Isaac E Hall

Publications (10)41.68 Total impact

• Article: Association between peritransplant kidney injury biomarkers and 1-year allograft outcomes.

  Isaac E Hall, Mona D Doshi, Peter P Reese, Richard J Marcus, Heather Thiessen-Philbrook, Chirag R Parikh
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  ABSTRACT: Current tools to predict outcomes after kidney transplantation are inadequate. The objective of this study was to determine the association of perioperative urine neutrophil gelatinase-associated lipocalin and IL-18 with poor 1-year allograft function (return to dialysis or estimated GFR<30 ml/min per 1.73 m(2)). Neutrophil gelatinase-associated lipocalin and IL-18 from early post-transplant urine was measured in this prospective, multicenter study of deceased-donor kidney transplant recipients. The outcome of poor allograft function at 1 year relative to these biomarkers using multivariable logistic regression and net reclassification improvement was examined. Also, the interaction between delayed graft function and the biomarkers on the outcome were evaluated, and the change in biomarkers over consecutive days related to the outcome using trend tests was examined. Mean age for the 153 recipients was 54 ± 13 years. Delayed graft function occurred in 42%, and 24 (16%) recipients had the 1-year outcome. Upper median values for neutrophil gelatinase-associated lipocalin and IL-18 on the first postoperative day had adjusted odds ratios (95% confidence interval) of 6.0 (1.5-24.0) and 5.5 (1.4-21.5), respectively. Net reclassification improvement (95% confidence interval) was significant for neutrophil gelatinase-associated lipocalin and IL-18 at 36% (1%-71%) and 45% (8%-83%), respectively. There was no significant interaction between biomarkers and delayed graft function on the outcome. Change in biomarkers moderately trended with the outcome. Perioperative urine neutrophil gelatinase-associated lipocalin and IL-18 are associated with poor 1-year allograft function, suggesting their potential for identifying patients for therapies that minimize the risk of additional injury.
  Clinical Journal of the American Society of Nephrology 06/2012; 7(8):1224-33. · 5.23 Impact Factor
• Article: Deceased-donor kidney perfusate and urine biomarkers for kidney allograft outcomes: a systematic review.

  Ronik S Bhangoo, Isaac E Hall, Peter P Reese, Chirag R Parikh
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  ABSTRACT: Accurate and reliable assessment of kidney quality before transplantation is needed to predict recipient outcomes and to optimize management and allocation of the allograft. The aim of this study was to systematically review the published literature on biomarkers in two mediums (the perfusate from deceased-donor kidneys receiving machine perfusion and deceased-donor urine) that were evaluated for their possible association with outcomes after kidney transplantation. We searched the Ovid Medline and Scopus databases using broad keywords related to deceased-donor biomarkers in kidney transplantation (limited to humans and the English language). Studies were included if they involved deceased-donor kidneys, measured perfusate or urine biomarkers and studied a possible relationship between biomarker concentrations and kidney allograft outcomes. Each included article was assessed for methodological quality. Of 1430 abstracts screened, 29 studies met the inclusion criteria. Of these, 23 were studies of perfusate (16 biomarkers examined) and 6 were studies of urine (18 biomarkers examined). Only 3 studies (two perfusate) met the criteria of 'good' quality and only 12 were published since 2000. Perfusate lactate dehydrogenase, glutathione-S-transferase (GST) and aspartate transaminase were all found to be significantly associated with delayed graft function in a majority of their respective studies (6/9, 4/6 and 2/2 studies, respectively). Urine neutrophil gelatinase-associated lipocalin, GST, Trolox-equivalent antioxidant capacity and kidney injury molecule-1 were found to be significantly associated with allograft outcomes in single studies that examined diverse end points. Higher quality studies are needed to investigate modern kidney injury biomarkers, to validate novel biomarkers in larger donor populations and to determine the incremental predictive value of biomarkers over traditional clinical variables.
  Nephrology Dialysis Transplantation 04/2012; 27(8):3305-14. · 3.40 Impact Factor
• Article: Resolution of proteinuria in a patient with focal segmental glomerulosclerosis following BiPAP initiation for obesity hypoventilation syndrome.

  Isaac E Hall, Michael Kashgarian, Gilbert W Moeckel, Neera K Dahl
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  ABSTRACT: Associations between secondary focal segmental glomerulosclerosis and both obesity and obstructive sleep apnea have been previously described. Current theory suggests obesity induces glomerular hyperfiltration, leading to glomerulosclerosis. We describe a case of focal segmental glomerulosclerosis in the setting of severe obesity and obstructive sleep apnea with complete resolution of heavy proteinuria following treatment with bi-level positive airway pressure. The patient's proteinuria resolved completely with treatment of obstructive sleep apnea although the patient remained morbidly obese.
  Clinical nephrology 01/2012; 77(1):62-5. · 1.17 Impact Factor
• Article: Risk of poor outcomes with novel and traditional biomarkers at clinical AKI diagnosis.

