2024
Adamts1 and Cyst Expansion in Polycystic Kidney Disease.
Kakade V, Akman Z, Motrapu M, Cassini M, Xu L, Moeckel G, Somlo S, Cantley L. Adamts1 and Cyst Expansion in Polycystic Kidney Disease. Journal Of The American Society Of Nephrology 2024 PMID: 39514301, DOI: 10.1681/asn.0000000557.Peer-Reviewed Original ResearchAutosomal dominant polycystic kidney diseasePolycystic kidney diseaseKidney diseaseLoss of Pkd1Cyst growthInterstitial macrophage accumulationDominant polycystic kidney diseaseInterstitial mononuclear cellsReduced cyst growthDetectable phenotypeMembrane remodelingMotif 1Progressive cyst growthIsoforms of versicanSimultaneous deletionPKD2 geneTubular basement membraneDisintegrin and metalloproteinaseRNA sequencingBasement membrane remodelingPKD1Thrombospondin motifs 1Cystic enlargementMacrophage accumulationCystic dilatationUsing Imaging Mass Cytometry to Define Cell Identities in AKI and CKD in Humans
Budiman T, Shelar A, Baker M, Weiss M, Cantley L, Kakade V. Using Imaging Mass Cytometry to Define Cell Identities in AKI and CKD in Humans. Journal Of The American Society Of Nephrology 2024, 35: 10.1681/asn.2024g4m5sdnf. DOI: 10.1681/asn.2024g4m5sdnf.Peer-Reviewed Original ResearchTubule-Specific Deletion of Adamts1 Slows Cyst Expansion in Polycystic Kidney Disease
Kakade V, Akman Z, Motrapu M, Cantley L. Tubule-Specific Deletion of Adamts1 Slows Cyst Expansion in Polycystic Kidney Disease. Journal Of The American Society Of Nephrology 2024, 35: 10.1681/asn.20246ecyxtfs. DOI: 10.1681/asn.20246ecyxtfs.Peer-Reviewed Original ResearchSegment-Specific Cyst Index (SSCI): A Quantitative Analysis of Segment-Specific Responses during Cystogenesis
Akman Z, Kakade V, Cantley L. Segment-Specific Cyst Index (SSCI): A Quantitative Analysis of Segment-Specific Responses during Cystogenesis. Journal Of The American Society Of Nephrology 2024, 35: 10.1681/asn.2024mpmapkd5. DOI: 10.1681/asn.2024mpmapkd5.Peer-Reviewed Original ResearchAnalysis of Kidney Biopsies from Patients with Glomerulonephritis Using Imaging Mass Cytometry Reveals Increase in Immune Cells with Associated Dedifferentiation and Injury of Tubular Cells
Weiss M, Kakade V, Baker M, Budiman T, Shelar A, Cantley L. Analysis of Kidney Biopsies from Patients with Glomerulonephritis Using Imaging Mass Cytometry Reveals Increase in Immune Cells with Associated Dedifferentiation and Injury of Tubular Cells. Journal Of The American Society Of Nephrology 2024, 35: 10.1681/asn.202490mzwbkc. DOI: 10.1681/asn.202490mzwbkc.Peer-Reviewed Original ResearchMyofibroblast-Macrophage Cross-Talk Supports Proliferative Tubule Repair after Kidney Injury
Bharathan B, Xu L, Guo J, Cantley L. Myofibroblast-Macrophage Cross-Talk Supports Proliferative Tubule Repair after Kidney Injury. Journal Of The American Society Of Nephrology 2024, 35: 10.1681/asn.20249phzkecs. DOI: 10.1681/asn.20249phzkecs.Peer-Reviewed Original ResearchUrine Proteomic Signatures of Kidney Function Decline after Hospitalization
Wen Y, Menez S, Philbrook H, Moledina D, Bhatraju P, Coca S, Chinchilli V, Go A, Siew E, Kimmel P, Ikizler T, Hsu C, Himmelfarb J, Cantley L, Parikh C. Urine Proteomic Signatures of Kidney Function Decline after Hospitalization. Journal Of The American Society Of Nephrology 2024, 35: 10.1681/asn.20245v3jz4vr. DOI: 10.1681/asn.20245v3jz4vr.Peer-Reviewed Original ResearchAKI in the Kidney Precision Medicine Project: Acute Tubular Injury vs. Acute Interstitial Nephritis
