Peter S. Aronson, MD

Research Interests

Acid-Base Imbalance; Cell Membrane Permeability; Hyperoxaluria; Urinary Tract Physiological Phenomena; Water-Electrolyte Imbalance; Nephrolithiasis; Cell Physiological Processes

Research Organizations

Internal Medicine: Nephrology

Cellular & Molecular Physiology: Epithelial Transport of Ions and Solutes | Membrane Proteins - Pumps and Transporters | Physiology of Human Disease

Faculty Research

Office of Cooperative Research

Research Summary

The general goal of our research is to understand how the kidney regulates the composition of the urine, especially as needed to maintain the salt (NaCl) and acid-base balance of the body. To eliminate waste products from the body, the kidney filters gigantic quantities of the plasma (over 160 quarts per day) resulting in the flow of huge quantities of water, NaCl and the base bicarbonate through the renal tubules. The first portion of each renal tubule is called the proximal tubule, and the proximal tubules are collectively responsible for reabsorbing the vast majority of the filtered NaCl, bicarbonate and water, and secreting acid in the form of ammonium ions.

Our lab has specifically focused on identifying the proteins involved in mediating the transport of bicarbonate, NaCl and ammonium in the proximal tubule. We found that “knockout” mice lacking one of these transport proteins have a high incidence of calcium oxalate urinary stones, the same type that is most common in human patients with kidney stones. We showed that the cause of the calcium oxalate kidney stones is a very high concentration of oxalate in the urine. We found that this kidney transport protein also plays a very crucial role in the intestine, where it secretes oxalate and thereby limits how much of ingested oxalate is absorbed and then excreted in the urine. Based on this discovery, our laboratory has been devoting increasing effort to understanding the role of transporters in governing oxalate homeostasis and excretion. We have also been studying mechanisms by which oxalate crystals induce inflammation and thereby cause damage to the kidney and other tissues.

Extensive Research Description

Our general goal is to characterize the mechanisms regulating sodium, acid-base, and anion excretion by the kidney. Our work is primarily focused on membrane transport proteins mediating ion exchange, namely NHE isoforms mediating Na⁺-H⁺ exchange, and SLC26 isoforms mediating anion exchange. One approach involves the generation of isoform- and phospho-specific polyclonal and monoclonal antibodies to identify the cellular and subcellular sites of expression of ion exchangers in the kidney and other tissues, and to study their regulation. A complementary approach uses mice with targeted gene disruption to elucidate the physiological roles of ion exchangers and associated proteins under in vivo conditions. For example, work with mice lacking anion exchanger Slc26a6, which can function as an oxalate transporter, revealed a phenotype of calcium oxalate kidney stones. This finding in turn has motivated studies on the mechanisms and regulation of oxalate transporters and their roles in oxalate homeostasis, urolithiasis, and crystal-induced inflammation and kidney disease.

• Regulation of Na⁺-H⁺ exchanger NHE3 in the proximal tubule, a process important for controlling the salt, fluid, and acid-base balance of the body.
• Roles of SLC26 anion exchangers in directly and indirectly governing urinary oxalate excretion, a urinary constituent that is very important for kidney stone formation.
• Mechanisms amd roles of oxalate crystal deposition in inducing inflammation and causing kidney failure.

Selected Publications

• N-glycosylation critically regulates function of oxalate transporter SLC26A6

  Thomson, R.B., Thomson, C.L., and Aronson, P.S. N-glycosylation critically regulates function of oxalate transporter SLC26A6. Am. J. Physiol. in press, 2017.

• Loss of CFTR impairs intestinal oxalate secretion

  Knauf, F., Thomson, R.B., Heneghan, J.F., Jiang, Z., Adebamiro, A., Thomson, C.L., Barone, C., Asplin, J.R., Egan, M.E., Alper. S.L., and Aronson, P.S. Loss of CFTR impairs intestinal oxalate secretion. J. Am. Soc. Nephrol., in press, 2016.

