 1 or higher) and severe AKI (AKIN stage 2 or higher). The secondary outcome was long-term mortality after discharge. Patients who developed AKI had higher levels of H-FABP pre- and postoperatively than patients who did not have AKI. In analyses adjusted for known AKI risk factors, first postoperative log(H-FABP) was associated with severe AKI (adjusted odds ratio (OR) 5.39 (95% confidence interval (CI), 2.87-10.11) per unit increase), while preoperative log(H-FABP) was associated with any AKI (2.07 (1.48-2.89)) and mortality (1.67 (1.17-2.37)). These relationships persisted after adjustment for change in serum creatinine (for first postoperative log(H-FABP)) and biomarkers of cardiac and kidney injury, including brain natriuretic peptide, cardiac troponin-I, interleukin-18, liver fatty acid binding protein, kidney injury molecule-1, and neutrophil gelatinase-associated lipocalin. Thus, perioperative plasma H-FABP levels may be used for risk stratification of AKI and mortality following cardiac surgery.Kidney International advance online publication, 1 April 2015; doi:10.1038/ki.2015.104.
    Kidney International 04/2015; DOI:10.1038/ki.2015.104 · 8.52 Impact Factor
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    ABSTRACT: Deceased donor kidneys with acute kidney injury (AKI) are often discarded due to fear of poor outcomes. We performed a multicenter study to determine associations of AKI (increasing admission-to-terminal serum creatinine by AKI Network stages) with kidney discard, delayed graft function (DGF) and 6-month estimated glomerular filtration rate (eGFR). In 1632 donors, kidney discard risk increased for AKI stages 1, 2 and 3 (compared to no AKI) with adjusted relative risks of 1.28 (1.08-1.52), 1.82 (1.45-2.30) and 2.74 (2.0-3.75), respectively. Adjusted relative risk for DGF also increased by donor AKI stage: 1.27 (1.09-1.49), 1.70 (1.37-2.12) and 2.25 (1.74-2.91), respectively. Six-month eGFR, however, was similar across AKI categories but was lower for recipients with DGF (48 [interquartile range: 31-61] vs. 58 [45-75] ml/min/1.73m(2) for no DGF, p < 0.001). There was significant favorable interaction between donor AKI and DGF such that 6-month eGFR was progressively better for DGF kidneys with increasing donor AKI (46 [29-60], 49 [32-64], 52 [36-59] and 58 [39-71] ml/min/1.73m(2) for no AKI, stage 1, 2 and 3, respectively; interaction p = 0.05). Donor AKI is associated with kidney discard and DGF, but given acceptable 6-month allograft function, clinicians should consider cautious expansion into this donor pool. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.
    American Journal of Transplantation 03/2015; 15(6). DOI:10.1111/ajt.13144 · 6.19 Impact Factor
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    ABSTRACT: To examine the relationship of cardiac biomarkers with postoperative acute kidney injury (AKI) among pediatric patients undergoing cardiac surgery. Data from TRIBE-AKI, a prospective study of children undergoing cardiac surgery, were used to examine the association of cardiac biomarkers (N-type pro-B-type natriuretic peptide, creatine kinase-MB [CK-MB], heart-type fatty acid binding protein [h-FABP], and troponins I and T) with the development of postoperative AKI. Cardiac biomarkers were collected before and 0 to 6 hours after surgery. AKI was defined as a ≥50% or 0.3 mg/dL increase in serum creatinine, within 7 days of surgery. Of the 106 patients included in this study, 55 (52%) developed AKI after cardiac surgery. Patients who developed AKI had higher median levels of pre- and postoperative cardiac biomarkers compared with patients without AKI (all P < .01). Preoperatively, higher levels of CK-MB and h-FABP were associated with increased odds of developing AKI (CK-MB: adjusted odds ratio 4.58, 95% confidence interval [CI] 1.56-13.41; h-FABP: adjusted odds ratio 2.76, 95% CI 1.27-6.03). When combined with clinical models, both preoperative CK-MB and h-FABP provided good discrimination (area under the curve 0.77, 95% CI 0.68-0.87, and 0.78, 95% CI 0.68-0.87, respectively) and improved reclassification indices. Cardiac biomarkers collected postoperatively did not significantly improve the prediction of AKI beyond clinical models. Preoperative CK-MB and h-FABP are associated with increased risk of postoperative AKI and provide good discrimination of patients who develop AKI. These biomarkers may be useful for risk stratifying patients undergoing cardiac surgery. Copyright © 2015 by the American Academy of Pediatrics.
    Pediatrics 03/2015; 135(4). DOI:10.1542/peds.2014-2949 · 5.30 Impact Factor
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    ABSTRACT: 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. 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, number NCT01862419. 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). An electronic alert system for acute kidney injury did not improve clinical outcomes among patients in hospital. Penn Center for Healthcare Improvement and Patient Safety. Copyright © 2015 Elsevier Ltd. All rights reserved.
