ACE inhibitors improve diabetic nephropathy through suppression of renal MCP-1.
OBJECTIVE
Chemokines play an important role in the pathogenesis of diabetic nephropathy. Angiotensin II induces several fibrogenic chemokines, namely monocyte chemoattractant protein-1 (MCP-1) and transforming growth factor-beta. The progression of diabetic nephropathy can be retarded by ACE inhibitors (ACEIs) in patients with type 1 and type 2 diabetes. We examined if blockade of the renin-angiotensin system lowered urinary levels of the chemokine MCP-1 and correlated urinary MCP-1 (uMCP-1) with parameters of renal function and glucose and lipid metabolism before and after 1 year of treatment with an ACE inhibitor.


METHODS
In 22 patients with type 2 diabetes and diabetic nephropathy in stages 3-5, treatment with the ACEI lisinopril was initiated. Before treatment and after 12 months of continuous therapy, proteinuria, creatinine clearance, uMCP-1 levels, BMI, HbA(1c), and serum cholesterol were assessed.


RESULTS
Lisinopril treatment improved renal function. Proteinuria decreased from 410 +/- 662 mg per 24 h to 270 +/- 389 mg per 24 h. Creatinine clearance rose from 61 +/- 26 to 77 +/- 41 ml/min. Urinary MCP-1 levels decreased from 0.456 +/- 0.22 ng/mg creatinine to 0.08 +/- 0.096 ng/mg creatinine. The change in uMCP-1 correlated significantly (r = 0.61, P < 0.001) with the change in proteinuria. No other parameter correlated with the improvement in renal function.


CONCLUSIONS
Blockade of the renin-angiotensin system in type 2 diabetic patients with diabetic nephropathy reduces uMCP-1 levels and improves renal function. Because MCP-1 induces monocyte immigration and differentiation to macrophages, which augment extracellular matrix production and tubulointerstitial fibrosis, pharmacological reduction of angiotensin II may also exert its beneficial effects in diabetic nephropathy by downregulation of renal MCP-1.
Amann
Berthold
B
Kamillianer Hospital Mönchengladbach, Mönchengladbach, Germany. berthold.amann@gmx.de
Tinzmann
Ralph
R
Angelkort
Bernhard
B
D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D018932:Chemokine CCL2 / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006801:Humans; D006977:Hypertension, Renal / Q000188:drug therapy / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D017706:Lisinopril / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011507:Proteinuria / Q000188:drug therapy / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects; D016896:Treatment Outcome
D000806:Angiotensin-Converting Enzyme Inhibitors; D018932:Chemokine CCL2; D017706:Lisinopril