Patient years lost due to cytomegalovirus serostatus mismatching in the scientific registry of transplant recipients

Abstract

Background: The cytomegalovirus (CMV) mismatch rate in deceased donor kidney transplant (DDKT) recipients in the US remains above 40%. Since CMV mismatching is common in DDKT recipients, the cumulative effects may be significant in the context of overall patient and graft survival. Our primary objective was to describe the short- and long-term risks associated with high-risk CMV donor positive/recipient negative (D+/R-) mismatching among DDKT recipients with the explicit goal of deriving a mathematical mismatching penalty.

Methods: We conducted a retrospective, secondary analysis of the Scientific Registry of Transplant Recipients (SRTR) database using donor-matched DDKT recipient pairs (N=105,608) transplanted between 2011-2022. All-cause mortality and graft failure hazard ratios were calculated from one year to ten years post-DDKT. All-cause graft failure included death events. Survival curves were calculated using the Kaplan-Meier estimation at 10 years post-DDKT and extrapolated to 20 years to provide the average graft days lost (aGDL) and average patient days lost (aPDL) due to CMV D+/R- serostatus mismatching. We also performed an age-based stratification analysis to compare the relative risk of CMV D+ mismatching by age.

Results: Among 31,518 CMV D+/R- recipients, at 1 year post-DDKT, the relative risk of death increased by 29% (p<0.001), and graft failure increased by 17% (p<0.001) as compared to matched CMV D+/R+ group (N=31,518). Age stratification demonstrated a significant increase in the risk associated with CMV mismatching in patients 40 years of age and greater. The aGDL per patient due to mismatching was 125 days and the aPDL per patient was 100 days.

Conclusion: The risks of CMV D+/R- mismatching are seen both at 1 year post-DDKT period and accumulated throughout the lifespan of the patient, with the average CMV D+/R- recipient losing more than three months of post-DDKT survival time. CMV D+/R- mismatching poses a more significant risk and a greater health burden than previously reported, thus obviating the need for better preventive strategies including CMV serodirected organ allocation to prolong lifespans and graft survival in high-risk patients.

Keywords: CMV; graft; kidney; serostatus; survival; transplant.

Figure 1

Graphical abstract of paired-deceased donor kidney CMV mismatch study design. This graphical abstract illustrates our study design (left panel) and the main outcomes (right panel). Here we illustrate our donor-paired kidney analysis, where we matched 31,518 CMV donor-positive (CMV D+) recipient pairs and 21,286 CMV donor-negative (CMV D-) recipient pairs. Risk ratios and survival curves were independently calculated for each CMV donor positive/recipient positive (CMV D+/R+) and CMV donor negative/recipient negative (CMV D-/R-) cohort from 1 year post-deceased donor kidney transplant (DDKT) to 10 years post-DDKT. CMV, cytomegalovirus; SRTR, Scientific Registry of Transplant Recipients.

Figure 2

1 year post-transplant mortality hazard ratios for CMV donor-matched recipients. Here we provide adjusted hazard ratio forest plots, comparing the all-cause mortality of the two donor-positive groups, CMV donor positive/recipient negative [CMV D+/R-] group versus the CMV donor positive/recipient positive [CMV D+/R+] (reference). The hazard ratios for the eight risk covariates are provided. The p-value notation is as follows: p < 0.05 *, p < 0.01 **, p < 0.001 ***.

Figure 3

1 year post-transplant graft failure hazard ratios for CMV seropositive donor-matched recipients. Here we provide hazard ratio forest plots, comparing all-cause graft failure in the two donor-positive groups, CMV D+/R- and CMV D+/R+ (reference). The hazard ratios for the eight risk covariates are provided. The p-value notation is as follows: p < 0.05 *, p < 0.01 **, p < 0.001 ***.

Figure 4

1 year post-transplant mortality hazard ratios for middle-aged CMV seropositive donors-matched recipients. Here we provide hazard ratio forest plots, comparing the mortality of the two middle-aged donor-positive groups. Middle-aged recipients were grouped according to their age at the time of transplant (41-64 years). The p-value notation is as follows: p < 0.05 *, p < 0.01 **, p < 0.001 ***.

Figure 5

1 year post-transplant mortality hazard ratios for older CMV seropositive donors-matched recipients. Here we provide hazard ratio forest plots, comparing the mortality of the two older donor-positive groups. Older recipients were grouped according to their age at the time of transplant (≥ 65 years). The p-value notation is as follows: p < 0.05 *, p < 0.01 **, p < 0.001 ***.

Figure 6

Estimated graft and patient days lost due to CMV donor-positive mismatching. This graph provides the average graft days lost (aGDL/patient) and average patient days lost (aPDL/patient) due to CMV mismatching for CMV donor-positive/recipient-negative (CMV D+/R-) mismatched DDKT recipients. All values from 1 to 10 years were calculated by subtracting the area under the CMV D+/R- Kaplan-Meier (KM) curve from the area under the CMV D+/R+ KM curve. Using parametric survival regression, we extrapolated the KM curves to 20 years and calculated the average graft days lost (orange) and average patient days lost (red). Graft Days Lost (GDL); Patient Days Lost (PDL).