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

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 5963
Author(s):  
Mirjam E. van de Velde ◽  
Emil den Bakker ◽  
Hester N. Blufpand ◽  
Gertjan L. Kaspers ◽  
Floor C. H. Abbink ◽  
...  

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.

2008 ◽  
Vol 132 (9) ◽  
pp. 1436-1438
Author(s):  
Giuseppe Lippi ◽  
Gian Luca Salvagno ◽  
Martina Montagnana ◽  
Giovanni Targher ◽  
Massimo Franchini ◽  
...  

Abstract Context.—Lipoprotein(a) (Lp(a)) is receiving major emphasis as an independent risk factor for cardiovascular disease. Results of studies on Lp(a) in patients with impaired renal function are contradictory, and no information is available on the association between Lp(a) and estimated glomerular filtration rate and cystatin C. Objective.—To evaluate the potential relationships among the biochemical markers creatinine, estimated glomerular filtration rate, and cystatin C and their association with Lp(a) in patients with impaired renal function. Design.—We performed a retrospective analysis using the database of our laboratory to retrieve results of Lp(a), creatinine, and cystatin C tests performed on consecutive outpatients referred by general practitioners for routine blood testing during the last year. Results.—Cumulative results for all of the above-mentioned variables were retrieved for 150 adults older than 35 years. After stratifying Lp(a) values according to thresholds of creatinine, estimated glomerular filtration rate, and cystatin C, no significant differences in Lp(a) concentration were observed in subjects with abnormal values of these biochemical markers. The prevalence of Lp(a) values greater than or equal to 300 mg/L was not significantly different in subjects with biochemical markers suggestive of impaired renal function, as compared with those without such markers. In multivariable linear regression analysis, none of the parameters tested was significantly associated with Lp(a). Conclusions.—We suggest that unless renal function is completely compromised, measurement of biochemical markers of renal function might be relatively unimportant to improve clinical usefulness of Lp(a) testing.


2011 ◽  
Vol 1 (1) ◽  
pp. 10 ◽  
Author(s):  
YingBin Jia ◽  
Yun Shi ◽  
XiaoDong Guan ◽  
Jian Li ◽  
BaiMeng Zhang ◽  
...  

This study aimed to assess the mid-term renal function of abdominal aortic aneurysm patients following suprarenal endovascular repair. From March 2005 to December 2009, 290 abdominal aortic aneurysm patients were included in the study and grouped according to whether they had received infrarenal or suprarenal endovascular aneurysm repair. Suprarenal endovascular aneurysm repair was performed in 173 patients, with a mean age of 72(±8) years (85.0% male). Infrarenal endovascular aneurysm repair was performed in 117 patients, with a mean age of 71(±9) years (90.6% male). Preoperative and one week, 1-, 3-, 6- and 12-month postoperative serum creatinine and cystatin C values were recorded. Estimated glomerular filtration rate was calculated by cystatin-based formula and Cr-based Cockcroft formula. The t-test was used to determine statistical differences between or within groups. All patients received Talent or Zenith endograft. Patients’ characteristics and operative files in the two groups were well matched. Preoperative serum creatinine and cystatin C were 82 (±8) mmol/L and 0.89 (±0.11) mg/L for suprarenal endovascular aneurysm repair, respectively, and 81 (±11) mmol/L and 0.87 (±0.15) mg/L, respectively, for infrarenal endovascular aneurysm repair; no differences were observed between the two groups. Compared to preoperative renal markers within each group, a deterioration in serum creatinine, cystatin C and estimated glomerular filtration rate values was found at one week and 12 months after surgery(P<0.05). A deterioration in cystatin C [SR:(0.93±0.17) mg/L, IR: (0.92±0.31) mg/L] and estimated glomerular filtration rate by cystatin C was also found at six months after surgery(P<0.05). However, no differences in patient serum creatinine, cystatin C and estimated glomerular filtration rate values were observed between groups at each follow-up time interval. There was no greater significant difference in the association of the use of suprarenal fixation with midterm postoperative renal injury than with infrarenal fixation.