Schaub J, Castro A, Menez S, Wen Y, Menon R, Bhatraju P, Wilson F, Coca S, Eadon M, Bomback A, Moledina D, Cantley L, Palevsky P, D'Agati V, Randhawa P, Murugan R, Alpers C, Kretzler M, Himmelfarb J, Parikh C. AKI in the Kidney Precision Medicine Project: Acute Tubular Injury vs. Acute Interstitial Nephritis. Journal Of The American Society Of Nephrology 2024, 35: 10.1681/asn.2024cxh8wvky. DOI: 10.1681/asn.2024cxh8wvky.Peer-Reviewed Original ResearchVCAM-1 mediates proximal tubule-immune cell cross talk in failed tubule recovery during AKI-to-CKD transition
Melchinger I, Guo K, Li X, Guo J, Cantley L, Xu L. VCAM-1 mediates proximal tubule-immune cell cross talk in failed tubule recovery during AKI-to-CKD transition. American Journal Of Physiology. Renal Physiology 2024, 327: f610-f622. PMID: 39116349, PMCID: PMC11483080, DOI: 10.1152/ajprenal.00076.2024.Peer-Reviewed Original ResearchAcute kidney injuryChronic kidney diseaseVCAM-1 expressionProximal tubule cellsVCAM-1Tubule cellsKidney Precision Medicine ProjectProinflammatory cytokinesAcute kidney injury to chronic kidney diseaseModel of chronic kidney diseaseExpression of vascular cell adhesion protein 1Cell adhesion pathwaysInflammatory response to injuryInjured proximal tubule cellsVascular cell adhesion protein 1Mouse model of chronic kidney diseaseRisk of progressionChronic kidney disease transitionIncreased immune cell adhesionVCAM-1-positive cellsOverexpression of VCAM-1Inhibition of NF-kB signalingActivation of NF-kBImmune cell adhesionSingle-cell transcriptome analysisIdentification and validation of urinary CXCL9 as a biomarker for diagnosis of acute interstitial nephritis
Moledina D, Obeid W, Smith R, Rosales I, Sise M, Moeckel G, Kashgarian M, Kuperman M, Campbell K, Lefferts S, Meliambro K, Bitzer M, Perazella M, Luciano R, Pober J, Cantley L, Colvin R, Wilson F, Parikh C. Identification and validation of urinary CXCL9 as a biomarker for diagnosis of acute interstitial nephritis. Journal Of Clinical Investigation 2024, 134: e180583. PMID: 38488004, PMCID: PMC10940080, DOI: 10.1172/jci180583.Peer-Reviewed Original ResearchRationale and Design of a Phase 2, Double-blind, Placebo-Controlled, Randomized Trial Evaluating AMP Kinase-Activation by Metformin in Focal Segmental Glomerulosclerosis
Barsotti G, Luciano R, Kumar A, Meliambro K, Kakade V, Tokita J, Naik A, Fu J, Peck E, Pell J, Reghuvaran A, Tanvir E, Patel P, Zhang W, Li F, Moeckel G, Perincheri S, Cantley L, Moledina D, Wilson F, He J, Menon M. Rationale and Design of a Phase 2, Double-blind, Placebo-Controlled, Randomized Trial Evaluating AMP Kinase-Activation by Metformin in Focal Segmental Glomerulosclerosis. Kidney International Reports 2024, 9: 1354-1368. PMID: 38707807, PMCID: PMC11068976, DOI: 10.1016/j.ekir.2024.02.006.Peer-Reviewed Original ResearchMinimal change diseaseRandomized controlled trialsSafety of metforminDouble-blindPodocyte injuryAdjunctive therapyPlacebo-controlled randomized controlled trialsPhase III studyPhase II trialPrimary glomerular diseaseFocal segmental glomerulosclerosisEffect of metforminPhase IIPlacebo-controlledPreclinical dataNovel urineChange diseaseTissue markersRandomized trialsSegmental glomerulosclerosisGlomerular diseaseMechanistic biomarkersObservational studyFSGSInexpensive agent