• Oxalate-induced chronic kidney disease with its uremic and cardiovascular complications in C57BL/6 mice

  Mulay, S.R., Eberhard, J.N., Pfann, V., Marschner, J.A., Darisipudi, M.N., Daniel, C., Romoli, S., Desai, J., Grigorescu, M., Kumar, S.V., Rathkolb, B., Wolf, E., Hrabě de Angelis, M., Bäuerle, T., Dietel, B., Wagner, C.A., Amann, K., Eckardt, K.U., Aronson, P.S., Anders, H.J., and Knauf, F. Oxalate-induced chronic kidney disease with its uremic and cardiovascular complications in C57BL/6 mice. Am. J. Physiol. in press, 2016.

• Oxalate, inflammasome, and progression of kidney disease.

  Ermer, T., Eckardt, K.U., Aronson, P.S., and Knauf, F. Oxalate, inflammasome, and progression of kidney disease. Curr. Opin. Nephrol. Hypertens. 25:363-371, 2016.

• Cyclic GMP kinase II (cGKII) inhibits NHE3 by altering its trafficking and phosphorylating NHE3 at three required sites: identification of a multifunctional phosphorylation site

  Chen, T., Kocinsky, H.S., Cha, B., Murtazina, R., Yang, J., Tse, C.M., Singh, V., Cole, R., Aronson, P.S., deJonge, H., Sarker, R., and Donowitz, M. Cyclic GMP kinase II (cGKII) inhibits NHE3 by altering its trafficking and phosphorylating NHE3 at three required sites: identification of a multifunctional phosphorylation site. J. Biol. Chem. 290:1952-1965, 2015.

• NALP3-mediated inflammation is the principal cause of progressive renal failure in oxalate nephropathy

  Knauf, F., Asplin, J.R., Granja, I., Schmidt, I.M., Moeckel, G., David, R., Flavell, R.A., and Aronson, P.S. NALP3-mediated inflammation is the principal cause of progressive renal failure in oxalate nephropathy. Kidney Int. 84:895-901, 2013

• Ezrin is required for the functional regulation of the epithelial sodium proton exchanger, NHE3

  Hayashi, H., Tamura, A., Krishnan, D., Tsukita, S., Suzuki, Y., Kocinsky, H.S., Aronson, P.S., Orlowski, J., Grinstein, S., and Alexander, R.T. Ezrin is required for the functional regulation of the epithelial sodium proton exchanger, NHE3. PLoS One 8:e55623, 2013

• Sat1 is dispensable for active oxalate secretion in mouse duodenum

  Ko, N., Knauf, F., Jiang, Z., Markovich, D., and Aronson, P.S. Sat1 is dispensable for active oxalate secretion in mouse duodenum. Am. J. Physiol. 303:C52-C57, 2012.

• Cholinergic signaling inhibits oxalate transport by human intestinal T84 cells

  Hassan, H.A., Cheng, M., and Aronson, P.S. Cholinergic signaling inhibits oxalate transport by human intestinal T84 cells. Am. J. Physiol. 302:C46-C58, 2012.

• Net intestinal transport of oxalate reflects passive absorption and SLC26A6-mediated secretion

  Knauf, F., Ko, N., Jiang, Z., Robertson, W.G., Van Itallie, C.M., Anderson, J.M., and Aronson, P.S. Net intestinal transport of oxalate reflects passive absorption and SLC26A6-mediated secretion. J. Am. Soc. Nephrol. 22:2247-2255, 2011.

• NHE3 phosphorylation at serines 552 and 605 does not directly affect NHE3 activity

  Kocinsky HS, Dynia DW, Wang T, Aronson PS. NHE3 phosphorylation at serines 552 and 605 does not directly affect NHE3 activity. Am J Physiol, 293:F212-8, 2007.

• Calcium oxalate urolithiasis in mice lacking anion transporter Slc26a6

  Jiang Z, Asplin JR, Evan AP, Rajendran VM, Velazquez H, Nottoli TP, Binder HJ, Aronson PS. Calcium oxalate urolithiasis in mice lacking anion transporter Slc26a6. Nat Genet, 38:474-8, 2006.

