Abstract There have been few reports of carboplatin‐based chemotherapy for anuric infants. As we had a chance to treat a one‐year‐old anuric hepatoblastoma patient with carboplatin, we performed a pharmacokinetic analysis and examined the optimal treatment strategy. A one‐year‐old anuric boy under peritoneal dialysis was diagnosed with hepatoblastoma. Surgical resection was performed, and administration of carboplatin was scheduled postoperatively aiming at 5 mg·min/mL of the area under the curve from the time of dosing to the time of the last observation ( AUC 0‐t ). We set the initial dose at 50 mg, higher than that calculated by the C alvert formula (34 mg); the time from the end of carboplatin infusion to the initiation of hemodialysis at 2 h; and the hemodialysis duration at 24 h. The actual AUC 0‐t was 3.05 mg·min/mL because the elimination half‐lives before and during hemodialysis were shorter than expected. The AUC 0‐t after the second dose (100 mg) and the third dose (80 mg) were 7.00 and 4.68 mg·min/mL, respectively. The Calvert formula is not suitable for hemodialysis patients because removal of platinum by hemodialysis is not taken into account. It appears that extrarenal clearance in anuric infants is different from that in adults. We obtained an optimal AUC 0‐t using a dose of 80 mg (200 mg/m 2 ), setting the time from the end of carboplatin infusion to the initiation of hemodialysis at 2 h, and performing 8‐h hemodialysis. Further accumulation of the pharmacokinetic data of carboplatin is necessary for anuric children.
Acute kidney injury (AKI) is a syndrome which has a broad range of etiologic factors depending on different clinical settings. Because AKI has significant impacts on prognosis in any clinical settings, early detection and intervention is necessary to improve the outcomes of AKI patients. This clinical guideline for AKI was developed by a multidisciplinary approach with nephrology, intensive care medicine, blood purification, and pediatrics. Of note, clinical practice for AKI management which was widely performed in Japan was also evaluated with comprehensive literature search.
Significance Statement Rituximab is the standard therapy for childhood-onset complicated frequently relapsing or steroid-dependent nephrotic syndrome (FRNS/SDNS). However, most patients redevelop FRNS/SDNS after peripheral B cell recovery. This multicenter, randomized, double-blind, placebo-controlled trial was conducted to examine whether mycophenolate mofetil (MMF) administration after rituximab can prevent treatment failure (FRNS, SDNS, steroid resistance, or use of immunosuppressive agents or rituximab) in these patients. MMF after rituximab decreased the risk of treatment failure during the MMF administration period by 80% and was well tolerated. However, after MMF discontinuation, the relapse-preventing effect disappeared, and most patients in the MMF group presented with treatment failure. In conclusion, MMF maintenance therapy after rituximab may be an option for sustaining remission in children with complicated FRNS/SDNS. Background Rituximab is the standard therapy for childhood-onset complicated frequently relapsing or steroid-dependent nephrotic syndrome (FRNS/SDNS). However, most patients redevelop FRNS/SDNS after peripheral B cell recovery. Methods We conducted a multicenter, randomized, double-blind, placebo-controlled trial to examine whether mycophenolate mofetil (MMF) administration after rituximab can prevent treatment failure (FRNS, SDNS, steroid resistance, or use of immunosuppressive agents or rituximab). In total, 39 patients (per group) were treated with rituximab, followed by either MMF or placebo until day 505 (treatment period). The primary outcome was time to treatment failure (TTF) throughout the treatment and follow-up periods (until day 505 for the last enrolled patient). Results TTFs were clinically but not statistically significantly longer among patients given MMF after rituximab than among patients receiving rituximab monotherapy (median, 784.0 versus 472.5 days, hazard ratio [HR], 0.59; 95% confidence interval [95% CI], 0.34 to 1.05, log-rank test: P =0.07). Because most patients in the MMF group presented with treatment failure after MMF discontinuation, we performed a post-hoc analysis limited to the treatment period and found that MMF after rituximab prolonged the TTF and decreased the risk of treatment failure by 80% (HR, 0.20; 95% CI, 0.08 to 0.50). Moreover, MMF after rituximab reduced the relapse rate and daily steroid dose during the treatment period by 74% and 57%, respectively. The frequency and severity of adverse events were similar in both groups. Conclusions Administration of MMF after rituximab may sufficiently prevent the development of treatment failure and is well tolerated, although the relapse-preventing effect disappears after MMF discontinuation.
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