2017
Randomized, Controlled Trial of TRC101 to Increase Serum Bicarbonate in Patients with CKD
Bushinsky DA, Hostetter T, Klaerner G, Stasiv Y, Lockey C, McNulty S, Lee A, Parsell D, Mathur V, Li E, Buysse J, Alpern R. Randomized, Controlled Trial of TRC101 to Increase Serum Bicarbonate in Patients with CKD. Clinical Journal Of The American Society Of Nephrology 2017, 13: 26-35. PMID: 29102959, PMCID: PMC5753317, DOI: 10.2215/cjn.07300717.Peer-Reviewed Original ResearchConceptsSerum bicarbonateEnd of treatmentMetabolic acidosisTreatment groupsBaseline serum bicarbonateMean baseline eGFRMEq/LSignificant adverse effectsBaseline eGFRGastrointestinal eventsAdverse eventsFirst doseControlled TrialsHeart failurePatientsCKDBaseline levelsMean increaseAbstractTextUnit studiesAcidosisAdverse effectsPlaceboTreatmentDays
2013
Treatment of Severe Metabolic Alkalosis in a Patient With Congestive Heart Failure
Peixoto AJ, Alpern RJ. Treatment of Severe Metabolic Alkalosis in a Patient With Congestive Heart Failure. American Journal Of Kidney Diseases 2013, 61: 822-827. PMID: 23481366, DOI: 10.1053/j.ajkd.2012.10.028.Peer-Reviewed Original ResearchConceptsCongestive heart failureHeart failureMetabolic alkalosisLow bicarbonate dialysisRenal bicarbonate excretionRenin-angiotensin systemSevere metabolic alkalosisDistal sodium deliveryCommon acid-base disorderAcid-base disordersDiuretic regimenDiuretic therapyAldosterone antagonistsNeurohormonal activationCirculatory failureBicarbonate excretionKidney failurePotassium repletionSodium deliveryBase excessUrine acidificationAppropriate managementAlkalosisDisease statesBicarbonate retention
2004
An autocrine role for endothelin-1 in the regulation of proximal tubule NHE3
Licht C, Laghmani K, Yanagisawa M, Preisig PA, Alpern RJ. An autocrine role for endothelin-1 in the regulation of proximal tubule NHE3. Kidney International 2004, 65: 1320-1326. PMID: 15086471, DOI: 10.1111/j.1523-1755.2004.00506.x.Peer-Reviewed Original ResearchConceptsChronic metabolic acidosisMetabolic acidosisReverse transcription-polymerase chain reactionProximal tubulesKidney cortexCompetitive reverse transcription-polymerase chain reactionProximal tubule NHE3NHE3 activityPreproET-1 expressionEndothelin B receptorEndothelin-1 expressionET-1 expressionPreproET-1 mRNA abundancePreproET-1 mRNA expressionTranscription-polymerase chain reactionProximal tubule cellsRenal proximal tubulesMRNA abundanceEndothelin-1Control ratsAbdominal aortaAutocrine roleAcidosisTubule cellsAutocrine regulation
2002
Bicarbonate reabsorption and NHE-3 expression: Abundance and activity are increased in Henle's loop of remnant rats
Capasso G, Rizzo M, Pica A, Di Maio FS, Moe OW, Alpern RJ, De Santo NG. Bicarbonate reabsorption and NHE-3 expression: Abundance and activity are increased in Henle's loop of remnant rats. Kidney International 2002, 62: 2126-2135. PMID: 12427137, DOI: 10.1046/j.1523-1755.2002.00681.x.Peer-Reviewed Original ResearchRole of c-SRC and ERK in acid-induced activation of NHE3
Tsuganezawa H, Sato S, Yamaji Y, Preisig PA, Moe OW, Alpern RJ. Role of c-SRC and ERK in acid-induced activation of NHE3. Kidney International 2002, 62: 41-50. PMID: 12081562, DOI: 10.1046/j.1523-1755.2002.00418.x.Peer-Reviewed Original ResearchMeSH KeywordsAcidosisAmmonium ChlorideAnimalsCells, CulturedCSK Tyrosine-Protein KinaseEnzyme ActivationJNK Mitogen-Activated Protein KinasesMaleMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Mitogen-Activated Protein KinasesPhosphorylationProtein Serine-Threonine KinasesProtein-Tyrosine KinasesProto-Oncogene Proteins c-fosRatsRats, Sprague-DawleySodium-Hydrogen Exchanger 3Sodium-Hydrogen ExchangersSrc-Family KinasesConceptsOKP cellsAcid-induced activationNHE3 activityERK/c-fosC-fos expressionC-Fos activationCytoplasmic pH (pHi) recoveryC-SrcRenal proximal tubulesAcid incubationActivation of NHE3Renal epithelial cellsCultured renal epithelial cellsProximal tubulesChronic acidosisInhibition of MEKNHE3 activationInhibited activationNormal levelsAcid loadImmune complex kinase assayERK kinaseAcidosisPH recoveryEpithelial cellsReversible acute renal failure and nephrotic syndrome in a Type 1 diabetic patient
