Nephrogenic Systemic Fibrosis, Gadolinium, and Iron Mobilization

Abstract

Dr. Pineda reports being employed by Diater Laboratories, a pharmaceutical company specializing in the production of allergenic extracts for in vivo diagnosis and treatment of allergies. No other potential conflict of interest relevant to this letter was reported.Ayr]es JG, Clark TJH. Alcoholic drinks and asthma: a survey. Br J Dis Chest 1983;77:370-5.Vally H, Carr A, El-Saleh J, Thompson P. Wine-induced asthma: a placebo-controlled assessment of its pathogenesis.

New Insights into Nephrogenic Systemic Fibrosis

“…27,28 Because iron is tightly bound to ferritin and hemosiderin, it has been suggested that its free concentration is insufficient to induce transmetallation of GBCM 25,29 ; however, we recently reported that GBCM administration in patients who have CKD and subsequently develop NSF results in a marked decrease in total iron-binding capacity, iron mobilization, profound transferrin oversaturation, and systemic inflammation. 8 In patients with renal insufficiency, several factors may aggravate free iron release, including prolonged retention of GBCM (t 1 ⁄2 13.4 to 89.2 h versus 1.5 h controls), 30 additional exogenous treatment with parenteral iron and low total iron-binding capacity secondary to malnutrition, urinary protein (transferrin) loss, sepsis, and chronic inflammation. 31-33 Available data suggest that iron is most potent in inducing transmetallation of GBCM because the thermodynamic stability of Fe 3ϩ -DTPA-BMA (10 21.9 ) far exceeds the thermodynamic stability constant of gadolinium-DTPA-BMA (10 16.9 ) 34 (Table 2).…”

“…On the basis of our clinical experience with 70 patients with NSF and other available large case series, 7,8,17 it is uncommon that patients do not receive any EPO before NSF diagnosis. It is possible that endogenous EPO released during stress-induced erythropoiesis, which could be several hundred-fold, 41 or other growth factors that synergize with EPO 42 might be important in patients who do not receive exogenous EPO before a diagnosis of NSF.…”

“…8 Decreased total iron-binding capacity, elevated serum ferritin, low serum albumin, and elevated C-reactive protein are invariably present. 7 Because many patients have critical illnesses such as sepsis, acute pancreatitis, hepatorenal syndrome, or acute graft dysfunction that precedes NSF, the acute phase of systemic fibrogenesis may go unrecognized.…”

Renal Transplantation Is Associated with Improved Clinical Outcomes in Nephrogenic Systemic Fibrosis

“…In another case report [19], a patient who was two years after kidney transplantation showed significant improvement of the sclerodermiform brownish plaques on her extremities after 4 cycles of ECP. Although ultraviolet-A phototherapy (UV-A) has the ability to inhibit procollagen synthesis in human skin [107], the response has been variable [8,19,47,108,109]. Furthermore, there has been improvement reported after three to five days of plasmapheresis treatment in three patients [53].…”

Nephrogenic systemic fibrosis: Clinical spectrum of disease

“…In their experience the following features of the acute phase may mimic systemic inflammatory response syndrome: fever, hypotension, acute kidney injury, anemia, leukoerythroblastic picture, leukocytosis, eosinophilia, monocytosis, elevated lipase, elevated c-glutamyl peptidase, elevated D-dimers, decreased total iron-binding capacity, elevated serum ferritin, low serum albumin, and elevated C-reactive protein (38,40,41). It should be noted that all findings are non-specific and most of the patients are critically ill or suffer from a proinflammatory condition (31).…”