**7.3 Strengths and limitations**

Iothalamate can be measured either by HPLC or XRF methods or by isotopic methods. This is the only one marker where this choice is possible. However, there is no evidence that all the techniques of measurement are fully equivalent. Iothalamate is certainly the marker that has been the most deeply studied from a physiological point of view (with inulin). Unhopefully, there are strong reasons to believe that iothalamate is secreted by renal tubules. Moreover, extra-renal clearance of iothalamate is not so negligible. These limitations are confirmed by most of the clinical studies showing that iothalamate slightly overestimates inulin clearance, especially in the high levels of GFR. A clinical limitation concerns the patients who are allergic to contrast product. This marker remains however

How Measuring Glomerular Filtration Rate? Comparison of Reference Methods 41

measurements in Sweden (1500 GFR measurements/y)(Nilsson-Ehle & Grubb, 1994; Nilsson-Ehle, 2002). This safety profile is, at least in part, explained by the low dose of

The results of the first clinical study on iohexol as a reference GFR marker will be published in 1983 (Olsson et al., 1983). Actually, GFR was measured in 10 healthy subjects with urinary clearances of iohexol and 51Cr-EDTA. In this study, the iohexol clearance was significantly higher than the 51Cr-EDTA clearance (110 versus 96 mL/min). In this first study, large dose of iohexol was injected to the patient (from 375 to 500 mg I/kg)(Olsson et al., 1983). Thereafter, the doses of iohexol used will be drastically reduced but it has been well described that the physiologic handling of iohexol was identical if different dosages are used (Back et al., 1988a). In table 5, we resumed the study results having compared the performance of iohexol to inulin in adult subjects. To the best of our knowledge, only two studies have compared urinary clearances of iohexol and inulin. The results seem excellent but Bland and Altman analysis have not been realized (Brown & O'Reilly, 1991; Perrone et al., 1990). Contrary to other markers, iohexol plasmatic clearances have been the most studied. The relatively worst results obtained by Erley are explained by the patients included (Erley et al., 2001). Actually, the patients hospitalized in intensive care are prone to develop edema and, in this situation, plasmatic clearances are not accurate, whatever the marker (Skluzacek et al., 2003). The study published by Gaspari demonstrated a good performance of iohexol plasma clearance compared to inulin but the number of samples was

iohexol injected, and by the exclusion of patients with contrast products allergy.

high and these samples were drawn lately (after 10h)(Gaspari et al., 1995).

**(mL/min/1.73 m²)** 

30 NA ±10 to 125 Inulin: urinary

9.6 to 116.8 Inulin: urinary

clearance and constant infused rate Iohexol (XRF) Plasma clearance: bolus and samples after 3 and 4

clearance and constant infused rate Iohexol (XRF) urinary clearance and plasma clearance: samples at 3 and 4 h +BM correction

**GFR methods Statistics Results** 

Correlation Regression Ratio

Correlation Regression Ratio

0.86 =0.85x+8.79 1.09±0.06

Urinary 0.986 =0.998-2.309 Plasma 0.983 =0.947+4.92 =1.102±0.286

**References Sample Population GFR range** 

29 10 heart

grafted 11 renal grafted 10 donors

**8.2 Clinical data** 

(Lewis et al., 1989)

> (Brown & O'Reilly, 1991)

important because it is the most used marker in USA. For example, iothalamate has been used in trials having built the new creatinine-based equations (Levey et al., 1999).
