Our objectives are to characterize the epidemiology and pathophysiology of chronic renal insufficiency (CRI) after hematopoietic stem cell transplantation (HSCT); to identify early markers of renal injury; and to devise strategies to lessen the burden of kidney disease in this population. To do this, we will utilize the massive patient database at the Fred Hutchinson Cancer Research Center (FHCRC). Over, 10,000 patients have undergone marrow or peripheral blood stem cell transplantation at this institution. Each year approximately 400 new HSCTs are performed. The Long-Term Follow-Up Unit (LTFU) at the Center has a well-developed tracking system and only 1.5% of long-term survivors have been lost to follow-up.
Specific Aim 1 will test the hypothesis that a thrombotic microangiopathic process initiates the development of CRI after HSCT. Markers of coagulation activation, PAl-1, t-PA, Fragment 1+2 and D-dimer will be measured prospectively on patients from the time of transplant to 1 year post-HSCT. Primary analyses will utilize Cox proportional hazards regression to assess whether levels of these markers affect the risk of developing CRI.
Specific Aim 2 will identify risk factors for the development of CRI after HSCT. Using univariable and multivariable Cox regression models, acute renal insufficiency, age, conditioning regimen, typeof transplant, graft vs. host disease, nephrotoxic medications, and serum creatinine at time of transplant will be analysed as risk factors for the development of CRI in a cohort of 3334 patients transplanted at FHCRC since 1990.
Specific Aim 3 will identify risk factors for progression and determine the natural history of CRI after HSCT. We will follow a subset of 826 patients transplanted since 1990 who developed BMT nephropathy forward in time and examine risk factors for progression of renal dysfunction such as hypertension, graft vs. host disease and cyclopsorine use using Cox regression modeling.
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