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Chirag parikh

Sanjiv M Baxi, Rebecca Scherzer, Vasantha Jotwani, Michelle M Estrella, Alison G Abraham, Chirag R Parikh, Michael R Bennett, Mardge H Cohen, Marek J Nowicki, Deborah R Gustafson, Anjali Sharma, Mary A Young, Michael G Shlipak
BACKGROUND: Urine biomarkers have helped identify persons at risk for progressing to kidney disease in the setting of HIV infection. We explored factors associated with changes in three urine biomarkers over 10 years among women living with HIV. METHODS: Prospective cohort of 294 HIV-infected women from the multicenter Women's Interagency HIV Study (WIHS). Predictors included HIV viral and immunological parameters, co-morbid conditions and health-related behaviors...
October 18, 2016: Journal of Acquired Immune Deficiency Syndromes: JAIDS
Jason H Greenberg, Michael Zappitelli, Prasad Devarajan, Heather R Thiessen-Philbrook, Catherine Krawczeski, Simon Li, Amit X Garg, Steve Coca, Chirag R Parikh
Importance: Acute kidney injury (AKI) after pediatric cardiac surgery is associated with high short-term morbidity and mortality; however, the long-term kidney outcomes are unclear. Objective: To assess long-term kidney outcomes after pediatric cardiac surgery and to determine if perioperative AKI is associated with worse long-term kidney outcomes. Design, Setting, and Participants: This prospective multicenter cohort study recruited children between ages 1 month to 18 years who underwent cardiopulmonary bypass for cardiac surgery and survived hospitalization from 3 North American pediatric centers between July 2007 and December 2009...
September 12, 2016: JAMA Pediatrics
Bixiao Zhao, Qiongshi Lu, Yuwei Cheng, Justin M Belcher, Edward D Siew, David E Leaf, Simon C Body, Amanda A Fox, Sushrut W Waikar, Charles D Collard, Heather Thiessen-Philbrook, T Alp Ikizler, Lorraine B Ware, Charles L Edelstein, Amit X Garg, Murim Choi, Jennifer A Schaub, Hongyu Zhao, Richard P Lifton, Chirag R Parikh
RATIONALE: Acute kidney injury is a common and severe complication of critical illness and cardiac surgery. Despite significant attempts at developing treatments, therapeutic advances to attenuate acute kidney injury and expedite recovery have largely failed. OBJECTIVES: Identifying genetic loci associated with increased risk of acute kidney injury may reveal novel pathways for therapeutic development. METHODS: We conducted an exploratory genome-wide association study to identify single-nucleotide polymorphisms associated with genetic susceptibility to in-hospital acute kidney injury...
August 30, 2016: American Journal of Respiratory and Critical Care Medicine
Steven G Coca, Girish N Nadkarni, Amit X Garg, Jay Koyner, Heather Thiessen-Philbrook, Eric McArthur, Michael G Shlipak, Chirag R Parikh
BACKGROUND: We previously demonstrated that assessment of the duration of AKI, in addition to magnitude of rise in creatinine alone, adds prognostic information for long-term survival. We evaluated whether post-operative kidney injury biomarkers in urine collected immediately after cardiac surgery associate with duration of serum creatinine elevation. METHODS: We studied 1199 adults undergoing cardiac surgery in a prospective cohort study (TRIBE-AKI) and examined the association between the levels of five urinary biomarkers individually at 0-6 hours after surgery: interleukin-18 (IL-18), neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), liver fatty acid binding protein (L-FABP) and albumin with duration of serum creatinine-based AKIN criteria for AKI (0 (no AKI), 1-2, 3-6, ≥7 days)...
