Cyclosporine A treatment in patients with Alport syndrome: a single-center experience

Abstract

Limited and discordant data are available on cyclosporine A (CsA) treatment for proteinuria in Alport syndrome (AS). To address this lack of consistent data, we have studied 15 AS patients (14 males; mean age 15.3 +/- 6.0 years) treated with CsA. Patient selection criteria included a urinary protein/creatinine ratio > or =1 mg/mg and a creatinine clearance >40 ml/min/1.73 m(2). CsA treatment was started at an initial dose of 5 mg/kg/day and subsequently adjusted to reach target C2 levels of 500 ng/ml. Renal function, proteinuria, and blood pressure were monitored. Blood pressure was treated to avoid the administration of angiotensin converting enzyme or angiotensin receptor blockers for the first 2 years of therapy. The average follow-up was 3.5 years. Five patients had chronic renal failure at the beginning of treatment, of whom three and one reached end-stage renal failure within 1 and 3 years, respectively. In the remaining 11 patients, the glomerular filtration rate declined by 11 +/- 6% within 6 months, but remained stable thereafter. Proteinuria decreased by 63 +/- 21% from baseline, but returned nearly to baseline after 2.5 years of follow-up. Based on these results, we suggest that CsA is effective in reducing proteinuria in patients with Alport syndrome but that this effect is temporary. Our data do not support the use of CsA therapy for proteinuric patients with AS, particularly if they have chronic renal failure.

X‐linked Alport syndrome in Hellenic families: Phenotypic heterogeneity and mutations near interruptions of the collagen domain in COL4A5

“…The boy is on cyclosporine therapy and the long‐term results will be of interest. We are aware that Massella et al studied 15 ATS patients and showed only short‐term effectiveness of cyclosporine therapy (32). The findings in families segregating mutations G624D and P628L are indicative of less severe phenotypes, stretching the phenotypic expression to only microhematuria with or without proteinuria, as a result of TBMN.…”

The Calcineurin Inhibitor Tacrolimus Reduces Proteinuria in Membranous Nephropathy Accompanied by a Decrease in Angiopoietin-Like-4

“…The immunosuppressive effects of tacrolimus [8], [9] may partially explain its therapeutic effects in autoimmune diseases and transplantation [10], [11]. In addition, calcineurin inhibitors can also reduce proteinuria in Alport syndrome, which is a non-immunological disease [23]. Other investigations have found that the actin cytoskeleton of podocytes is a direct target of the antiproteinuric effect of the calcineurin inhibitor CsA [12].…”

Early RAAS Blockade Exerts Renoprotective Effects in Autosomal Recessive Alport Syndrome

“…Although cyclosporine was reported to have an anti-proteinuric and renoprotective effect in AS patients during the late 1990s (Callis et al 1999), recent reports showed that its anti-proteinuric effects are transient (Massella et al 2010), and the prolonged use of cyclosporine results in nephrotoxicity (Charbit et al 2007). At the beginning of the 2010s, RAAS blockade was shown to delay renal replacement therapy in AS patients (Gross et al 2012).…”

“…Callis et al (1999) reported the beneficial effect of cyclosporine on AS progression, although recent reports suggest that the effect is limited and also associated with nephrotoxicity (Charbit et al 2007;Massella et al 2010). Recently, the renoprotective effect of renin-angiotensin-aldosterone system (RAAS) blockade by angiotensin-converting enzyme inhibition (ACEi) in AS has become evident (Gross et al 2012), and there is increasing evidence that anigiotensin II receptor blocker (ARB) (Webb et al 2011) and aldosterone inhibitor (Kaito et al 2006) are antiproteinuric and renoprotective.…”