  Isaac E Hall, Steven G Coca, Mark A Perazella, Umo U Eko, Randy L Luciano, Patricia R Peter, Won K Han, Chirag R Parikh
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  ABSTRACT: Studies have evaluated acute kidney injury (AKI) using biomarkers in various settings, but their prognostic utility within current practice is unclear. Thus, we sought to determine the prognostic utility of newer biomarkers or traditional markers (fractional excretion of sodium [FeNa] and urea [FeUrea] and microscopy) over clinical assessment alone. This is a prospective cohort study of adults on the first day of meeting AKI criteria. We measured urine concentrations of neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and IL-18 and determined FeNa, FeUrea, and microscopy score for casts and tubular cells. Primary outcome was worsened AKI stage from enrollment to peak serum creatinine or in-hospital death. In 249 recipients, 57% were ≥65 years old, 48% were from intensive care, and mean baseline GFR was 69 ± 30 ml/min per 1.73 m(2). AKI was considered prerenal in 164 (66%), acute tubular necrosis (ATN) in 51 (20%), and "other" in 34 (14%). All mean protein biomarker concentrations, FeNa, FeUrea, and microscopy scores were statistically different between prerenal and ATN. Seventy-two patients (29%) developed the primary outcome. There was an approximate three-fold increase in adjusted risk for the outcome for upper versus lower values of NGAL, KIM-1, IL-18, and microscopy score (P values <0.05). Net reclassification improved after adding these to baseline clinical assessment. FeNa and FeUrea were not useful. On the first day of AKI, urine protein biomarkers and microscopy significantly improve upon clinical determination of prognosis, indicating their potential utility in current practice.
  Clinical Journal of the American Society of Nephrology 12/2011; 6(12):2740-9. · 5.23 Impact Factor
• Article: A comparison of alternative serum biomarkers with creatinine for predicting allograft function after kidney transplantation.

  Isaac E Hall, Mona D Doshi, Emilio D Poggio, Chirag R Parikh
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  ABSTRACT: The role of serum cystatin C (Scyc), neutrophil gelatinase-associated lipocalin, and interleukin-18 in predicting early graft function after kidney transplant is poorly defined. We conducted a multicenter prospective cohort study of deceased-donor kidney transplants. We collected serial blood samples for the first 3 days of transplant and monitored need for dialysis within 1 week and graft function at 3 months after transplant. Among 78 recipients with serum biomarker measurements, 26 had delayed graft function (DGF; hemodialysis within 1 week of transplant). Of those not dialyzed, 29 had slow graft function (serum creatinine [Scr] reduction from transplantation to day 7 <70%), and 23 had immediate graft function (IGF; reduction in Scr ≥70%). Scyc levels were statistically different between groups by the first postoperative day (POD), whereas Scr levels were not. Serum neutrophil gelatinase-associated lipocalin and serum interleukin-18 levels were not different between groups. Scyc on the first POD demonstrated good utility for predicting DGF and non-IGF (DGF or slow graft function) with areas under the receiver-operating characteristic curve of 0.83 and 0.85, respectively. Areas under the receiver-operating characteristic curve for predicting DGF and non-IGF using Scr on the first POD were 0.65 and 0.53, respectively. Substituting Scyc for Scr in a clinical algorithm improved its utility for predicting DGF or non-IGF, with adjusted odds ratios of 2.4 and 3.3 for Scyc levels on the first POD. The change in Scyc during the first POD demonstrated a dose-response relationship with 3-month graft function. Scyc outperforms Scr as a predictor of early graft function after deceased-donor kidney transplant.
  Transplantation 01/2011; 91(1):48-56. · 4.00 Impact Factor
• Article: Urine cystatin C as a biomarker of proximal tubular function immediately after kidney transplantation.

  Isaac E Hall, Jay L Koyner, Mona D Doshi, Richard J Marcus, Chirag R Parikh
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  ABSTRACT: Clinical methods to predict allograft function soon after kidney transplantation are ineffective. 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%. 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. Urine CyC on the day after transplant differs between degrees of perioperative graft function and modestly corresponds with 3-month function.
  American Journal of Nephrology 01/2011; 33(5):407-13. · 2.54 Impact Factor
• Article: Human models to evaluate urinary biomarkers of kidney injury.

  Isaac E Hall, Chirag R Parikh
  Clinical Journal of the American Society of Nephrology 12/2010; 5(12):2141-3. · 5.23 Impact Factor
• Article: Urine microscopy is associated with severity and worsening of acute kidney injury in hospitalized patients.

