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Studies of a rare systemic fibrosing condition-entitled nephrogenic systemic fibrosis (NSF) are linked to gadolinium-based contrast (GBC) agent exposure in patients with advanced kidney disease. However, many patients with kidney disease are exposed to GBC agents, yet they do not develop this devastating disorder.NSF appears more likely to develop when the combination of advanced kidney disease, linear GBC agent exposure, and the presence of unique patient features converge. Linear GBC agents are more likely to promote NSF, probably due to chelate-Gd+ binding instability ± underlying proinflammatory effects. Patients with advanced acute or chronic kidney disease (CKD) are at highest risk, in contrast to those with lower stages of CKD (stages I–III). Finally, whereas exposure to GBC agents in patients with advanced kidney disease is required for NSF to develop, it does not appear sufficient. Additional patient-specific co-factors, such as metabolic disorders, vascular injury, and inflammation, may also be necessary for NSF to occur.NSF develops when ‘the perfect storm’ of factors is present: unstable/pro-inflammatory GBC agent exposure, advanced kidney disease, and unique patient factors. Recognizing this combination of factors will hopefully allow this devastating condition to become of historical interest only.