Correcting the Sex Disparity in MELD-na

Nicholas L. Wood; Douglas VanDerwerken; Dorry L. Segev; Sommer E. Gentry

Disclosures

American Journal of Transplantation. 2021;21(10):3296-3304. 

In This Article

Methods

Data Source

This study used data from the Scientific Registry of Transplant Recipients (SRTR). The SRTR data system includes data on all donor, wait-listed candidates, and transplant recipients in the United States, submitted by the members of the Organ Procurement and Transplantation Network (OPTN). The Health Resources and Services Administration (HRSA), U.S. Department of Health and Human Services provides oversight of the activities of the OPTN and SRTR contractors. This dataset has previously been described elsewhere.[21]

Study Population

For the transplant-censored survival analysis, we studied all adult liver transplant candidates on the waitlist from January 1, 2003 to January 1, 2019. We excluded candidates who received an exception score or status 1A. For each candidate, status updates missing values required for the calculation of MELD-Na or any of the MELD-Na corrections were imputed with the values from the candidate's previous status update if available, otherwise they were removed. For the simulated allocation modeling, we used the SRTR's LSAM, using data on all liver transplant candidates and recovered deceased donor livers from July 1, 2011 to June 30, 2016.

Survival Analysis

Kaplan-Meier analysis gives a nonparametric estimate of the probability of survival up to any given time, given a dataset of independent censored survival times. We recently described a framework for performing Kaplan-Meier survival analysis which utilizes MELD-Na throughout a candidate's history on the waitlist as opposed to MELD-Na at listing alone.[22] We computed bias-corrected[23] Kaplan-Meier estimates of the 90-day without-transplant survival by MELD-Na. Because transplants tend to go to candidates at high MELD-Na, censoring by transplant introduces bias in survival estimation. We corrected for this using inverse probability censoring weights, like what was described in Robbins and Finkelstein[23] (see the Appendix for more details).

For each MELD-Na score, we found all candidates who ever had that score during our study period. If a candidate had multiple updates at the same MELD-Na, the first update was selected, such that the model estimates the probability of surviving 90 days without a transplant since first arriving at a certain MELD-Na. The time from that update to an event—either death or censoring—was recorded. Candidates with removal code 8 ("Died"), 5 ("Medically unsuitable"), or 13 ("Candidate condition deteriorated, too sick for transplant") were counted as death, unless the cause of death was suicide, which we treated as censoring. All other candidates were censored, either by transplant, by the conclusion of the study period, or by waitlist removal for any other reason.

MELD-Na Corrections

We investigated three changes to MELD-Na as possible corrections for the sex bias we found in without-transplant survival. For MELD-Na and each correction, we calculated the 90-day without-transplant survival for men and compared it that for women. The distribution of MELD-Na (and each correction) was assessed for our study population based on the candidate's score at listing.

MELD-Na-MDRD. The first correction involved adjusting female serum creatinine based on the modification of diet in renal disease (MDRD) formula for eGFR as others have done.[5,7,18] Because age and race are not directly accounted for, the adjustment simplifies to approximately 1.295 times each woman's serum creatinine. The adjusted serum creatinine was constrained to the usual bounds of a minimum of 1.0 and a maximum of 4.0 mg/dl, and the current coefficients of MELD-Na were applied without refitting. Policy additionally dictates that a candidate who received two or more dialysis treatments in the prior 7 days, or who received 24 h of continuous veno-venous hemodialysis within the prior 7 days, is assigned a serum creatinine of 4.0 mg/dl for the purpose of calculating MELD-Na. For such a candidate, we left her serum creatinine at 4.0 mg/dl.

MELD-GRAIL-Na. The second correction involved using MELD-GRAIL-Na, a recently proposed modification to MELD-Na that replaces serum creatinine with eGFR via the glomerular filtration rate in liver disease (GRAIL) formula.[19] GRAIL takes into account serum creatinine, age, sex, race, albumin, and blood urea nitrogen.[20] MELD-GRAIL-Na was scaled to a minimum of 6 and a maximum of 50 and then capped at 40.

MELD-Na-Shift. The final correction involved shifting female MELD-Na to the corresponding male MELD-Na that equalized 90-day without-transplant survival. For example, we found that women at MELD-Na of 25 had a 90-day without-transplant survival rate of 0.740, whereas men at the same MELD-Na had a survival rate of 0.766. The MELD-Na at which men had a 90-day without-transplant survival rate closest to 0.740 was 26, where their survival rate was 0.725. Therefore we shifted the MELD-Na of women at MELD-Na of 25–26.

Simulating MELD-Na Corrections in LSAM

We used LSAM to simulate the effect of our MELD-Na corrections for liver allocation on outcomes for men and women on the liver waitlist. We ran 10 iterations of the acuity circles allocation system from July 1, 2013 to June 30, 2016, first with MELD-Na and then with each of the three MELD-Na corrections. The LSAM input files were adjusted as follows. For each correction, we calculated a corrected score for every candidate older than 12 throughout the simulation. The corrected score was then used as the match MELD for each candidate, unless the candidate had an exception with an exception score higher than the corrected score, in which case the exception score was retained as the match MELD. Output metrics were calculated for adult candidates only, and differences in output metrics were evaluated using the matched-pairs t test.

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