C2 monitoring: a reliable tool in pediatric renal transplant recipients

Strologo, Luca Dello; Pontesilli, C.; Rizzoni, Gianfranco; Tozzi, Alberto Eugenio

doi:10.1097/01.tp.0000074312.93200.7a

Cited by 10 publications

(4 citation statements)

References 3 publications

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“…More recently, a single blood concentration measurement 2 h after CsA administration (C 2 ) was reported as an accurate predictor of drug exposure in adults [25] and also in transplanted children [26]. This parameter (reported in Table 1 as CsA C 2 level) correlates with AUC better than the trough level, but less well than the mean CsA blood concentration obtained with abbreviated AUC [26].…”

Section: Discussionmentioning

confidence: 97%

Cyclosporine therapy monitored with abbreviated area under curve in nephrotic syndrome

et al. 2004

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Cyclosporin A (CsA) is an effective therapy for children with long-lasting nephrotic syndrome (NS). Long-term treatment can result in chronic CsA nephropathy (CsAN) and there is controversy concerning its incidence and severity. Trough levels are commonly used to monitor the drug concentration. We report a retrospective clinical and histological analysis of 18 children (12 males, 6 females) with steroid-dependent nephrotic syndrome (15 patients) and partially steroid-sensitive nephrotic syndrome (3 patients) treated with CsA for a long-term period (mean 4.9 years, range 2.2-6.9). Before CsA treatment all patients had normal creatinine clearance. CsA was started at a dose of 5 mg/kg per day administered orally in two divided doses and adjusted to maintain the mean CsA blood concentration between 250 and 350 ng/ml obtained from abbreviated area under the curve (AUC). A renal biopsy was performed after a mean period of 3.9 years (range 2.2-6.2) from the start of CsA treatment. Tubular, interstitial, and arteriolar lesions were evaluated in order to assess CsAN. The mean CsA dose and the mean CsA blood concentration were 4.4 mg/kg per day (range 3.6-5.8) and 276.6 ng/ml (range 162-346), respectively. No child had a worsening creatinine clearance during CsA treatment and follow-up after CsA discontinuation. If compared with the year before the start of CsA treatment, NS relapses and prednisone (PDN) dose significantly decreased during CsA treatment, 4/year versus 0.8/year (P <0.0001) and 0.9 mg/kg per day versus 0.2 mg/kg per day (P <0.0001), respectively. Histological analysis showed 15 patients with minimal change disease and 3 with focal segmental glomerulosclerosis. Clear-cut lesions diagnostic of CsAN were never found and only mild lesions were observed in 5 children (suggestive of CsAN in 2 patients and consistent with CsAN in 3 patients). Long-term CsA treatment is confirmed to be effective in preventing NS relapses and reducing PDN dose. Renal function is not a reliable indicator of CsAN. With the mean CsA blood concentrations used in our patients CsAN presented a low incidence (28%) and was generally mild. Renal biopsy should be performed 2-3 years from the start of long-term CsA treatment, especially if the mean CsA blood concentrations are not regularly monitored.

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Section: Discussionmentioning

confidence: 97%

Cyclosporine therapy monitored with abbreviated area under curve in nephrotic syndrome

et al. 2004

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“…On the other hand, among those with the lowest average trough levels in the 1st month after transplant (<250 ng/ml) only 2 of 16 showed CRF (12.5%). It must be stressed that, even though trough levels do not provide reliable information about actual exposure to CsA in the same way as plasma concentration 2 h after administration (C2) does [24,25], very high trough levels are suggestive of correspondingly high exposures. This observation may suggest the possible enhancing effect of an individual predisposition to CsA nephrotoxicity.…”

Section: Discussionmentioning

confidence: 98%

Long-term renal function in heart transplant children on cyclosporine treatment

et al. 2006

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Renal function deterioration is a reason of concern in heart transplantation. Our aim was to evaluate long-term renal function in heart transplant children on cyclosporine (CsA) treatment and to investigate the effect of several variables possibly involved in renal function deterioration. Creatinine clearances were retrospectively reviewed in 50 children (median follow 99.7 months after heart transplant). Gender, age, and body weight at transplant, rejection episodes, CsA cumulative dose, and trough levels were analyzed. After an initial increase of the glomerular filtration rate (GFR), renal function worsened in most patients; 28% of the children developed renal insufficiency (defined as GFR <80 ml/min per 1.73 m2), which was already evident in the first 3 years. Neither CsA dose, trough levels, nor other patient characteristics were found to be associated with renal function deterioration. In this study renal failure occurred in one-third of the patients. The lack of association of CsA with renal insufficiency may be explained by several reasons, including the limitations of the retrospective design of the study. However, it is possible that the nephrotoxic effect of CsA is more likely to occur in a set of predisposed patients. These must be soon identified to evaluate early a calcineurin inhibitor-sparing strategy.