Full List of PubMed Publications

• Ermer T, Kopp C, Asplin JR, Granja I, Perazella MA, Reichel M, Nolin TD, Eckardt KU, Aronson PS, Finkelstein FO, Knauf F: Impact of Regular or Extended Hemodialysis and Hemodialfiltration on Plasma Oxalate Concentrations in Patients With End-Stage Renal Disease. Kidney Int Rep. 2017 Nov; 2017 Jun 8. PMID: 29270514
• Knauf F, Thomson RB, Heneghan JF, Jiang Z, Adebamiro A, Thomson CL, Barone C, Asplin JR, Egan ME, Alper SL, Aronson PS: Loss of Cystic Fibrosis Transmembrane Regulator Impairs Intestinal Oxalate Secretion. J Am Soc Nephrol. 2017 Jan; 2016 Jun 16. PMID: 27313231
• Thomson RB, Thomson CL, Aronson PS: N-glycosylation critically regulates function of oxalate transporter SLC26A6. Am J Physiol Cell Physiol. 2016 Dec 1; 2016 Sep 28. PMID: 27681177
• Ermer T, Eckardt KU, Aronson PS, Knauf F: Oxalate, inflammasome, and progression of kidney disease. Curr Opin Nephrol Hypertens. 2016 Jul. PMID: 27191349
• Mulay SR, Eberhard JN, Pfann V, Marschner JA, Darisipudi MN, Daniel C, Romoli S, Desai J, Grigorescu M, Kumar SV, Rathkolb B, Wolf E, Hrabě de Angelis M, Bäuerle T, Dietel B, Wagner CA, Amann K, Eckardt KU, Aronson PS, Anders HJ, Knauf F: Oxalate-induced chronic kidney disease with its uremic and cardiovascular complications in C57BL/6 mice. Am J Physiol Renal Physiol. 2016 Apr 15; 2016 Jan 13. PMID: 26764204
• Chen T, Kocinsky HS, Cha B, Murtazina R, Yang J, Tse CM, Singh V, Cole R, Aronson PS, de Jonge H, Sarker R, Donowitz M: Cyclic GMP kinase II (cGKII) inhibits NHE3 by altering its trafficking and phosphorylating NHE3 at three required sites: identification of a multifunctional phosphorylation site. J Biol Chem. 2015 Jan 23; 2014 Dec 5. PMID: 25480791
• Knauf F, Asplin JR, Granja I, Schmidt IM, Moeckel GW, David RJ, Flavell RA, Aronson PS: NALP3-mediated inflammation is a principal cause of progressive renal failure in oxalate nephropathy. Kidney Int. 2013 Nov; 2013 Jun 5. PMID: 23739234
• Ko N, Knauf F, Jiang Z, Markovich D, Aronson PS: Sat1 is dispensable for active oxalate secretion in mouse duodenum. Am J Physiol Cell Physiol. 2012 Jul 1; 2012 Apr 18. PMID: 22517357
• Knauf F, Ko N, Jiang Z, Robertson WG, Van Itallie CM, Anderson JM, Aronson PS: Net intestinal transport of oxalate reflects passive absorption and SLC26A6-mediated secretion. J Am Soc Nephrol. 2011 Dec; 2011 Oct 21. PMID: 22021714
• Aronson PS, Giebisch G: Effects of pH on potassium: new explanations for old observations. J Am Soc Nephrol. 2011 Nov; 2011 Oct 6. PMID: 21980112
• Aronson PS: Role of SLC26A6-mediated Cl⁻-oxalate exchange in renal physiology and pathophysiology. J Nephrol. 2010 Nov-Dec. PMID: 21170874
• Knauf F, Aronson PS: ESRD as a window into America's cost crisis in health care. J Am Soc Nephrol. 2009 Oct; 2009 Sep 3. PMID: 19729435
• Bai JP, Surguchev A, Montoya S, Aronson PS, Santos-Sacchi J, Navaratnam D: Prestin's anion transport and voltage-sensing capabilities are independent. Biophys J. 2009 Apr 22. PMID: 19383462
• Kocinsky HS, Dynia DW, Wang T, Aronson PS: NHE3 phosphorylation at serines 552 and 605 does not directly affect NHE3 activity. Am J Physiol Renal Physiol. 2007 Jul; 2007 Apr 4. PMID: 17409282
