PMID- 12882873
OWN - NLM
STAT- MEDLINE
DCOM- 20031104
LR  - 20190516
IS  - 0149-5992 (Print)
IS  - 0149-5992 (Linking)
VI  - 26
IP  - 8
DP  - 2003 Aug
TI  - ACE inhibitors improve diabetic nephropathy through suppression of renal MCP-1.
PG  - 2421-5
AB  - 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. 
      RESEARCH DESIGN AND 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.
FAU - Amann, Berthold
AU  - Amann B
AD  - Kamillianer Hospital Monchengladbach, Monchengladbach, Germany. 
      berthold.amann@gmx.de
FAU - Tinzmann, Ralph
AU  - Tinzmann R
FAU - Angelkort, Bernhard
AU  - Angelkort B
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PL  - United States
TA  - Diabetes Care
JT  - Diabetes care
JID - 7805975
RN  - 0 (Angiotensin-Converting Enzyme Inhibitors)
RN  - 0 (Chemokine CCL2)
RN  - E7199S1YWR (Lisinopril)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Angiotensin-Converting Enzyme Inhibitors/*therapeutic use
MH  - Chemokine CCL2/*metabolism
MH  - Diabetes Mellitus, Type 2/drug therapy/metabolism
MH  - Diabetic Nephropathies/*drug therapy/metabolism
MH  - Female
MH  - Humans
MH  - Hypertension, Renal/drug therapy/metabolism
MH  - Kidney/metabolism
MH  - Lisinopril/*therapeutic use
MH  - Male
MH  - Middle Aged
MH  - Proteinuria/drug therapy/metabolism
MH  - Renin-Angiotensin System/drug effects
MH  - Treatment Outcome
EDAT- 2003/07/29 05:00
MHDA- 2003/11/05 05:00
CRDT- 2003/07/29 05:00
PHST- 2003/07/29 05:00 [pubmed]
PHST- 2003/11/05 05:00 [medline]
PHST- 2003/07/29 05:00 [entrez]
AID - 10.2337/diacare.26.8.2421 [doi]
PST - ppublish
SO  - Diabetes Care. 2003 Aug;26(8):2421-5. doi: 10.2337/diacare.26.8.2421.