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“…These include full AUC 0−12 , a restricted AUC 0−4 , other LSSs and non‐trough single concentration points [e.g. 2‐h post‐dose ( C 2 ) sample ] (21, 22, 24, 29, 30, 35, 44).…”

Section: Discussionmentioning

confidence: 99%

“…CSA, cyclosporine; AUC 0)12 , area under the curve from 0 to 12 h post-dose; AUC 0)4 , area under the curve from 0 to 4 h post-dose; C max , maximum concentration obtained during dosing interval; T max , time to reach C max ; t 1/2 , apparent half-life; C min trough, minimum concentration obtained before the next dose. (21,22,24,29,30,35,44). Calculating either a full AUC 0)12 or an AUC 0)4 requires obtaining serial blood samples over the full dosing interval, or the first 4 h postdose, respectively.…”

Section: Discussionmentioning

confidence: 99%

Limited sampling strategy for cyclosporine (Neoral^®) area under the curve monitoring in pediatric kidney transplant recipients

Strong¹,

Lai²,

Primmett³

et al. 2005

Pediatric Transplantation

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Cyclosporine (CSA; Neoral) is one of the most common immunosuppressants used in pediatric renal transplantation. Research in adult renal transplant recipients has shown that 2-h post-dose concentration (C2) monitoring and limited sampling strategies (LSSs) are better at predicting drug exposure and outcome than trough concentrations (C0). While C0 monitoring is the usual practice in pediatric renal transplant patients, area under the curve (AUC) monitoring has been shown to be superior in terms of predictive ability and outcomes. However, AUC monitoring is impractical and inconvenient in a clinic setting because it involves many blood samples. An LSS provides a reliable alternative. The purpose of this study was to prospectively define an LSS (AUC(0-12)) for CSA monitoring and to test its predictive performance. As well, an LSS (AUC(0-4)) for CSA was developed and its predictive performance tested. Blood samples for CSA concentrations were collected in 29 stable pediatric renal transplant patients prior to (t = 0) and at 0.5, 1, 2, 4, 6, and 8 h following a steady-state morning CSA dose. AUC was calculated by the trapezoidal method; LSSs for AUC(0-12) and AUC(0-4) were determined using multiple regression analysis in 14 patients; and the LSSs' predictive performance was tested in 15 additional patients. Both LSSs require two blood samples. For the LSS (AUC(0-12)), blood samples are required immediately before the dose and 2 h post-dose: AUC(0-12) = 12.45 C0 + 2.17 C2 + 723.16 (r2 = 0.909). For the LSS (AUC(0-4)), blood samples are required at one and 2 h post-dose, AUC(0-4) = 1.17 C1 + 1.85 C2 - 41.00 (r2 = 0.971). The LSSs demonstrated low bias and high precision for both AUC(0-12) and AUC(0-4). Our two-concentration LSSs are accurate and precise predictors that are more clinically useful for our patient population than other LSSs that have been developed for pediatric renal transplant patients. Our study template provides a guide for other centers to develop accurate and precise LSSs specific to their own patient population.

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C2 monitoring: a reliable tool in pediatric renal transplant recipients

Cited by 10 publications

References 3 publications

Cyclosporine therapy monitored with abbreviated area under curve in nephrotic syndrome

Cyclosporine therapy monitored with abbreviated area under curve in nephrotic syndrome

Long-term renal function in heart transplant children on cyclosporine treatment

Limited sampling strategy for cyclosporine (Neoral^®) area under the curve monitoring in pediatric kidney transplant recipients

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C2 monitoring: a reliable tool in pediatric renal transplant recipients

Cited by 10 publications

References 3 publications

Cyclosporine therapy monitored with abbreviated area under curve in nephrotic syndrome

Cyclosporine therapy monitored with abbreviated area under curve in nephrotic syndrome

Long-term renal function in heart transplant children on cyclosporine treatment

Limited sampling strategy for cyclosporine (Neoral®) area under the curve monitoring in pediatric kidney transplant recipients

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Resources

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Limited sampling strategy for cyclosporine (Neoral^®) area under the curve monitoring in pediatric kidney transplant recipients