Validation of Tikhonov adaptively regularized gamma variate fitting with 24-h plasma clearance in cirrhotic patients with ascites

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Abstract

Purpose

The aim was to compare late-time extrapolation of plasma clearance (CL) from Tikhonov adaptively regularized gamma variate fitting (Tk-GV) and from mono-exponential (E1) fitting.

Methods

Ten 51Cr-ethylenediaminetetraacetic acid bolus IV studies in adults—8 with ascites—assessed for liver transplantation, with 12-16 plasma samples drawn from 5-min to 24-h, were fit with Tk-GV and E1 models and CL results were compared using Passing-Bablok fitting.

Results

The 24-h CL(Tk-GV) values ranged from 11.4 to 79.7 ml/min. Linear regression of 4- versus 24-h CL(Tk-GV) yielded no significant departure from a slope of 1, whereas the 4- versus 24-h CL(E1) slope, 1.56, was significantly increased. For CL(Tk-GV-24-h) versus CL(E1-24-h), there was a biased slope and intercept (0.85, 5.97 ml/min). Moreover, the quality of fitting of 24-h data was significantly better for Tk-GV than for E1, as follows. For 10 logarithm of concentration curves, higher r values were obtained for each Tk-GV fit (median 0.998) than for its corresponding E1 fit (median 0.965), with p < 0.0001 (paired t-test of z-statistics from Fisher r-z transformations). The E1 fit quality degraded with increasing V/W [volume of distribution (l) per kg body weight, p = 0.003]. However, Tk-GV fit quality versus V/W was uncorrelated (p = 0.8).

Conclusion

CL(E1) values were dependent on sample time and the quality of fit was poor and degraded with increasing ascites, consistent with current opinion that CL(E1) is contraindicated in ascitic patients. CL(Tk-GV) was relatively more accurate and the good quality of fit was unaffected by ascites. CL(Tk-GV) was the preferred method for the accurate calculation of CL and was useful despite liver failure and ascites.

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