2023
Analysis of the human kidney transcriptome and plasma proteome identifies markers of proximal tubule maladaptation to injury
Wen Y, Su E, Xu L, Menez S, Moledina D, Obeid W, Palevsky P, Mansour S, Devarajan P, Cantley L, Cahan P, Parikh C, Project K, Injury T. Analysis of the human kidney transcriptome and plasma proteome identifies markers of proximal tubule maladaptation to injury. Science Translational Medicine 2023, 15: eade7287. PMID: 38091407, PMCID: PMC11405121, DOI: 10.1126/scitranslmed.ade7287.Peer-Reviewed Original ResearchThe ASSESS-AKI Study found urinary epidermal growth factor is associated with reduced risk of major adverse kidney events
Menez S, Wen Y, Xu L, Moledina D, Thiessen-Philbrook H, Hu D, Obeid W, Bhatraju P, Ikizler T, Siew E, Chinchilli V, Garg A, Go A, Liu K, Kaufman J, Kimmel P, Himmelfarb J, Coca S, Cantley L, Parikh C. The ASSESS-AKI Study found urinary epidermal growth factor is associated with reduced risk of major adverse kidney events. Kidney International 2023, 104: 1194-1205. PMID: 37652206, PMCID: PMC10840723, DOI: 10.1016/j.kint.2023.08.007.Peer-Reviewed Original ResearchConceptsMajor adverse kidney eventsUEGF/CrUrinary epidermal growth factorAdverse kidney eventsChronic kidney diseaseEpidermal growth factorKidney eventsKidney failureEGF expressionUrinary EGF/CrAcute Kidney Injury studyGrowth factorIschemia-reperfusion injuryProportional hazards regressionTubular healthKidney atrophyObservational cohortHospitalized participantsTubular functionClinical findingsHazards regressionKidney diseaseClinical variablesProgressive atrophyUrinary EGFIdentification and validation of urinary CXCL9 as a biomarker for diagnosis of acute interstitial nephritis
Moledina D, Obeid W, Smith R, Rosales I, Sise M, Moeckel G, Kashgarian M, Kuperman M, Campbell K, Lefferts S, Meliambro K, Bitzer M, Perazella M, Luciano R, Pober J, Cantley L, Colvin R, Wilson F, Parikh C. Identification and validation of urinary CXCL9 as a biomarker for diagnosis of acute interstitial nephritis. Journal Of Clinical Investigation 2023, 133: e168950. PMID: 37395276, PMCID: PMC10313360, DOI: 10.1172/jci168950.Peer-Reviewed Original ResearchConceptsUrinary CXCL9External validation cohortValidation cohortControl groupAIN diagnosisDiscovery cohortKidney tissueDiagnostic biomarkersAcute interstitial nephritisCXCL9 mRNA expressionAcute kidney injuryBiopsy-confirmed diagnosisAvailable clinical testsNational InstituteKidney injuryTubulointerstitial nephritisInterstitial nephritisKidney biopsyHistological confirmationHistological diagnosisTreatment optionsLymphocyte chemotaxisCXCL9MRNA expression differencesPatientsLongitudinal biomarkers and kidney disease progression after acute kidney injury
