Kathleen Hering-Smith, MS, PhD, FASN

Assoc. Professor of Nephrology & Hypertension

Dir., TUSOM Research Resources & Freezer Farm, Dir., Nephrology & Hypertension Core
(504) 554-5889
School of Medicine

Education & Affiliations

PhD: Tulane University, 2004

Areas of Expertise

Nephrology and Hypertension


  • Kidney Epithelial Transport Physiology and the relationship to Aging and Disease, specifically in Kidney Stones and Hypertension

Calcium nephrolithiasis remains a frequent and serious cause of morbidity and health care costs. As is well known, urinary citrate is the most important inhibitor of calcium stones in the kidney because citrate, a tricarboxylate, keeps calcium soluble in the urine. The regulation of citrate transport in the kidney has received inadequate investigation and remains poorly understood at the cell and molecular level. Urinary citrate excretion is primarily determined by its fractional reabsorption in the proximal tubule. The dicarboxylate transporter (NaDC1) cloned by Pajor has been considered the main mechanism of apical reabsorption of filtered citrate. Knockout mice, without NaDC1, are viable with normal kidney anatomy, have no severe phenotype, and appear to have significant residual citrate reabsorption. Our recently published studies in OK cells demonstrate a novel mechanism which may explain the remaining citrate reabsorption. This mechanism is sensitive to calcium and magnesium by decreasing citrate transport with increasing concentrations of these ions, and may explain the increase in citrate excretion with increases in urinary calcium found in vivo in both humans and animals. In our published studies utilizing OK (opossum kidney) cells and in our preliminary studies utilizing mouse S1 and S2 proximal tubule cell lines, citrate transport increases significantly when apical calcium is acutely decreased. Thus, our in vitro studies correspond to the in vivo observations made decades ago in humans, demonstrating that urinary citrate normally increases with urinary calcium. This physiological process is a key mechanism that prevents calcium stone formation. We have shown NaDC1 is not sensitive to calcium. What is not known is how the level of calcium in the urine regulates the transport of citrate and the contributions of the known and novel transporters. Without this knowledge we will not be able effectively target citrate transport to protect against nephrolithiasis.

Our long-term goal is to understand the physiological mechanisms leading to the development of calcium stones in order to discover treatment and prevention strategies. Our overall objective is to determine the mechanisms and regulation of apical citrate transport via a novel apical calcium-sensitive transporter, and the relative roles of NaDC1, NaDC3 and SLC26A6. Our central hypothesis is that the novel apical calcium-sensitive citrate reabsorptive process limits citrate transport in the proximal tubule when calcium is increased. This hypothesis is based on our published and preliminary data. The rationale that underlies this line of research is that the elucidation of previously unidentified citrate transporters can potentially lead to new methods of specific inhibition of proximal reabsorption of citrate, enabling increase of urinary citrate and inhibition of calcium stone formation. Our expected outcomes will establish new paradigms in understanding citrate reabsorption in the kidney proximal tubule, and how these paradigms are impacted in acidosis and hypercalciuria. These outcomes are expected to have an important impact since understanding the regulation of citrate transport in the proximal tubule will dramatically improve strategies in the prevention of calcium stones.

Lab Members:

Laura Nussdorf

Laura Nussdorf - Physiology MS Student and Summer Researcher

Current Funding:
NIH/NIDDK R01 DK095879-01, Project Period: 09/15/2012-08/31/2016
“A New Target for Kidney Stone Prevention: Calcium-Sensitive Transport of Citrate.”


Nakhoul NL, Hering-Smith KS, Abdulnour-Nakhoul SM, and LL Hamm. Ammonium Interaction with the Epithelial Sodium Channel. Am J Physiol 281:F493-F502, 2001.

Liu L, Hering-Smith KS, Schiro FR, and LL Hamm. Serine protease activity in M-1 cortical collecting duct cells. Hypertension 39(4):860-4, 2002.

Hamm LL and Hering-Smith KS. Pathophysiology of Hypocitraturic Nephrolithiasis. Endocrinology & Metabolism Clinics of North America 31(4):885-93, viii, 2002.

Prieto-Carrasquero MC, Harrison-Bernard LM, Kobori H, OzawaY, Hering-Smith, KS, Hamm LL, and LG Navar. Enhancement of distal tubular renin expression in Angiotensin IIhypertensive rats. Hypertension 44(2):223-9, 2004.

Nakhoul NL, Dejong H, Abdulnour-Nakhoul SM, Boulpaep EL, Hering-Smith K, Hamm LL. Characteristics of renal Rhbg as an NH4(+) transporter. American Journal of Physiology - Renal Physiology 288(1):F170-81, 2005 Jan.

Leung JC, Barac-Nieto M, Hering-Smith K, Silverstein DM. Expression of the rat renal PiT-2 phosphate transporter. Hormone & Metabolic Research 37(5):265-9, 2005 May.

Li M, Hering-Smith KS, Simon EE and Batuman V. Myeloma light chains induce epitheliamesenchymal transition in human renal proximal tubule epithelial cells. Nephrol Dial Transplant: 23(3):860-870, 2008 Mar.

Hamm LL, Feng Z and Hering-Smith KS. Regulation of sodium transport by ENaC in the Kidney. Curr Opin Nephrol Hypertens 19:98–105, 2010.

Hamm LL and Hering-Smith KS. Pivotal Role of the Kidney in Hypertension. Am J Med Sci. 340(1):30-2, 2010, Jul.

Li K, Guo D, Zhu H, Hering-Smith KS, Hamm LL, Ouyang J, Dong Y. Interleukin-6 Stimulates Epithelial Sodium Channels in Mouse Collecting Duct cells. Am J Physiol Regul Integr Comp Physiol. 299(2):R590-5, 2010, Aug.

Recent Publications: A PubMed listing of research publications for Kathleen Hering-Smith, Ph.D.