Gadolinium-Based Contrast Agents in Kidney Disease: Comprehensive Review and Clinical Practice Guideline Issued by the Canadian Association of Radiologists

Abstract

Use of gadolinium-based contrast agents (GBCAs) in renal impairment is controversial, with physician and patient apprehension in acute kidney injury (AKI), chronic kidney disease (CKD), and dialysis because of concerns regarding nephrogenic systemic fibrosis (NSF). The position that GBCAs are absolutely contraindicated in AKI, CKD stage 4 or 5 (estimated glomerular filtration rate [eGFR] <30 mL/min/1.73 m) and dialysis-dependent patients is outdated, and may limit access to clinically necessary contrast-enhanced MRI examinations. Following a comprehensive review of the literature and reported NSF cases to date, a committee of radiologists and nephrologists developed clinical practice guidelines to assist physicians in making decisions regarding GBCA administrations. In patients with mild-to-moderate CKD (eGFR ≥30 and <60 mL/min/1.73 m), administration of standard doses of GBCA is safe and no additional precautions are necessary. In patients with AKI, with severe CKD (eGFR <30 mL/min/1.73 m), or on dialysis, administration of GBCAs should be considered individually and alternative imaging modalities utilized whenever possible. If GBCAs are necessary, newer GBCAs may be administered with patient consent obtained by a physician (or their delegate), citing an exceedingly low risk (much less than 1%) of developing NSF. Standard GBCA dosing should be used; half or quarter dosing is not recommended and repeat injections should be avoided. Dialysis-dependent patients should receive dialysis; however, initiating dialysis or switching from peritoneal to hemodialysis to reduce the risk of NSF is unproven. Use of a macrocyclic ionic instead of macrocyclic nonionic GBCA or macrocyclic instead of newer linear GBCA to further prevent NSF is unproven. Gadopentetate dimeglumine, gadodiamide, and gadoversetamide remain absolutely contraindicated in patients with AKI, with stage 4 or 5 CKD, or on dialysis. The panel agreed that screening for renal disease is important but less critical when using macrocyclic and newer linear GBCAs. Monitoring for and reporting of potential cases of NSF in patients with AKI or CKD who have received GBCAs is recommended.

Multi‐modality cardiac imaging in advanced chronic kidney disease

“…For the general population, the best described technique is based on the delayed washin and washout of the contrast agent from the tissues with increased extracellular space—late gadolinium enhancement (LGE). In advanced CKD, the usage of gadolinium based contrast agents (GBCA) should be considered individually as it is limited by the risk (<1%) of developing a potentially lethal condition, nephrogenic systemic fibrosis (NSF) . In the past years, it was shown that persons with normal renal function can also develop NSF when exposed to GBCA, but until the exact pathophysiology of GBCA‐induced disease is better understood, alternative gadolinium‐free methods should be used whenever possible in advanced CKD …”

“…In advanced CKD, the usage of gadolinium based contrast agents (GBCA) should be considered individually as it is limited by the risk (<1%) of developing a potentially lethal condition, nephrogenic systemic fibrosis (NSF). 86,87 In the past years, it was shown that persons with normal renal function can also develop NSF when exposed to GBCA, but until the exact pathophysiology of GBCA-induced disease is better understood, alternative gadolinium-free methods should be used whenever possible in advanced CKD. 87,88 Native T1 is a novel noncontrast CMR technique based on the longitudinal recovery time of hydrogen atoms following their excitation.…”

“…86,87 In the past years, it was shown that persons with normal renal function can also develop NSF when exposed to GBCA, but until the exact pathophysiology of GBCA-induced disease is better understood, alternative gadolinium-free methods should be used whenever possible in advanced CKD. 87,88 Native T1 is a novel noncontrast CMR technique based on the longitudinal recovery time of hydrogen atoms following their excitation. In any given magnetic field strength, every tissue will produce a specific range of values.…”

Observational study on the incidence of nephrogenic systemic fibrosis in patients with renal impairment following gadoterate meglumine administration: the NSsaFe study.

“…This life‐threatening condition is characterized by extensive fibrosis of the skin and internal organs, with delay from exposure to onset of the first signs ranging from the day of exposure to 2–3 months . To date, several hundred cases have been diagnosed worldwide and data over subsequent years indicated that NSF is strongly associated with the administration of GBCAs in patients with severe renal impairment or on dialysis . The use of less stable linear GBCAs is another major risk factor due to their higher propensity to release free gadolinium .…”

“…6 To date, several hundred cases have been diagnosed worldwide and data over subsequent years indicated that NSF is strongly associated with the administration of GBCAs in patients with severe renal impairment or on dialysis. 7 The use of less stable linear GBCAs is another major risk factor due to their higher propensity to release free gadolinium. 5,8 Gadolinium deposits were found in cutaneous biopsies of patients 9 but the exact mechanism by which gadolinium triggers NSF is still incompletely understood.…”