Editor:
In 1998, Academic Radiology published our study dealing with the pharmacokinetics of intravenously injected gadodiamide (Omniscan) in patients with either chronic kidney disease (CKD) stage 5 (glomerular filtration rate [GFR] <15 mL/min) and undergoing hemodialysis or being treated with continuous ambulatory peritoneal dialysis (CAPD) . The study was powered to access the classical parameters of pharmacokinetics as well as the dialyzability among our patients on hemo- or peritoneal dialysis. Contrast-induced nephropathy was also an important parameter. The conclusion was that gadodiamide could be used safely in the evaluated patient groups.
The reason for performing the study was that it was well-known at that time that gadodiamide provided contrast enhancement and facilitated visualization of abnormal structures or lesions in various parts of the body including the central nervous system just as the other gadolinium-based agents available in the early 1990s. Because patients with CKD stage 5 could be in need of visualization of abnormal structures, we felt that it was justified to perform the above-mentioned study. However, since our publication, the nephrological and radiological communities worldwide have unfortunately learned that gadodiamide is far from safe in patients with GFR <15 mL/min or on dialysis. Thus, several patients have developed nephrogenic systemic fibrosis (NSF)—a disabling and potentially deadly disease that is associated with exposure to a gadolinium-based agent based on a linear chelate. Therefore, with the present knowledge, our conclusion of 13 years ago is no longer justified as gadodiamide is far from safe in CKD.
The concept of safety in our study included only “no adverse event related to the Omniscan given” during a follow-up of a total of 5 days among patients with CKD stage 5 during an 8-day follow-up period in those on hemodialysis and up to 22 days in patients on CAPD. Thus, no sufficient and confidence rewarding safety parameters were evaluated (eg, skin inspection after 3, 12, or 36 months, biopsies of bone, skin, or liver). Furthermore, our study was a single-dose study and therefore gave no data on the safety and side effects in patients that were exposed to two or more doses. Thus, it gave no data on the safety in patients being exposed more than once.
Regarding the dose, we would like to emphasize that we studied only one single bolus injection of 0.1 mmol/kg. Thus, we did not evaluate higher doses, although the Danish Medicines Agency and other European Medicines agencies later approved doses up to 0.3 mmol/kg in patients with reduced renal function or on dialysis. Unfortunately, time has shown us that gadodiamide was not safe or harmless in patients with CKD stage 5 with or without being dialyzed. Had that knowledge been made available to us in 1993–94, we would never have performed the this study.
Reference
- 1. Joffe P., Thomsen H.S., Meusel M.: The pharmacokinetics of gadodiamide in patients with severe renal insufficiency treated conservatively or undergoing hemodialysis or continuous ambulatory peritoneal dialysis. Acad Radiol 1998; 5: pp. 491-502.