Avilés-Santa L, Alpern R, Raskin P. Reversible acute renal failure and nephrotic syndrome in a Type 1 diabetic patient. Journal Of Diabetes And Its Complications 2002, 16: 249-254. PMID: 12015196, DOI: 10.1016/s1056-8727(01)00221-5.Peer-Reviewed Original ResearchConceptsReversible acute renal failureAcute renal failureBlood urea nitrogenNephrotic syndromeRenal failureDiabetic nephropathyDiabetic patientsRenal parametersRenal conditionsAcute oliguric renal failureEnd-stage renal diseaseType 1 diabetic patientsDiscontinuation of dialysisOliguric renal failureEarly diabetic nephropathyUrinary protein excretionMinimal change diseasePatient's renal conditionDiuretic therapyOvert proteinuriaRenal insufficiencyRenal functionSerum creatinineRenal biopsyRenal disease
2000
Chronic metabolic acidosis increases NaDC-1 mRNA and protein abundance in rat kidney
Aruga S, Wehrli S, Kaissling B, Moe O, Preisig P, Pajor A, Alpern R. Chronic metabolic acidosis increases NaDC-1 mRNA and protein abundance in rat kidney. Kidney International 2000, 58: 206-215. PMID: 10886565, DOI: 10.1046/j.1523-1755.2000.00155.x.Peer-Reviewed Original ResearchMeSH KeywordsAcidosisAcidsAcute DiseaseAlkaliesAmmonium ChlorideAnimalsCarrier ProteinsChronic DiseaseCitratesDicarboxylic Acid TransportersGene ExpressionKidney CortexKidney Tubules, ProximalMaleMembrane ProteinsOrganic Anion Transporters, Sodium-DependentRatsRats, Sprague-DawleyRNA, MessengerSodium BicarbonateSymportersRenal citrate metabolism and urinary citrate excretion in the infant rat
Melnick J, Preisig P, Alpern R, Baum M. Renal citrate metabolism and urinary citrate excretion in the infant rat. Kidney International 2000, 57: 891-897. PMID: 10720942, PMCID: PMC4089854, DOI: 10.1046/j.1523-1755.2000.057003891.x.Peer-Reviewed Original ResearchConceptsUrinary citrate excretionHigher urinary citrateCitrate excretionInfant ratsAdult ratsUrinary citrateRenal citrate metabolismMitochondrial aconitase activityCreatinine ratioCitrate metabolismRenal excretionSame prevalenceRenal stonesTwofold higher concentrationLower plasmaATP citrate lyase activityProximal tubulesHigher plasmaMetabolic cagesRat kidneyRatsAdult levelsInfantsMaturational differencesExcretion
1998
Converting enzyme inhibition causes hypocitraturia independent of acidosis or hypokalemia
Melnick J, Preisig P, Haynes S, Pak C, Sakhaee K, Alpern R. Converting enzyme inhibition causes hypocitraturia independent of acidosis or hypokalemia. Kidney International 1998, 54: 1670-1674. PMID: 9844143, DOI: 10.1046/j.1523-1755.1998.00150.x.Peer-Reviewed Original ResearchConceptsUrinary citrate excretionCitrate excretionUrinary citrateMetabolic acidosisATP-citrate lyaseEffects of enalaprilRenal citrate metabolismUrine citrate concentrationRenal cortical tissueChronic metabolic acidosisProximal tubular cellsPlasma pHNa/H antiporterAngiotensin IIIntracellular acidosisEnalaprilTubular cellsCitrate lyaseHypokalemiaEnzyme inhibitorsATP citrate lyase activityAcidosisCortical tissueRatsCitrate metabolismRenal Na/H exchanger NHE-3 and Na-PO4 cotransporter NaPi-2 protein expression in glucocorticoid excess and deficient states.