2014 ◽  
Vol 39 (2) ◽  
pp. 74-79
Author(s):  
F Jahan ◽  
MNU Chowdhury ◽  
T Mahbub ◽  
SM Arafat ◽  
S Jahan ◽  
...  

To ensure that potential kidney donors in Bangladesh have no renal impairment, it is extremely important to have accurate methods for evaluating the glomerular filtration rate (GFR). We evaluated the performance of serum creatinine based GFR in healthy adult potential kidney donors in Bangladesh to compare GFR determined by DTPA with that determined by various prediction equations. In this study GFR in 61 healthy adult potential kidney donors were measured with 99mTc-diethylenetriamine penta-acetic acid (DTPA) renogram. We also estimated GFR using a four variable equation modification of diet in renal disease (MDRD), Cockcroft-Gault creatinine clearance (CG CrCl), Cockcroft-Gault glomerular filtration rate (CG-GFR). The mean age of study population was 34.31±9.46 years and out of them 65.6% was male. In this study mean mGFR was 85.4±14.8. Correlation of estimated GFR calculated by CG-CrCl, CG-GFR and MDRD were done with measured GFR DTPA using quartile. Kappa values were also estimated which was found to be 0.104 for (p=0.151), 0.336 for (p=0.001) and 0.125 for (p=0.091) respectively. This indicates there is no association between estimated GFR calculated by CG-CrCl, CG-GFR, MDRD with measured GFR DTPA. These results show poor performance of these equations in evaluation of renal function among healthy population and also raise question regarding validity of these equations for assessment of renal function in chronic kidney disease in our population. DOI: http://dx.doi.org/10.3329/bmrcb.v39i2.19646 Bangladesh Med Res Counc Bull 2013; 39: 74-79


Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
James Shepherd ◽  
Chuan-Chuan Wun ◽  
Daniel J Wilson ◽  
Andrea L Zuckerman

We previously demonstrated a dose-dependent improvement in renal function and reduction in cardiovascular risk in TNT with intensive lipid lowering with atorvastatin (ATV) 80 mg vs 10 mg. This post hoc analysis examines the relationship between the observed improvement in estimated glomerular filtration rate (eGFR) and reduction of major cardiovascular events (MCVE). After 8 weeks open-label therapy with ATV 10 mg, 10,001 patients with CHD were randomized to double-blind therapy with either ATV 10 or 80 mg. Patients were followed for a median of 4.9 years for the occurrence of MCVEs (CHD death, nonfatal MI, and stroke). The relationship between change from baseline eGFR (using the MDRD equation) at the final visit prior to a MCVE and the risk of MCVE was assessed using a Cox proportional hazards model adjusting for baseline eGFR and other baseline characteristics. Of 9656 patients with complete renal data, 156 had a MCVE before follow-up eGFR assessment and were excluded. In the remaining 9500 patients, mean baseline eGFR was 65.3 mL/min/1.73 m 2 and mean change from baseline was 4.3 mL/min/1.73 m 2 . This represented a reduction in the risk of MCVE of 2.7% per mL increase in eGFR (HR 0.973, 95% CI 0.967– 0.980, P <0.0001). This association remained significant in patients with eGFR <60 and those with eGFR ≥60 mL/min/1.73 m 2 at baseline, with no significant interaction between eGFR change and baseline renal status ( P =0.98). A 5 mL/min on-treatment improvement in eGFR was associated with a 12.6% reduction in MCVE, while a 5 mL/min reduction was associated with a 14.4% increase in MCVE. Mean change from baseline eGFR was 3.5 mL/min/1.73 m 2 with ATV 10 mg and 5.2 mL/min/1.73 m 2 with ATV 80 mg, representing significant 9.3% and 12.4% reductions in risk, respectively. Analysis of interaction between treatment and eGFR change for prediction of MCVE demonstrated a stronger association between eGFR change and MCVE in the ATV 80 mg treatment group ( P =0.011). Improvement in eGFR was highly associated with a reduction in MCVE, irrespective of baseline renal function. This relationship was dose dependent. Improvement in eGFR may be a biomarker for the response to atorvastatin, and for the stabilization of atherosclerotic cardiovascular disease.