Wen Y, Xu L, Melchinger I, Thiessen-Philbrook H, Moledina D, Coca S, Hsu C, Go A, Liu K, Siew E, Ikizler T, Chinchilli V, Kaufman J, Kimmel P, Himmelfarb J, Cantley L, Parikh C, Consortium T. Longitudinal biomarkers and kidney disease progression after acute kidney injury. JCI Insight 2023, 8: e167731. PMID: 36951957, PMCID: PMC10243801, DOI: 10.1172/jci.insight.167731.Peer-Reviewed Original ResearchConceptsAcute kidney injuryIschemic reperfusion injuryKidney disease progressionKidney injuryTubular healthDisease progressionChronic kidney disease (CKD) incidenceCox proportional hazards regressionMurine acute kidney injuryKidney disease incidenceUrine KIM-1Proportional hazards regressionCKD progressionCKD transitionUrine uromodulinIncident CKDComposite outcomeKidney atrophyProspective cohortReperfusion injuryHazards regressionKIM-1Prognostic valueMCP-1Initial insultThe Lymphatic System in Kidney Disease
Baker M, Cantley L. The Lymphatic System in Kidney Disease. Kidney360 2023, 4: e841-e850. PMID: 37019177, PMCID: PMC10371377, DOI: 10.34067/kid.0000000000000120.Peer-Reviewed Original ResearchConceptsKidney diseaseLymphatic systemSetting of AKIKidney allograft rejectionNormal kidney functionImmune response modulationAllograft rejectionLymph nodesInflammatory infiltrateKidney functionImmune cellsTissue edemaNovel therapiesImmune surveillanceNumerous disease statesSystemic circulationFluid removalKidney tissueResident cellsTherapeutic potentialSurveillance cellsAKIDisease statesKidneyResponse modulationThe ion transporter Na+-K+-ATPase enables pathological B cell survival in the kidney microenvironment of lupus nephritis
Chernova I, Song W, Steach H, Hafez O, Al Souz J, Chen P, Chandra N, Cantley L, Veselits M, Clark M, Craft J. The ion transporter Na+-K+-ATPase enables pathological B cell survival in the kidney microenvironment of lupus nephritis. Science Advances 2023, 9: eadf8156. PMID: 36724234, PMCID: PMC9891690, DOI: 10.1126/sciadv.adf8156.Peer-Reviewed Original ResearchConceptsB cellsAutoimmune diseasesAmelioration of proteinuriaLupus nephritis biopsiesB cell infiltrationSodium-potassium adenosine triphosphataseB cell survivalPotassium adenosine triphosphataseLupus nephritisCell infiltrationKidney microenvironmentTissue injuryTherapeutic targetPharmacological inhibitionElevated sodium concentrationLupusHostile microenvironmentHigh expressionKidneySodium concentrationGenetic knockoutCell survivalDiseaseCellsAdenosine triphosphatase
2022
Multi-Scalar Data Integration Links Glomerular Angiopoietin-Tie Signaling Pathway Activation With Progression of Diabetic Kidney Disease
Liu J, Nair V, Zhao Y, Chang D, Limonte C, Bansal N, Fermin D, Eichinger F, Tanner E, Bellovich K, Steigerwalt S, Bhat Z, Hawkins J, Subramanian L, Rosas S, Sedor J, Vasquez M, Waikar S, Bitzer M, Pennathur S, Brosius F, De Boer I, Chen M, Kretzler M, Ju W, Group F, Knight R, Lecker S, Stillman I, Bogen S, Amodu A, Ilori T, Maikhor S, Schmidt I, Beck L, Henderson J, Onul I, Verma A, Waikar S, McMahon G, Valerius M, Waikar S, Weins A, Colona M, Greka A, Hacohen N, Hoover P, Marshall J, Aulisio M, Chen Y, Janowczyk A, Jayapandian C, Viswanathan V, Bush W, Crawford D, Madabhushi A, Bush L, Cooperman L, Gonzalez-Vicente A, Herlitz L, Jolly S, Nguyen J, O’toole J, Palmer E, Poggio E, Sedor J, Sendrey D, Spates-Harden K, Taliercio J, Bjornstad P, Pyle L, Vinovskis C, Appelbaum P, Barasch J, Bomback A, Canetta P, D’Agati V, Kiryluk K, Kudose S, Mehl K, Shang N, Balderes O, Bansal S, Alexandrov T, Rennke H, El-Achkar T, Barwinska D, Bledsoe S, Borner K, Bueckle A, Cheng Y, Dagher P, Dunn K, Eadon M, Ferkowicz M, Herr B, Kelly K, Ferreira R, Quardokus E, Record E, Rivera M, Su J, Sutton T, Williams J, Winfree S, Menez S, Parikh C, Rosenberg