Carboplatin Dosing in Children Using Estimated Glomerular Filtration Rate: Equation Matters.

Renal function-based carboplatin dosing using measured glomerular filtration rate (GFR) results in more consistent drug exposure than anthropometric dosing. We aimed to validate the Newell dosing equation using estimated GFR (eGFR) and study which equation most accurately predicts carboplatin clearance in children with retinoblastoma. In 13 children with retinoblastoma 38 carboplatin clearance values were obtained from individual fits using MWPharm++. Carboplatin exposure (AUC) was calculated from administered dose and observed carboplatin clearance and compared to predicted AUC calculated with a carboplatin dosing equation (Newell) using different GFR estimates. Different dosing regimens were compared in terms of accuracy, bias and precision. All patients had normal eGFR. Carboplatin exposure using cystatin C-based eGFR equations tended to be more accurate compared to creatinine-based eGFR (30% accuracy 76.3-89.5% versus 76.3-78.9%, respectively), which led to significant overexposure, especially in younger (aged ≤ 2 years) children. Of all equations, the Schwartz cystatin C-based equation had the highest accuracy and lowest bias. Although anthropometric dosing performed comparably to many of the eGFR equations overall, we observed a weight-dependent change in bias leading to underdosing in the smallest patients. Using cystatin C-based eGFR equations for carboplatin dosing in children leads to more accurate carboplatin-exposure in patients with normal renal function compared to anthropometric dosing. In children with impaired kidney function, this trend might be more pronounced. Anthropometric dosing is hampered by a weight-dependent bias.

Why pediatricians fail to diagnose hypertension: a multicenter survey.

OBJECTIVE: To elucidate why pediatricians fail to diagnose childhood hypertension, with special emphasis on the use of blood pressure (BP) reference data. We hypothesized that pediatricians frequently omit BP measurements and do not routinely relate BP measurements to reference data. STUDY DESIGN: We conducted a multicenter survey on BP measurement among 197 participants. Respondents were asked to estimate BP percentiles and classify BP readings in 12 example cases. Questionnaires were completed onsite in the presence of the researchers, without access to BP reference data. RESULTS: We found that 71% of physicians measure BP during ambulatory visits only if the child has risk factors for hypertension. After measuring BP, 65% compare the reading with reference data only if they suspect that it is elevated. Their ability to rate a reading at its true value is limited, however; 47% of the physicians classified 1 or more of the prehypertensive or hypertensive cases as normal. CONCLUSIONS: Most pediatricians do not screen for hypertension, contrary to recommendations. After obtaining a BP measurement, the majority do not compare the reading with reference standards; however, without the use of reference data, they commonly underestimate the BP percentile and potentially miss cases of childhood hypertension.

Diversity in renal function monitoring and dose modifications during treatment for childhood cancer: a call for standardization.

Despite changes in survival and drug tolerability, nephrotoxicity remains an important complication of chemotherapy. To provide cutting-edge care for children with cancer oncologist must be familiar with their nephrotoxic potential. Careful monitoring of renal function during treatment is therefore indicated. Well-defined guidelines for this are lacking. We reviewed current DCOG protocols and showed that monitoring of renal function during treatment varies widely between protocols. In some protocols recommended renal function measures are inappropriate given the chemotherapy prescribed. Advices on dose modifications in case of renal dysfunction also vary, even with comparable regimens. These differences are unwanted and call for standardization.

Height-independent estimation of glomerular filtration rate in children: an alternative to the Schwartz equation.

OBJECTIVE: To compare the diagnostic performance of 2 height-independent equations used to calculate estimated glomerular filtration rate (eGFR), those of Pottel (eGFR-Pottel) and the British Columbia Children's Hospital (BCCH) (eGFR-BCCH), with the commonly used Schwartz equation (eGFR-Schwartz). STUDY DESIGN: We externally validated eGFR-Pottel and eGFR-BCCH in a well-characterized pediatric patient population (n = 152) and compared their diagnostic performance with that of eGFR-Schwartz using Bland-Altman analysis. All patients underwent glomerular filtration rate measurement using the gold standard single-injection inulin clearance method (GFR-inulin). RESULTS: Median GFR-inulin was 92.0 mL/min/1.73 m² (IQR, 76.1-107.4 mL/min/1.73 m²). Compared with GFR-inulin, the mean bias for eGFR-Schwartz was -10.1 mL/min/1.73 m(2) (95% limits of agreement [LOA], -77.5 to 57.2 mL/min/1.73 m(2)), compared with -12.3 mL/min/1.73 m² (95% LOA, -72.6 to 47.9 mL/min/1.73 m(2)) for eGFR-Pottel and -22.1 mL/min/1.73 m² (95% LOA, -105.0 to 60.8 mL/min/1.73 m(2)) for eGFR-BCCH. eGFR-Pottel showed comparable accuracy to eGFR-Schwartz, with 77% and 76% of estimates within 30% of GFR-inulin, respectively. eGFR-BCCH was less accurate than eGFR-Schwartz (66% of estimates within 30% of GFR-inulin; P < .01). CONCLUSION: The performance of eGFR-Pottel is superior to that of eGFR-BCCH and comparable with that of eGFR-Schwartz. eGFR-Pottel is a valid alternative to eGFR-Schwartz in children and could be reported by the laboratory if height data are not available.

Cystatin C more accurately detects mildly impaired renal function than creatinine in children receiving treatment for malignancy.

BACKGROUND: Monitoring of renal function is crucial in pediatric oncology. The use of creatinine to estimate glomerular filtration rate (GFR) is hampered by its dependency on muscle mass. Muscle wasting is common in children with cancer, leading to overestimation of GFR. Data on cystatin C are sparse in pediatric oncology, although this marker could be particularly useful in this population. PROCEDURE: Inulin clearance, estimated GFR using serum cystatin C according to Filler (eGFRcys) and serum creatinine according to Schwartz (eGFRcrea) were measured in 68 children with malignancy and 121 controls. We analyzed the difference between measured and estimated GFR and performance, bias and accuracy. RESULTS: Multiple linear regression analysis showed overestimation of GFR by eGFRcrea in females (B = -21.18; P = 0.001), and in patients with malignancy (B = -21.77; P = 0.014). eGFRcys overestimated GFR in females (B = -10.47; P = 0.001), but was independent of treatment for malignancy. Agreement with gold standard in detecting GFR below 90 ml/min/1.73 m(2) is better for eGFRcys (AUC 0.854) than for eGFRcrea (AUC 0.675) in the group with cancer. They performed comparably in the control group. Bland-Altman analysis showed considerable bias for eGFRcrea compared to eGFRcys (-14.3 ml/min/1.73 m(2) vs. -7.3 ml/min/1.73 m(2)). The proportion of estimates within 30% of true GFR for eGFRcrea (72.1%) was lower than for eGFRcys (82.4%) in the group with cancer. In the control group eGFRcrea (84.3%) outperformed eGFRcys (76.0%). When using the 50% limits of agreement, eGFRcys outperformed eGFRcrea in both groups. CONCLUSION: Cystatin C more accurately detects mildly impaired renal function than creatinine in children receiving treatment for malignancy.