Overview

Chronic kidney disease (CKD) is a significant and growing public health problem. It is currently estimated that 13% of the adult population has CKD and it confers a 5-fold increased risk of premature cardiovascular disease and death. Those who survive long enough eventually require renal replacement therapy with dialysis or a kidney transplant. Many of the risk factors for CKD begin in childhood. a patient develops CKD, the pathological changes that worsen dysfunction are similar in all kidney diseases, and are characterized by a process of ongoing scarring or fibrosis. Despite tremendous progress in our understanding of the causes and consequences of CKD, effective therapies are unknown. Using experimental models of CKD, our studies are designed to investigate how specific cells and molecules mediate kidney fibrosis, with the ultimate goal of translating our findings into new human therapies.

Publications

Range and Heterogeneity of Outcomes in Randomized Trials of Pediatric Chronic Kidney Disease.
The Journal of pediatrics
DOI: 10.1016/j.jpeds.2017.03.034
PubMed: 28449820
07/2017

Standardised Outcomes in Nephrology-Children and Adolescents (SONG-Kids): a protocol for establishing a core outcome set for children with chronic kidney disease.
Tong A, Samuel S, Zappitelli M, Dart A, Furth S, Eddy A, Groothoff J, Webb NJ, Yap HK, Bockenhauer D, Sinha A, Alexander SI, Goldstein SL, Gipson DS, Hanson CS, Evangelidis N, Crowe S, Harris T, Hemmelgarn BR, Manns B
DOI: 10.1186/s13063-016-1528-5
PubMed: 27519274
2016

The impact of small kidneys.
Pediatric nephrology (Berlin, Germany)
DOI: 10.1007/s00467-015-3079-5
PubMed: 25794549
09/2015

Overview of the cellular and molecular basis of kidney fibrosis.
Eddy AA
DOI: 10.1038/kisup.2014.2
PubMed: 25401038
11/2014

Cysteamine modulates oxidative stress and blocks myofibroblast activity in CKD.
Okamura DM, Bahrami NM, Ren S, Pasichnyk K, Williams JM, Gangoiti JA, Lopez-Guisa JM, Yamaguchi I, Barshop BA, Duffield JS, Eddy AA
DOI: 10.1681/asn.2012090962
PubMed: 24009239
01/2014

The Canadian Childhood Nephrotic Syndrome (CHILDNEPH) Project: overview of design and methods.
Samuel S, Scott S, Morgan C, Dart A, Mammen C, Parekh R, Nettel-Aguirre A, Eddy A, Flynn R, Pinsk M, Wade A, Arora S, Benoit G, Bitzan M, Erickson R, Feber J, Filler G, Geier P, Girardin C, Grisaru S
DOI: 10.1186/2054-3581-1-17
PubMed: 25960884
2014

Acute kidney injury and its association with in-hospital mortality among children with acute infections.
Imani PD, Odiit A, Hingorani SR, Weiss NS, Eddy AA
DOI: 10.1007/s00467-013-2544-2
PubMed: 23872929
11/2013

Social paediatrics: From 'lip service' to the health and well-being of Canada's children and youth.
Daneman D, Kellner J, Bernstein M, Dow K, Dugas MA, Duffy C, Eddy A, Filler G, Frappier JY, Gilmour S, Givelichian L, Huang L, Rockman-Greenberg C, Shevell M, Vardy C, Walti H, Orrbine E, Williams M
PubMed: 24421706
08/2013

The origin of scar-forming kidney myofibroblasts.
Eddy AA
DOI: 10.1038/nm.3299
PubMed: 23921738
08/2013

Rising part-time work in the academic pediatric workforce in Canada.
Filler G, Givelichian L, Walti H, Piedboeuf B, Pediatric Chairs of Canada
DOI: 10.1016/j.jpeds.2013.04.040
PubMed: 23885849
08/2013

Investigating mechanisms of chronic kidney disease in mouse models.
Eddy AA, López-Guisa JM, Okamura DM, Yamaguchi I
DOI: 10.1007/s00467-011-1938-2
PubMed: 21695449
08/2012