2015 ◽  
Vol 42 (2) ◽  
pp. 141-147 ◽  
Author(s):  
Carmen A. Peralta ◽  
Paul Muntner ◽  
Rebecca Scherzer ◽  
Suzanne Judd ◽  
Mary Cushman ◽  
...  

Background/Aims: Persons with occult-reduced estimated glomerular filtration rate (eGFR <60 ml/min/1.73 m2 detected by serum cystatin C but missed by creatinine) have high risk for complications. Among persons with preserved kidney function by creatinine-based eGFR (eGFRcreat >60 ml/min/1.73 m2), tools to guide cystatin C testing are needed. Methods: We developed a risk score to estimate an individual's probability of reduced eGFR by cystatin C (eGFRcys <60 ml/min/1.73 m2) in The Reasons for Geographic and Racial Differences in Stroke (REGARDS) study and externally validated in the Third National Health and Nutrition Examination Survey (NHANES III). We used logistic regression with Bayesian model averaging and variables available in practice. We assessed performance characteristics using calibration and discrimination measures. Results: Among 24,877 adults with preserved kidney function by creatinine, 13.5% had reduced eGFRcys. Older and Black participants, current smokers and those with higher body mass index, lower eGFRcreat, diabetes, hypertension and history of cardiovascular disease were more likely to have occult-reduced eGFR (p < 0.001). The final risk function had a c-statistic of 0.87 in REGARDS and 0.84 in NHANES. By risk score, 72% of occult-reduced eGFR cases were detected by screening only 22% of participants. Conclusions: A risk score using characteristics readily accessible in clinical practice can identify the majority of persons with reduced eGFRcys, which is missed by creatinine.


2015 ◽  
Vol 61 (10) ◽  
pp. 1265-1272 ◽  
Author(s):  
Jeffrey W Meeusen ◽  
Andrew D Rule ◽  
Nikolay Voskoboev ◽  
Nikola A Baumann ◽  
John C Lieske

Abstract BACKGROUND The Kidney Disease Improving Global Outcomes (KDIGO) guideline recommends use of a cystatin C–based estimated glomerular filtration rate (eGFR) to confirm creatinine-based eGFR between 45 and 59 mL · min−1 · (1.73 m2)−1. Prior studies have demonstrated that comorbidities such as solid-organ transplant strongly influence the relationship between measured GFR, creatinine, and cystatin C. Our objective was to evaluate the performance of cystatin C–based eGFR equations compared with creatinine-based eGFR and measured GFR across different clinical presentations. METHODS We compared the performance of the CKD-EPI 2009 creatinine-based estimated GFR equation (eGFRCr) and the newer CKD-EPI 2012 cystatin C–based equations (eGFRCys and eGFRCr-Cys) with measured GFR (iothalamate renal clearance) across defined patient populations. Patients (n = 1652) were categorized as transplant recipients (n = 568 kidney; n = 319 other organ), known chronic kidney disease (CKD) patients (n = 618), or potential kidney donors (n = 147). RESULTS eGFRCr-Cys showed the most consistent performance across different clinical populations. Among potential kidney donors without CKD [stage 2 or higher; eGFR &gt;60 mL · min−1 · (1.73 m2)−1], eGFRCys and eGFRCr-Cys demonstrated significantly less bias than eGFRCr; however, all 3 equations substantially underestimated GFR when eGFR was &lt;60 mL · min−1 · (1.73 m2)−1. Among transplant recipients with CKD stage 3B or greater [eGFR &lt;45 mL · min−1 · (1.73 m2)−1], eGFRCys was significantly more biased than eGFRCr. No clear differences in eGFR bias between equations were observed among known CKD patients regardless of eGFR range or in any patient group with a GFR between 45 and 59 mL · min−1 · (1.73 m2)−1. CONCLUSIONS The performance of eGFR equations depends on patient characteristics that are readily apparent on presentation. Among the 3 CKD-EPI equations, eGFRCr-Cys performed most consistently across the studied patient populations.


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