85: NEPHROGENIC SYSTEMIC FIBROSIS

PATIENT STORY

A dialysis-dependent 48-year-old white man with polycystic kidney disease was admitted to the hospital for a living-related renal transplantation. In the immediate post-op course he was evaluated for arrhythmias via cardiac magnetic resonance imaging (MRI) with gadolinium contrast. Three weeks post-op he underwent a renal biopsy for an elevated serum creatinine, which showed acute tubular necrosis (ATN). At that time he developed a painful, erythematous sclerotic plaque with a small erosion in the center of his abdominal wall. Skin biopsies were consistent with nephrogenic systemic fibrosis (NSF).

EPIDEMIOLOGY

• Rare systemic fibrosing disorder presenting as symmetrical, thickened, fibrotic skin leading to flexion contractures and immobility.^1,2

• Skin involvement is the predominant feature, leading to its former description as nephrogenic fibrosing dermopathy (NFD). However, increased understanding of this disorder as a systemic process with systemic manifestations has necessitated changing the nomenclature to NSF.

• 95% of cases occur in patients with advanced stages of renal dysfunction.

  • This represents mostly hemodialysis, but also includes peritoneal dialysis, reduced transplant allograft function, and acute kidney injury (AKI) not requiring dialysis.

• Rate of incidence is estimated between 1% and 5% of dialysis-dependent patients.

  • Risk is higher in peritoneal dialysis versus hemodialysis.

  • Gadolinium dose-response relationship has been suggested in a study comparing double dose versus single dose. Odds ratio comparing the two doses was found to be 22.3 for the double dose versus single dose.

• First published case series chronicled patients from 1997 to 2002.

ETIOLOGY

• Gadolinium-based contrast agents^{3,4,5, and 6}

  • Gadolinium is a cationic contrast agent used in MRI. Free gadolinium is relatively water insoluble and toxic to tissue. Thus it is chelated for use in humans. There are various molecular structures used to accomplish this with varying degrees of binding strength. Ionic and cyclical compounds are more stable, compared to nonionic, linear structures.

  • Chelates are excreted unchanged through the kidney, thus diminished renal function significantly prolongs the half-life of gadolinium, from 1.5 to 2 hours with normal renal function, to greater than 30 hours in renal failure.

  • One US/FDA registry of 75 cases revealed an exposure to gadolinium 2 days to 18 months prior to diagnosis of NSF. An international registry noted more than 95% of cases reported fell within 2 to 3 months of exposure.

  • The acidosis, hyperphosphatemia, and abnormal iron metabolism associated with renal failure may contribute to destabilization of the gado-linium-chelate complex causing the release of free gadolinium into circulation.

• Erythropoietin therapy

  • Postulated because of its fibrogenic properties, bone marrow stimulation, and iron mobilization.

  • An association has been described, suggesting that high and escalated doses of erythropoietin are an additional risk factor for NSF.

• Infection

  • One single center, retrospective study found that the presence of infection at the time of gadolinium administration markedly increased the risk of NSF in dialysis patients (odds ratio [OR] 25, 95% confidence interval [CI] ...