BACKGROUND AND OBJECTIVES: Risk factor analysis of long-term graft survival in kidney transplant recipients is usually based on Cox regression models of time to first occurrence of doubling of serum creatinine or graft loss (DSCGL). However, death is a competing cause of failure, and censoring patients who die could bias estimates. We therefore compared estimates of time to first event versus estimates that included death as a competing risk and recurrent events. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A Cox regression analysis of 1997-2002 data from the Assessment of Lescol in Renal Transplant (ALERT) trial population identified an eight-factor risk model, by analyzing time to first occurrence of DSCGL. The same factors were re-analyzed, allowing for death as competing. The probability of survival free of DSCGL was estimated; and two recurrent models (marginal and conditional) were used for time to events. RESULTS: Creatinine, systolic BP, and HLA-DR mismatches lost 33%-46% of their strength of association with DSCGL when death was included as a competing risk. Small changes were observed if recurrent events were analyzed in the marginal model. CONCLUSION: The relationship between serum creatinine and DSCGL was attenuated when death was considered as a competing risk; inclusion of recurrent events had little effect. These findings have important implications for analysis and trial design in populations at high mortality risk.
BACKGROUND AND OBJECTIVES: Risk factor analysis of long-term graft survival in kidney transplant recipients is usually based on Cox regression models of time to first occurrence of doubling of serum creatinine or graft loss (DSCGL). However, death is a competing cause of failure, and censoring patients who die could bias estimates. We therefore compared estimates of time to first event versus estimates that included death as a competing risk and recurrent events. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A Cox regression analysis of 1997-2002 data from the Assessment of Lescol in Renal Transplant (ALERT) trial population identified an eight-factor risk model, by analyzing time to first occurrence of DSCGL. The same factors were re-analyzed, allowing for death as competing. The probability of survival free of DSCGL was estimated; and two recurrent models (marginal and conditional) were used for time to events. RESULTS:Creatinine, systolic BP, and HLA-DR mismatches lost 33%-46% of their strength of association with DSCGL when death was included as a competing risk. Small changes were observed if recurrent events were analyzed in the marginal model. CONCLUSION: The relationship between serum creatinine and DSCGL was attenuated when death was considered as a competing risk; inclusion of recurrent events had little effect. These findings have important implications for analysis and trial design in populations at high mortality risk.
Authors: Manuel Pascual; Tom Theruvath; Tatsuo Kawai; Nina Tolkoff-Rubin; A Benedict Cosimi Journal: N Engl J Med Date: 2002-02-21 Impact factor: 91.245
Authors: Shani Shastri; Navdeep Tangri; Hocine Tighiouart; Gerald J Beck; Panagiotis Vlagopoulos; Daniel Ornt; Garabed Eknoyan; John W Kusek; Charles Herzog; Alfred K Cheung; Mark J Sarnak Journal: Clin J Am Soc Nephrol Date: 2011-11-10 Impact factor: 8.237
Authors: H Holdaas; B Fellström; E Cole; G Nyberg; A G Olsson; T R Pedersen; S Madsen; C Grönhagen-Riska; H-H Neumayer; B Maes; P Ambühl; A Hartmann; B Staffler; A G Jardine Journal: Am J Transplant Date: 2005-12 Impact factor: 8.086
Authors: Elke S Schaeffner; Manuela Födinger; Reinhard Kramar; Ulrich Frei; Walter H Hörl; Gere Sunder-Plassmann; Wolfgang C Winkelmayer Journal: Am J Kidney Dis Date: 2006-03 Impact factor: 8.860
Authors: Hallvard Holdaas; Bengt Fellström; Alan G Jardine; Ingar Holme; Gudrun Nyberg; Per Fauchald; Carola Grönhagen-Riska; Søren Madsen; Hans-Hellmut Neumayer; Edward Cole; Bart Maes; Patrice Ambühl; Anders G Olsson; Anders Hartmann; Dag O Solbu; Terje R Pedersen Journal: Lancet Date: 2003-06-14 Impact factor: 79.321
Authors: Stephanie A Mason; Avery B Nathens; James P Byrne; Alejandro Gonzalez; Rob Fowler; Paul J Karanicolas; Rahim Moineddin; Marc G Jeschke Journal: J Trauma Acute Care Surg Date: 2017-11 Impact factor: 3.313