Loffing J, Lötscher M, Kaissling B, Biber J, Murer H, Seikaly M, Alpern RJ, Levi M, Baum M, Moe OW. Renal Na/H exchanger NHE-3 and Na-PO4 cotransporter NaPi-2 protein expression in glucocorticoid excess and deficient states. Journal Of The American Society Of Nephrology 1998, 9: 1560-7. PMID: 9727362, PMCID: PMC4131923, DOI: 10.1681/asn.v991560.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Protein Complex 3Adaptor Protein Complex beta SubunitsAdrenalectomyAnalysis of VarianceAnimalsBiological Transport, ActiveCarrier ProteinsDisease Models, AnimalGlucocorticoidsImmunoblottingImmunohistochemistryKidney CortexMaleNerve Tissue ProteinsPhosphoproteinsRatsRats, Sprague-DawleySensitivity and SpecificitySodium-Hydrogen Exchanger 3Sodium-Hydrogen ExchangersSodium-Phosphate Cotransporter ProteinsSymportersConceptsNa/H exchangeNHE-3 protein abundanceNHE-3Glucocorticoid excessPharmacologic dosesNaPi-2 proteinProximal tubulesSham-operated ratsNaPi-2Sham-operated animalsThick ascending limbSignificant reciprocal increaseBilateral adrenalectomyDexamethasone administrationIntrarenal distributionControl ratsProtein abundanceAscending limbReciprocal increaseAdrenalectomyRatsDeficient stateCotransport activityProtein expressionAdministrationRenal cortical mitochondrial aconitase is regulated in hypo- and hypercitraturia
Melnick J, Preisig P, Moe O, Srere P, Alpern R. Renal cortical mitochondrial aconitase is regulated in hypo- and hypercitraturia. Kidney International 1998, 54: 160-165. PMID: 9648074, DOI: 10.1046/j.1523-1755.1998.00974.x.Peer-Reviewed Original Research
1997
Chronic metabolic acidosis enhances NHE-3 protein abundance and transport activity in the rat thick ascending limb by increasing NHE-3 mRNA.
Laghmani K, Borensztein P, Ambühl P, Froissart M, Bichara M, Moe OW, Alpern RJ, Paillard M. Chronic metabolic acidosis enhances NHE-3 protein abundance and transport activity in the rat thick ascending limb by increasing NHE-3 mRNA. Journal Of Clinical Investigation 1997, 99: 24-30. PMID: 9011571, PMCID: PMC507763, DOI: 10.1172/jci119128.Peer-Reviewed Original Research
1996
Adenosine triphosphate citrate lyase mediates hypocitraturia in rats.
Melnick JZ, Srere PA, Elshourbagy NA, Moe OW, Preisig PA, Alpern RJ. Adenosine triphosphate citrate lyase mediates hypocitraturia in rats. Journal Of Clinical Investigation 1996, 98: 2381-2387. PMID: 8941657, PMCID: PMC507690, DOI: 10.1172/jci119051.Peer-Reviewed Original ResearchConceptsChronic metabolic acidosisMetabolic acidosisATP citrate lyase activityATP-citrate lyaseCitrate lyase activityCitrate lyaseHypocitraturiaAcid dietAcidosisCitrate metabolismProtein abundanceRatsMRNA abundanceLyase activityMetabolismPresent studySignificant changesCitrate uptakeInhibitionHypercitraturiaHypokalemiaCytosolic enzymeCompetitive inhibitorActivityImportant roleChronic metabolic acidosis increases NHE3 protein abundance in rat kidney
Ambuhl P, Amemiya M, Danczkay M, Lotscher M, Kaissling B, Moe OW, Preisig PA, Alpern RJ. Chronic metabolic acidosis increases NHE3 protein abundance in rat kidney. American Journal Of Physiology 1996, 271: f917-f925. PMID: 8898023, DOI: 10.1152/ajprenal.1996.271.4.f917.Peer-Reviewed Original ResearchConceptsNHE3 protein abundanceChronic metabolic acidosisNHE3 mRNA abundanceMetabolic acidosisThick ascending limbProximal tubulesAscending limbNa/H antiporter activityAcidosis-induced increaseMRNA abundanceNa/H antiporterNHE3 abundanceProtein abundanceAcidosisRat kidneyWestern blotS2 segmentsH antiporterRatsNHE3 isoformPresent studyLimbTubules
1993
Renin expression in renal proximal tubule.
