Differences in the size of the recipient and donor have been shown to influence kidney transplant outcomes. This difference in outcomes is postulated to be secondary to the individual’s kidney size and the number of nephrons, which is proportional to the overall size of the individual. The deficit in nephron endowment at the time of birth is permanent and does not change with the increase in demand later in life (1). There is no consensus on the anthropometric measure that best correlates with an individual’s kidney size and nephron mass. From a physiological standpoint, transplantation of a kidney with a smaller number of nephrons into a larger individual may cause the nephrons to undergo hypertrophy, hyperfiltration injury, and eventually, sclerosis, exhaustion, and fibrosis (1,2).

Size mismatch between the donor and the recipient has been studied based on differences in their weight, body mass index (BMI), and body surface area (BSA) as surrogates for kidney size and nephron mass (2,3). These studies have shown conflicting results on the effect of these discrepancies on kidney transplant outcomes. In a population based study conducted on transplant patients in the UK Transplant Registry, there was no difference in graft survival and higher mortality in patients receiving kidneys from donors with a higher weight and BMI (2). In contrast, another study from the Scientific Registry of Transplant Recipients (SRTR) based on discrepancies of BSA showed that those receiving organs from smaller sized donors based on their BSA had increased risk of graft loss, an effect that was modulated by the recipient and donor ages (3).

We hypothesized that adult height may be a more optimal measure of nephron mass in an individual. The reasons for this are 1) adult height has a strong association with birth weight and length, which are known predictors of nephron mass (4–6), 2) adult height is strongly correlated with the length of the kidney (7), 3) adult height is less prone to distortion by an individual’s lifestyle such as eating habits and physical activity, or by fluid balance in end stage renal disease (ESRD) patients, both of which may alter an individual’s weight and composite anthropometric measures such as BMI and BSA, and 4) adult height is less likely to change once an individual enters adulthood, unlike weight, BMI and BSA, which may show wide temporal fluctuations within a person’s lifespan.

This study aimed to determine whether height discrepancies in the donors and recipients predicted kidney transplant outcomes such as death censored graft survival, overall graft survival, patient survival, delayed graft function, and death with a functioning graft.

Size mismatch between the recipient and donor is known to influence transplant outcomes. However, the impact of height mismatch specifically is not known. In this analysis of a large database of deceased and living donor kidney transplant patients from SRTR, we found that height mismatch between the recipient and donor is an independent factor predicting kidney transplant outcomes.

Prior studies have evaluated size mismatch between the recipient and donor on the basis of body surface area (BSA), body mass index (BMI), and weight (2,3,8,9). These parameters have been used as surrogates for discrepancies in kidney size and/or nephron mass in the recipient-donor pair. We found that there is a poor correlation between an individual’s height and weight. At a given weight, there was a wide variation of heights in the population (Supplementary Figures S3, S4). Similarly, despite the derivation of BSA from height and weight of the individual, we only found a modest correlation of BSA with height (r = 0.69 for DD, r = 0.7 for LD), but a high correlation with weight (r = 0.98 for DD, r = 0.98 for LD).

Height discrepancy in the recipient-donor pairs has not been studied rigorously as a predictor of outcomes in kidney transplant patients without being included in a composite measure such as BSA or BMI. In a study done by Vinson et al, their risk prediction model showed a statistically significant lower hazard ratio with increasing donor-recipient height difference in DD transplants [0.726 (0.664–0.794)] (10). Our study had similar findings, with a more robust categorization of height discrepancies, and included DD and LD cohorts separately. Donor-recipient height ratios have also been included in a kidney graft survival calculator that showed a lower hazard ratio for a height ratio >1.06 [0.94 (0.91–0.98)] and a higher hazard ratio for a height ratio <0.94 [1.05 (1.02–1.09)] (11).