2016: PloS One
Jennifer S Hanberg, Veena Rao, Jozine M Ter Maaten, Olga Laur, Meredith A Brisco, F Perry Wilson, Justin L Grodin, Mahlet Assefa, J Samuel Broughton, Noah J Planavsky, Tariq Ahmad, Lavanya Bellumkonda, W H Wilson Tang, Chirag R Parikh, Jeffrey M Testani
BACKGROUND: Recent epidemiological studies have implicated chloride, rather than sodium, as the driver of poor survival previously attributed to hyponatremia in heart failure. Accumulating basic science evidence has identified chloride as a critical factor in renal salt sensing. Our goal was to probe the physiology bridging this basic and epidemiological literature. METHODS AND RESULTS: Two heart failure cohorts were included: (1) observational: patients receiving loop diuretics at the Yale Transitional Care Center (N=162) and (2) interventional pilot: stable outpatients receiving ≥80 mg furosemide equivalents were studied before and after 3 days of 115 mmol/d supplemental lysine chloride (N=10)...
August 2016: Circulation. Heart Failure
Isaac E Hall, Peter P Reese, Mona D Doshi, Francis L Weng, Bernd Schröppel, William S Asch, Joseph Ficek, Heather Thiessen-Philbrook, Chirag R Parikh
BACKGROUND: Ischemia-reperfusion injury (IRI) leading to delayed graft function, defined by the United Network for Organ Sharing as dialysis in the first week (UNOS-DGF), associates with poor kidney transplant outcomes. Controversies remain, however, about dialysis initiation thresholds and the utility for other criteria to denote less severe IRI, or slow graft function (SGF). METHODS: Multicenter, prospective study of deceased-donor kidney recipients to compare UNOS-DGF to a definition that combines impaired creatinine reduction in the first 48 hours or >1 dialysis session for predicting 12-month estimated glomerular filtration rate (eGFR)...
August 4, 2016: Transplantation
Mona D Doshi, Peter P Reese, Isaac E Hall, Bernd Schröppel, Joseph Ficek, Richard N Formica, Francis L Weng, Rick D Hazs, Heather Thiessen Philbrook, Chirag Parikh
BACKGROUND: Kidneys with "high" kidney donor profile index (KDPI) are often biopsied and pumped, yet frequently discarded. METHODS: In this multicenter study, we describe the characteristics and outcomes of kidneys with KDPI ≥80 that were procured from 338 deceased donors. We excluded donors with anatomical kidney abnormalities. RESULTS: Donors were categorized by the number of kidneys discarded: 1) none (n=154, 46%), 2) 1 discarded and 1 transplanted (n=48, 14%), 3) both discarded (n=136, 40%)...
August 3, 2016: Transplantation
Jeremy Puthumana, Isaac E Hall, Peter P Reese, Bernd Schröppel, Francis L Weng, Heather Thiessen-Philbrook, Mona D Doshi, Veena Rao, Chun Geun Lee, Jack A Elias, Lloyd G Cantley, Chirag R Parikh
Deceased donor kidneys with AKI are often discarded for fear of poor transplant outcomes. Donor biomarkers that predict post-transplant renal recovery could improve organ selection and reduce discard. We tested whether higher levels of donor urinary YKL-40, a repair phase protein, associate with improved recipient outcomes in a prospective cohort study involving deceased kidney donors from five organ procurement organizations. We measured urinary YKL-40 concentration in 1301 donors (111 had AKI, defined as doubling of serum creatinine) and ascertained outcomes in the corresponding 2435 recipients, 756 of whom experienced delayed graft function (DGF)...
July 22, 2016: Journal of the American Society of Nephrology: JASN
Meredith A Brisco, Michael R Zile, Jennifer S Hanberg, F Perry Wilson, Chirag R Parikh, Steven G Coca, W H Wilson Tang, Jeffrey M Testani
BACKGROUND: Worsening renal function (WRF) is a common endpoint in decompensated heart failure clinical trials because of associations between WRF and adverse outcomes. However, WRF has not universally been identified as a poor prognostic sign, challenging the validity of WRF as a surrogate endpoint. Our aim was to describe the associations between changes in creatinine and adverse outcomes in a clinical trial of decongestive therapies. METHODS AND RESULTS: We investigated the association between changes in creatinine and the composite endpoint of death, rehospitalization or emergency room visit within 60 days in 301 patients in the Diuretic Optimization Strategies Evaluation (DOSE) trial...