• Hassan HA, Mentone S, Karniski LP, Rajendran VM, Aronson PS: Regulation of anion exchanger Slc26a6 by protein kinase C. Am J Physiol Cell Physiol. 2007 Apr; 2006 Dec 6. PMID: 17151144
• Dudas PL, Mentone S, Greineder CF, Biemesderfer D, Aronson PS: Immunolocalization of anion transporter Slc26a7 in mouse kidney. Am J Physiol Renal Physiol. 2006 Apr; 2005 Nov 1. PMID: 16263805
• Jiang Z, Asplin JR, Evan AP, Rajendran VM, Velazquez H, Nottoli TP, Binder HJ, Aronson PS: Calcium oxalate urolithiasis in mice lacking anion transporter Slc26a6. Nat Genet. 2006 Apr; 2006 Mar 12. PMID: 16532010
• Aronson PS: Role of SLC26-mediated Cl-/base exchange in proximal tubule NaCl transport. Novartis Found Symp. 2006. PMID: 17120766
• Thomson RB, Wang T, Thomson BR, Tarrats L, Girardi A, Mentone S, Soleimani M, Kocher O, Aronson PS: Role of PDZK1 in membrane expression of renal brush border ion exchangers. Proc Natl Acad Sci U S A. 2005 Sep 13; 2005 Sep 2. PMID: 16141316
• Kocinsky HS, Girardi AC, Biemesderfer D, Nguyen T, Mentone S, Orlowski J, Aronson PS: Use of phospho-specific antibodies to determine the phosphorylation of endogenous Na+/H+ exchanger NHE3 at PKA consensus sites. Am J Physiol Renal Physiol. 2005 Aug; 2005 Feb 1. PMID: 15687252
• Goyal S, Mentone S, Aronson PS: Immunolocalization of NHE8 in rat kidney. Am J Physiol Renal Physiol. 2005 Mar; 2004 Nov 2. PMID: 15522984
• Bailey MA, Giebisch G, Abbiati T, Aronson PS, Gawenis LR, Shull GE, Wang T: NHE2-mediated bicarbonate reabsorption in the distal tubule of NHE3 null mice. J Physiol. 2004 Dec 15; 2004 Oct 7. PMID: 15604231
• Girardi AC, Knauf F, Demuth HU, Aronson PS: Role of dipeptidyl peptidase IV in regulating activity of Na+/H+ exchanger isoform NHE3 in proximal tubule cells. Am J Physiol Cell Physiol. 2004 Nov; 2004 Jun 22. PMID: 15213057
• Kahle KT, Gimenez I, Hassan H, Wilson FH, Wong RD, Forbush B, Aronson PS, Lifton RP: WNK4 regulates apical and basolateral Cl- flux in extrarenal epithelia. Proc Natl Acad Sci U S A. 2004 Feb 17; 2004 Feb 9. PMID: 14769928
• Thomson RB, Mentone S, Kim R, Earle K, Delpire E, Somlo S, Aronson PS: Histopathological analysis of renal cystic epithelia in the Pkd2WS25/- mouse model of ADPKD. Am J Physiol Renal Physiol. 2003 Nov; 2003 Jul 8. PMID: 12851251
• Goyal S, Vanden Heuvel G, Aronson PS: Renal expression of novel Na+/H+ exchanger isoform NHE8. Am J Physiol Renal Physiol. 2003 Mar; 2002 Oct 29. PMID: 12409279
• Wagner CA, Finberg KE, Stehberger PA, Lifton RP, Giebisch GH, Aronson PS, Geibel JP: Regulation of the expression of the Cl-/anion exchanger pendrin in mouse kidney by acid-base status. Kidney Int. 2002 Dec. PMID: 12427135
• Knauf F, Rogina B, Jiang Z, Aronson PS, Helfand SL: Functional characterization and immunolocalization of the transporter encoded by the life-extending gene Indy. Proc Natl Acad Sci U S A. 2002 Oct 29; 2002 Oct 21. PMID: 12391301
• Jiang Z, Grichtchenko II, Boron WF, Aronson PS: Specificity of anion exchange mediated by mouse Slc26a6. J Biol Chem. 2002 Sep 13; 2002 Jul 15. PMID: 12119287
• Wang T, Giebisch G, Aronson PS: Use of transgenic animals to study renal acid-base transport. J Nephrol. 2002 Mar-Apr. PMID: 12027214
• Aronson PS: Ion exchangers mediating NaCl transport in the renal proximal tubule. Cell Biochem Biophys. 2002. PMID: 12139400

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