Major Finding: Discharge of kidney transplant recipients on corticosteroid-based immunosuppression was independently associated with a 45% increased risk in major fractures over the next 4 years compared to patients managed with early corticosteroid withdrawal while still in-hospital.
Data Source: Retrospective analysis of nearly 78,000 kidney transplant recipients in the United States Renal System database.
Disclosures: Dr. Nikkel declared having no financial conflicts.
SAN DIEGO – Early corticosteroid withdrawal after kidney transplantation is associated with a marked reduction in major fracture rate, according to an analysis of the United States Renal Data System database.
Indeed, discharge on corticosteroids was independently associated with a 45% increased risk of major fractures requiring hospitalization during a median follow-up of about 4 years, Dr. Lucas Nikkel reported at the meeting.
Early corticosteroid withdrawal regimens are gaining popularity at renal transplant centers as a means of reducing a wide range of immunosuppression-related side effects. The documented major clinical advantages include reduced rates of hyperlipidemia, posttransplant diabetes, cardiovascular events, infections, and cancer. Until now, however, no study had examined whether early corticosteroid withdrawal regimens are also effective in reducing fracture incidence, noted Dr. Nikkel, who earned the ASBMR Young Investigator Award for his work.
Early corticosteroid withdrawal regimens consist of 4-7 days of high-dose methylprednisolone administered at the time of transplantation, followed by withdrawal of the drug in favor of long-term immunosuppression with calcineurin inhibitors and mycophenolic acid. More than 30% of kidney transplant recipients in the United States are now managed using such protocols.
Dr. Nikkel identified 77,625 adults in the USRDS database who received a kidney transplant during 2000-2006. Pretransplant fracture rates were similar in the 11,178 patients not on steroids at discharge and the 66,447 who were.
The incidence of fractures requiring hospitalization during the follow-up period was 1.7% in patients with early corticosteroid withdrawal, significantly less than the 3.3% for those discharged on corticosteroid-based immunosuppression. The rate was 5.8 major fractures per 1,000 patient-years in the early steroid withdrawal group, compared with 8.0 per 1,000 patient-years in those on corticosteroid-based immunosuppression. The increased fracture risk in patients discharged on steroids became apparent at 1 year of follow-up and significant at 2 years.
“It's noteworthy that patients in the youngest age group discharged on corticosteroids had a similar risk of fractures compared to the oldest patients discharged without corticosteroids,” observed Dr. Nikkel, who is with Columbia University, New York.
In addition to discharge on steroids, other fracture risk factors identified in the study included older age, female gender, white race, pretransplant diabetes, a positive fracture history, and being on dialysis.
Since most fractures are treated on an outpatient basis, it is likely that these study results greatly underestimate the true fracture burden that is associated with kidney transplantation, he added.
Dr. Nikkel pointed out that his study was a retrospective analysis of observational data and said that prospective, long-term studies are needed to confirm the results.
Each year, more than 17,000 kidney transplants are performed in the United States, and more than 68,000 worldwide. Bone loss is high in these patients, especially in the first 18 months after transplantation.
Kidney transplant recipients have a 4.5-fold greater fracture risk than do the general population and a 30% greater risk than do hemodialysis patients during the first 3 years post transplant.
Audience members said that there is evidence to suggest calcineurin inhibitors adversely affect bone health as well, and they urged Dr. Nikkel to extend his follow-up to monitor this situation.
Younger patients given steroids had a risk similar to older patients discharged without corticosteroids.
Source DR. NIKKEL