Renin–angiotensin system inhibitors reduce the progression of mesangioproliferative glomerulonephritis: 10year follow-up

Presta, Pierangela; Minutolo, Roberto; Iodice, Carmela; Comi, Nicola; Casoria, Vincenzo; Fuiano, Laura; Caglioti, Chiara; Conte, Giuseppe; Fuiano, Giorgio

doi:10.1016/j.ejim.2011.08.021

Cited by 4 publications

(3 citation statements)

References 15 publications

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“…Indeed, losartan was recently reported to prolong the occlusion time in a mouse model of carotid injury [ 40 ]. Moreover, the therapeutic use of losartan goes beyond hypertension: Losartan is used for its protective effect against dilation in aortic aneurysm [ 41 – 43 ] and proteinuria in glomerulonephritis [ 44 , 45 ]; it is proposed to be anti-fibrotic, with some studies supporting the hypothesis of a cross-talk between AT1R and TGF-β1 [ 46 ]. It is worth noting that platelet activation may be associated with aneurysm dilatation [ 47 ] and glomerulonephritis, in which GPVI was shown to contribute [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Glycoprotein VI Clustering by Collagen as a Mechanism of Inhibiting Collagen-Induced Platelet Responses: The Example of Losartan

et al. 2015

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Exposure of platelets to collagen triggers the formation of a platelet clot. Pharmacological agents capable of inhibiting platelet activation by collagen are thus of potential therapeutic interest. Thrombus formation is initiated by the interaction of the GPIb-V-IX complex with collagen-bound vWF, while GPVI interaction with collagen triggers platelet activation that is reinforced by ADP and thromboxane A2. Losartan is an angiotensin II (Ang II) type I receptor (AT1R) antagonist proposed to have an antiplatelet activity via the inhibition of both the thromboxane A2 (TXA2) receptor (TP) and the glycoprotein VI (GPVI). Here, we characterized in vitro the effects of losartan at different doses on platelet responses: losartan inhibited platelet aggregation and secretion induced by 1 μg.mL-1 and 10 μg.mL-1 of collagen with an IC50 of ~ 6 μM. Losartan inhibited platelet responses induced by the GPVI specific collagen related peptide but not by the α2β1 specific peptide. However, losartan did not inhibit the binding of recombinant GPVI to collagen, which is not in favor of a simple competition. Indeed, the clustering of GPVI observed in flow cytometry and using the Duolink methodology, was inhibited by losartan. The impact of a therapeutic dose of losartan (100 mg/day) on platelet responses was analyzed ex vivo in a double blind study. No statistically significant differences were observed between losartan-treated (n=25) and non-treated (n=30) patients in terms of collagen and U46619-induced platelet activation. These data indicate that in treated patients, losartan does not achieve a measurable antiplatelet effect but provide the proof of concept that inhibiting collagen-induced GPVI clustering is of pharmacological interest to obtain an antithrombotic efficacy.Trial RegistrationClinicalTrials.gov NCT00763893

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Section: Discussionmentioning

confidence: 99%

Inhibition of Glycoprotein VI Clustering by Collagen as a Mechanism of Inhibiting Collagen-Induced Platelet Responses: The Example of Losartan

et al. 2015

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“…This therapy was abandoned because of lack of benefit and the increase of bleeding risk in case of renal failure [ 2 , 16 ]. In the late 1990s, RAAS blockade were introduced in the treatment of MPGN based on their antiproteinuric effect [ 17 ]. This could explain the evolution of the therapeutic attitude in our center with a decrease in the prescription of antiplatelet therapy since the 2000s against an increase in the prescription of RAAS blockade.…”

Section: Discussionmentioning

confidence: 99%

Primary membranoproliferative glomerulonephritis in Sfax, Tunisia: epidemiologic profile and prognostic factors

