Article Text

  1. S. Phisitkul,
  2. J. Simoni,
  3. D. E. Wesson
  1. Departments of Internal Medicine, Physiology, and Surgery, Texas Tech University Health Sciences Center, Lubbock, TX


Purpose Renal endothelin 1 (ET-1) production is increased in the 5/6 nephrectomy experimental model of chronic kidney disease (CKD) and in rats with normal GFR ingesting mineral acid or acid-producing dietary protein. Unpublished data from our laboratory support that amelioration of the acid retention in experimental CKD with dietary alkali decreases renal ET-1 production as measured by urine excretion of endothelin 1 (UET-1V). We hypothesized that the same is true in human CKD.

Methods We recruited 18 healthy controls, 21 subjects with primary hypertension without CKD, and 19 subjects with CKD (plasma creatinine 1.5-6.0 mg/dL) and primary hypertension without diabetes, evidence of glomerulonephritis, or history of renal replacement therapy. We reduced systolic blood pressure (SBP) in the latter 2 groups toward 130 mm Hg over 6 months. We then prescribed oral Na+ citrate to CKD subjects with TCO2 < 22 mM (n = 12) but not to those with TCO2 $ 22 mM (n = 7) and followed each for an additional 6 months. We measured UET-1V (ng/g creatinine or ng/g Cr) in a spot am specimen and venous blood TCO2 at 0, 6, and 12 months.

Summary UET-1V was higher than healthy controls (3.1 6 0.4 ng/g Cr) in hypertensives without CKD (5.9 6 1.1 ng/g Cr, p < .03 vs controls) and in hypertensives with CKD (5.1 6 0.7 ng/g Cr, p < .02 vs controls). After SBP reduction, UET-1V in hypertensives without CKD (3.5 6 0.4 ng/g Cr) was not different from healthy controls (p = .23) but that for hypertensives with CKD (5.3 6 0.5 ng/g Cr) remained higher than control (p < .001) and was now higher than hypertensives without CKD (p < .007). TCO2 increased in CKD subjects prescribe Na+ citrate (20.1 6 0.4 to 23.9 6 0.4 mM, p < .001 paired t) but decreased in those not prescribed Na+ citrate (23.6 6 0.5 to 23.0 6 0.5 mM, p < .03 paired t). Although UET-1V was not different between CKD subjects before Na+ citrate (p = .85), UET-1V decreased in those prescribed Na+ citrate (5.4 6 0.6 to 4.1 6 0.4 ng/g Cr, p < .02, paired t) but did not change in those not prescribed Na+ citrate (5.2 6 1.0 to 6.1 6 1.0 ng/g Cr, p = .10, paired t). Follow-up UET-1V was lower in CKD subjects prescribed compared to those not prescribed Na+ citrate (p < .04).

Conclusions The data show that primary hypertensives with compared to those without CKD have higher UET-1V despite improved BP control that is decreased by oral Na+ citrate. These studies support the contention that subjects with CKD have increased renal ET-1 production that is mediated by the associated positive acid balance.

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