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Which urinary proteins are decreased after angiotensin converting--enzyme inhibition?
E Guidi1, A Giglioni, M G Cozzi
1Centro di Ricerca Clinica in Nefrologia e Ipertensine Arteriosa Unità Operativa di Nefrologia Dialisi e Trapianto, Milano, Italy.
Insights
Angiotensin converting-enzyme (ACE) inhibitors reduced both albumin and Tamm-Horsfall Glycoprotein (THGP) excretion in hypertensive patients. This suggests ACE inhibitors may impact renal tubular cells, not just glomerular hemodynamics.
Area of Science:
- Nephrology
- Pharmacology
- Biochemistry
Background:
- Angiotensin converting-enzyme (ACE) inhibitors are thought to reduce proteinuria by altering glomerular hemodynamics.
- This mechanism implies that urinary excretion of tubular proteins should remain unchanged following ACE inhibition.
Purpose of the Study:
- To investigate the effect of ACE inhibition on the urinary excretion of albumin and Tamm-Horsfall Glycoprotein (THGP).
- To determine if ACE inhibitors have effects beyond glomerular hemodynamics, potentially at the renal tubular level.
Main Methods:
- A study involving 15 essential hypertensive patients after a 4-week drug washout period.
- Patients received oral Quinapril for 2 months, with urinary protein excretion measured before and after treatment.
- Urinary protein levels were analyzed using SDS polyacrylamide gel electrophoresis and silver staining (Phast System).
Main Results:
- After 2 months of ACE inhibition, plasma ACE activity significantly decreased (p = 0.0001).
- Urinary excretion of both albumin and THGP significantly decreased (p = 0.05 and p = 0.02, respectively).
- No significant changes were observed in blood pressure, body weight, or creatinine clearance.
Conclusions:
- The observed reduction in THGP excretion, a protein solely secreted by renal tubules, is unexpected.
- These findings suggest that ACE inhibitors may exert effects directly on renal tubular cells, in addition to their known impact on glomerular hemodynamics.
Abstract:
It is believed that angiotensin converting-enzyme (ACE) inhibitors lower proteinuria by acting on glomerular hemodynamics. This hypothesis predicts that the urinary excretion of a tubular protein should be unaffected by ACE inhibition. In the present study we have compared the excretion of albumin and Tamm-Horsfall Glycoprotein (THGP), a protein secreted only by renal tubules, before and after ACE inhibition. Urinary protein excretion was measured with the Phast System, a method based on SDS polyacrylamide gel electrophoresis followed by silver staining, in 15 essential hypertensives, after at least 4 weeks of wash-out from any drug and after 2 months of ACE inhibition with oral Quinapril. After 2 months of ACE inhibition, blood pressure (BP), body weight, urinary output, heart rate, plasma glucose, plasma and urinary creatinine, urate and electrolytes, and creatinine clearance, were not different from baseline values. Plasma ACE activity decreased from 76 +/- 7 to 10 +/- 4 U/mL (mean +/- SEM, 2 tails paired t test, p = 0.0001). Both albumin and THP urinary excretions decreased from 51 +/- 6 to 43 +/- 4 mg/ 24 h (p = 0.05) and from 19 +/- 3 to 12 +/- 1 mg/24 h (p = 0.02), respectively. This unexpected result suggests that ACE inhibitors may act also at the level of renal tubular cells.