Agrebi¹,

Kammoun²,

Dammak³

et al. 2021

Pan Afr Med J

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Introduction membranoproliferative glomerulo nephritis (MPGN) is a rare kidney disease with a poor prognosis as 50% of patients attend the end stage renal failure after 10 years of follow up. Several factors have been described associated with poor renal prognosis. The aim of our study is to determine the epidemiologic profile and to identify prognostic factors of MPGN. Methods our study is retrospective over a period of 16 years (January 1996 - December 2011) including all cases of primary MPGN aged more than 15 years, collected at the nephrology department of Hedi Chaker University Hospital, Sfax, Tunisia. Results we collected 118 cases of primary MPGN, with mean age of 45 (SD 19) years. The incidence of MPGN has decreased from 10 cases/year between 1996 and 1999 to 5 cases/year between 2008 and 2011. Seventy-nine percent of patients (n=93) had renal failure at the moment of diagnosis (e-GFR less than 60 ml/min/1.73m 2 ;). After a mean follow-up of 51.9 (SD 44) months, progression to end stage renal failure was observed in 43.5% of followed cases (n=20). On univariate analysis, factors associated with death or progression to end stage renal failure were initial renal failure and sclerotic glomeruli (respectively p at 0.040 and 0.032). Multivariate analysis indicated that initial renal failure was significantly correlated with death or progression to end stage renal failure (HR: 0.14, 95% CI (0.033-0.593), p=0.008). Conclusion there has been a decline in the number of cases of MPGN diagnosed in our hospital. The presence of renal failure at diagnosis was associated with death or progression to end stage renal failure.

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“…Ramipril is a long acting lipophilic drug with two major ways of excretion. It not only effectively normalizes blood pressure (BP), but also improve the prognosis of patients with nephropathy due to lower the tone of efferent arterioles and intraglomerular pressure that inhibits proliferation of mesangial cells, decreases synthesis of mesangial matrix components and level of proteinuria [8,9]. However, ACE inhibitor therapy is used too late because the clinical signs of renal failure show up only after losing more than 50 % of nephrons.…”

Section: Introductionmentioning

confidence: 99%

Assessment of nephroprotective action of angiotensin-converting enzyme inhibitor ramipril in patients with chronic glomerulonephritis

Kraydaschenko¹,

Berezin²,

Dolinnaya³

et al. 2017

bmgt

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Aim: to study links between morphological glomerular kidney lesion parameters and serum cystatin C (CysC) in patients with chronic glomerulonephritis (CGN) with saved renal function, and to assess therapeutic correction of identified changes using ACE inhibitor ramipril. Methods: eighty one patients with CGN were enrolled in the study. Blood samples of the biomarker were collected. The diagnosis of "chronic glomerulonephritis" was verified on the basis of clinical, laboratory and morphological data. Patients were divided into 2 clinical groups: patients with CGN and arterial hypertension (AH) and without AH. We used data of renal biopsies to analyze the indicators of glomerular kidney lesion in patients with CGN. The level of serum CysC was measured using ELISA kits. Treatment of patients was carried out over 24 weeks using the ACE inhibitor ramipril. The average daily dose of ramipril for the entire treatment period for patients with AH was 12.8±5.6 mg, patients of the second group-8 Oleg Kraydaschenko et al. without AH, were treated with ramipril at a dose of 2.5 mg. Results: according to the results of renal microscopy 88% patients had mesangial proliferative glomerulonephritis, 7%membranous nephropathy, 5%membranous proliferative glomerulonephritis. On the basis of rank correlation analysis we proved that the level of serum CysC directly correlated with glomerulosclerosis (r = 0.85, p < 0.05). Levels of blood creatinine, proteinuria and CysC reduced under the influence of 24-week ramipril treatment. Conclusion: serum CysC is the most sensitive marker of glomerular kidney lesion with diagnostic efficiency up to 97%. The 24-week treatment with ACE inhibitor ramipril in patients with CGN with and without AH reduced levels of glomerular kidney lesion markers that confirmed nephroprotective effect of the drug.

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Renin–angiotensin system inhibitors reduce the progression of mesangioproliferative glomerulonephritis: 10year follow-up

Cited by 4 publications

References 15 publications

Inhibition of Glycoprotein VI Clustering by Collagen as a Mechanism of Inhibiting Collagen-Induced Platelet Responses: The Example of Losartan

Inhibition of Glycoprotein VI Clustering by Collagen as a Mechanism of Inhibiting Collagen-Induced Platelet Responses: The Example of Losartan

Primary membranoproliferative glomerulonephritis in Sfax, Tunisia: epidemiologic profile and prognostic factors

Assessment of nephroprotective action of angiotensin-converting enzyme inhibitor ramipril in patients with chronic glomerulonephritis

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