Erschienen in:
01.10.2013 | Article
The effect of aliskiren on urinary cytokine/chemokine responses to clamped hyperglycaemia in type 1 diabetes
verfasst von:
David Z. I. Cherney, Heather N. Reich, James W. Scholey, Denis Daneman, Farid H. Mahmud, Ronnie L. H. Har, Etienne B. Sochett
Erschienen in:
Diabetologia
|
Ausgabe 10/2013
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Abstract
Aims/hypothesis
Acute clamped hyperglycaemia activates the renin–angiotensin–aldosterone system (RAAS) and increases the urinary excretion of inflammatory cytokines/chemokines in patients with uncomplicated type 1 diabetes mellitus. Our objective was to determine whether blockade of the RAAS would blunt the effect of acute hyperglycaemia on urinary cytokine/chemokine excretion, thereby giving insights into potentially protective effects of these agents prior to the onset of clinical nephropathy.
Methods
Blood pressure, renal haemodynamic function (inulin and para-aminohippurate clearances) and urinary cytokines/chemokines were measured after 6 h of clamped euglycaemia (4–6 mmol/l) and hyperglycaemia (9–11 mmol/l) on two consecutive days in patients with type 1 diabetes mellitus (n = 27) without overt nephropathy. Measurements were repeated after treatment with aliskiren (300 mg daily) for 30 days.
Results
Before aliskiren, clamped hyperglycaemia increased filtration fraction (from 0.188 ± 0.007 to 0.206 ± 0.007, p = 0.003) and urinary fibroblast growth factor-2 (FGF2), IFN-α2 and macrophage-derived chemokine (MDC) (p < 0.005). After aliskiren, the filtration fraction response to hyperglycaemia was abolished, resulting in a lower filtration fraction after aliskiren under clamped hyperglycaemic conditions (p = 0.004), and none of the biomarkers increased in response to hyperglycaemia. Aliskiren therapy also reduced levels of urinary eotaxin, FGF2, IFN-α2, IL-2 and MDC during clamped hyperglycaemia (p < 0.005).
Conclusions/interpretation
The increased urinary excretion of inflammatory cytokines/chemokines in response to acute hyperglycaemia is blunted by RAAS blockade in humans with uncomplicated type 1 diabetes mellitus.