A, Corona-Villalobos C, Wen Y, Johansen C, Rosas S, Roy N, Sun J, Williams M, Azeloglu E, Hansen J, He C, Iyengar R, Xiong Y, Prasad P, Srivastava A, Madhavan S, Parikh S, Rovin B, Shapiro J, Anderton C, Lukowski J, Pasa-Tolic L, Velickovic D, Oliver G, Ardayfio J, Bebiak J, Brown K, Campbell T, Campbell C, Hayashi L, Jefferson N, Roberts G, Saul J, Shpigel A, Stutzke C, Koewler R, Pinkeney R, Sealfon R, Troyanskaya O, Wong A, Tuttle K, Pollack A, Goltsev Y, Lucarelli N, Sarder P, Lake B, Zhang K, Boada P, Laszik Z, Nolan G, Anjani K, Sarwal M, Mukatash T, Sigdel T, Alloway R, Burg A, Lee P, Rike A, Shi T, Woodle E, Balis U, Blanc V, Conser N, Eddy S, Frey R, He Y, Hodgin J, Kretzler M, Lienczewski C, Luo J, Mariani L, Menon R, Otto E, Schaub J, Steck B, Elder M, Gilliam M, Hall D, Murugan R, Palevsky P, Randhawa P, Rosengart M, Tublin M, Vita T, Kellum J, Winters J, Alpers C, Berglund A, Blank K, Carson J, Daniel S, De Boer I, Dighe A, Dowd F, Grewenow S, Himmelfarb J, Hoofnagle A, Limonte C, McClelland R, Mooney S, Rezaei K, Shankland S, Snyder J, Wang R, Wilcox A, Williams K, Park C, Bansal S, Montellano R, Pamreddy A, Sharma K, Venkatachalam M, Ye H, Zhang G, Hedayati S, Kermani A, Lee S, Lu C, Miller R, Moe O, Patel J, Pillai A, Sambandam K, Torrealba J, Toto R, Vazquez M, Wang N, Wen N, Zhang D, Park H, Caprioli R, Patterson N, Sharman K, Spraggins J, Van de Plas R, Basta J, Diettman S, Gaut J, Jain S, Rauchman M, Vijayan A, Cantley L, Kakade V, Moledina D, Shaw M, Ugwuowo U, Wilson F, Arora T, Bitzer M, Brosius F, Gadegbeku C, Gipson D, Hawkins J, Kretzler M, Lienczewski C, Pennathur S, Troost J, Gadegbeku C, Bellovich K, Bhat Z, Massengill S, Perumal K. Multi-Scalar Data Integration Links Glomerular Angiopoietin-Tie Signaling Pathway Activation With Progression of Diabetic Kidney Disease. Diabetes 2022, 71: 2664-2676. PMID: 36331122, PMCID: PMC9750948, DOI: 10.2337/db22-0169.Peer-Reviewed Original ResearchConceptsEnd-stage kidney diseaseDiabetic kidney diseaseKidney diseaseAngiopoietin-2ANGPT2 levelsChinese cohort studyChronic kidney diseaseGlomerular filtration rateCardiovascular Health StudyPlasma angiopoietin-2High receptor expressionStandard clinical parametersSignaling Pathway ActivationPathway scoresThree-marker panelKidney outcomesCohort studyComposite outcomeClinical parametersEndothelial biomarkersFiltration rateReceptor expressionPrognostic biomarkerClinical phenotypingHealth StudyAuthors' Reply: Most Arginase-1 Positive Cells Are Likely Injured S3 Proximal Tubular Cells Carrying Upregulated Phagocytotic Capacity rather than M2 Macrophages—Too Many To Be True
Shin N, Marlier A, Xu L, Doilicho N, Linberg D, Guo J, Cantley L. Authors' Reply: Most Arginase-1 Positive Cells Are Likely Injured S3 Proximal Tubular Cells Carrying Upregulated Phagocytotic Capacity rather than M2 Macrophages—Too Many To Be True. Journal Of The American Society Of Nephrology 2022, 33: 2124-2125. PMID: 36316094, PMCID: PMC9678031, DOI: 10.1681/asn.2022070836.Peer-Reviewed Original ResearchImmune-Mediated Tubule Atrophy Promotes AKI to CKD Transition
Xu L, Guo J, Moledina D, Cantley L. Immune-Mediated Tubule Atrophy Promotes AKI to CKD Transition. Journal Of The American Society Of Nephrology 2022, 33: 872-872. DOI: 10.1681/asn.20223311s1872b.Peer-Reviewed Original Research