Kaiser study of 3.3 million members finds single case of NSF

May 7, 2008

A comprehensive evaluation of Magnevist use among the 3.3 million members of Kaiser Permanente in Northern California has found a lower risk for developing nephrogenic systemic fibrosis than reported in previous studies in renal disease patients who received gadolinium-based MR contrast media.

A comprehensive evaluation of Magnevist use among the 3.3 million members of Kaiser Permanente in Northern California has found a lower risk for developing nephrogenic systemic fibrosis than reported in previous studies in renal disease patients who received gadolinium-based MR contrast media.

Lead author Thomas A. Hope, Ph.D., noted that four earlier reports on the prevalence of NSF found that 2.3% to 4% of dialysis-dependent patients who underwent a gadolinium-enhanced MRI study developed NSF. The reported rate for patients with decreased renal function is about 1.5%

Hope did not cite a specific prevalence rate for the preliminary results of the Kaiser study, but the exhaustive investigation identified only one definitive NSF case among 671 current and former dialysis patients and 2862 patients with creatinine levels high enough to be susceptible to the disease. Dr. Robert Herfkens, director of MRI at Stanford University Medical Center, and Kaiser physicians Drs. Kwame Denianke and Eli Weil were coauthors.

To tabulate that data, Hope and colleagues drilled through Kaiser's carefully maintained utilization database to identify all of the HMO's dialysis-dependent and diabetes-susceptible patients with creatinine levels above 1.8 mg/dL who received gadolinium contrast from Jan. 1, 2004, to May 31, 2007.

They searched electronic patient records for all patients diagnosed with NSF, nephrogenic fibrosing dermopathy, scleroderma, or similar skin diseases. Additional information was gathered from surveys of all of Kaiser's nephrologists, rheumatologists, and dermatologists in Northern California.

Results pertain exclusively to cases possibly associated with Magnevist (gadopentetate dimeglumine) because of Kaiser's exclusive contract with its maker Bayer Healthcare Pharmaceuticals, formerly Berlex Laboratories.

During the 41-month study period, 115,252 contrast-enhanced MRIs were performed on 84,659 Kaiser members. Of that number, 511 current and 160 former dialysis patients underwent at least one Magnevist-enhanced MRI. Another 2862 patients had measured creatinine levels of at least 1.8 within a year of a contrast-enhanced MR scan.

Four techniques were used to identify patients who may have developed NSF: surveying Kaiser's nephrologists, rheumatologists, and dermatologists; tracking patient visits to relevant medical specialists in the months following contrast-enhanced MRI; manually reviewing problem lists of coded diagnoses in the electronic medical records; and manually examining pathology biopsies.

Based on the survey and reviews of the coded diagnoses and specialists, Hope and his colleagues identified 932 suspicious records, but only one definitive NSF case emerged from this evaluation. Three patients had lower extremity wounds and dermatitis that may have indicated the presence of NSF.

The pathology database held 7700 pathology samples taken from the patient population after an MRI was performed. By concentrating on cases that could have involved NSF, researchers cut the total down to 923 biopsies. These were read manually to find biopsies that could have been confused with NSF. Fifty suspicious cases were referred to a dermatological pathologist for a final evaluation. No other definitive cases were identified during the pathology review, though additional review has been scheduled for four cases, Hope said.

The confirmed case is a 66-year-old patient who has been on dialysis for 13 years. He received five contrast-enhanced MRI or MRA exams in 2001 and single exams in 2006 and 2007.

"It is safe to say that at Kaiser Northern California the incidence of NSF is markedly lower that previously reported," Love said.