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
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 Research
2001
Endothelin-1/endothelin-B receptor–mediated increases in NHE3 activity in chronic metabolic acidosis
Laghmani K, Preisig P, Moe O, Yanagisawa M, Alpern R. Endothelin-1/endothelin-B receptor–mediated increases in NHE3 activity in chronic metabolic acidosis. Journal Of Clinical Investigation 2001, 107: 1563-1569. PMID: 11413164, PMCID: PMC200190, DOI: 10.1172/jci11234.Peer-Reviewed Original ResearchMeSH KeywordsAcidosisAmmoniaAnimalsBicarbonatesChronic DiseaseCitric AcidCulture TechniquesEndothelin-1EndothelinsKidney Tubules, ProximalMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicProtein PrecursorsReceptor, Endothelin BReceptors, EndothelinRNA, MessengerSodiumSodium-Hydrogen Exchanger 3Sodium-Hydrogen ExchangersConceptsTg/tgAcid ingestionTitratable acid excretionMetabolic acidosisNHE3 activityAcid excretionReceptor-deficient miceEndothelin B receptorET-1 expressionChronic metabolic acidosisProximal tubule suspensionsAmmonium excretionM endothelinNa/H antiporterC57BL/6 miceApical membrane NHE3Renal epithelial cellsCultured renal epithelial cellsEndothelin-1/Tubule suspensionsMRNA expressionControl dietMiceExcretionEpithelial cells
1997
The clinical spectrum of chronic metabolic acidosis: Homeostatic mechanisms produce significant morbidity
Alpern R, Sakhaee K. The clinical spectrum of chronic metabolic acidosis: Homeostatic mechanisms produce significant morbidity. American Journal Of Kidney Diseases 1997, 29: 291-302. PMID: 9016905, DOI: 10.1016/s0272-6386(97)90045-7.Peer-Reviewed Original ResearchMeSH KeywordsAcid-Base EquilibriumAcidosisAgingBicarbonatesBone and BonesChronic DiseaseHomeostasisHumansKidneyConceptsChronic metabolic acidosisMetabolic acidosisHomeostatic responseSerum HCO3Acid loadBody's homeostatic responseHomeostatic mechanismsMuscle protein breakdownNormal homeostatic mechanismsSignificant morbidityClinical spectrumMeat ingestionBone demineralizationRenal growthClinical conditionsPathologic processesPathologic consequencesAcidosisProtein breakdownBloodResponseMorbidityPatientsNephrolithiasisIngestionChronic 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
1995
Chronic regulation of the proximal tubular Na/H antiporter: From HCO3 to SRC
Alpern R, Moe O, Preisig P. Chronic regulation of the proximal tubular Na/H antiporter: From HCO3 to SRC. Kidney International 1995, 48: 1386-1396. PMID: 8544394, DOI: 10.1038/ki.1995.427.Peer-Reviewed Original ResearchConceptsNa/H antiporterChronic regulationH secretionProximal tubulesH antiporterNaCl absorptionProximal tubular acidificationMajor siteNa/K pumpCitrate reabsorptionBasolateral membraneTubular acidificationAcute regulationLuminal membraneK pumpExcretionReabsorptionSecretionPivotal roleVacuolar H-ATPaseH-ATPaseTubules
1993
Cell pH and transepithelial H/HCO3 transport in the renal proximal tubule
Krapf R, Alpern R. Cell pH and transepithelial H/HCO3 transport in the renal proximal tubule. The Journal Of Membrane Biology 1993, 131: 1-10. PMID: 8381871, DOI: 10.1007/bf02258529.Peer-Reviewed Original Research
1991
Inhibition of Na(+)-independent H+ pump by Na(+)-induced changes in cell Ca2+.
Hays SR, Alpern RJ. Inhibition of Na(+)-independent H+ pump by Na(+)-induced changes in cell Ca2+. The Journal Of General Physiology 1991, 98: 791-813. PMID: 1660062, PMCID: PMC2229082, DOI: 10.1085/jgp.98.4.791.Peer-Reviewed Original ResearchConceptsCell pH recoveryCell Ca2PH recoveryAcid loadPump activityRenal outer medullaryDelayed activationCell acidificationRapid cell acidificationUnits/minApical membraneCell pHSustained elevationFura-2Outer medullaryExtracellular Ca2Inner stripeIntracellular Ca2Steady-state cell pHSustained increaseDimethyl-BAPTAInitial suppressionSpike increasePhysiologic ratesMicrofilament-disrupting agentChronic adaptations in proximal tubular H/HCO3 transporters.
Alpern RJ, Horie S, Moe O, Tejedor A, Miller RT, Preisig PA. Chronic adaptations in proximal tubular H/HCO3 transporters. Kidney International Supplement 1991, 33: s29-32. PMID: 1653870.Peer-Reviewed Original ResearchConceptsCultured proximal tubule cellsChronic hyperfiltrationNa/H antiporterProximal tubule cellsChronic acidosisTubule cellsNa/H antiporter activityH antiporterK deficiencyEffect of acidosisExtracellular fluid pHChronic adaptationsAcidosisHyperfiltrationCotransporter activityAbundance of mRNAParallel increaseHCO3- transportersAcid preincubationDeficiencyFluid pHCellsAntiporter activityProtein synthesisExtracellular signalsBasolateral membrane H/HCO3 transport in renal tubules
Preisig P, Alpern R. Basolateral membrane H/HCO3 transport in renal tubules. Kidney International 1991, 39: 1077-1086. PMID: 1895662, DOI: 10.1038/ki.1991.137.Peer-Reviewed Original ResearchMeSH KeywordsAcidsAnimalsBicarbonatesBiological TransportHumansHydrogenKidneyKidney TubulesMembranesConceptsCell exitRegulation of proximal reabsorption by effective arterial blood volume.
