Rituximab in children with resistant idiopathic nephrotic syndrome.

Idiopathic nephrotic syndrome resistant to standard treatments remains a therapeutic dilemma in pediatric nephrology. To test whether the anti-CD20 monoclonal antibody rituximab may benefit these patients, we conducted an open-label, randomized, controlled trial in 31 children with idiopathic nephrotic syndrome unresponsive to the combination of calcineurin inhibitors and prednisone. All children continued prednisone and calcineurin inhibitors at the doses prescribed before enrollment, and one treatment group received two doses of rituximab (375 mg/m(2) intravenously) as add-on therapy. The mean age was 8 years (range, 2-16 years). Rituximab did not reduce proteinuria at 3 months (change, -12% [95% confidence interval, -73% to 110%]; P=0.77 in analysis of covariance model adjusted for baseline proteinuria). Additional adjustment for previous remission and interaction terms (treatment by baseline proteinuria and treatment by previous remission) did not change the results. In conclusion, these data do not support the addition of rituximab to prednisone and calcineurin inhibitors in children with resistant idiopathic nephrotic syndrome.

Saquinavir in steroid-dependent and -resistant nephrotic syndrome: a pilot study.

BACKGROUND: Some difficult cases of idiopathic nephrotic syndrome (NS) have been treated with a HIV protease inhibitor provided with proteasome-inhibiting activity. The objective of this study was to limit nuclear factor κB (NF-κB) activation which is up-regulated in these patients, aiming at decreasing proteinuria and prednisone need. METHODS: Ten cases with long-lasting (up to 15 years) history of NS with steroid dependence (six cases, of which three with secondary steroid resistance) or resistance to steroids (four cases) unsuccessfully treated with multiple immunosuppressive drugs, accepted a treatment with the protease inhibitor saquinavir. p50/p65 NF-κB nuclear localization and immunoproteasome/proteasome messenger RNA (mRNA) were monitored in peripheral blood mononuclear cells (PBMCs). The effects of saquinavir on NF-κB nuclear localization in cultured PBMCs and in immortalized human podocytes were assessed. RESULTS: After a median follow-up of 14.7 months (6-68.7), 1/4 primary steroid-resistant NS (SRNS) and 5/6 steroid-dependent NS or secondary SRNS became infrequent (5) or frequent (1) relapsers, with 63% prednisone reduction (from 25.3 to 8.4 mg/kg/month, P = 0.015). Saquinavir was effective in association with low doses of calcineurin inhibitors (cyclosporine 2 mg/kg/day or tacrolimus 0.01-0.06 mg/kg/day). No side effects were observed apart from transitory mild diarrhoea. In PBMCs, NF-κB was down-regulated, while MECL-1 immunoproteasome/beta2 proteasome mRNA ratio was reversed to normal values. In culture, saquinavir blunted NF-κB activation in human podocytes and in PBMCs. CONCLUSIONS: In this pilot study, a HIV antiprotease drug reduced proteinuria and had a steroid-sparing effect in some multidrug-resistant/-dependent NS. This observation warrants further investigation.

High-potency statins increase the risk of acute kidney injury: evidence from a large population-based study.

OBJECTIVE: To assess the association between acute kidney injury and exposure to either high-potency statins or low-potency statins. DESIGN: A population-based, nested case-control study was performed on a cohort of 316,449 patients from Lombardy (Italy) newly treated with statins between 2007 and 2010 aged 40 years or older. 458 patients experienced acute kidney injury within six months after initial statin prescription. Up to four controls were randomly selected for each case. Logistic regression was used to model the outcome risk associated with high-potency contrasted with low-potency statins dispensed at starting therapy, and during follow-up. RESULTS: Patients at whom high-potency statins were initially dispensed were more likely to be hospitalized for acute kidney injury within six months after starting treatment than those on low-potency statins (adjusted OR 1.54, 95% confidence interval 1.25-1.91). Patients receiving high-potency statins within three weeks before the outcome onset had a significant increased risk respect to those who did not receive statins during the same time-window (adjusted OR 1.45, 95% confidence interval 1.04-2.03). When follow-up was extended from 6 months to 12 months the difference was not significant anymore (adjusted OR 1.17, 95% confidence interval 0.89-1.54). CONCLUSIONS: Use of high-potency statins is associated with an increased risk of acute kidney injury compared with low-potency statins in the first 6 months after starting therapy.