2024
Rationale 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
Profilin1 is required to prevent mitotic catastrophe in murine and human glomerular diseases
Tian X, Pedigo C, Li K, Ma X, Bunda P, Pell J, Lek A, Gu J, Zhang Y, Rangel P, Li W, Schwartze E, Nagata S, Lerner G, Perincheri S, Priyadarshini A, Zhao H, Lek M, Menon M, Fu R, Ishibe S. Profilin1 is required to prevent mitotic catastrophe in murine and human glomerular diseases. Journal Of Clinical Investigation 2023, 133: e171237. PMID: 37847555, PMCID: PMC10721156, DOI: 10.1172/jci171237.Peer-Reviewed Original ResearchConceptsProteinuric kidney diseaseKidney diseasePodocyte lossHuman glomerular diseasesMitotic catastrophePodocyte cell cycleSevere proteinuriaCell cycle reentryKidney failureGlomerular diseaseCell cycleKidney tissueG1/S checkpointUnsuccessful repairCyclin D1Glomerular integrityIrregular nucleiTissue-specific lossMouse podocytesPodocytesAltered expressionDiseaseCyclin B1Ribosome affinity purificationMultinucleated cellsMultiscale genetic architecture of donor-recipient differences reveals intronic LIMS1 mismatches associated with kidney transplant survival
Sun Z, Zhang Z, Banu K, Gibson I, Colvin R, Yi Z, Zhang W, De Kumar B, Reghuvaran A, Pell J, Manes T, Djamali A, Gallon L, O'Connell P, He J, Pober J, Heeger P, Menon M. Multiscale genetic architecture of donor-recipient differences reveals intronic LIMS1 mismatches associated with kidney transplant survival. Journal Of Clinical Investigation 2023, 133: e170420. PMID: 37676733, PMCID: PMC10617779, DOI: 10.1172/jci170420.Peer-Reviewed Original ResearchConceptsDeath-censored graft lossHuman leukocyte antigenExpression quantitative trait lociT cellsTGF-β1TGF-β1/Smad pathwayDonor-recipient differencesKidney allograft lossChronic allograft rejectionKidney transplant survivalDonor-recipient mismatchActive TGF-β1Allograft lossGraft lossAllograft rejectionTransplant cohortPeripheral bloodLeukocyte antigenClinical trialsImmune cellsHaplotype mismatchGenome-wide scaleTransplant survivalQuantitative trait lociSingle nucleotide polymorphism dataNonpodocyte Roles of APOL1 Variants: An Evolving Paradigm
Pell J, Nagata S, Menon M. Nonpodocyte Roles of APOL1 Variants: An Evolving Paradigm. Kidney360 2023, 4: e1325-e1331. PMID: 37461136, PMCID: PMC10550003, DOI: 10.34067/kid.0000000000000216.Peer-Reviewed Original ResearchConceptsApolipoprotein L1Progressive renal failureAPOL1 risk variantsImmune response genesParadigm of diseasesMechanisms of diseaseRenal failureKidney diseaseBody of evidenceImmune cellsClinical dataRecent African ancestryRisk genotypesAPOL1 variantsDiseaseEndothelial cellsPutative signaling pathwaysGenetic factorsSeminal dataPhenotype progressionCausal rolePodocytesRisk variantsSignaling pathwaysEvolving ParadigmComparative evaluation of glomerular morphometric techniques reveals differential technical artifacts between focal segmental glomerulosclerosis and normal glomeruli
Reghuvaran A, Lin Q, Basgen J, Banu K, Shi H, Vashist A, Pell J, Perinchery S, He J, Moledina D, Wilson F, Menon M. Comparative evaluation of glomerular morphometric techniques reveals differential technical artifacts between focal segmental glomerulosclerosis and normal glomeruli. Physiological Reports 2023, 11: e15688. PMID: 37423891, PMCID: PMC10329935, DOI: 10.14814/phy2.15688.Peer-Reviewed Original ResearchWCN23-0470 BAC-transgenic mice show a novel T-cell intrinsic role for FSGS-associated APOL1 risk-variants in T-cell activation
Pell J, Reghuvaran A, Nagata S, Banu K, He J, Craft J, Shi H, Chernova I, Ishibe S, Menon M. WCN23-0470 BAC-transgenic mice show a novel T-cell intrinsic role for FSGS-associated APOL1 risk-variants in T-cell activation. Kidney International Reports 2023, 8: s392-s393. DOI: 10.1016/j.ekir.2023.02.882.Peer-Reviewed Original Research
2022
Walking the Line Between Antidonor and Antiviral Immunity: A Potential Role for Belatacept
Gunasekaran D, Pell J, Menon M. Walking the Line Between Antidonor and Antiviral Immunity: A Potential Role for Belatacept. Kidney International Reports 2022, 8: 1-3. PMID: 36644356, PMCID: PMC9832058, DOI: 10.1016/j.ekir.2022.11.005.Commentaries, Editorials and LettersBlood Transcriptomes of SARS-CoV-2–Infected Kidney Transplant Recipients Associated with Immune Insufficiency Proportionate to Severity
Sun Z, Zhang Z, Banu K, Al Azzi Y, Reghuvaran A, Fredericks S, Planoutene M, Hartzell S, Kim Y, Pell J, Tietjen G, Asch W, Kulkarni S, Formica R, Rana M, Maltzman JS, Zhang W, Akalin E, Heeger PS, Cravedi P, Menon MC. Blood Transcriptomes of SARS-CoV-2–Infected Kidney Transplant Recipients Associated with Immune Insufficiency Proportionate to Severity. Journal Of The American Society Of Nephrology 2022, 33: 2108-2122. PMID: 36041788, PMCID: PMC9678030, DOI: 10.1681/asn.2022010125.Peer-Reviewed Original ResearchConceptsKidney transplant recipientsImmune activation pathwaysImmunosuppressant useKTR cohortAcute illnessBlood transcriptomeAcute casesT cellsCOVID-19Most kidney transplant recipientsPost-acute COVID-19Adaptive immune system activationManagement of immunosuppressionReinstitution of immunosuppressionAcute COVID-19Serum inflammatory cytokinesCOVID-19 severity scoreCOVID-19 infectionImmune system activationUpregulation of neutrophilActivation pathwayTransplant recipientsChart reviewImmune signaturesLymphocyte countA Novel Role of APOL1 Risk-Alleles in T-Cell Activation and Focal Segmental Glomerulosclerosis
Pell J, Reghuvaran A, Nagata S, Banu K, Shi H, Chernova I, Ishibe S, Menon M. A Novel Role of APOL1 Risk-Alleles in T-Cell Activation and Focal Segmental Glomerulosclerosis. Journal Of The American Society Of Nephrology 2022, 33: 410-411. DOI: 10.1681/asn.20223311s1410d.Peer-Reviewed Original Research