This study embarked on a critical evaluation of CT-derived kidney length and volume measurements in the context of identifying asymmetric kidney function (AKF) among prospective living kidney donors, a group for whom accurate and non-invasive screening methods are paramount. Despite the potential of CT metrics to streamline donor evaluation by negating the need for radionuclide imaging, they must be highly sensitive to avoid false negative results and potential harm to donors [9, 10]. . Unfortunately, our findings cast doubt on their reliability and predictive value. The observed sensitivity and specificity of these measurements suggest a significant shortfall with existing guidelines recommending differential function assessment primarily based on anatomical discrepancies. The assumption that CT-derived measurements alone can suffice for donor screening, which underlies current practice and guidelines in screening living kidney donors, merits reconsideration.
Bipolar kidney lengths
Our results demonstrate an apparent inadequacy in the value of kidney length discrepancy for detecting AKF in living kidney donor assessments. The alarmingly low sensitivities (0% for > 2 cm and only 28% for > 10% differences), alongside prohibitively high false negative rates, sharply question the reliability of such measurements. Indeed, with a 100% false negative rate for a > 2 cm discrepancy and 72% for a > 10% discrepancy, reliance on these metrics to exclude AKF is flawed. Consequently, this study suggests the use of kidney length differentials as a standalone criterion for the decision-making process needs to be reconsidered.
Echoing our findings, Akoh et al. [6] noted a modest but statistically significant correlation (r = 0.333, P = 0.005) between renal lengths measured by ultrasound and split renal function determined by MAG3 scans. Their study also uncovered cases where a longer kidney corresponded with reduced function, further complicating the assumption that larger kidney size equates to superior function. These parallel findings reinforce the notion that kidney length, whether assessed by CT or ultrasound, is an unreliable surrogate for functional assessment in prospective kidney donors.
Kidney and cortical volumes
The assessment of kidney and cortical volumes offers a more promising sensitivity in detecting AKF, with observed rates of 80% for kidney volumes and 88% for cortical volumes when discrepancies exceed 10%. Despite these relatively high sensitivities, the attendant false negative rates—20% for kidney volumes and 12% for cortical volumes—suggest their standalone utility as screening tools remains questionable. These rates imply that a notable minority of potential donors with significant AKF could be erroneously cleared for donation should we rely solely on these CT volumetric measurements.
A recent retrospective cohort study by Montgomery et al found a weak correlation between their split [radionuclide] scan ratio and cortical volume ratio (ρ = 0.361) despite showing a moderate correlation between the cortical volume ratio and the post-donation eGFR [11]. Another retrospective study by Gardan et al also showed a weak to moderate correlation between cortical volume and pre-donation split renal function (r = 0.35–0.48) [12].
Due to a range of correlation values yielded from different retrospective studies, a meta-analysis by Habbous et al [5] pooled the Pearson correlation coefficients from 19 studies (n = 1479). The meta-analysis suggested a significant correlation between CT-derived split renal volume and radionuclide scan measurements of split renal function (r = 0.74, CI 0.61–0.82) and both measurements reliably predicted post-donation eGFR at 12 months (r = 0.75 and 0.73 respectively). However, as part of the same paper and in addition to the meta-analysis, Habbous et al performed their own retrospective cohort study of 115 kidney donors and found weak correlations between kidney volume, kidney length and pre-donation split renal function (r = 0.22 and 0.24 respectively), which directly contradicts the findings of the meta-analysis section of the same paper [5]. To explain this, the paper is clear that there is very substantial heterogeneity across the included studies (I2 = 94%, p < 0.0001). This suggests that the correlation achieved between renal volume and split renal function as measured by radionuclide imaging is highly centre-dependent. Furthermore, only 7 studies in the meta-analysis identified a difference in split renal function of > 10%. On analysis of these 7 studies, the pooled positive predictive value of CT-derived renal volume was comparable to our study at 40% as was their negative predictive value of 86%. The sensitivity was 35% and specificity was 88%. Therefore, the meta-analysis concludes that, while a correlation between renal volume and split renal function may exist, this observed correlation is highly centre-dependent. They advocate for future prospective studies to answer the question of whether CT-derived metrics can be reliable and reproducible. The current variability between centres makes CT-derived metrics an unreliable proxy for split renal function. This supports our conclusion that CT volumetry, although informative, cannot singularly determine AKF with the requisite accuracy in screening prospective donors.
These findings highlight our current limited understanding and the need for a cautious approach when considering CT volumetric data in the preoperative evaluation of living kidney donors.
Split renal function and clinical outcomes
This study attempts to answer the question of whether CT-derived metrics can accurately predict split renal function. It logically follows to then ask if a difference in split renal function of > 10% actually leads to clinically relevant difference in donor outcomes. Our analysis did not collect post-donation eGFR results in donors or recipients and future studies should aim to address the question of whether a difference in split renal function of > 10% has clinical significance. Crucial evidence has already been presented by Seo et al [13] who performed a retrospective cohort study of 217 living kidney transplant cases where the donors underwent radionuclide imaging with both recipients and donors undergoing 12 month follow-up to assess the change in eGFR. Interestingly, there was no association between the recipient’s eGFR (at 12 months post-donation) and whether they received the higher or lesser functioning kidney. However, donors in the study who donated the higher functioning kidney did have poorer renal function at 12 months, despite the fact that no donor had a difference in split renal function of > 10%. This suggests that there are clinical implications for the donor when the better functioning kidney is removed and further studies are required to confirm this finding.
Significance of study
Our study contributes to the existing literature in two primary ways. Firstly, it joins the other published study where prospective kidney donors are uniformly subjected to CT and functional renal imaging. All other published studies have eligibility criteria for functional imaging, or their study population was less than 30 [6, 14,15,16,17,18,19]. Our approach mitigates the possible selection bias prevalent in other studies. The comparable study corroborates our findings, demonstrating a similarly weak correlation between kidney volume and function, thus reinforcing the need for a more reliable diagnostic tool [16].
Secondly, we have evaluated the sensitivity and specificity of UK guidelines for pre-donation renal imaging. Our analysis reveals that the current guidelines may not accurately identify candidates who require functional renal imaging. This data helps inform future guideline development to ensure that all prospective donors are assessed for differential renal function, which we suggest is incompletely described by kidney size measurements. The current study provides evidence that split renal function assessment be a standard part of the evaluation for all potential kidney donors to safeguard against inadvertent harm and align donor selection processes with the best evidence available.
Limitations
A notable limitation is the exclusion of patients who underwent DMSA scanning but not CT imaging. At our centre, both tests are completed for all patients, but this is not the case at other centres. This exclusion could introduce a selection bias, as potential contraindications for donation might preclude the necessity of CT imaging, leading to a study cohort that may not fully represent the broader population of prospective donors. Consequently, our findings might not be generalisable to all individuals undergoing initial screening.
Furthermore, the kidney volume assessments were conducted by a single operator, introducing the possibility of observer bias. However, to mitigate this risk and enhance the reliability of our measurements, a senior radiologist performed a thorough double-read of the initial CT volume measurement protocols during the early phase of data collection.
Lastly, the study’s insights are derived from a single centre within a specific region of the UK and may not capture regional variations in donor characteristics or medical practices. The cohort size, while adequate for initial hypotheses, is relatively small. Future studies with larger, more diverse populations across multiple centres are imperative to validate and possibly extrapolate our findings, ensuring robust, widespread clinical applicability for the detection of AKF in potential kidney donors.
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- Source: https://bmcnephrol.biomedcentral.com/articles/10.1186/s12882-024-03634-7