The effect of mild hyperuricemia on urinary transforming growth factor beta and the progression of chronic kidney disease

Am J Nephrol. 2007;27(5):435-40. doi: 10.1159/000105142. Epub 2007 Jul 4.


Although mild hyperuricemia is common in patients with renal disease, it has usually been considered a marker of reduced nephron mass rather than a risk factor for progression of kidney disease. On the other hand, experiments in a rat model demonstrated important deleterious effects of mild hyperuricemia on several aspects of renal structure and function. In the present investigation, the impact of the discontinuation of allopurinol therapy on the control of hypertension and the rate of progression of chronic kidney disease was considered. The present work involved 50 patients, suffering from stage 3 and 4 chronic kidney disease. All of them were on chronic allopurinol therapy for the treatment of mild hyperuricemia. Their blood pressure, serum creatinine and uric acid levels were followed for 12 months following allopurinol withdrawal. Urinary transforming growth factor beta-1 (TGF-beta1) was assayed by a solid-phase enzyme-linked immunosorbent assay. After allopurinol withdrawal, significant worsening of hypertension, significant acceleration of the rate of loss of kidney function and a significant increase in the urinary excretion of TGF-beta1 were observed in the group of patients who were not receiving pharmacological blockers of the renin-angiotensin system. In conclusion, asymptomatic hyperuricemia has a deleterious effect on the progression of chronic kidney disease and the control of hypertension. This effect was blocked by treatment with renin-angiotensin system blockers.

MeSH terms

  • Adult
  • Allopurinol / administration & dosage
  • Allopurinol / therapeutic use
  • Antihypertensive Agents / therapeutic use
  • Disease Progression
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Humans
  • Hypertension / complications
  • Hypertension / drug therapy
  • Hypertension / physiopathology
  • Hyperuricemia / complications*
  • Hyperuricemia / drug therapy
  • Hyperuricemia / physiopathology*
  • Hyperuricemia / urine
  • Kidney / physiopathology
  • Kidney Failure, Chronic / complications*
  • Kidney Failure, Chronic / physiopathology*
  • Male
  • Middle Aged
  • Renin-Angiotensin System / drug effects
  • Severity of Illness Index
  • Transforming Growth Factor beta1 / urine*


  • Antihypertensive Agents
  • Transforming Growth Factor beta1
  • Allopurinol