October 2016: Journal of Cardiac Failure
Jeremiah R Brown, William M Hisey, Emily J Marshall, Donald S Likosky, Elizabeth L Nichols, Allen D Everett, Sara K Pasquali, Marshall L Jacobs, Jeff P Jacobs, Chirag R Parikh
BACKGROUND: Acute kidney injury (AKI) is a common complication after cardiac surgery. While AKI severity is known to be associated with increased risk of short-term outcomes, its long-term impact is less well understood. METHODS: Adult patients undergoing isolated coronary artery bypass graft surgery at eight centers were enrolled into the Northern New England biomarker registry (n = 1,610). Patients were excluded if they had renal failure (n = 15) or died during index admission (n = 38)...
June 17, 2016: Annals of Thoracic Surgery
Jennifer A Schaub, Chirag R Parikh
Acute kidney injury is strongly associated with increased mortality and other adverse outcomes. Medical researchers have intensively investigated novel biomarkers to predict short- and long-term outcomes of acute kidney injury in many patient care settings, such as cardiac surgery, intensive care units, heart failure, and transplant. Future research should focus on leveraging this relationship to improve enrollment for clinical trials of acute kidney injury.
2016: F1000Research
Girish N Nadkarni, Veena Rao, Faramarz Ismail-Beigi, Vivian A Fonseca, Sudhir V Shah, Michael S Simonson, Lloyd Cantley, Prasad Devarajan, Chirag R Parikh, Steven G Coca
BACKGROUND AND OBJECTIVES: Current measures for predicting renal functional decline in patients with type 2 diabetes with preserved renal function are unsatisfactory, and multiple markers assessing various biologic axes may improve prediction. We examined the association of four biomarker-to-creatinine ratio levels (monocyte chemotactic protein-1, IL-18, kidney injury molecule-1, and YKL-40) with renal outcome. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We used a nested case-control design in the Action to Control Cardiovascular Disease Trial by matching 190 participants with ≥40% sustained eGFR decline over the 5-year follow-up period to 190 participants with ≤10% eGFR decline in a 1:1 fashion on key characteristics (age within 5 years, sex, race, baseline albumin-to-creatinine ratio within 20 μg/mg, and baseline eGFR within 10 ml/min per 1...
August 8, 2016: Clinical Journal of the American Society of Nephrology: CJASN
Jennifer S Hanberg, Krishna Sury, F Perry Wilson, Meredith A Brisco, Tariq Ahmad, Jozine M Ter Maaten, J Samuel Broughton, Mahlet Assefa, W H Wilson Tang, Chirag R Parikh, Jeffrey M Testani
BACKGROUND: It is widely believed that a reduced cardiac index (CI) is a significant contributor to renal dysfunction in patients with heart failure (HF). However, recent data have challenged this paradigm. OBJECTIVES: This study sought to determine the relationship between CI and renal function in a multicenter population of HF patients undergoing pulmonary artery catheterization (PAC). METHODS: Patients undergoing PAC in either the randomized or registry portions of the ESCAPE (Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness) trial were included (n = 575)...
May 17, 2016: Journal of the American College of Cardiology
Chirag R Parikh, Dennis G Moledina, Steven G Coca, Heather R Thiessen-Philbrook, Amit X Garg
The use of novel biomarkers of acute kidney injury (AKI) in clinical trials may help evaluate treatments for AKI. Here we explore potential applications of biomarkers in simulated clinical trials of AKI using data from the TRIBE-AKI multicenter, prospective cohort study of patients undergoing cardiac surgery. First, in a hypothetical trial of an effective therapy at the time of acute tubular necrosis to prevent kidney injury progression, use of an indirect kidney injury marker such as creatinine compared to a new direct biomarker of kidney injury reduces the proportion of true acute tubular necrosis cases enrolled...
June 2016: Kidney International
Meredith A Brisco, Michael R Zile, Jozine M Ter Maaten, Jennifer S Hanberg, F Perry Wilson, Chirag Parikh, Jeffrey M Testani
BACKGROUND: Renal dysfunction (RD) is associated with reduced survival in HF; however, not all RD is mechanistically or prognostically equivalent. Notably, RD associated with "pre-renal" physiology, as identified by an elevated blood urea nitrogen to creatinine ratio (BUN/Cr), identifies a particularly high risk RD phenotype. Proteinuria, another domain of renal dysfunction, has also been associated with adverse events. Given that several different mechanisms can cause proteinuria, we sought to investigate whether the mechanism underlying proteinuria also affects survival in HF...
