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Water Balance Disorders

Disorders of water balance are relatively common in hospitalized patients. They include: (a) abnormal water retention by the kidney causing dilutional hyponatremia, as if often seen with congestive heart failure, cirrhosis, and various malignancies (syndrome of inappropriate antidiuresis); and (b) excessive water excretion or polyuria, as is often seen with hypercalcemia, hypokalemia, and with lithium therapy for bipolar disorder. Successful management of water balance disorders depends on an understanding of the normal regulation of salt and water transport in the epithelial cells that line the renal tubule. The research done in the Epithelial Systems Biology Laboratory of the NHLBI is focused on discovering the mechanistic basis of regulation of salt and water transport in the kidney with emphasis on the role of the peptide hormone vasopressin. For more information, see recent review articles: (3-5).

Recent work has used systems biology techniques, especially RNA-Seq based transcriptomics in microdissected collecting duct segments, to identify the underlying signaling mechanisms involved with the renal response to hyponatremia (2) and the development of lithium-induced nephrogenic diabetes insipidus (1).


  1. Sung CC, Chen L, Limbutara K, Jung HJ, Gilmer GG, Yang CR, Lin SH, Khositseth S, Chou CL, Knepper MA. RNA-Seq and protein mass spectrometry in microdissected kidney tubules reveal signaling processes initiating lithium-induced nephrogenic diabetes insipidus. Kidney Int. 2019; S0085-2538 30267-4. PMID: 31146973.

  2. Lee JW, Alsady M, Chou CL, de Groot T, Deen PMT, Knepper MA, Ecelbarger CM. Single-tubule RNA-Seq uncovers signaling mechanisms that defend against hyponatremia in SIADH. Kidney Int. 2018; 93:128-146. PMID: 28843412.

  3. Knepper MA, Kwon TH, Nielsen S. Molecular physiology of water balance. N Engl J Med. 2015; 372: 1349-58. PMID: 25830425.

  4. Fenton RA, Knepper MA. Mouse models and the urinary concentrating mechanism in the new millennium. Physiol Rev. 2007; 87:1083-112. PMID: 17928581.

  5. Nielsen S, Frøkiaer J, Marples D, Kwon TH, Agre P, Knepper MA. Aquaporins in the kidney: from molecules to medicine. Physiol Rev. 2002; 82:205-44. PMID: 11773613.