Carboplatin Dosing Accuracy by Estimation of Glomerular Filtration versus Creatinuria in Cancer Patients

Chemotherapy ◽  
2018 ◽  
Vol 63 (3) ◽  
pp. 137-142 ◽  
Author(s):  
Noiver Graciano Vera ◽  
Luis Pino Villarreal ◽  
Jenny Ureña Vargas

Background: The glomerular filtration rate (GFR) is essential for calculating the dose and the monitoring of carboplatin. Although GFR measurement (mGFR) by external markers is ideal, in most cases these are not employed; the most used method is GFR estimation (eGFR) by formulae, hence the need to identify the formula with the best performance. Methods: Patients admitted between 2011 and 2017 and diagnosed with ovarian, endometrial, lung, esophageal, or testicular cancer were assessed retrospectively. The accuracy of the carboplatin dose calculated by creatinine concordance and by the Cockroft-Gault (CG), CKD-EPI, MDRD, Wright, and Jelliffe formulae was assessed using the intraclass correlation coefficient. Results: Fifty-six medical histories were analyzed. The best accuracy was observed between the Wright formula (i.e., 0.71) and the dose calculated based on the 24-h creatinine clearance. Stratification by CKD was made in depurations < 60 mL/min, where the Jelliffe value was excellent (i.e., 0.75). In depurations ≥60 mL/min, CKD-EPI was the best formula, with an accuracy of 0.65. CG was the formula with the worst performance in calculating the dose and glomerular filtration, losing its usefulness with very low filtrations. Conclusions: GFR formulae and calculation of the carboplatin dose have good accuracy with the GFR obtained based on the 24-h creatinine clearance, with the Wright formula being the one with best performance and CG the one with worst performance.

1982 ◽  
Vol 60 (12) ◽  
pp. 1499-1504 ◽  
Author(s):  
B. Moulin ◽  
P. Vinay ◽  
N. Duong ◽  
A. Gougoux ◽  
G. Lemieux

A progressive reduction of renal blood flow and glomerular filtration rate induced by the stepwise clamping of a Goldblatt clamp increases the urate over creatinine clearance ratio from 1.2 to 1.9 in normal urate-secreting Dalmatian dogs. These clearance data support the existence of a predominant postreabsorptive secretory flux of urate in the normal Dalmatian dog. In contrast, in Dalmatians loaded with pyrazinoic acid which suppresses urate secretion, net reabsorption of urate is unmasked and the urate over creatinine clearance ratio decreases with the progressive reduction in glomerular filtration rate (down to 0.44). It is concluded that the net reabsorption of urate measured by conventional clearance techniques after pharmacologic depression of the urate secretory flux probably reflects true urate reabsorption in the nephron of this species.


2018 ◽  
Vol 25 (7) ◽  
pp. 1651-1657 ◽  
Author(s):  
Amy Morrow ◽  
Campbell Garland ◽  
Fei Yang ◽  
Mike De Luna ◽  
Jon D Herrington

The use of the Calvert formula to calculate carboplatin doses allows clinicians to achieve the appropriate carboplatin area under the concentration (AUC) curve. Thrombocytopenia is the dose limiting toxicity of carboplatin and optimizing AUC minimizes the risk of thrombocytopenia. Carboplatin clearance directly correlates with glomerular filtration rate (GFR) and, therefore, an accurate estimation of the renal function is needed. The Calvert formula was designed using the GFR measured by 51Cr-EDTA; however, many clinicians substitute estimated creatinine clearance (CrCl) as calculated by the Cockcroft–Gault (C–G) equation. The potential for overestimating AUC occurs when clinicians substitute actual weight in obese patients or use a low serum creatinine when calculating C–G estimated CrCl. In 2010, the National Cancer Institute recommended the GFR value within the Calvert formula should not exceed 125 mL/min, thereby capping the carboplatin dose. However, there are studies demonstrating that certain patients’ actual GFR values do exceed 125 mL/min. Therefore, capping the carboplatin dose in these patients may lead to underestimating the carboplatin AUC. A single-center, retrospective study was performed to evaluate the change in platelet count pre- and post-carboplatin exposure in patients with C–G estimated CrCl greater than 125 mL/min receiving capped versus uncapped carboplatin doses. A review of carboplatin dosing strategies is also presented. This study indicated there was a larger mean difference in pre- and post-platelet count in patients receiving uncapped carboplatin compared to patients receiving capped carboplatin with no differences in toxicities. Dose capping this patient population will likely lead to a lower AUC rather than the intended AUC target, which could ultimately lead to substandard outcomes.


2013 ◽  
Vol 03 (04) ◽  
pp. 184-188
Author(s):  
Leopoldo Muniz da Silva ◽  
Pedro Thadeu Galvão Vianna ◽  
Mariana Takaku ◽  
Glênio Bittencourt Mizubuti ◽  
Yara Marcondes Machado Castiglia

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Mokhamad Khasun ◽  
Ivan Kayukov, ◽  
Olga Beresneva ◽  
Marina Parastaeva ◽  
Anatoly Kucher ◽  
...  

