ESRD Cause Affects Post-Transplant Fracture Risk

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DENVER—The risk of fracture during the first five years after a renal transplant may be associated with the underlying cause of a patient's end-stage renal disease (ESRD), according to new data presented here at the 31st annual meeting of the American Society for Bone and Mineral Research.

Fractures are common following renal transplantation. Studies suggest that certain patient and transplant characteristics are associated with higher risk for fracture.

These characteristics include race, older age, human leukocyte antigen (HLA) mismatches, organ rejection, deceased donor organs, and more aggressive induction of immunosuppression. The extent to which these factors may affect fracture risk in different ESRD patient populations is unknown, however.  

Investigators at Pennsylvania State University College of Medicine in Hershey retrospectively studied 49,494 patients who underwent renal transplantation between 1988 and 1998. Using data from the United States Renal Data System, the researchers grouped patients by their cause of disease: diabetes mellitus, hypertension, glomerulonephritis, and autosomal dominant polycystic kidney disease (PKD). They identified fractures that occurred in the first five years after transplantation.

Fractures occurred in 31.3% of patients with diabetes, 19.4% of patients with glomerulonephritis, 19.7% of patients with hypertension, and 23.3% of patients with PKD. Femoral fractures were most likely to occur in diabetic patients, while wrist fractures were most likely to occur in PKD patients. 

“We think it is important to look at the various risk factors,” said investigator Lucas Nikkel, a medical student. “We also looked at cold ischemia time, but that didn't appear to play a role.”

The rate of spine fractures was fairly consistent across each underlying condition. Female gender was associated with increased fracture risk regardless of the ESRD cause, especially among female subjects with PKD, who were at 63% increased risk.

Among transplant recipients with hypertension, glomerulonephritis, and PKD, those older than 65 years were about twice as likely to experience a fracture compared with those under age 45. Age was not a significant factor in fracture risk in patients with diabetes mellitus.

Co-investigator Edward Fox, MD, Associate Professor of Orthopedics, said these findings are clinically important because they encourage earlier osteoporosis intervention in certain ESRD patients where it may be needed the most. “Etiologic subtypes of end-stage renal disease have an increased frequency of fractures in specific locations,” said Dr. Fox, who presented study findings.

“This information may have an important impact on preventive fracture intervention in these subtypes of end-stage renal disease patients. For example, in a patient who has diabetes as their cause of end-stage renal disease and with neuropathy or proprioception loss, emphasis would be placed on balance and strength training to lessen the chance of a hip fragility fracture.”

The researchers also found that underweight patients with diabetes mellitus or glomerulonephritis had a significant 23% and 18% increased risk of fracture, respectively. Underweight patients with hypertension or PKD were not at increased risk.

Additionally, recipients with HLA mismatches were at 24% increased risk of fracture if they had glomerulonephritis, but not if they had diabetes, hypertension, or PKD.  Receiving a kidney from a deceased donor was associated with a 25%, 25%, and 51% increased risk of fracture among patients with diabetes, glomerulonephritis, and hypertension, respectively.

“The most important point is that diabetes is the largest factor when it comes to increased risk for fracture among end-stage renal disease patients who have had a transplant,” Nikkel said.

He noted that the study is strong because of its large cohort, but it has some limitations because the data are from the 1990s, and immunosuppressive regimens have improved.

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