Precocious activation of genes of the renin-angiotensin system and the fibrogenic cascade in IgA glomerulonephritis

Prete, Dorella Del; Gambaro, Giovanni; Lupo, Antonio; Anglani, Franca; Brezzi, Brigida; Magistroni, Riccardo; Graziotto, Romina; Furci, Luciana; Modena, F.; Bernich, Patrizia; Albertazzi, A; D’Angelo, Angela; Maschio, Giuseppe

doi:10.1046/j.1523-1755.2003.00065.x

Cited by 57 publications

(66 citation statements)

References 42 publications

(1 reference statement)

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“…Therefore, when ACE-I were demonstrated to be capable of reducing proteinuria after a few months of treatment in IgAN (9,23), most nephrologists thought that there was no longer any need for demonstrating the benefit, and ACE-I indeed became a first-choice treatment in proteinuric IgAN, even without hypertension or reduced renal function. Our group was one of the first to emphasize that in IgAN, particularly in proteinuric cases, there was a local hyperreactivity of the RAS (24), and a precocious activation of the RAS has recently been demonstrated (25). However, ACE-I induced a limited reduction in proteinuria (by 20 to 50% of the baseline values) in a subgroup only (40 to 60%) of IgAN (9,23), and it was not proved that this was enough for renoprotection, so leaving open the need for an RCT (19).…”

Section: Discussionmentioning

confidence: 99%

IgACE

Coppo

Peruzzi

Amore

et al. 2007

Journal of the American Society of Nephrology

222

130

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2 ) for >6 mo. Analysis was by intention to treat. A single patient (3.1%) in the ACE-I group and five (14.7%) in the placebo group showed a worsening of CrCl >30%. The composite end point of >30% decrease of CrCl or worsening of proteinuria until nephrotic range was reached by one (3.1%) of 32 patients in the ACE-I group, and nine (26.5%) of 34 in the placebo group; the difference was significant (log-rank P ‫؍‬ 0.035). A stable, partial remission of proteinuria was observed in 13 (40.6%) of 32 patients in the ACE-I group versus three (8.8%) of 34 in the placebo group (log-rank P ‫؍‬ 0.033), with total remission in 12.5% of ACE-I-treated patients and in none in the placebo group (log-rank P ‫؍‬ 0.029). The multivariate Cox analysis showed that treatment with ACE-I was the independent predictor of prognosis; no influence on the composite end point was found for gender, age, baseline CrCl, systolic or diastolic BP, mean arterial pressure, or proteinuria.

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Section: Discussionmentioning

confidence: 99%

IgACE

Coppo

Peruzzi

Amore

et al. 2007

Journal of the American Society of Nephrology

222

130

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“…Proteinuria persisting after the acute phase might be due to two different mechanisms: either hyperfiltration due to nephronic mass reduction during the acute phase or the effect of chemokines produced by persistently stimulated MCs on podocytes (47,48,116,117). Theoretically, both mechanisms could be counteracted by ACE inhibitors, whereas corticosteroids might prevent MC proliferation and metabolic stimulation.…”

Section: Mesangial Proliferation Glomerulosclerosis and Proteinuriamentioning

confidence: 99%

Henoch-Schönlein Purpura Nephritis

Davin¹

2011

Clinical Journal of the American Society of Nephrology

146

123

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SummaryHenoch-Schö nlein purpura nephritis is a rare kidney disease leading to chronic kidney disease in a non-negligible percentage of patients. Although retrospective studies suggest beneficial effects of some therapies, prospective randomized clinical trials proving treatment efficacy are still lacking. The dilemma of spontaneous recovery even in patients with severe clinical and histologic presentation and of late evolution to chronic kidney disease in patients with mild initial symptoms renders it difficult for clinicians to expose patients to treatment protocols that are not evidence-based. A better understanding of the pathophysiology of progression to chronic kidney disease in Henoch-Schö nlein purpura patients could be achieved by designing prospective international multicenter studies looking at determinants of clinical and histopathological evolution as well as possible circulating and urinary markers of progression. Such studies should be supported by a database available on the web and a new histologic classification of kidney lesions. This paper reports clinical, pathologic, and experimental data to be used for this strategy and to assist clinicians and clinical trial designers to reach therapeutic decisions.

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“…Increases in intrarenal RAS components, particularly AngII, in parallel with the severity of fibrotic renal damage, have been demonstrated in chronic progressive nephropathy in rat (14) and human (15). Although urinary AngII was proposed previously as a marker of intrarenal AngII activity (16), it has not been consistently shown to reflect intrarenal AngII activity.…”

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confidence: 98%

Urinary Angiotensinogen as a Marker of Intrarenal Angiotensin II Activity Associated with Deterioration of Renal Function in Patients with Chronic Kidney Disease

Yamamoto

Nakagawa

Suzuki

et al. 2007

Journal of the American Society of Nephrology

175

185

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In chronic kidney disease (CKD), enhanced intrarenal angiotensin II (AngII) is involved in deterioration of renal function, but it is difficult to measure it. For assessment of the potential of urinary angiotensinogen as a marker of intrarenal AngII activity, the correlation of plasma and urinary renin-angiotensin system components, including angiotensinogen, with deterioration of renal function was investigated in 80 patients who had CKD and were not treated with AngII blocking agents. Changes that were induced by 14 d of losartan treatment (25 mg/d) were also measured in 28 patients. Angiotensinogen was measured by RIA of AngI after incubation with renin. Urinary angiotensinogen levels were greater in patients with low estimated GFR and elevated urinary protein and type IV collagen and correlated with renal AngII and type I collagen immunostaining intensities. The risk for deterioration of renal function (i.e., estimated GFR decline of >2.5 ml/min per yr) during a mean follow-up period of 23 mo (maximum 43 mo) was associated with urinary angiotensinogen of >3.0 nmol AngI equivalent per 1 g of urinary creatinine (AngI Eq/g Cre) at enrollment (hazard ratio 3.52). The event-free survival for deterioration of renal function was better in patients with urinary angiotensinogen <3.0 nmol AngI Eq/g Cre than those >3.0 nmol AngI Eq/g Cre. Losartan reduced urinary and plasma angiotensinogen, urinary protein and type IV collagen, and systolic BP, despite concomitant increases in plasma renin and AngII. These data suggest that urinary angiotensinogen is a potentially suitable marker of intrarenal AngII activity associated with increased risk for deterioration of renal function in patients with CKD.

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Precocious activation of genes of the renin-angiotensin system and the fibrogenic cascade in IgA glomerulonephritis

Cited by 57 publications

References 42 publications

IgACE

IgACE

Henoch-Schönlein Purpura Nephritis

Urinary Angiotensinogen as a Marker of Intrarenal Angiotensin II Activity Associated with Deterioration of Renal Function in Patients with Chronic Kidney Disease

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