Moe OW, Ujiie K, Star RA, Miller RT, Widell J, Alpern RJ, Henrich WL. Renin expression in renal proximal tubule. Journal Of Clinical Investigation 1993, 91: 774-779. PMID: 7680667, PMCID: PMC288027, DOI: 10.1172/jci116296.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceBlotting, SouthernCells, CulturedCloning, MolecularColforsinEnalaprilIn Vitro TechniquesIsoproterenolKidney Tubules, ProximalKineticsMaleMolecular Sequence DataMuscle, Smooth, VascularOligodeoxyribonucleotidesPoly APolymerase Chain ReactionRabbitsRatsRats, Sprague-DawleyReninRNARNA, MessengerTranscription, GeneticConceptsProximal tubule cellsCultured proximal tubule cellsRenin-angiotensin systemProximal tubulesRenal proximal tubulesTubule cellsRenin activityLocal renin-angiotensin systemPrimary culturesPresence of reninRabbit proximal tubule cellsAngiotensin-converting enzymeMammalian renal proximal tubulePrevious immunohistochemical studiesSynthesized reninAngiotensin receptorsAngiotensin IIRenin contentPolymerase chain reactionRenin expressionImmunohistochemical studyM isoproterenolM forskolinNormal ratsRenin mRNA
1992
Citraturic Response to Oral Citric Acid Load
Sakhaee K, Alpern R, Poindexter J, Pak C. Citraturic Response to Oral Citric Acid Load. Journal Of Urology 1992, 147: 975-976. PMID: 1552616, DOI: 10.1016/s0022-5347(17)37437-2.Peer-Reviewed Original ResearchConceptsAcid loadCitraturic responseUrinary citrateCarbon dioxide pressureSingle oral loadUrinary citrate excretionSingle oral doseSerum citrate concentrationAcid-base balanceCitraturic effectsOral loadVenous pHOral doseSerum electrolytesUrinary pHCitrate excretionNormal subjectsAlkali loadPotassium citrateSignificant differencesHoursTotal carbon dioxideCitrateExcretionCitrate concentrationLong-term activation of protein kinase c causes chronic Na/H antiporter stimulation in cultured proximal tubule cells.
Horie S, Moe O, Miller RT, Alpern RJ. Long-term activation of protein kinase c causes chronic Na/H antiporter stimulation in cultured proximal tubule cells. Journal Of Clinical Investigation 1992, 89: 365-372. PMID: 1310692, PMCID: PMC442861, DOI: 10.1172/jci115594.Peer-Reviewed Original ResearchConceptsNa/H antiporter activityProximal tubule cellsCultured proximal tubule cellsLong-term activationTubule cellsProtein kinase CShort-term activationDose-dependent increaseKinase CActivity 24 hActinomycin DAntiporter activityNa/H antiporterChronic conditionsTwo- to threefold increaseAcute increaseEffect of phorbolProtein kinase C activationChronic effectsTransient increaseMicroM cycloheximidePersistent increaseAlpha-PMAKinase C activationChronic regulator
1991
Chronic K depletion stimulates rat renal brush-border membrane Na-citrate cotransporter
Levi M, McDonald LA, Preisig PA, Alpern RJ. Chronic K depletion stimulates rat renal brush-border membrane Na-citrate cotransporter. American Journal Of Physiology 1991, 261: f767-f773. PMID: 1683169, DOI: 10.1152/ajprenal.1991.261.5.f767.Peer-Reviewed Original ResearchIncreased Na/H antiporter and Na/3HCO3 symporter activities in chronic hyperfiltration. A model of cell hypertrophy.
Preisig PA, Alpern RJ. Increased Na/H antiporter and Na/3HCO3 symporter activities in chronic hyperfiltration. A model of cell hypertrophy. The Journal Of General Physiology 1991, 97: 195-217. PMID: 1849958, PMCID: PMC2216475, DOI: 10.1085/jgp.97.2.195.Peer-Reviewed Original ResearchConceptsHyperfiltration groupChronic hyperfiltrationNa/H antiporterKidney weightCell hypertrophyHigher glomerular filtration rateNa/H antiporter activityH antiporterGlomerular filtration rateVivo microperfused rat proximal tubuleCell pHRat proximal tubuleSymporter activityFiltration rateProximal tubulesUltrafiltrate-like solutionHyperfiltrationSteady-state cell pHProtein feedingPeritubular perfusateDietary proteinParallel increaseUninephrectomyHypertrophyCell acidificationContrasting Effects of Various Potassium Salts on Renal Citrate Excretion*
SAKHAEE K, ALPERN R, JACOBSON H, PAK C. Contrasting Effects of Various Potassium Salts on Renal Citrate Excretion*. The Journal Of Clinical Endocrinology & Metabolism 1991, 72: 396-400. PMID: 1899422, DOI: 10.1210/jcem-72-2-396.Peer-Reviewed Original ResearchConceptsCitrate clearanceAcid-base statusUrinary citratePotassium citrateRenal citrate excretionMeq/dayPotassium citrate treatmentWeeks of treatmentNet acid excretionCitraturic responseUrinary ammoniumOral administrationCitrate excretionAcid excretionPotassium chlorideUrinary bicarbonateCitrate treatmentAlkali loadPotassium bicarbonateClearanceML/minExcretionDaysTreatmentTitratable acid