Renal responses to three types of renin–angiotensin system blockers in patients with diabetes mellitus on a high-salt diet

Hollenberg, Norman K.; Fisher, Naomi D.L.; Nussberger, Juerg; Moukarbel, George V.; Barkoudah, Ebrahim; Danser, A.H. Jan

doi:10.1097/hjh.0b013e32834c627a

Cited by 24 publications

(23 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Whether the protective effect observed with lowsodium diet and RAAS inhibition in this post hoc analysis was due to greater haemodynamic effects, enhanced antiinflammatory effects or both, is unknown and requires further study. Nevertheless, as previously reported by our group [17][18][19] and by other investigators [46], RAAS inhibitors still exert prominent haemodynamic effects on the intrarenal RAAS in the presence of relative RAAS suppression induced by a high-salt diet in diabetic patients. Our results extend this previous haemodynamic-focused body of work by suggesting that RAAS inhibition during salt repletion also reduces inflammatory urinary cytokines/chemokines.…”

Section: Discussionsupporting

confidence: 69%

The effect of aliskiren on urinary cytokine/chemokine responses to clamped hyperglycaemia in type 1 diabetes

et al. 2013

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 69%

The effect of aliskiren on urinary cytokine/chemokine responses to clamped hyperglycaemia in type 1 diabetes

et al. 2013

View full text Add to dashboard Cite

show abstract

“…14 In healthy humans and diabetic patients, administration of aliskiren decreased filtration fraction and increased RBF and GFR. 16,20 It is therefore surprising that the effects of aliskiren on GFR (and RBF) in our cohort of HFREF patients with moderately decreased GFR seem to point in the opposite direction.…”

Section: Discussionmentioning

confidence: 77%

“…The renal effects of aliskiren 300 mg are equivalent to 25 mg captopril or 300 mg irbesartan. 20 This dose may have been too high as add-on therapy. In comparison, add-on spironolactone reduced morbidity and mortality in HFREF patients at doses lower than originally used for treatment of hypertension.…”

Section: Discussionmentioning

confidence: 99%

Effect of additive renin inhibition with aliskiren on renal blood flow in patients with Chronic Heart Failure and Renal Dysfunction (Additive Renin Inhibition with Aliskiren on renal blood flow and Neurohormonal Activation in patients with Chronic Heart Failure and Renal Dysfunction)

Schroten

Damman

Hemmelder

et al. 2015

American Heart Journal

View full text Add to dashboard Cite

“…1,2 Elevated levels of prorenin relative to renin can be found, for example, in diabetics with microvascular disease. [3][4][5] A (pro)renin receptor allows prorenin to display full enzymatic activity. 6 Transgenic rats overexpressing the (pro)renin receptor have elevated aldosterone levels, 7,8 and (pro)renin receptor gene polymorphisms not only associate with blood pressure but also with serum aldosterone levels 9,10 consistent with intra-adrenal, angiotensin II-stimulated aldosterone production.…”

mentioning

confidence: 99%

Plasma Levels of Prorenin and Renin in Blacks and Whites: Their Relative Abundance and Associations With Plasma Aldosterone Concentration

Eckert

Pratt

et al. 2012

Am J Hypertens

View full text Add to dashboard Cite

Renin occupies a pivotal position in the generation of angiotensin II and production of aldosterone. Although all renin is derived from prorenin, the prorenin-to-renin ratio tends to differ among individuals with various clinical conditions. 1,2 Elevated levels of prorenin relative to renin can be found, for example, in diabetics with microvascular disease. 3-5 A (pro)renin receptor allows prorenin to display full enzymatic activity. 6 Transgenic rats overexpressing the (pro)renin receptor have elevated aldosterone levels, 7,8 and (pro)renin receptor gene polymorphisms not only associate with blood pressure but also with serum aldosterone levels 9,10 consistent with intra-adrenal, angiotensin II-stimulated aldosterone production. Since blacks, in comparison to whites, are more likely to have an expanded extracellular volume, 11 they tend to have lower levels of plasma renin activity (PRA). 12 Despite the lower renin levels in blacks, Sealey and colleagues noted that blacks and whites had similar levels of prorenin and angiotensinogen. 13 It is unclear, however, whether the disproportionate plasma prorenin and renin levels have differential effects on aldosterone, the final product of the renin-angiotensin-aldosterone system (RAAS), in blacks and whites.We sought in this study to determine if there is a relationship of volume to the relative proportion of renin-to-total renin (total renin consisting of renin and prorenin with the preponderance being prorenin). In other words, does a higher volume accompany a lower level of prorenin? Blacks, serving as the volume expanded group, were compared to whites. All subjects were healthy and thus unaffected by antihypertensive treatment. We measured PRA and the plasma concentrations of renin (PRC), levels of prorenin, angiotensinogen, and plasma aldosterone concentration (PAC), thus allowing for a comparison of the plasma levels of prorenin and renin, the reninto-total renin ratios, and the effects of prorenin and renin on aldosterone production in subjects of the two race groups. MethodsStudy protocol. Subjects were participants of an ongoing observational study which started in 2009. Upon enrollment, 129 subjects came to Indiana University Medical Center for 1 Department of medicine, Indiana University school of medicine, Indianapolis, Indiana, UsA; 2 regenstrief Institute, Inc., Indianapolis, Indiana, UsA; 3 roudebush Veteran Administration medical Center, Indianapolis, Indiana, UsA Background All renin arises from prorenin. the proportion of renin relative to prorenin could influence overall renin-angiotensin-aldosterone activity. We sought to determine whether prorenin levels were related to extracellular volume, as reflected by the levels of plasma renin activity (prA), and to aldosterone.

show abstract

Renal responses to three types of renin–angiotensin system blockers in patients with diabetes mellitus on a high-salt diet

Cited by 24 publications

References 34 publications

The effect of aliskiren on urinary cytokine/chemokine responses to clamped hyperglycaemia in type 1 diabetes

The effect of aliskiren on urinary cytokine/chemokine responses to clamped hyperglycaemia in type 1 diabetes

Effect of additive renin inhibition with aliskiren on renal blood flow in patients with Chronic Heart Failure and Renal Dysfunction (Additive Renin Inhibition with Aliskiren on renal blood flow and Neurohormonal Activation in patients with Chronic Heart Failure and Renal Dysfunction)

Plasma Levels of Prorenin and Renin in Blacks and Whites: Their Relative Abundance and Associations With Plasma Aldosterone Concentration

Contact Info

Product

Resources

About