Hypothesis: Uric acid, nephron number, and the pathogenesis of essential hypertension

Daniel I. Feig, Takahiko Nakagawa, S. Ananth Karumanchi, William J. Oliver, Duk Hee Kang, Jennifer Finch, Richard J. Johnson

Research output: Contribution to journalArticlepeer-review

210 Scopus citations


Background. Essential hypertension affects more than 25% of the world's population. Genetic, physiologic, and epidemiologic studies provide clues to its origins, but a clear understanding has been elusive. Recent experimental and clinical studies have implicated uric acid in the onset of essential hypertension. Methods. In a retrospective chart review, we identified 95 children with confirmed, new onset hypertension, and evaluated the cause of hypertension and parental history of hypertension, birth weight, and serum uric acid. In an open-label, cross-over trial we treated 5 children with confirmed essential hypertension with allopurinol as single treatment agent, and screened for change in blood pressure by casual and ambulatory methods. In tissue culture experiments, we evaluated the effect of uric acid on glomerular endothelial cell function. Results. Elevation of serum uric acid is related to the onset of essential hypertension in children, reduced birth weight, and endothelial dysfunction. Normalization of uric acid appears to ameliorate new onset essential hypertension. Conclusion. These findings, combined with animal model data, support the hypothesis that uric acid has a key role in the pathogenesis of early onset essential hypertension, and may unify some of the disparate theories of the origins of essential hypertension.

Original languageEnglish
Pages (from-to)281-287
Number of pages7
JournalKidney International
Issue number1
StatePublished - Jul 2004

Bibliographical note

Funding Information:
Support for this paper was provided by an NIH K-23 award DK-064587 (DF), by NIH HL-68607 (RJ) and a George O'Brien Center P50-DK064233-01 (RJ). The clinical studies described in this manuscript were reviewed and approved by the Baylor College of Medicine Institutional Review Board. Oral and written informed consent and informed assent (as appropriate) was obtained from all subjects. The data as present are free of identifying markers to maintain confidentiality.


  • Children
  • Clinical trial
  • Endothelium
  • Essential hypertension


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