Abstract Background and Aims Glomerular filtration rate (GFR) is the most important and accurate parameter of kidney function in the course of chronic kidney disease (CKD). Renal or plasma inulin, diethylenetriaminepentaacetate (DTPA), ethylenediaminetetraacetate (EDTA), radiocontrast agents (iohexol, iothalamate) and some other substances clearances are the reference methods for determining GFR. However, these methods cannot be applied routinely because of the inconvenience. Several available methods have been developed to estimate GFR in a simpler manner and at low costs. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation is widely used to evaluate the GFR in practice. However, this equation is not accurate for the full age spectrum. In 2016, the new equation, full age spectrum equation, based on the serum creatinine (FAScr), was developed and can be applicable to all ages. However, data on the benefits of using the FAScr-method in different populations are contradictory. In particular, it is unclear whether the FAScr provides any advantages over the CKD-EPI method in adults. In this regards, we attempted to compare data obtained FAScr method with results some non-reference and reference methods in adult Russian population. Method We examined 120 Caucasian patients (M:F - 52:68; age 18-76 year) with CKD 1 - 5 stages. Patients with nephrotic syndrome and congestive heart failure were excluded. GFR (reference method) measured by plasma clearance of 99mTc-DTPA (CDTPA). CDTPA determined by one- compartment model 2-4 h method using a Chantler-Barratt linear correction. Estimation GFRs (eGFR) were established by Cockcroft-Gault creatinine clearance (CG), CKD-EPI (creatinine), FAScr and Modification of Diet in Renal Disease (MDRD) methods. Also, renal creatinine clearance (Ccr; UV/P method) was measured. Only GFRs values corrected on 1.73 m2 body surface area had been use. Results The values of GFR (Mean(SEM)) are: CDTPA 67.0(2.46); FAS 69.7(2.50); CKD-EPI 64.3(2.54); MDRD 60.9(2.62); CG 77.6(3.31); Ccr 85.2(3.40), мл/мин/1.73 m2. MDRD was significantly lower (paired Student t-test with correction on multiply comparison by Benjamini-Hochberg method) than CDTPA (P=0.0024), CG (P=0.0001) or Ccr (P&lt;0.0001) were significantly higher. The bias (CDTPA minus non reference GFR) were: FAS -2.67(1.71); CKD-EPI 2.72(1.58); MDRD 6.12(1.78); CG -10.57(2.51); Ccr -18.22(2.26), ml/min. All biases are significantly differ between themselves (P from 0.00064 to &lt;0.000001). The percentage of P30 of the FAS 81.6(3.5) was not significant differ from P30 of CKD-EPI (78.3(3.8); P=0.524) or MDRD (71.7(4.1); P=0.071). However, P30 of CG (67.5(4.3),%; P=0.01) or Ccr (54.2(5.42),%; P&lt;0,001) were significant lower, than P30 of FAS. There were significant comparable direct correlations between CDTPA and FAS (r=0.764), CKD-EPI (r=0.801), MDRD (r=0.756), CG (r=0.656), Ccr (r=0.749); P&lt;0.00001 in all cases. Conclusion In adult Russian population FAScr-method of GFR estimation had not any advantage over CKD-EPIcr-method.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Chee Keong Thye ◽  
Yee Wan Lee ◽  
Maisarah Jalalonmuhali ◽  
Soo Kun Lim ◽  
Kok Peng Ng

Abstract Background and Aims All living kidney donors undergo assessment of renal function by evaluation of Glomerular Filtration Rate (GFR). 51Cr-EDTA is one of the most widely used marker for measuring GFR but it is hampered by cost and laboriousness as well as not being widely available in Malaysia. Measuring 24-hour urine for creatinine clearance (Ccr) is a common alternative when exogenous filtration markers are not available. Ccr suffers from over/underestimation of measured GFR (mGFR) due to errors in urine collection and tubular secretion of creatinine. This is a study to compare the correlation of Ccr against 51Cr-EDTA in measuring GFR among the living donors in Malaysian population. Method This is a cross-sectional, single-centre study of a cohort of living kidney donor candidates from January 2007 to March 2019. All candidates who had mGFR done with both 51Cr-EDTA and Ccr in University Malaya Medical Centre were enrolled. Special consideration was taken to account for adequate urine sampling for Ccr. Clinical data was analysed for correlation, bias, precision and accuracy between Ccr and 51Cr-EDTA. Results A total of 83 living kidney donors with a mean age of 45.60 ± 11.06 years and body mass index (BMI) of 24.36 ± 4.03 were enrolled. Female comprised 74.7% of the donors while Chinese, Malay and Indian accounted for 67.5%, 20.5% and 7.2% of the donors respectively. The study group had a mean serum creatinine of 63.37 ± 16.00 umol/L with a urine volume of 2.03 ± 0.81 L (range 0.70 – 3.82). mGFR from 51Cr-EDTA was 125.56 ± 27.64 ml/min/1.73m2 (range 77.0 – 194.3) whereas calculated Ccr was 136.05 ± 36.15 ml/min/1.73m2 (range 75.32 – 280.06). The correlation coefficient between Ccr and 51Cr-EDTA is moderate (r = 0.43) (p &lt; 0.01). Mean absolute bias between Ccr and 51Cr-EDTA was 10.59 ± 37.99 ml/min/1.73m2 (p &lt; 0.05). The accuracy of Ccr within 30% of 51Cr-EDTA was 77.11%. Conclusion Our study showed that Ccr significantly overestimates mGFR compared to 51Cr-EDTA. However, there is a significantly moderate positive correlation between Ccr and 51Cr-EDTA. Thus, in the absence of 51Cr-EDTA, Ccr is a clinically acceptable alternative if utilized with care and understanding its limitations.


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