Seldin DW, Preisig PA, Alpern RJ. Regulation of proximal reabsorption by effective arterial blood volume. Seminars In Nephrology 1991, 11: 212-9. PMID: 2034926.Peer-Reviewed Original ResearchConceptsEffective arterial blood volumeEffective arterial volumeRenal nerve activityProximal tubular transportAtrial natriuretic factorArterial blood volumeLevels of hormonesRenal hemodynamicsNerve activityDietary NaClAngiotensin IIProximal reabsorptionNatriuretic factorBlood volumeTubular transportProximal tubulesChronic effectsArterial volumeOncotic pressureNorepinephrineHemodynamicsEpinephrineHormoneReabsorptionIncreased 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
1990
Cellular model of proximal tubule NaCl and NaHCO3 absorption
Moe O, Preisig P, Alpern R. Cellular model of proximal tubule NaCl and NaHCO3 absorption. Kidney International 1990, 38: 605-611. PMID: 2172616, DOI: 10.1038/ki.1990.249.Peer-Reviewed Original ResearchPreincubation in acid medium increases Na/H antiporter activity in cultured renal proximal tubule cells.
Horie S, Moe O, Tejedor A, Alpern RJ. Preincubation in acid medium increases Na/H antiporter activity in cultured renal proximal tubule cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 1990, 87: 4742-4745. PMID: 2162055, PMCID: PMC54193, DOI: 10.1073/pnas.87.12.4742.Peer-Reviewed Original ResearchConceptsNa/H antiporter activityProximal tubule cellsTubule cellsCultured renal proximal tubule cellsCultured proximal tubule cellsRenal proximal tubule cellsPreincubation of fibroblastsExtracellular fluidAntiporter activityChronic acidosisAcidotic environmentCO2/HCO3Small inhibitionPreincubationPreincubation mediumAddition of cycloheximideCell acidificationAcid preincubationPresent studyProtein synthesisCellsAcidosisActivityEpitheliumBasolateral membrane H/OH/HCO3 transport mechanisms along the nephron: role in control of pHi and transepithelial bicarbonate transport.
Preisig PA, Hays SR, Alpern RJ. Basolateral membrane H/OH/HCO3 transport mechanisms along the nephron: role in control of pHi and transepithelial bicarbonate transport. Seminars In Nephrology 1990, 10: 104-14. PMID: 2156327.Peer-Reviewed Original ResearchBasolateral membrane Na(+)-independent Cl-/HCO3- exchange in the inner stripe of the rabbit outer medullary collecting tubule.
Hays SR, Alpern RJ. Basolateral membrane Na(+)-independent Cl-/HCO3- exchange in the inner stripe of the rabbit outer medullary collecting tubule. The Journal Of General Physiology 1990, 95: 347-367. PMID: 2307960, PMCID: PMC2216319, DOI: 10.1085/jgp.95.2.347.Peer-Reviewed Original ResearchConceptsInner stripePeritubular ClDistal nephron segmentsBasolateral membraneCell acidificationCell pHLuminal changesUrinary acidificationNephron segmentsPH-sensitive fluorescent dyeIndependent ClCell alkalinizationCO2/HCO3Peritubular pHVoltage clampTubulesTwo-thirdsRabbitsTotal replacementCell pH changes
1989
Contributions of cellular leak pathways to net NaHCO3 and NaCl absorption.
Preisig PA, Alpern RJ. Contributions of cellular leak pathways to net NaHCO3 and NaCl absorption. Journal Of Clinical Investigation 1989, 83: 1859-1867. PMID: 2542374, PMCID: PMC303906, DOI: 10.1172/jci114092.Peer-Reviewed Original ResearchBasolateral membrane H-OH-HCO3 transport in the proximal tubule
Preisig P, Alpern R. Basolateral membrane H-OH-HCO3 transport in the proximal tubule. American Journal Of Physiology 1989, 256: f751-f765. PMID: 2541627, DOI: 10.1152/ajprenal.1989.256.5.f751.Peer-Reviewed Original ResearchConceptsProximal tubulesS3 proximal tubuleChronic respiratory acidosisChronic metabolic acidosisRabbit proximal tubuleChronic hyperfiltrationMetabolic acidosisNa-H antiporterRespiratory acidosisCl-HCO3 exchangerCl absorptionGreater transport capacityAlkalosisAcidosisTubulesTransporter activityMembrane mechanismsBasolateral membraneCotransporterHyperfiltrationRatsEpithelium
1988
Chronic metabolic acidosis causes an adaptation in the apical membrane Na/H antiporter and basolateral membrane Na(HCO3)3 symporter in the rat proximal convoluted tubule.
Preisig PA, Alpern RJ. Chronic metabolic acidosis causes an adaptation in the apical membrane Na/H antiporter and basolateral membrane Na(HCO3)3 symporter in the rat proximal convoluted tubule. Journal Of Clinical Investigation 1988, 82: 1445-1453. PMID: 2844858, PMCID: PMC442703, DOI: 10.1172/jci113750.Peer-Reviewed Original ResearchConceptsChronic metabolic acidosisNa/H antiporterMetabolic acidosisAcidotic animalsH antiporterVivo microperfused rat proximal tubuleDpHi/dtRat proximal tubuleBasolateral membraneTransporter activityDietary acidPeritubular capillariesProximal tubulesNa/HPH-sensitive fluorescent dyeAcidosisTubulesSubsequent studiesAnimalsCarboxy-fluoresceinAbsence of contactCells