Albumin-induced apoptosis of glomerular parietal epithelial cells is modulated by extracellular signal-regulated kinase 1/2.
Chang AM, Ohse T, Krofft RD, Wu JS, Eddy AA, Pippin JW, Shankland SJ
DOI: 10.1093/ndt/gfr483
PubMed: 21896500
04/2012

Mannose receptor 2 attenuates renal fibrosis.
López-Guisa JM, Cai X, Collins SJ, Yamaguchi I, Okamura DM, Bugge TH, Isacke CM, Emson CL, Turner SM, Shankland SJ, Eddy AA
DOI: 10.1681/asn.2011030310
PubMed: 22095946
02/2012

Vascular endothelial cadherin modulates renal interstitial fibrosis.
Yamaguchi I, Tchao BN, Burger ML, Yamada M, Hyodo T, Giampietro C, Eddy AA
DOI: 10.1159/000332026
PubMed: 22126970
2012

The TGF-ß route to renal fibrosis is not linear: the miR-21 viaduct.
Eddy AA
DOI: 10.1681/asn.2011070698
PubMed: 21836141
09/2011

Scraping fibrosis: UMODulating renal fibrosis.
Eddy AA
DOI: 10.1038/nm0511-553
PubMed: 21546974
05/2011

Galectin-3 preserves renal tubules and modulates extracellular matrix remodeling in progressive fibrosis.
Okamura DM, Pasichnyk K, Lopez-Guisa JM, Collins S, Hsu DK, Liu FT, Eddy AA
DOI: 10.1152/ajprenal.00326.2010
PubMed: 20962111
01/2011

Nicotinic acetylcholine receptor a1 promotes calpain-1 activation and macrophage inflammation in hypercholesterolemic nephropathy.
Zhang G, Thomas AL, Marshall AL, Kernan KA, Su Y, Zheng Y, Takano J, Saido TC, Eddy AA
DOI: 10.1038/labinvest.2010.135
PubMed: 20661225
01/2011

A novel signaling pathway: fibroblast nicotinic receptor alpha1 binds urokinase and promotes renal fibrosis.
Zhang G, Kernan KA, Thomas A, Collins S, Song Y, Li L, Zhu W, Leboeuf RC, Eddy AA
DOI: 10.1074/jbc.m109.010249
PubMed: 19690163
10/2009

Serine proteases, inhibitors and receptors in renal fibrosis.
Eddy AA
PubMed: 19350108
04/2009

CD36 regulates oxidative stress and inflammation in hypercholesterolemic CKD.
Okamura DM, Pennathur S, Pasichnyk K, López-Guisa JM, Collins S, Febbraio M, Heinecke J, Eddy AA
DOI: 10.1681/asn.2008010009
PubMed: 19211715
03/2009

Phase I trial of rosiglitazone in FSGS: I. Report of the FONT Study Group.
Joy MS, Gipson DS, Dike M, Powell L, Thompson A, Vento S, Eddy A, Fogo AB, Kopp JB, Cattran D, Trachtman H
DOI: 10.2215/cjn.02310508
PubMed: 19073787
01/2009

Macrophage diversity in renal injury and repair.
Ricardo SD, van Goor H, Eddy AA
DOI: 10.1172/jci36150
PubMed: 18982158
11/2008

Angiotensin converting enzyme inhibitor but not angiotensin receptor blockade or statin ameliorates murine adriamycin nephropathy.
Tang SC, Leung JC, Chan LY, Eddy AA, Lai KN
DOI: 10.1038/sj.ki.5002674
PubMed: 18033243
02/2008

Urokinase and its receptors in chronic kidney disease.
Zhang G, Eddy AA
DOI: 10.2741/3093
PubMed: 18508599
2008

Atherogenic scavenger receptor modulation in the tubulointerstitium in response to chronic renal injury.
Okamura DM, López-Guisa JM, Koelsch K, Collins S, Eddy AA
DOI: 10.1152/ajprenal.00063.2007
PubMed: 17537985
08/2007

