Total nitric oxide production is low in patients with chronic renal disease

Kidney Int. 2000 Sep;58(3):1261-6. doi: 10.1046/j.1523-1755.2000.00281.x.


Background: A deficiency of the endogenous vasodilator nitric oxide (NO) has been implicated as a potential cause of hypertension in chronic renal disease (CRD) patients. This study was conducted to determine whether 24-hour NOX (NO2 and NO3) excretion (a qualitative index of total NO production) is reduced in patients with CRD.

Methods: Measurements were made in 13 CRD patients and 9 normotensive healthy controls after 48 hours on a controlled low-NOX diet. Urine was collected over the second 24-hour period for analysis of 24-hour NOX, and cGMP and blood drawn at the completion. Plasma levels of arginine (the substrate for endogenous renal NO synthesis), citrulline (substrate for renal arginine synthesis), and the endogenous NO synthesis inhibitor asymmetrical dimethylarginine (ADMA) and its inert isomer and symmetrical dimethylarginine (SDMA) were also determined.

Results: Systolic blood pressure was higher in CRD patients (12 of whom were already on antihypertensive therapy) than in controls (P < 0.05). Twenty-four-hour urinary NOX excretion was low in CRD patients compared with controls despite similar dietary NO intake, suggesting that net endogenous NO production is decreased in renal disease. In contrast, the 24-hour urinary cGMP did not correlate with UNOXV. Plasma citrulline was increased in CRD patients, possibly reflecting reduced conversion of citrulline to arginine. Plasma arginine was not different, and plasma ADMA levels were elevated in CRD versus controls, changes that would tend to lower NO synthase.

Conclusion: These results suggest that NO production is low in CRD patients and may contribute to hypertension and disease progression in CRD.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Arginine / metabolism
  • Blood Pressure
  • Creatinine / blood
  • Female
  • Humans
  • Hypertension, Renal / metabolism
  • Kidney Failure, Chronic / metabolism*
  • Male
  • Middle Aged
  • Nitrates / pharmacokinetics
  • Nitric Oxide / biosynthesis*
  • Nitrites / pharmacokinetics
  • Oxidation-Reduction
  • Regression Analysis
  • Vasodilation


  • Nitrates
  • Nitrites
  • Nitric Oxide
  • Arginine
  • Creatinine