    The Lancet 02/2015; 385(9981). DOI:10.1016/S0140-6736(15)60266-5 · 45.22 Impact Factor
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    ABSTRACT: Background: There is an epidemic of chronic kidney disease (CKD) of unknown etiology in Central American workers. Objectives: To investigate changes and job-specific differences in kidney function over a 6-month sugarcane harvest season, explore the potential role of hydration, and measure proteinuria. Methods: We recruited 284 Nicaraguan sugarcane workers performing seven distinct tasks. We measured urine albumin and serum creatinine and estimated glomerular filtration rate (eGFR). Results: eGFR varied by job and decreased during the harvest in seed cutters (-8·6 ml/min/1·73 m(2)), irrigators (-7·4 ml/min/1·73 m(2)), and cane cutters (-5·0 ml/min/1·73 m(2)), as compared to factory workers. The number of years employed at the company was negatively associated with eGFR. Fewer than 5% of workers had albumin-to-creatinine ratio (ACR) >30 mg/g. Conclusions: The decline in kidney function during the harvest and the differences by job category and employment duration provide evidence that one or more risk factors of CKD are occupational.
    International journal of occupational and environmental health 01/2015; DOI:10.1179/2049396714Y.0000000102 · 1.10 Impact Factor
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    ABSTRACT: Net fluid and weight loss are ubiquitously employed to monitor diuretic response in acute decompensated heart failure research and patient care. However, the performance of these metrics has never been critically evaluated. The weight and volume of aqueous fluids such as urine should be nearly perfectly correlated and with very good agreement. As a result significant discrepancy between fluid and weight loss during the treatment of acute decompensated heart failure would indicate measurement error in one or both of the parameters. The correlation and agreement (Bland-Altman method) between diuretic-induced fluid/weight loss were examined in three acute decompensated heart failure trials and cohorts: 1) DOSE (n=254) 2) ESCAPE (n=348) the 3) Penn (n=486). The correlation between fluid and weight loss was modest (DOSE r=0.55; ESCAPE r=0.48; Penn r=0.51; p<0.001 for all) and the 95% limits of agreement were wide (DOSE -7.9 to 6.4 Kg-L; ESCAPE -11.6 to 7.5 Kg-L; Penn -14.5 to 11.3 Kg-L). The median relative disagreement ranged from ± 47.0% to 63.5%. A bias toward greater fluid than weight loss was found across populations (-0.74 to -2.1 Kg-L p≤0.002). A consistent pattern of baseline characteristics or in-hospital treatment parameters that could identify patients at risk of discordant fluid and weight loss was not found. Considerable discrepancy between fluid balance and weight loss is common in patients treated for acute decompensated heart failure. Awareness of the limitations inherent to these commonly used metrics and efforts to develop more reliable measures of diuresis are critical for both patient care and research in acute decompensated heart failure. Copyright © 2015 Elsevier Inc. All rights reserved.
    The American Journal of Medicine 01/2015; 128(7). DOI:10.1016/j.amjmed.2014.12.020 · 5.30 Impact Factor
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    ABSTRACT: This paper proposes a new statistical approach for predicting postoperative morbidity such as intensive care unit length of stay and number of complications after cardiac surgery in children. In a recent multi-center study sponsored by the National Institutes of Health, 311 children undergoing cardiac surgery were enrolled. Morbidity data are count data in which the observations take only nonnegative integer values. Often, the number of zeros in the sample cannot be accommodated properly by a simple model, thus requiring a more complex model such as the zero-inflated Poisson regression model. We are interested in identifying important risk factors for postoperative morbidity among many candidate predictors. There is only limited methodological work on variable selection for the zero-inflated regression models. In this paper, we consider regularized zero-inflated Poisson models through penalized likelihood function and develop a new expectation–maximization algorithm for numerical optimization. Simulation studies show that the proposed method has better performance than some competing methods. Using the proposed methods, we analyzed the postoperative morbidity, which improved the model fitting and identified important clinical and biomarker risk factors. Copyright © 2014 John Wiley & Sons, Ltd.
    Statistics in Medicine 12/2014; 33(29). DOI:10.1002/sim.6314 · 2.04 Impact Factor
  • Duminda N Wijeysundera, Chirag R Parikh
    Anesthesiology 12/2014; DOI:10.1097/ALN.0000000000000548 · 6.17 Impact Factor
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    Jason H Greenberg, Steven Coca, Chirag R Parikh
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    ABSTRACT: Acute kidney injury (AKI) is associated with significant short-term morbidity and mortality in children. However, the risk for long-term outcomes after AKI is largely unknown. We performed a systematic review and meta-analysis to determine the cumulative incidence rate of proteinuria, hypertension, decline in glomerular filtration rate (GFR), and mortality after an episode of AKI. After screening 1934 published articles from 1985-2013, we included 10 cohort studies that reported long-term outcomes after AKI in children. A total of 346 patients were included in these studies with a mean follow-up of 6.5 years (range 2-16) after AKI. The studies were of variable quality and had differing definitions of AKI with five studies only including patients who required dialysis during an AKI episode. There was a substantial discrepancy in the outcomes across these studies, most likely due to study size, disparate outcome definitions, and methodological differences. In addition, there was no non-AKI comparator group in any of the published studies. The cumulative incidence rates for proteinuria, hypertension, abnormal GFR (<90 ml/min/1.73 m2), GFR < 60 ml/min/1.73 m2, end stage renal disease, and mortality per 100 patient-years were 3.1 (95% CI 2.1-4.1), 1.4 (0.9-2.1), 6.3 (5.1-7.5), 0.8 (0.4 -1.4), 0.9 (0.6-1.4), and 3.7 (2.8-4.5) respectively. AKI appears to be associated with a high risk of long-term renal outcomes in children. These findings may have implications for care after an episode of AKI in children. Future prospective studies with appropriate non-AKI comparator groups will be required to confirm these results.
