Kidney international
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Kidney international · Nov 2013
Rituximab is a safe and effective long-term treatment for children with steroid and calcineurin inhibitor-dependent idiopathic nephrotic syndrome.
In children with idiopathic nephrotic syndrome, rituximab can maintain short-term remission with withdrawal of prednisone and calcineurin inhibitors. Long-term effects including the number of repeated infusions to maintain remission are unknown. To test this, we treated 46 consecutive children with idiopathic nephrotic syndrome lasting for at least 1 year (mean 6.3 years), maintained in remission with oral prednisone and calcineurin inhibitors. ⋯ Podocyte Src phosphorylation was normal. Thus, rituximab can be safely and repeatedly used as a prednisone and calcineurin inhibitor-sparing therapy in a considerable proportion of children with dependent forms of idiopathic nephrotic syndrome. Further study is needed to identify patients who will benefit most from rituximab therapy.
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Kidney international · Oct 2013
Distinct injury markers for the early detection and prognosis of incident acute kidney injury in critically ill adults with preserved kidney function.
The use of novel biomarkers to detect incident acute kidney injury (AKI) in the critically ill is hindered by heterogeneity of injury and the potentially confounding effects of prevalent AKI. Here we examined the ability of urine NGAL (NGAL), L-type fatty acid-binding protein (L-FABP), and cystatin C to predict AKI development, death, and dialysis in a nested case-control study of 380 critically ill adults with an eGFR over 60 ml/min per 1.73 m(2). One-hundred thirty AKI cases were identified following biomarker measurement and were compared with 250 controls without AKI. ⋯ Both urine NGAL and L-FABP independently predicted AKI during multivariate regression; however, risk reclassification indices were mixed. Neither urine biomarker was independently associated with death or acute dialysis (NGAL hazard ratio 1.35 (95% CI: 0.93-1.96), L-FABP 1.15 (0.82-1.61)), although both independently predicted the need for acute dialysis alone (NGAL 3.44 (1.73-6.83), L-FABP 2.36 (1.30-4.25)). Thus, urine NGAL and L-FABP independently associated with the development of incident AKI and receipt of dialysis but exhibited poor discrimination for incident AKI using conventional definitions.
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Emerging evidence suggests that fibroblast growth factor 23 (FGF23) levels are elevated in patients with acute kidney injury (AKI). In order to determine how early this increase occurs, we used a murine folic acid-induced nephropathy model and found that plasma FGF23 levels increased significantly from baseline already after 1 h of AKI, with an 18-fold increase at 24 h. Similar elevations of FGF23 levels were found when AKI was induced in mice with osteocyte-specific parathyroid hormone receptor ablation or the global deletion of parathyroid hormone or the vitamin D receptor, indicating that the increase in FGF23 was independent of parathyroid hormone and vitamin D signaling. ⋯ The levels were significantly higher than in those without postoperative AKI. Thus, circulating FGF23 levels rise rapidly during AKI in rodents and humans. In mice, this increase is independent of established modulators of FGF23 secretion.
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Kidney international · Oct 2013
CommentBiomarkers and creatinine in AKI: the trough of disillusionment or the slope of enlightenment?
Assessment of acute kidney biomarkers against changes in plasma creatinine is beset by issues of heterogeneity of study cohorts and timing of sampling. Siew and colleagues attempt to minimize these issues in a case-control study of three biomarkers in the intensive care unit. The results highlight the inherent methodological difficulties and the need to reference structural injury biomarkers against more meaningful outcomes.