Model Comparisons of Competing Risk and Recurrent Events for Graft Failure in Renal Transplant Recipients

Abstract

SummaryBackground 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. ConclusionThe 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.

The effect of delayed graft function on graft and patient survival in kidney transplantation: an approach using competing events analysis

“…In this study, application of a regression model for subdistribution hazard showed that DGF, alone and independent of AR, has a significant detrimental effect on long‐term graft survival but not on patient survival. Despite the common use in clinical cancer research, the estimation of CIF and the application of competing risks models in nephrology is relatively recent . To the best of our knowledge, this is the first study that used a competing risks approach to address the impact of DGF on graft and patient survival.…”

Association of age with risk of first and subsequent allograft failure and mortality among young kidney transplant recipients in the USA – a retrospective cohort study

“…Among 20 960 patients, 3850 (18%) patients received kidney transplants twice or more and up to five times 1638 (8) 1670 (8) 2185 102321 (11) 3778 (18) 3522 172858 (14) 2988 (14) Male (19) 186 (11) 270 (16) 375 (17) 425 (18) 720 (19) 743 (21) 609 (21) 566 (19) Other 2215 (11) 171 (10) 206 (12) 238 (11) 273 (12) 411 (11) 374 (11) 288 (10) 254 (9) Hispanic (%) 4728 (23) 287 (18) 381 (23) 478 (22) 551 (24) 915 (24) 855 (24) 636 (22) 625 (21) Medicaid (%) 140 (6) 212 9445 (12) 523 (15) 543 (19) 728 (24) FSGS 2523 1225 (2) 129 (8) 274 (13) 267 (12) 479 (13) 495 (14) 447 (16)…”

“…16 110 119 (1) 15 132 127 136 146 2Missing 3279 (16) 275 (17) 275 (16) 345 (16) 382 (16) 595 (16) 563 (16) 425 (15) 419 (14) Living donor (%) 14 (9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19) 13 (9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19) 14 (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21) 17 (11)(12)…”

“…Although these prior studies have consistently shown a high graft failure risk in adolescents, most results were obtained from only the first or second transplant, and no studies took into account repeated transplants and graft failures. Considering many children and young adults with end-stage renal disease (ESRD) require repeated kidney transplants in their lifetime [15], the risk for graft failure associated with adolescence needs to be assessed with consideration for repeated transplants and graft failures [16]. Moreover, there are scarce data on the association between age at transplantation and mortality.…”

Prediction scores for risk of allograft loss in patients receiving kidney transplants: nil satis nisi optimum

“…It would be more accurate to perform a risk analysis accounting for death as a competing event of graft failure. In competing risk analyses, smoking, systolic blood pressure and haemoglobin remained independent predictors of graft failure or doubling of creatinine (an endpoint indicating worsening of graft function) [ 9 , 25 ].…”