Endogenous urokinase lacks antifibrotic activity during progressive renal injury.
Yamaguchi I, Lopez-Guisa JM, Cai X, Collins SJ, Okamura DM, Eddy AA
DOI: 10.1152/ajprenal.00380.2006
PubMed: 17356128
07/2007

Plasmin(ogen) promotes renal interstitial fibrosis by promoting epithelial-to-mesenchymal transition: role of plasmin-activated signals.
Zhang G, Kernan KA, Collins SJ, Cai X, López-Guisa JM, Degen JL, Shvil Y, Eddy AA
DOI: 10.1681/asn.2006080886
PubMed: 17267741
03/2007

Plasminogen activator inhibitor-1 in chronic kidney disease: evidence and mechanisms of action.
Eddy AA, Fogo AB
DOI: 10.1681/asn.2006050503
PubMed: 17035608
11/2006

Chronic kidney disease progression.
Eddy AA, Neilson EG
DOI: 10.1681/asn.2006070704
PubMed: 17035605
11/2006

Ramping up endogenous defences against chronic kidney disease.
Eddy AA
DOI: 10.1093/ndt/gfl102
PubMed: 16574685
05/2006

Subepithelial humps and microthrombi: looking for a mechanism.
Simon D, Finn L, Eddy A
DOI: 10.1053/j.ajkd.2005.07.052
PubMed: 16431268
02/2006

Plasminogen activator inhibitor-1 deficiency has renal benefits but some adverse systemic consequences in diabetic mice.
Collins SJ, Alexander SL, Lopez-Guisa JM, Cai X, Maruvada R, Chua SC, Zhang G, Okamura DM, Matsuo S, Eddy AA
PubMed: 16735799
2006

Progression in chronic kidney disease.
Eddy AA
DOI: 10.1053/j.ackd.2005.07.011
PubMed: 16198274
10/2005

Can renal fibrosis be reversed?
Eddy AA
DOI: 10.1007/s00467-005-1995-5
PubMed: 15947978
10/2005

Multifunctionality of PAI-1 in fibrogenesis: evidence from obstructive nephropathy in PAI-1-overexpressing mice.
Matsuo S, López-Guisa JM, Cai X, Okamura DM, Alpers CE, Bumgarner RE, Peters MA, Zhang G, Eddy AA
DOI: 10.1111/j.1523-1755.2005.00327.x
PubMed: 15882265
06/2005

Why is proteinuria an ominous biomarker of progressive kidney disease?
Zandi-Nejad K, Eddy AA, Glassock RJ, Brenner BM
PubMed: 15485426
11/2004

Mitogenic signaling of urokinase receptor-deficient kidney fibroblasts: actions of an alternative urokinase receptor and LDL receptor-related protein.
Zhang G, Cai X, López-Guisa JM, Collins SJ, Eddy AA
DOI: 10.1097/01.asn.0000135057.41526.2c
PubMed: 15284295
08/2004

The NPHP1 gene deletion associated with juvenile nephronophthisis is present in a subset of individuals with Joubert syndrome.
Parisi MA, Bennett CL, Eckert ML, Dobyns WB, Gleeson JG, Shaw DW, McDonald R, Eddy A, Chance PF, Glass IA
DOI: 10.1086/421846
PubMed: 15138899
07/2004

Expression of nephrin in acquired forms of nephrotic syndrome in childhood.
Hingorani SR, Finn LS, Kowalewska J, McDonald RA, Eddy AA
DOI: 10.1007/s00467-003-1346-3
PubMed: 14747939
03/2004

Proteinuria and interstitial injury.
Eddy AA
DOI: 10.1093/ndt/gfg533
PubMed: 14736944
02/2004

Nephrotic syndrome in childhood.
Eddy AA, Symons JM
DOI: 10.1016/s0140-6736(03)14184-0
PubMed: 12944064
08/2003

Urokinase receptor deficiency accelerates renal fibrosis in obstructive nephropathy.
Zhang G, Kim H, Cai X, López-Guisa JM, Alpers CE, Liu Y, Carmeliet P, Eddy AA
DOI: 10.1097/01.asn.0000064292.37793.fb
PubMed: 12707394
05/2003

