Abstract
Treatment with cyclosporine A (CsA), a calcineurin inhibitor, is effective in children with difficult idiopathic nephrotic syndrome (INS). Prolonged CsA treatment can result in several adverse effects, the most significant being nephrotoxicity (CsAN). The plasma and urine levels of the proteins annexin V (AnV) and uromodulin (UM) were investigated in order to assess their usefulness as indicators of early-stage CsAN. Uromodulin is considered a distal tubular damage marker. Annnexin V is present in the distal tubules. To measure AnV in children with INS receiving CsA treatment and to assess the usefulness of this biomarker for monitoring CsAN and as an indicator of changes in the distal tubules of the nephron. The prospective study included 30 patients with INS and 22 controls. Plasma and urinary AnV levels were measured 3 times: before CsA treatment, and after 6 and 12 months of therapy. The AnV levels were compared to those of UM. The urinary AnV and UM levels were significantly higher in the INS patients before CsA therapy in comparison to the reference group. A progressive increase of urinary AnV was observed after 6 and 12 months of therapy. Urinary UM only increased after 6 months. No significant correlations were found between plasma and urinary concentrations of the proteins studied. The increased urinary excretion of AnV in children with INS receiving CsA treatment may suggest its usefulness as an early marker of subclinical CsAN. Annexin V seems to be a more sensitive indicator of tubular damage in the course of CsA therapy than UM, though large, multicenter studies are needed.
Highlights
Idiopathic nephrotic syndrome (INS) is the most common form of primary glomerulopathy in children
The urinary annexin V (AnV) and UM levels were significantly higher in the idiopathic nephrotic syndrome (INS) patients before cyclosporine A (CsA) therapy in comparison to the reference group
The increased urinary excretion of AnV in children with INS receiving CsA treatment may suggest its usefulness as an early marker of subclinical CsA long-term mainly stem from its nephrotoxicity (CsAN)
Summary
Idiopathic nephrotic syndrome (INS) is the most common form of primary glomerulopathy in children. 80% of children with INS, this disease is marked by a tendency towards relapses and steroid dependence. In cases with a history of nephrotic syndrome and frequent relapses, steroid-dependent nephrotic syndrome (SDNS) or steroid-resistant nephrotic syndrome (SRNS), alternative treatments are employed, including the use of cyclosporine A (CsA). It is estimated that CsA therapy leads to remission in 80–100% of cases of SDNS and in 30% of cases of SRNS. Short-term therapies are associated with frequent relapses after the treatment ends, while the administration of drugs at low dosages for 18 months does not provide satisfactory results.[5]. Treatment with cyclosporine A (CsA), a calcineurin inhibitor, is effective in children with difficult idiopathic nephrotic syndrome (INS). Prolonged CsA treatment can result in several adverse effects, the most significant being nephrotoxicity (CsAN).
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