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The Laboratory of Charles Edelstein, M.D., Ph.D.


 

My research interests are 1) the pathophysiology acute Kidney injury (AKI), 2) the pathophysiology of polycystic kidney disease (PKD) and 3) biomarkers of acute kidney injury (AKI). 1) My NIH –funded PKD research studies are a) caspases and apoptosis in PKD, b) mammalian target of rapamycin (mTOR) signaling in PKD. We were the first to demonstrate that caspase and apoptosis inhibition reduces proliferation, cyst formation and renal failure in PKD. We were also the first to demonstrate that mTOR inhibition with rapamycin reduces cyst formation and kidney failure in an animal model of PKD. We are presently studying the new generation of mTOR inhibitors in rat and mouse models of PKD. The rapamycin in PKD studies have been translated from the bench to the bedside and we are studying the effect of rapamycin on native polycystic kidney size in kidney transplant patients. 2) My NIH-funded AKI research focuses on the sources and targets of interleukin-18 in animal models of AKI. We are investigating macrophages and NK cells as sources and targets of IL-18 and other caspase-1 related cytokines in AKI in mice. We have also demonstrated that IL-33, the newest member of the IL-1 family of cytokines, is a mediator of cisplatin-induced AKI.  In collaboration with Dr Alkesh Jani we are studying cold preservation injury in mice, pigs and squirrels and are developing a model of kidney transplantation in pigs.  3) I am also a co-investigator of TRIBE-AKI (Translational Research Involving Biomarkers of Early Acute kidney Injury) consortium that is studying biomarkers of acute kidney injury. In this regard urinary interleukin-18 is an early diagnostic marker of acute kidney injury in the intensive care unit. We have demonstrated that urine IL-18, urinary and plasma NGAL are early biomarkers of AKI post cardiac surgery in a cohort of over 1000 patients. We are also studying urinary IL-18 and other biomarkers as early markers of AKI in delayed kidney graft function, post cardiac surgery and in patients receiving a liver transplant.

 

PKD

Tao Y, Kim J, Schrier RW, Edelstein CL. Rapamycin markedly slows disease progression in a rat model of polycystic kidney disease (PKD). J. Am. Soc. Nephrol 16, 46-51, 2005.

Tao Y, Kim J, Schrier RW, Edelstein CL. Caspase inhibition reduces tubular apoptosis and proliferation and slows disease progression in polycystic kidney disease. Proc Natl Acad Sci USA102, 6954-6959, 2005

 Tao Y, Zafar I, Kim J,. Schrier RW and Edelstein CL. Deletion of the caspase-3 gene markedly prolongs survival in the cpk mouse model of  polycystic kidney disease (PKD). J. Am. Soc. Nephrol 19, 749-755, 2008.

Belibi FA, Edelstein CL. Unified ultrasonographic criteria for the diagnosis of ADPKD - Editorial. J. Am. Soc. Nephrol 20(1):6-8, 2009

Belibi F, Ravichandran K, Zafar I, He Z, Edelstein CL, mTORC1/2 and rapamycin in female Han:SPRD rats with polycystic kidney disease (PKD). Am. J. Physiol. Renal Physiol  2011 Jan;300(1):F236-44.

 

Belibi F, Zafar I, Ravichandran K, Bauer Segvic A, Jani A, Galesic Ljubanovic D, Edelstein CL. Hypoxia-inducible  factor-1α and autophagy in polycytic kidney disease. Am. J. Physiol Renal Physiol (in press)

 

AKI

Lee DW, Faubel S, Edelstein CL . Cytokines in acute kidney injury. Clin. Nephrol (in press)

Alkesh Jani , Michael Zimmerman, Jessica Martin , Li Lu, Kultigin Turkmen, K Ravichandran, Arijana Pacic, Danica Ljubanović and Charles L. Edelstein. Pulsatile perfusion reduces apoptosis in a porcine kidney model of donation after cardiac death (DCD). Transplantation 2011 E pub

He Z, Dursun B, Oh DJ, Lu L, FaubelS, Edelstein CL. Macrophages are not the source of injurious IL-18 in ischemic AKI.  Am J. Physiol Renal Physiol 296, F535-42, 2009. PMC2660194

He Z, Lu L, Hoke T, Altmann C, Ljubanovic D, Dinarello C, FaubelS, Edelstein CL. IL-18 binding protein transgenic mice are protected against ischemic acute kidney injury, Am J. Physiol Renal Physiol 295 (5), F414-421, 2008. PMC2584896

Lu L, Oh DJ, Dursun B, He Zhibin, Hoke T, Faubel S, Edelstein CL. Increased macrophage infiltration and fractalkine expression in cisplatin-induced acute renal failure in mice. J. Pharmacol. Exp.Therap. 324(1):111-7, 2008.

Oh DJ , Dursun B, He Z, Lu L , Hoke TS ,  Ljubanovic D , Faubel  S and Edelstein CL. Fractalkine receptor (CX3CR1) inhibition is protective against ischemic acute renal failure in mice. Am. J. Physiol. Renal Physiol 294(1):F264-71, 2008.

Faubel S, Lewis EC, Reznikov L, Ljubanovic D, Hoke TS, Somerset H, Oh DJ, Lu L, Klein CL, Dinarello CA, Edelstein CL. Cisplatin-induced ARF is associated with an increase in the cytokines IL-1β, IL-18, IL-6 and neutrophil infiltration in the kidney. J. Pharmacol. Exp.Therap. 322(1):8-15, 2007.

 

BIOMARKERS OF AKI

Biomarkers of Kidney Disease. Edited by Charles l. Edelstein 437 pages. Published by Academic Press (Elsevier), San Diego 2011

Parikh CR, Devarajan P, Zapitelli M, Sint K, Thiessen-Philbrook H, Li S, Kim RW, Koyner J, Coca S, Edelstein CL, Schlipak MG, Garg AX and Krawczeski            CD      for the TRIBE-AKI consortium. Early post-operative urine and serum    biomarkers predict AKI and poor outcomes after pediatric cardiac surgery.          J. Am. Soc. Nephrol 2011 (in press)

Parikh CR, Coca S, Thiessen-Philbrook H, Schlipak MG, Koyner J, Wang Z, Edelstein CL, Devarajan P, Patel UD, Zapitelli M, Krawczeski CD Passik     CS, Swaminathan M, Garg for the TRIBE-AKI consortium. Post-operative          biomarkers predict AKI and poor outcomes after cardiac surgery in adults.             J. Am. Soc. Nephrol 2011 (in press)

Parikh CR, Jani A, Mishra J, Ma Q, Kelly C, Barasch J, Edelstein CL, Devarajan P. Urine NGAL and IL-18 are predictive biomarkers for delayed graft function following kidney transplantation. Am J Transplant 6, 1639-45, 2006

Parikh CR, Abraham E, Ancukiewicz M, Edelstein CL. Urine IL-18 Is an Early Diagnostic Marker for Acute Kidney Injury and Predicts Mortality in the Intensive Care Unit. J. Am. Soc. Nephrol 16, 3046-3052, 2005

Parikh CR, Mishra J, Thiessen-Philbrook H, Dursun B, Ma Q, Kelly K, Dent C, Devarajan P, Edelstein CL. Urinary IL-18 is an early predictive biomarker of acute kidney injury after cardiac surgery. Kidney Int 70, 199-203, 2006

Alkesh Jani-Associate Professor

Zhibin He- Senior PRA and Lab Manager

Kameswaran Ravichandran - Postdoctoral Fellow

Iram Zafar- PRA

Quocan Nguyen –Medical Student​

DongWon Lee-Research Fellow from Korea