Urokinase receptor modulates cellular and angiogenic responses in obstructive nephropathy.
Zhang G, Kim H, Cai X, Lopez-Guisa JM, Carmeliet P, Eddy AA
DOI: 10.1097/01.asn.0000064701.70231.3f
PubMed: 12707393
05/2003

Longterm followup of childhood lupus nephritis.
Hagelberg S, Lee Y, Bargman J, Mah G, Schneider R, Laskin C, Eddy A, Gladman D, Urowitz M, Hebert D, Silverman E
PubMed: 12465165
12/2002

An introduction to frontiers in nephrology.
Eddy AA, Couser WG
DOI: 10.1097/01.asn.0000026725.09795.90
PubMed: 12138153
08/2002

Plasminogen activator inhibitor-1 and the kidney.
Eddy AA
PubMed: 12110504
08/2002

PAI-1 deficiency attenuates the fibrogenic response to ureteral obstruction.
Oda T, Jung YO, Kim HS, Cai X, López-Guisa JM, Ikeda Y, Eddy AA
DOI: 10.1046/j.1523-1755.2001.030002587.x
PubMed: 11473641
08/2001

Mast cells find their way to the kidney.
Eddy AA
DOI: 10.1046/j.1523-1755.2001.00811.x
PubMed: 11422775
07/2001

TIMP-1 deficiency does not attenuate interstitial fibrosis in obstructive nephropathy.
Kim H, Oda T, López-Guisa J, Wing D, Edwards DR, Soloway PD, Eddy AA
PubMed: 11274235
04/2001

Role of cellular infiltrates in response to proteinuria.
Eddy A
PubMed: 11158857
01/2001

Molecular basis of renal fibrosis.
Eddy AA
DOI: 10.1007/s004670000461
PubMed: 11149129
12/2000

Interstitial fibrosis in mice with overload proteinuria: deficiency of TIMP-1 is not protective.
Eddy AA, Kim H, López-Guisa J, Oda T, Soloway PD
DOI: 10.1046/j.1523-1755.2000.00208.x
PubMed: 10916085
08/2000

Renal remodelling in dietary protein modified rat polycystic kidney disease.
Bankovic-Calic N, Eddy A, Sareen S, Ogborn MR
DOI: 10.1007/s004670050744
PubMed: 10460502
09/1999

Tubulointerstitial nephritis and uveitis in children and adolescents. Four new cases and a review of the literature.
Vohra S, Eddy A, Levin AV, Taylor G, Laxer RM
DOI: 10.1007/s004670050634
PubMed: 10412864
06/1999

A morbid course in a girl with mixed connective tissue disease.
Essalah AA, Eddy AA
DOI: 10.1007/s004670050562
PubMed: 10100290
01/1999

The nephrotic syndrome: from the simple to the complex.
Eddy AA, Schnaper HW
PubMed: 9613871
05/1998

Interstitial fibrosis in hypercholesterolemic rats: role of oxidation, matrix synthesis, and proteolytic cascades.
Eddy AA
DOI: 10.1046/j.1523-1755.1998.00889.x
PubMed: 9573532
05/1998

Failure of antioxidant therapy to attenuate interstitial disease in rats with reversible nephrotic syndrome.
Drukker A, Eddy AA
PubMed: 9527400
02/1998

Molecular insights into renal interstitial fibrosis.
Eddy AA
PubMed: 8989727
12/1996

Interstitial inflammation and fibrosis in rats with diet-induced hypercholesterolemia.
Eddy AA
DOI: 10.1038/ki.1996.421
PubMed: 8887271
10/1996

Expression of genes that promote renal interstitial fibrosis in rats with proteinuria.
Eddy AA
PubMed: 8731195
05/1996

Antiribosomal P antibodies in pediatric patients with systemic lupus erythematosus and psychosis.
Press J, Palayew K, Laxer RM, Elkon K, Eddy A, Rakoff D, Silverman ED
DOI: 10.1002/art.1780390420
PubMed: 8630119
04/1996

