The theoretical number of functional nephrons transplanted is increasingly being considered as an important non-immunological determinant of long-term allograft function. Anthropomorphic measures such as BMI and BSA have been used in large registry data analyses as estimates of donor nephron mass (8
). In a study of over 1000 deceased-donor kidney transplants, Giral et al. (14
) have shown that a donor kidney weight to recipient weight less than 2.3 g/kg was associated with a 55% increased risk for allograft failure at 2 years. They also showed that recipients with a lower donor kidney weight to recipient body weight ratio had an increased risk of developing proteinuria, hypertension, and glomerulosclerosis. This pattern of injury is consistent with the well-described “remnant kidney” phenomenon in rats, in which removal of 5/6th of the total kidney mass leads to a progressive sclerosing glomerulopathy (15
). Although the results of Giral et al. provide support for a similar process in humans, translation of these results to donor selection in clinical kidney transplantation is limited by the relatively poor performance of existing surrogates for cortical volume and functional nephron number/mass. The poorer the correlation between any proxy and the true nephron mass (e.g., what might be learned from a large wedge biopsy), the more likely there will be misclassification and thus poorer discrimination when evaluating the association between the “nephron dose” and the eventual performance of the allograft.
Among noninvasive measurements of the kidney in a potential donor, cortical volume would be the best measure of functional nephron mass. Recent improvements in radiologic imaging techniques allow for accurate determination of cortical volume before organ retrieval. We showed in this study that correlations among cortical volume and height, weight, and BMI were relatively poor. Of the existing surrogate measures, BSA had the highest correlation with cortical (R2
= 0.29) and kidney volumes (R2
= 0.37). Other common assumptions of kidney size were tested and quantified. For example, the majority of subjects had symmetric kidney volumes, with 90.7% of the population having right and left kidney volumes that differed less than 10%. Although the assumption of equivalent size implicit in studies using mate-kidney data of transplant registries is reasonable, the cohort in this study represents a healthy segment of the population; a larger degree of asymmetry may exist in the general population. We also showed that men have larger cortical volumes than women (224 ± 37 mL vs. 189 ± 37 mL; t
< 0.001). Our results are consistent with autopsy studies, which have shown that women have 15% fewer glomeruli than males, and similarly, kidney weighs 16% lower (1
). Larger cortical volumes in men could not be entirely attributed to their larger body size. In contrast to previous studies, we did not find a significant correlation between cortical or total kidney volume and age. In general, kidney volume and functional nephron mass are expected to decline with advancing age; however, the process of donor selection may have restricted our older donor sample to only the most robust.
The range of cortical volume in this population was large (105–355 mL), representing a threefold difference. This range is smaller than the reported fourfold to ninefold range of nephron number in autopsy studies of normal humans (1
). Again, the narrower range may be due to the selection process of living kidney donors, as those with lower glomerular filtration rates would not have proceeded to this final stage of living donor image studies. Yet, even in this selected population of subjects, the range of nephron mass, as estimated by cortical volume, was large enough for the “remnant kidney” phenomenon to be plausible. For example, transplantation of a single kidney from the smallest individual (44 mL) to the largest individual (with native two-kidney cortical volumes of 355 mL) would be physiologically similar to the loss of more than 5/6th of original nephron mass. In recipients of living donor kidneys, higher allograft weight/recipient body weight (16
) and higher donor kidney volume/recipient BSA (5
) have been shown to correlate with better outcomes after transplantation.
This study has several strengths. First, the sample was relatively large, with broad racial/ethnic diversity, including a large fraction of donors of minority backgrounds. To our knowledge, it is the largest series of cortical volumes reported to date. Second, we measured cortical volumes in addition to total kidney volumes and used 3-dimensional (3D) reconstruction algorithms that have been validated in animal models. Previous autopsy reports demonstrated a direct correlation between BSA and kidney weight, but sample sizes for these studies were small (n = 39 and 78) (1
). Their measurements also differed from ours in that total kidney weight (which contains the medulla and ureter in addition to cortex) was used for analysis, and it was assessed ex vivo. A recent study using radiologic imaging focused on total kidney volume and approximated the kidney to be a prolate ellipsoid to estimate the volume (5
). Finally, in developing models to predict cortical and total kidney volume from routinely collected demographic and anthropometric data, we used traditional least squares regression techniques, along with other techniques that may offer better discrimination in the face of biological variability. Although we toiled diligently and creatively to derive an equation that might serve as a better surrogate of cortical volume, our best model showed a marginal improvement in its predictive power compared with the widely used BSA. Future studies using larger samples with greater variability in age, weight, and height might lead us toward a better method for estimating functional nephron mass. It is also noteworthy that BMI, which has been frequently used in studies as a proxy for body size, is a poor surrogate for cortical volume.
There are several limitations to this study. There were no septuagenarians or octogenarians in our donor pool. Thus, although we cannot extrapolate our results to elderly prospective donors, the data derived in this study are reasonably representative of the living donor population. Whether extrapolation of these findings to donors is valid is unknown. Although we believe that cortical volume may be the best proxy of functional nephron mass among healthy donors, we cannot be certain that intact cortex accurately represents functional tissue among the deceased donor population.
In summary, we examined a large cohort of living kidney donors using MRA or CTA to measure cortical and total kidney volume as a proxy for functional nephron mass. We found a high degree of symmetry between right and left kidneys and confirmed the expected associations among sex and body size and the volume parameters. Using multiple analytic techniques, we constructed equations to predict cortical and total kidney volumes from routinely collected demographic and anthropometric data. Although we were able to identify models with better predictive power, we concluded that the improvement was not substantial enough to recommend replacing BSA given its simplicity for practical application. At least among selected living donors, BSA seems to be a reasonably good proxy of functional nephron mass. Conducting a similar exercise among less selected populations more reflective of the deceased donor pool would be a logical next step. A better understanding of the role of the transplanted nephron mass and how best to measure it will be required to optimize organ allocation and maximize allograft survival under conditions of organ scarcity.