Death With Function and Graft Failure After Kidney Transplantation: Risk Factors at Baseline Suggest New Approaches to Management

Abstract

Background: Improving both patient and graft survival after kidney transplantation are major unmet needs. The goal of this study was to assess risk factors for specific causes of graft loss to determine to what extent patients who develop either death with a functioning graft (DWFG) or graft failure (GF) have similar baseline risk factors for graft loss.

Methods: We retrospectively studied all solitary renal transplants performed between January 1, 2006, and December 31, 2018, at 3 centers and determined the specific causes of DWFG and GF. We examined outcomes in different subgroups using competing risk estimates and cause-specific Cox models.

Results: Of the 5752 kidney transplants, graft loss occurred in 21.6% (1244) patients, including 12.0% (691) DWFG and 9.6% (553) GF. DWFG was most commonly due to malignancy (20.0%), infection (19.7%), cardiac disease (12.6%) with risk factors of older age and pretransplant dialysis, and diabetes as the cause of renal failure. For GF, alloimmunity (38.7%), glomerular diseases (18.6%), and tubular injury (13.9%) were the major causes. Competing risk incidence models identified diabetes and older recipients with higher rates of both DWFG and nonalloimmune GF.

Conclusions: These data suggest that at baseline, 2 distinct populations can be identified who are at high risk for renal allograft loss: a younger, nondiabetic patient group who develops GF due to alloimmunity and an older, more commonly diabetic population who develops DWFG and GF due to a mixture of causes-many nonalloimmune. Individualized management is needed to improve long-term renal allograft survival in the latter group.

FIGURE 1.

Multivariable analysis for DWFG. Other induction is comparing alemtuzumab vs Thymoglobulin and anti-CD25. Anti-CD25 induction use mostly was basiliximab, and only 2 patients used daclizumab. Diabetes is defined as diabetes mellitus as a cause pretransplant of ESRD. Adjusted for recipient age (10 y), sex, deceased donor, period of transplant, induction, dialysis pretransplant, prednisone therapy, delayed graft functioning, diabetes mellitus as a cause pretransplant of ESRD, and transplant site (Table S10, SDC, http://links.lww.com/TXD/A398). Risk factors for DWFG are increased age, male sex, pretransplant dialysis, and diabetes mellitus as the cause of renal failure and use of prednisone. cPRA, calculated panel reactive antibody; DGF, delayed graft functioning; DWFG, death with a functioning graft; ESRD, end-stage renal disease.

FIGURE 2.

Multivariable analysis for GF (not due to death). Other induction is comparing alemtuzumab vs Thymoglobulin and anti-CD25. Anti-CD25 induction use mostly was basiliximab, and only 2 patients used daclizumab. The use of diabetes is defined as diabetes mellitus as a cause pretransplant of ESRD. Adjusted for age (10 y), deceased donor, HLA A, B mismatch, HLA DR mismatch, induction, dialysis pretransplant, prednisone therapy, prior kidney transplant, donor race, recipient race, delayed graft functioning, diabetes mellitus as a cause pretransplant of ESRD, and transplant site (Table S7, SDC, http://links.lww.com/TXD/A398). Risk factors for GF are increased younger age, prior kidney transplant, pretransplant dialysis, African-American donor and recipient, diabetes mellitus as the cause of renal failure, and HLA DR mismatch. cPRA, calculated panel reactive antibody; DGF, delayed graft functioning; ESRD, end-stage renal disease; GF, graft failure.

FIGURE 3.

Overlap of risk scores for either DWFG or GF patients at baseline in patients who developed graft loss. In patients who develop either DWFG or GF, we generated risk scores for each outcome based on factors present at the time of transplantation. A, Scatter plot of the linear predictor from cause-specific Cox regression models for GF showing high-risk scores (earlier the overall mean) in many patients. A red circle indicates the patient who actually developed GF, and a black circle indicates the  patient who actually developed DWFG. Each quadrant percentage for GF is displayed to represent the different causes of graft loss. BK, polyoma virus; DWFG, death with a functioning graft; GF, graft failure.

FIGURE 4.

Competing risk cumulative incidences of GF and DWFG. A, Overall graft loss, GF, and DWFG. DWFG is more common over time than GF (P = 0.006). B, Incidence curves for each type of GF. Alloimmune causes are more common than all other causes (P < 0.001 comparing restricted mean survival). C, GF and DWFG for recipients <55 y old vs >55 y old. GF is higher in younger group (P < 0.001), and DWFG is higher in older recipients (P < 0.001). D, GF and DWFG in recipients stratified by diabetes as the cause of ESRD. DWFG is more common in diabetics (P < 0.001), whereas GF is similar in diabetics and nondiabetics (P = 0.071). E, GF due to alloimmune and nonalloimmune causes for recipients <55 vs >55. Younger patients have higher rates of GF due to alloimmune causes (P < 0.001); GF due to nonalloimmune causes are similar. F, GF from alloimmune and nonalloimmune causes stratified by diabetes as the cause of ESRD. Diabetics have higher rates of nonalloimmune GF (P = 0.002) but similar rates of alloimmune GF. BK, polyoma virus; DWFG, death with a functioning graft; ESRD, end-stage renal disease; GF, graft failure.