    BMC Nephrology 11/2014; 15(1):184. DOI:10.1186/1471-2369-15-184 · 1.52 Impact Factor
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    ABSTRACT: Importance: Acute kidney injury, a common complication of surgery, is associated with poor outcomes and high health care costs. Some studies suggest aspirin or clonidine administered during the perioperative period reduces the risk of acute kidney injury; however, these effects are uncertain and each intervention has the potential for harm. Objective: To determine whether aspirin compared with placebo, and clonidine compared with placebo, alters the risk of perioperative acute kidney injury. Design, Setting, and Participants: A 2 × 2 factorial randomized, blinded, clinical trial of 6905 patients undergoing noncardiac surgery from 88 centers in 22 countries with consecutive patients enrolled between January 2011 and December 2013. Interventions: Patients were assigned to take aspirin (200 mg) or placebo 2 to 4 hours before surgery and then aspirin (100 mg) or placebo daily up to 30 days after surgery, and were assigned to take oral clonidine (0.2 mg) or placebo 2 to 4 hours before surgery, and then a transdermal clonidine patch (which provided clonidine at 0.2 mg/d) or placebo patch that remained until 72 hours after surgery. Main Outcomes and Measures: Acute kidney injury was primarily defined as an increase in serum creatinine concentration from the preoperative concentration by either an increase of 0.3 mg/dL or greater (≥26.5 μmol/L) within 48 hours of surgery or an increase of 50% or greater within 7 days of surgery. Results: Aspirin (n = 3443) vs placebo (n = 3462) did not alter the risk of acute kidney injury (13.4% vs 12.3%, respectively; adjusted relative risk, 1.10; 95% CI, 0.96-1.25). Clonidine (n = 3453) vs placebo (n = 3452) did not alter the risk of acute kidney injury (13.0% vs 12.7%, respectively; adjusted relative risk, 1.03; 95% CI, 0.90-1.18). Aspirin increased the risk of major bleeding. In a post hoc analysis, major bleeding was associated with a greater risk of subsequent acute kidney injury (23.3% when bleeding was present vs 12.3% when bleeding was absent; adjusted hazard ratio, 2.20; 95% CI, 1.72-2.83). Similarly, clonidine increased the risk of clinically important hypotension. In a post hoc analysis, clinically important hypotension was associated with a greater risk of subsequent acute kidney injury (14.3% when hypotension was present vs 11.8% when hypotension was absent; adjusted hazard ratio, 1.34; 95% CI, 1.14-1.58). Conclusions and Relevance: Among patients undergoing major noncardiac surgery, neither aspirin nor clonidine administered perioperatively reduced the risk of acute kidney injury.
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    ABSTRACT: Acute kidney injury, a common complication of surgery, is associated with poor outcomes and high health care costs. Some studies suggest aspirin or clonidine administered during the perioperative period reduces the risk of acute kidney injury; however, these effects are uncertain and each intervention has the potential for harm.

Publication Stats

7k Citations
1,487.62 Total Impact Points


  • 2006–2015
    • Yale University
      • School of Medicine
      New Haven, Connecticut, United States
  • 2005–2015
    • Yale-New Haven Hospital
      • Department of Pathology
      New Haven, Connecticut, United States
  • 2012
    • University of Toronto
      Toronto, Ontario, Canada
    • Indiana University-Purdue University Indianapolis
      • Department of Medicine
      Indianapolis, IN, United States
    • McGill University Health Centre
      Montréal, Quebec, Canada
  • 2011
    • Wayne State University
      • Department of Internal Medicine
      Detroit, MI, United States
  • 2009–2011
    • The University of Western Ontario
      • Division of Nephrology
      London, Ontario, Canada
  • 2008
    • Rochester General Hospital
      • Division of Internal Medicine
      Rochester, NY, United States
  • 2007–2008
    • Virginia Commonwealth University
      • Division of Nephrology
      Ричмонд, Virginia, United States
    • Minneapolis Veterans Affairs Hospital
      Minneapolis, Minnesota, United States
  • 2002–2004
    • University of Colorado Hospital
      • Department of Medicine
      Denver, Colorado, United States
    • University of Colorado
      Denver, Colorado, United States
    • Nassau County Medical Center
      East Meadow, New York, United States