Expression and function of monocyte chemoattractant protein-1 in experimental nephrotic syndrome.
Eddy AA, Warren JS
DOI: 10.1006/clin.1996.0023
PubMed: 8625556
02/1996

An immunological renal disease in transgenic mice that overexpress Fli-1, a member of the ets family of transcription factor genes.
Zhang L, Eddy A, Teng YT, Fritzler M, Kluppel M, Melet F, Bernstein A
DOI: 10.1128/mcb.15.12.6961
PubMed: 8524263
12/1995

Neurologic manifestations of pediatric systemic lupus erythematosus.
Steinlin MI, Blaser SI, Gilday DL, Eddy AA, Logan WJ, Laxer RM, Silverman ED
DOI: 10.1016/0887-8994(95)00110-2
PubMed: 8554655
10/1995

Experimental insights into the tubulointerstitial disease accompanying primary glomerular lesions.
Eddy AA
PubMed: 7893992
12/1994

Protein restriction reduces transforming growth factor-beta and interstitial fibrosis in nephrotic syndrome.
Eddy AA
PubMed: 8023968
06/1994

Xanthogranulomatous pyelonephritis in children. Etiology, pathogenesis, clinical and radiologic features, and management.
Levy M, Baumal R, Eddy AA
PubMed: 8200171
06/1994

Renal extracellular matrix accumulation in acute puromycin aminonucleoside nephrosis in rats.
Jones CL, Buch S, Post M, McCulloch L, Liu E, Eddy AA
PubMed: 1281619
12/1992

Tubulointerstitial nephritis.
Jones CL, Eddy AA
DOI: 10.1007/bf00866512
PubMed: 1482649
11/1992

Intrarenal distribution of clusterin following reduction of renal mass.
Correa-Rotter R, Hostetter TH, Manivel JC, Eddy AA, Rosenberg ME
DOI: 10.1038/ki.1992.144
PubMed: 1513115
04/1992

The contribution of antibody-mediated cytotoxicity and immune-complex formation to tubulointerstitial disease in passive Heymann nephritis.
Eddy AA, Ho GC, Thorner PS
DOI: 10.1016/0090-1229(92)90021-f
PubMed: 1728979
01/1992

Pathogenesis of interstitial fibrosis in chronic purine aminonucleoside nephrosis.
Jones CL, Buch S, Post M, McCulloch L, Liu E, Eddy AA
DOI: 10.1038/ki.1991.310
PubMed: 1762303
12/1991

Pulmonary hemorrhage and necrotizing glomerulonephritis without glomerular immune deposits: report of two cases.
Jones CL, Shields M, Eddy AA, Baumal R, O'Neill M, Geary DF
DOI: 10.1016/s0272-6386(12)80887-0
PubMed: 1867183
08/1991

Presence of thyroid abnormalities in children with systemic lupus erythematosus.
Eberhard BA, Laxer RM, Eddy AA, Silverman ED
DOI: 10.1016/s0022-3476(05)80741-3
PubMed: 1861215
08/1991

A relationship between proteinuria and acute tubulointerstitial disease in rats with experimental nephrotic syndrome.
Eddy AA, McCulloch L, Liu E, Adams J
PubMed: 2024704
05/1991

Localization of clusterin in the epimembranous deposits of passive Heymann nephritis.
Eddy AA, Fritz IB
DOI: 10.1038/ki.1991.29
PubMed: 2002638
02/1991

Tubulointerstitial nephritis during the heterologous phase of nephrotoxic serum nephritis.
Eddy AA
PubMed: 1956493
1991

Intraglomerular leukocyte recruitment during nephrotoxic serum nephritis in rats.
Eddy AA, McCulloch LM, Adams JA
DOI: 10.1016/0090-1229(90)90118-a
PubMed: 2245521
12/1990

Coagulation abnormalities in chronic peritoneal dialysis.
Jones CL, Andrew M, Eddy A, O'Neil M, Shalom NI, Balfe JW
DOI: 10.1007/bf00858827
PubMed: 2397181
03/1990