July 15, 2016: International Journal of Cardiology
Vasantha Jotwani, Rebecca Scherzer, Michelle M Estrella, Lisa P Jacobson, Mallory D Witt, Frank Palella, Bernard Macatangay, Michael Bennett, Chirag R Parikh, Joachim H Ix, Michael Shlipak
Tenofovir disoproxil fumarate (TDF) can cause kidney damage, but current clinical tests are insensitive for detecting toxicity. Among 884 HIV-infected men enrolled in the Multicenter AIDS Cohort Study, we measured urine biomarkers specific for tubular damage (interleukin-18, kidney injury molecule-1, procollagen type III N-terminal propeptide) and albuminuria. In adjusted analyses, each year of TDF exposure was independently associated with 3.3% higher interleukin-18 (95% CI: 0.8% to 5.8%), 3.4% higher kidney injury molecule-1 (1...
October 1, 2016: Journal of Acquired Immune Deficiency Syndromes: JAIDS
Emilie P Belley-Côté, Chirag R Parikh, Colleen R Shortt, Steven G Coca, Amit X Garg, John W Eikelboom, Peter Kavsak, Eric McArthur, Heather Thiessen-Philbrook, Richard P Whitlock
OBJECTIVE: Acute kidney injury is common after cardiac surgery and associated with postoperative mortality. Perioperative cardiac biomarkers may predict acute kidney injury and mortality. We evaluated whether cardiac biomarkers were associated with severe acute kidney injury, defined as a doubling in serum creatinine or requiring renal replacement therapy during hospital stay after surgery, and mortality. METHODS: In a prospective multicenter cohort of adults undergoing cardiac surgery, we measured the following biomarkers in preoperative and postoperative banked plasma: high-sensitivity troponin T, cardiac troponin I, creatine kinase-MB, and N-terminal prohormone of brain natriuretic peptide...
July 2016: Journal of Thoracic and Cardiovascular Surgery
Nilay N Suthar, Khushali L Patel, Chirag Saparia, Ami P Parikh
BACKGROUND: Incidence of intracerebral hemorrhage (ICH) is twice as high as in Western countries. Prognostic factors for predicting function outcome and mortality play a major role in determining the treatment outcome. METHODS: A prospective study of male and female patients ≥12 years with primary nontraumatic intracranial hemorrhage were included. Hemorrhage caused by trauma, anticoagulant or thrombolytic drugs, brain tumor, saccular arterial aneurysm or vascular malformation were excluded...
April 2016: Annals of African Medicine
Zhixuan Fu, Chirag R Parikh, Bingqing Zhou
Penalized variable selection methods have been extensively studied for standard time-to-event data. Such methods cannot be directly applied when subjects are at risk of multiple mutually exclusive events, known as competing risks. The proportional subdistribution hazard (PSH) model proposed by Fine and Gray (J Am Stat Assoc 94:496-509, 1999) has become a popular semi-parametric model for time-to-event data with competing risks. It allows for direct assessment of covariate effects on the cumulative incidence function...
March 26, 2016: Lifetime Data Analysis
Meyeon Park, Michael G Shlipak, Heather Thiessen-Philbrook, Amit X Garg, Jay L Koyner, Steven G Coca, Chirag R Parikh
BACKGROUND: Acute kidney injury is a risk factor for death in cardiac surgical patients. Plasma cystatin C and creatinine have different temporal profiles in the postoperative setting, but the associations of simultaneous changes in both filtration markers compared with change in only one marker with prognosis after hospital discharge are not well described. METHODS: This is a longitudinal study of 1,199 high-risk adult cardiac surgical patients in the TRIBE-AKI (Translational Research Investigating Biomarker Endpoints for Acute Kidney Injury) Consortium who survived hospitalization...
April 2016: Annals of Thoracic Surgery
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