  Mark A Perazella, Steven G Coca, Isaac E Hall, Umo Iyanam, Madiha Koraishy, Chirag R Parikh
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  ABSTRACT: Serum creatinine concentration at the time of nephrology consultation is not necessarily indicative of the severity of acute kidney injury (AKI). Although urine microscopy is useful to differentiate AKI, its role in predicting adverse clinical outcomes has not been well described. The relationship between urine microscopy findings at the time of nephrology consultation for AKI and clinical outcomes was evaluated prospectively. A urinary sediment scoring system was created on the basis of the number of renal tubular epithelial cells and granular casts. The primary outcome was worsening of AKI (progressing to higher AKI Network stage, dialysis, or death) during hospitalization. Of 249 patients consulted for AKI, 197 had acute tubular necrosis or prerenal AKI and were included in the analysis. At consultation, 80 (40%) had stage 1, 53 (27%) had stage 2, and 66 (33%) had stage 3 AKI. The urinary sediment combined scores were lowest in those with stage 1 and highest in stage 3 AKI. Seventy-nine patients (40%) experienced worsening of AKI from the time of consultation. The urinary scoring system was significantly associated with increased risk of worsening AKI (adjusted relative risk: 7.3; 95% confidence interval: 4.5 to 9.7 for worsening with score of > or =3 versus score of 0) and was more predictive than AKI Network stage at the time of consultation. The urinary sediment score may be a useful tool to predict worsening of AKI due to either acute tubular necrosis or prerenal AKI during hospitalization.
  Clinical Journal of the American Society of Nephrology 03/2010; 5(3):402-8. · 5.23 Impact Factor
• Article: IL-18 and urinary NGAL predict dialysis and graft recovery after kidney transplantation.

  Isaac E Hall, Sri G Yarlagadda, Steven G Coca, Zhu Wang, Mona Doshi, Prasad Devarajan, Won K Han, Richard J Marcus, Chirag R Parikh
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  ABSTRACT: Current methods for predicting graft recovery after kidney transplantation are not reliable. We performed a prospective, multicenter, observational cohort study of deceased-donor kidney transplant patients to evaluate urinary neutrophil gelatinase-associated lipocalin (NGAL), IL-18, and kidney injury molecule-1 (KIM-1) as biomarkers for predicting dialysis within 1 wk of transplant and subsequent graft recovery. We collected serial urine samples for 3 d after transplant and analyzed levels of these putative biomarkers. We classified graft recovery as delayed graft function (DGF), slow graft function (SGF), or immediate graft function (IGF). Of the 91 patients in the cohort, 34 had DGF, 33 had SGF, and 24 had IGF. Median NGAL and IL-18 levels, but not KIM-1 levels, were statistically different among these three groups at all time points. ROC curve analysis suggested that the abilities of NGAL or IL-18 to predict dialysis within 1 wk were moderately accurate when measured on the first postoperative day, whereas the fall in serum creatinine (Scr) was not predictive. In multivariate analysis, elevated levels of NGAL or IL-18 predicted the need for dialysis after adjusting for recipient and donor age, cold ischemia time, urine output, and Scr. NGAL and IL-18 quantiles also predicted graft recovery up to 3 mo later. In summary, urinary NGAL and IL-18 are early, noninvasive, accurate predictors of both the need for dialysis within the first week of kidney transplantation and 3-mo recovery of graft function.
  Journal of the American Society of Nephrology 09/2009; 21(1):189-97. · 9.66 Impact Factor
• Source

  Available from: PubMed Central

  Article: Predictors of venous thromboembolism in patients with advanced common solid cancers.

  Isaac E Hall, Martin S Andersen, Harlan M Krumholz, Cary P Gross
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  ABSTRACT: There is uncertainty about risk heterogeneity for venous thromboembolism (VTE) in older patients with advanced cancer and whether patients can be stratified according to VTE risk. We performed a retrospective cohort study of the linked Medicare-Surveillance, Epidemiology, and End Results cancer registry in older patients with advanced cancer of lung, breast, colon, prostate, or pancreas diagnosed between 1995-1999. We used survival analysis with demographics, comorbidities, and tumor characteristics/treatment as independent variables. Outcome was VTE diagnosed at least one month after cancer diagnosis. VTE rate was highest in the first year (3.4%). Compared to prostate cancer (1.4 VTEs/100 person-years), there was marked variability in VTE risk (hazard ratio (HR) for male-colon cancer 3.73 (95% CI 2.1-6.62), female-colon cancer HR 6.6 (3.83-11.38), up to female-pancreas cancer HR 21.57 (12.21-38.09). Stage IV cancer and chemotherapy resulted in higher risk (HRs 1.75 (1.44-2.12) and 1.31 (1.0-1.57), resp.). Stratifying the cohort by cancer type and stage using recursive partitioning analysis yielded five groups of VTE rates (nonlocalized prostate cancer 1.4 VTEs/100 person-years, to nonlocalized pancreatic cancer 17.4 VTEs/100 patient-years). In a high-risk population with advanced cancer, substantial variability in VTE risk exists, with notable differences according to cancer type and stage.
  Journal of Cancer Epidemiology 01/2009; 2009:182521.