A study by immunofluorescence microscopy of the NC1 domain of collagen type IV in glomerular basement membranes of two patients with hereditary nephritis.
Thorner PS, Baumal R, Eddy A, Marrano PM
DOI: 10.1007/bf01678979
PubMed: 2105558
1990

Prolongation of acute renal failure in two patients with hemolytic-uremic syndrome due to excessive plasma infusion therapy.
Eddy AA, Geary DF, Balfe JW, Clark WF, Baumal R
DOI: 10.1007/bf00850219
PubMed: 2642111
10/1989

Interstitial nephritis induced by protein-overload proteinuria.
Eddy AA
PubMed: 2801886
10/1989

Characterization of the NC1 domain of collagen type IV in glomerular basement membranes (GBM) and of antibodies to GBM in a patient with anti-GBM nephritis.
Thorner PS, Baumal R, Eddy A, Marrano P
PubMed: 2706812
03/1989

Acute tubulointerstitial nephritis associated with aminonucleoside nephrosis.
Eddy AA, Michael AF
DOI: 10.1038/ki.1988.3
PubMed: 3258389
01/1988

Identification of lymphohemopoietic cells in the kidneys of normal rats.
Eddy AA, Crary GS, Michael AF
PubMed: 3488687
08/1986

Subtotal nephrectomy in the rabbit: a model of chronic hypercalcemia, nephrolithiasis, and obstructive nephropathy.
Eddy AA, Falk RJ, Sibley RK, Hostetter TH
PubMed: 3711720
06/1986

Decreased plasma fibronectin levels in children with hemolytic-uremic syndrome.
Cosio FG, Eddy A, Mentser MI, Bergstein JM
DOI: 10.1016/0002-9343(85)90394-8
PubMed: 3885728
04/1985

Pseudohermaphroditism, glomerulopathy, and Wilms tumor (Drash syndrome): frequency in end-stage renal failure.
Eddy AA, Mauer SM
DOI: 10.1016/s0022-3476(85)80076-7
PubMed: 2984395
04/1985

Renal allograft failure due to recurrent dense intramembranous deposit disease.
Eddy A, Sibley R, Mauer SM, Kim Y
PubMed: 6380848
06/1984

The distribution of the CR3 receptor on human cells and tissue as revealed by a monoclonal antibody.
Eddy A, Newman SL, Cosio F, LeBien T, Michael A
DOI: 10.1016/0090-1229(84)90090-4
PubMed: 6232029
06/1984

Immune cell populations in cutaneous delayed-type hypersensitivity.
Platt JL, Grant BW, Eddy AA, Michael AF
DOI: 10.1084/jem.158.4.1227
PubMed: 6604784
10/1983

Research
Grants

T32 DK07662 (Eddy PI). NIH/NRSA, Pediatric Nephrology Training Program, $274,895 current year. (2006-2016). The goal is to train academic pediatric nephrologists.

N/A (Okamura PI, Eddy Co-PI). Cystinosis Research Foundation, "Elucidating the Role of Cystinosin-Deficient Macrophages in Nephropathic Cystinosis", $218,966/2 years. (2011-2013). The goal of this project is to investigate the hypothesis that cystinosin deficiency leads to macrophage dysfunction that contributes to the pathogenesis of chronic kidney disease.

Pilot and Feasibility Grant (Eddy PI). Washington Global Health Alliance, Impact of Kidney Dysfunction on Mortality Rates in Ugandan Children Hospitalized with Acute Infections. $75,000. (2007-2010). The goal of this project is to establish a mechanism to evaluate renal function for children admitted to Mulago hospital with pneumonia, malaria and gastroenteritis and to determine the impact of renal failure on acute mortality rates.

Honours & Awards

Elected to the Council of the International Society of Pediatric Nephrology (1995-2001) and the International Society of Nephrology (2009-2015).

Scientific Program Committee Co-chair for triannual congresses on the International Society of Pediatric Nephrology in 1989, 2011 and 2013.

First recipient of The Robert O. Hickman Endowed Chair in Pediatric Nephrology, University of Washington (2007-2012).

Research Group Members

Olena Maydan