Recent data suggest that the renin-angiotensin system may participate in inflammatory responses and that angiotensin II is a proinflammatory mediator in renal damage (1). An association between C-reactive protein (CRP), a sensitive marker of inflammation, and urinary albumin excretion in the microalbuminuric range has been reported in nondiabetic as well as type 2 diabetic subjects in the Insulin Resistance Atherosclerosis Study (2). Angiotensin II type 1 (AT1) receptor antagonists have been shown to have a renal protective effect and to reduce proteinuria in type 2 diabetic patients with either microalbuminuria or overt nephropathy (3,4,5); therefore, we investigated whether the beneficial effects of these agents are partly mediated through an anti-inflammatory action as a result of angiotensin II blockade. We did this by evaluating the effect of losartan on plasma CRP levels in a group of type 2 diabetic patients with microalbuminuria.

Concentration of CRP was measured from stored plasma samples from a previous 6-month randomized double-blind placebo-controlled study investigating the effect of losartan (50 mg daily) on endothelial function in 80 type 2 diabetic patients with microalbuminuria. A full description of the design and methods has been published (6). Plasma CRP levels were measured at baseline and 6 months after treatment, and 80 nondiabetic control subjects matched for age, sex, BMI, and smoking status were recruited to establish a reference range for CRP. High-sensitivity CRP (hs-CRP) was measured by a particle-enhanced immunoturbidimetric assay (Roche Diagnostics, Mannheim, Germany) using anti-CRP mouse monoclonal antibodies coupled to latex microparticles. Urinary mean albumin excretion rate (MAER) was determined from two consecutive 12-h overnight urine collections. Statistical analyses were performed using logarithmically transformed data because of their skewed distribution. Within-group comparisons were analyzed by paired t tests, and between-group comparisons were analyzed by two-sample t tests.

At baseline, the diabetic patients had significantly higher plasma hs-CRP levels (median [interquartile range]) than the nondiabetic control subjects (1.58 [0.71–3.25] vs. 0.86 [0.42–2.16] mg/l, respectively; P < 0.01). There were no significant differences in MAER in the losartan- and placebo-treated groups at the beginning of the study. Within-group analysis showed that treatment with losartan reduced MAER (baseline vs. 6 months: 70.8 [41.8–112.6] vs. 54.5 [27.6–85.9] μg/min, respectively; P = 0.007), whereas an increase in MAER was observed in the placebo group (53.0 [38.4–102.6] vs. 78.5 [40.5–141.0] μg/min, respectively; P = 0.02). As a result, the losartan-treated group had significantly lower MAER than the placebo-treated group at 6 months (P = 0.04). No differences were found in plasma hs-CRP between the losartan- and the placebo-treated groups at baseline (1.61 [0.93–3.39] vs. 1.44 [0.54–2.79] mg/l, respectively) or at 6 months (1.74 [0.98–2.92] vs. 1.46 [0.69–3.49] mg/l, respectively).

In conclusion, type 2 diabetic patients with microalbuminuria have elevated plasma CRP levels. Losartan significantly reduces the degree of microalbuminuria in these patients, but the lowering of urinary albumin excretion by AT1 receptor antagonist is not associated with any changes in plasma hs-CRP concentration. Our data would suggest that losartan, at a dose sufficient to reduce microalbuminuria, does not have a significant anti-inflammatory effect.

1.
Ruiz-Ortega M, Lorenzo O, Suzuki Y, Ruperez M, Egido J: Proinflammatory actions of angiotensins.
Curr Opin Nephrol Hypertens
10
:
321
–329,
2001
2.
Festa A, D’Agostino R, Howard G, Mykkanen L, Tracy RP, Haffner SM: Inflammation and microalbuminuria in nondiabetic and type 2 diabetic subjects: the Insulin Resistance Atherosclerosis Study.
Kidney Int
58
:
1703
–1710,
2000
3.
Parving HH, Lehnert H, Brochner-Mortensen J, Gomis R, Andersen S, Arner P: The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes.
N Engl J Med
345
:
870
–878,
2001
4.
Brenner BM, Cooper ME, de Zeeuw D, Keane WF, Mitch WE, Parving HH, Remuzzi G, Snapinn SM, Zhang Z, Shahinfar S: Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy.
N Engl J Med
345
:
861
–869,
2001
5.
Lewis EJ, Hunsicker LG, Clarke WR, Berl T, Pohl MA, Lewis JB, Ritz E, Atkins RC, Rohde R, Raz I: Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes.
N Engl J Med
345
:
851
–860,
2001
6.
Tan KC, Chow WS, Ai VH, Lam KS: Effects of angiotensin II receptor antagonist on endothelial vasomotor function and urinary albumin excretion in type 2 diabetic patients with microalbuminuria.
Diabetes Metab Res Rev
18
:
71
–76,
2002

Address correspondence to Dr. Kathryn Tan, Department of Medicine, Queen Mary Hospital, Pole Fulam Road, Hong Kong, People’s Republic of China. E-mail: kebtan@hkucc.hku.hk.