What Nephrologists Need to Know About Gadolinium: Gadolinium Clearance and Renal Disease

Gadolinium Clearance and Renal Disease

The half-life and clearance of gadolinium chelates have been examined in patients with CKD or ESRD who are on hemodialysis or peritoneal dialysis.^{[36,39,75-82]} Swan et al.^[81] measured concentrations of gadolinium in serum, urine and stool after a single dose of gadobenate dimeglumine (0.2 mmol/kg) in patients with varying degrees of renal function. In people with a normal GFR, the half-life of gadolinium was 1.96 hours. It increased to 6.11 ± 2.95 hours in those with a GFR of 31-60 ml/min per 1.73 m². and to 9.48 ± 3.08 hours in those with a GFR of 10-30 ml/min per 1.73 m². Other studies of the half-life of gadobenate dimeglumine and gadoversetamide in patients with CKD yielded similar results.^[79,80] In nine patients with stage 5 CKD (GFR 2-10 ml/min per 1.73 m²) who received a single dose of gadodiamide (0.1 mmol/kg), Joffe and co-workers found that the half-life of gadolinium was prolonged to 34.3 ± 22.9 hours.^[39]

There have been several studies of gadolinium pharmacokinetics in hemodialysis patients; data from peritoneal dialysis patients are limited. Published reports have several limitations. For example, conclusions are often drawn on the basis of decay curves of serum gadolinium concentration. During formulation of these curves, it is assumed that gadolinium is removed from serum solely by dialysis. This might not be the case; sequestration of gadolinium in interstitial or intracellular compartments would be erroneously interpreted as dialytic removal. Joffe et al.^[39] noted that the half-life of gadolinium (gadodiamide; 0.1 mmol/kg) during hemodialysis was 2.6 ± 0.4 hours when a low-flux biocompatible dialyzer was used for 4 hours three times per week. The authors reported that one hemodialysis session removed 65% of gadolinium; however, gadolinium levels in dialysate were not measured. Saitoh and colleagues^[78] reported a gadolinium half-life of 1.93 hours during hemodialysis in 13 patients dialyzed with a 1.5 m² synthetic-polymer dialyzer at low dialysate flow rates (200 ml/min). Gadodiamide was the administered chelate (0.1 mmol/kg), and dialysis was carried out on days 1, 3, and 5 after exposure to gadolinium. The estimated proportion of gadolinium removed after each of these three dialysis sessions was 73.8%, 92.4%, and 98.9%, respectively; however, dialysate was only collected during the first hemodialysis session. Okada and co-workers^[36] studied 70 hemodialysis patients who received a 0.1 mmol/kg dose of gadopentetate dimeglumine, and estimated the proportions of gadolinium removed after four 4-hour dialysis sessions to be 72.8%, 95.6%, 98.7%, and 99.5%. Dialysate samples were not collected-- percentage gadolinium removal was estimated on the basis of serum concentration decay curves. The first dialysis session occurred at variable intervals after gadolinium administration (same day in 16 patients, next day in 34 patients, 2 days later in 14 patients, and 3 days later in 6 patients). The type of dialyzer used in the study was not reported.

Data from the largest series of peritoneal dialysis patients who had received a gadolinium chelate were reported by Joffe et al.^[39] Nine patients underwent continuous ambulatory peritoneal dialysis with four exchanges per day. Dialysate was collected and gadolinium halflife was estimated to be 52.7 ± 6.2 hours. Only 69% of gadolinium had been removed after 22 days of peritoneal dialysis. In a case report of another peritoneal dialysis patient, who had received gadoversetamide (0.1 mmol/kg), the gadolinium half-life was reported to be 9 hours.^[76] The patient, however, was producing 3 liters of residual urine per day. The rate of removal of gadolinium by peritoneal clearance was low in both studies, at 3.8 ± 0.6 ml/min and 5.13 ml/min, respectively.

We will not review in vitro studies in detail in this article, but some useful insights can be gained from them. First-order kinetic modeling showed that 12.2-14.7 hours of dialysis were required to remove 97% of an injected gadolinium dose.^[75] Gadolinium clearance during dialysis is more efficient when membranes with a large pore size are used,^[83] and nonionic gadolinium chelates are more easily removed via positively-charged dialysis membranes than ionic gadolinium chelates (see Table 1 for charge status of gadolinium chelates).^[77]