It is not clear from the literature which anthropometric measurement is the best surrogate for nephron mass. One of the predictors of nephron mass is birth weight and length (1,4–6), which has a strong association with adult height (12). It is well known that nephron endowment at the time of birth is final and any deficit due to pre-maturity exposes the individual to a higher likelihood of developing kidney disease during their lifetime, due to the increased demands placed on the lower number of nephrons. Although these do influence adult weight as well, it is prone to be modified by an individual’s lifestyle such as dietary habits and physical activity, and fluid balance. Higher weight has been shown to be associated with larger nephron size, but not necessarily with a higher number of nephrons (4). A larger nephron size may be a reflection of increased metabolic demand on a limited number of nephrons. Higher recipient BMI has been shown to be associated with increased morbidity and graft loss after kidney transplantation (13,14).

In their population based study from the UK Transplant Registry, Arshad et al did not find any differences in DGF or DCGL due to donor-recipient weight differences but they did find increased mortality in patients receiving kidneys from donors whose weights were over 25% of recipient weight (2). Miller et al found that a concurrent mismatch in donor-recipient weight and donor-recipient sex was associated with a higher risk of DCGL (8). This finding could be secondary to a higher weight in the donor being a reflection of other co-morbidities that accompany obesity such as diabetes mellitus and hypertension. In addition, obesity could lead to hyperfiltration injury in the donor kidney that would likely not be the case in non-obese donors. Lepeytre et al reported that the effect of donor-recipient size mismatch based on their BSA on long-term transplant outcomes is modulated by the recipient and donor age in their population based study from SRTR (3). This is not surprising as a serial decline in the number of nephrons with age parallels the progressive decline in glomerular filtration rate with age (4,15,16). Instead of using a composite measure such as BSA or BMI in prior studies, we evaluated the individual components of these measures to reconcile the discrepant results in prior studies.

Gender differences are also an important factor to consider when assessing size mismatch (8,9,17,18). We found that the influence of height discrepancies persisted within different combinations of donor-recipient genders in a predictable pattern just as in the overall cohort of DD and LD transplants. In subgroups that contained a large number of patients, the trends were statistically significant. However, we suspect some categories failed to show statistical significance due to the relatively fewer number of patients in the category. Regardless, the trends show that Recipient < Donor have better outcomes and Recipient > Donor have poorer outcomes compared to the Recipient = Donor group (Figure 7). Inclusion of height differences to a model including gender pair differences improved the model fit for DCGL and mortality but the interaction effect was not significant, suggesting that the height differences do not impact the outcomes differently among those with different donor-recipient gender combinations.

Our study has several strengths. It is based on a large database of transplant populations from SRTR in the modern era of tacrolimus-based maintenance immunosuppression and transplant care. Our study utilizes height as an anthropometric measure to assess size mismatch, which likely correlates best with nephron mass and is less likely to be influenced by an individual’s lifestyle choices. The use of height mismatch is also simpler to use compared to other composite anthropometric measures such as BMI and BSA. Although donor height is incorporated into the allocation system as a part of the KDPI score, height mismatch between the donor-recipient pair may be a more important factor to consider in terms of transplant outcomes. Our study also incorporates analyses of multiple models with interactions between donor-recipient height differences and differences in weight and gender to determine the differential impact of these co-occurring donor-recipient mismatches.

The results of this population-based study must be interpreted within the limitations of the design of these studies. While we made efforts to minimize bias by incorporating multiple covariates that could influence transplant outcomes, it is not possible to include all the variables. We acknowledge that there could be residual confounding resulting from variables that could not be incorporated into our analysis. We could not assess the degree of proteinuria in the patients in the different subgroups as this information was not available in the database. This would have allowed us to see the impact of height mismatch on downstream physiologic effects such as progressive glomerular sclerosis and resultant urinary protein excretion. The results of our study are based on data from the US population and may not be generalizable to other populations.

In conclusion, our study finds that transplantation of kidneys from individuals of shorter stature into taller recipients leads to worse transplant outcomes. This effect appeared more pronounced in deceased donors than in living donors. This information may be used while counseling living donors and their recipients that height mismatch may not have a major influence in determining post-transplant outcomes, especially when multiple donors are available. The quality of a living donor kidney and recipient comorbidities likely supersede the influence of height mismatch in living donor transplantation. Size mismatch in the donor-recipient pair based on discrepancies in their heights may be more reliable compared to other anthropometric measures in determining post-transplant outcomes.