Combined therapy of enalapril and losartan attenuates histologic progression in immunoglobulin A nephropathy

Tanaka, Hiroshi; Suzuki, Koichi; Nakahata, Tohru; Tsugawa, Koji; Konno, Yasuhiko; Tsuruga, Kazushi; Ito, Etsuro; Waga, Shinobu

doi:10.1111/j.1442-200x.2004.01955.x

Cited by 35 publications

(29 citation statements)

References 15 publications

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“…It is reported that urinary angiotensinogen levels are higher in IgAN patients compared to control subjects [14,15]. Furthermore, recent studies showed that treatment with an ACE inhibitor and/or an Ang II type 1 (AT1) receptor blocker (ARB) provides antiproteinuric and renoprotective effects in normotensive pediatric patients with IgAN [16,17]. These results suggest that intrarenal RAS activation plays a critical role in the progression of IgAN.…”

Section: Introductionmentioning

confidence: 62%

Glomerular Angiotensin-Converting Enzyme 2 in Pediatric IgA Nephropathy

Urushihara¹,

Seki²,

Tayama³

et al. 2013

Am J Nephrol

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Background: Angiotensin-converting enzyme (ACE) 2 is a homolog of ACE and is thought to be a potent counter-regulator against ACE activity. However, the role of ACE2 has not been investigated in pediatric patients with IgA nephropathy (IgAN). This study was performed to examine the relationship between ACE2 expression and the development of pediatric IgAN. Methods: We performed immunohistochemical analysis of ACE2 and ACE in 39 patients with pediatric IgAN and 14 patients with minor glomerular abnormalities, and elucidated the effects of various cytokines on ACE2 expression in cultured human mesangial cells. Results: ACE2 expression levels in glomeruli and tubules were positively correlated with the mesangial hypercellularity score, while ACE expression levels in glomeruli and tubules are not. Multiple regression analysis showed that the mesangial hypercellularity score correlated with the ACE2 expression level in glomeruli and the urinary protein-creatinine ratio. In IgAN patients not treated with a renin-angiotensin system blocker, ACE2 expression levels in glomeruli were significantly increased compared to patients with minor glomerular abnormalities. IgAN patients treated with a renin-angiotensin system blocker did not show this increase in ACE2 expression. Furthermore, cultured human MC showed increased ACE2 mRNA and protein after treatment with IL-1β, a pro-inflammatory cytokine in IgAN. In fact, glomerular expressions of IL-1β were remarkably increased in patients with IgAN. Conclusion: These data indicate that ACE2 expression in glomeruli is associated with mesangial hypercellularity in early lesions of pediatric IgAN.

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Section: Introductionmentioning

confidence: 62%

Glomerular Angiotensin-Converting Enzyme 2 in Pediatric IgA Nephropathy

Urushihara¹,

Seki²,

Tayama³

et al. 2013

Am J Nephrol

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show abstract

“…With the exception of Praga et al [61], these were case studies involving adult patients. There have been few studies in children with IgA nephropathy, except Tanaka et al [63] and Bhattacharjee and Filler [64], who demonstrated the combination ACE inhibitor and losartan to ameliorate progression. But these were also case series and neither was a double-blinded, randomized, controlled trial.…”

Section: Clinical Studies In Prevention Of Progression In Iga Nephropmentioning

confidence: 99%

Modulating the Progression in IgA Nephropathy

Chan

Trachtman

2006

Nephron Clin Pract

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IgA nephropathy affects almost 1% of the population and yet the diagnosis is often missed. This significant kidney disease is often progressive with 25% of the patients going on to end-stage kidney disease over the course of 25 years. This minireview describes the clinical presentations in children and young adults. Therapeutic options are discussed including angiotensin-converting enzyme blockade, steroids, cytotoxics, tonsillectomy, fish oil, vitamin E, singly or in combination, in order to modulate the rate of progression.

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“…To our knowledge, only two published studies describe the use of combination therapy in children, both in children with IgA nephropathy [5,6]. In neither of the studies were the patients treated only with angiotensin blockade; most received concomitant immunosuppressive therapy.…”

Section: Discussionmentioning

confidence: 96%

“…This combination has been shown to reduce proteinuria and blood pressure (BP) more effectively than either drug alone [3], and in a single randomized controlled study, it was also associated with better renal survival [4]. While there are some case studies in children that have reported the safety and efficacy of combination angiotensin blockade, none has used angiotensin blockade as the sole therapy for treatment [5,6].…”

Section: Introductionmentioning

confidence: 99%

Angiotensin blockade in children with chronic glomerulonephritis and heavy proteinuria

Butani

2005

Pediatr Nephrol

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Patients with chronic proteinuric nephropathies are at high risk of developing progressive renal insufficiency. There are limited controlled data on the efficacy of potentially toxic immunosuppressive therapies for many of these diseases such as immunoglobulin A nephropathy and idiopathic membranoproliferative glomerulonephritis. This limitation has not deterred healthcare providers from using such agents based on anecdotal experience. We report our experience taking care of three children with heavy proteinuria from chronic glomerular diseases. All were treated with a combination of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers without concomitant immunosuppression. All went into complete remission soon after starting therapy, allowing corticosteroid avoidance. The purpose of this report is to make healthcare professionals more aware of the potential success that can be achieved with this relatively nontoxic drug regimen. Larger controlled clinical trials using this strategy are needed to better evaluate the efficacy and safety of this approach in children with glomerular diseases.

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Combined therapy of enalapril and losartan attenuates histologic progression in immunoglobulin A nephropathy

Abstract: Although only a small number of patients were examined, these clinical findings suggest that a combined therapy of enalapril and losartan may attenuate histologic progression in at least a proportion of patients with severe proteinuric IgA nephropathy.

Cited by 35 publications

References 15 publications

Glomerular Angiotensin-Converting Enzyme 2 in Pediatric IgA Nephropathy

Glomerular Angiotensin-Converting Enzyme 2 in Pediatric IgA Nephropathy

Modulating the Progression in IgA Nephropathy

Angiotensin blockade in children with chronic glomerulonephritis and heavy proteinuria

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