Progression of chronic kidney disease: the role of blood pressure control, proteinuria, and angiotensin-converting enzyme inhibition: a patient-level meta-analysis

Ann Intern Med. 2003 Aug 19;139(4):244-52. doi: 10.7326/0003-4819-139-4-200308190-00006.


Background: Angiotensin-converting enzyme (ACE) inhibitors reduce blood pressure and urine protein excretion and slow the progression of chronic kidney disease.

Purpose: To determine the levels of blood pressure and urine protein excretion associated with the lowest risk for progression of chronic kidney disease during antihypertensive therapy with and without ACE inhibitors.

Data sources: 11 randomized, controlled trials comparing the efficacy of antihypertensive regimens with or without ACE inhibitors for patients with predominantly nondiabetic kidney disease.

Study selection: MEDLINE database search for English-language studies published between 1977 and 1999.

Data extraction: Data on 1860 nondiabetic patients were pooled in a patient-level meta-analysis. Progression of kidney disease was defined as a doubling of baseline serum creatinine level or onset of kidney failure. Multivariable regression analysis was performed to assess the association of systolic and diastolic blood pressure and urine protein excretion with kidney disease progression at 22 610 patient visits.

Data synthesis: Mean duration of follow-up was 2.2 years. Kidney disease progression was documented in 311 patients. Systolic blood pressure of 110 to 129 mm Hg and urine protein excretion less than 2.0 g/d were associated with the lowest risk for kidney disease progression. Angiotensin-converting enzyme inhibitors remained beneficial after adjustment for blood pressure and urine protein excretion (relative risk, 0.67 [95% CI, 0.53 to 0.84]). The increased risk for kidney progression at higher systolic blood pressure levels was greater in patients with urine protein excretion greater than 1.0 g/d (P < 0.006).

Conclusion: Although reverse causation cannot be excluded with certainty, a systolic blood pressure goal between 110 and 129 mm Hg may be beneficial in patients with urine protein excretion greater than 1.0 g/d. Systolic blood pressure less than 110 mm Hg may be associated with a higher risk for kidney disease progression.

Publication types

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

MeSH terms

  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Antihypertensive Agents / therapeutic use*
  • Blood Pressure / physiology*
  • Chronic Disease
  • Creatinine / blood
  • Disease Progression
  • Follow-Up Studies
  • Humans
  • Hypertension / drug therapy*
  • Kidney Diseases / complications
  • Kidney Diseases / physiopathology*
  • Proteinuria / physiopathology*
  • Regression Analysis
  • Risk Factors


  • Angiotensin-Converting Enzyme Inhibitors
  • Antihypertensive Agents
  • Creatinine