Critical review of the article on ‘Using implantation biopsies as a surrogate to evaluate selection criteria for living kidney donors’

Citation: Chauhan, A., Diwan, T. S., Palacios, C. R. F., Dean, P. G., Heimbach, J. K., Chow, G. K., … & Stegall, M. D. (2013). Using implantation biopsies as a surrogate to evaluate selection criteria for living kidney donors. Transplantation, 96(11), 975-980.

In this study, they analyzed histologic characteristics of kidney biopsies obtained at the time of living-donor kidney transplantation (implantation biopsies) using the Banff criteria. Their goal was to use the presence of moderate to severe changes (MSC) in implantation biopsies from living kidney donors as a surrogate “outcome” to determine if there were certain donor characteristics that led to a higher prevalence of MSC that might then suggest the need for changes in current donor selection criteria.
Living kidney donation results in superior long-term patient/graft survival with reduced time to transplantation compared with deceased kidney donation [1]. Increased living kidney donation rate has been accompanied by an interest in quantifying the risks associated with donation particularly related to kidney function. Though several studies appear to support the concept that kidney donation is relatively safe both in the short term and long term, morbidity and mortality still occur [2,3]. Although, donor kidney biopsies might supply valuable information regarding the suitability of selection criteria, relatively few studies have examined this issue yet.
The authors conducted a retrospective analysis of the medical records of 1600 sequential living kidney donors who underwent hand-assisted laparoscopic nephrectomy from January 2001 to March 2011 at the Mayo Clinic Rochester, USA. Protocol selection criteria included, estimated glomerular filtration rate (eGFR) measurement with iothalamate renal clearance above the 5th percentile adjusted for age, 24-hr urine microalbumin excretion less than 30 mg/day, fasting plasma glucose 110 mg/dL or lower adjusted for age, and overnight ambulatory blood pressure measurements within the normal range or easily controlled with simple antihypertensive treatment.
Renal allograft implantation biopsies were collected after vascular anastomosis and reperfusion. Follow-up assessment of living donors were done at 4-month post-donation. Donors who did not have follow-up measurement of their renal function within the past 1 year were encouraged to obtain a serum creatinine with a 24-hr urine microalbumin excretion measurement.
MSC was present in 4% (n=65) of implantation biopsies. According to the multivariate analysis, donor age (OR: 1.060 [1.035–1.086]; P<0.0001) and donor systolic blood pressure (OR: 1.022 [1.006–1.037]; P=0.0060) were associated with MSC. MSC was further increased in donors older than 60 years with SBP>140 mmHg (30% [7/23]) and donors older than 60 years with SBP>140 mmHg and eGFR above the 25th percentile (42.8% [3/7]). At follow-up, kidney function was similar in donors with and without MSC. Hence, the final conclusion of the study was that MSC occurred occasionally in donors with varied characteristics. Although we did not identify patterns to support specific changes in our acceptance criteria, certain subgroups of kidney donors might benefit from close follow-up.

The title ” Using implantation biopsies as a surrogate to evaluate selection criteria for living kidney donors’’ accurately summarizes the key focus of this retrospective study by Chauhan et al.
This large-scale retrospective analysis among 1600 kidney donor implantation biopsies, providing a considerable dataset to draw a generalized conclusion of the usefulness of implantation biopsies as a surrogate outcome marker to evaluate donor selection criteria. It is a novel and practical approach which gives the rarity of adverse outcomes in living kidney donors. This study found that MSC were relatively uncommon among kidney donor biopsies, occurring in only 4%, which is reassuring the kidney donation. However, the authors thoroughly examined the potential risk factors for MSC, including age, hypertension, obesity, and kidney function, using univariate & multivariate analysis. They identified older age and higher systolic blood pressure as independent predictors of MSC, providing valuable insights into potential modifications to donor selection criteria. Additionally, the researchers collected follow-up data on kidney function for donors with MSC, demonstrating no significant differences compared to those without MSC at the end of 4 month post-donation. Overall, this study offers a comprehensive evaluation of living kidney donor characteristics and their association with histological abnormalities, informing the ongoing optimization of donor selection criteria while highlighting the relatively low risk of chronic changes in carefully screened donors.
However, several limitations should be considered when interpreting the findings of this study. As a retrospective study, it may be subject to biases and unmeasured confounding factors. Secondly, although it assessed a large cohort of live kidney donors, being a single-center study limits its generalizability. Thirdly, the follow-up period for donors with MSC was relatively short, with only a 4-month follow-up clinical assessment, so longer follow-up monitoring is needed. Finally, the study did not evaluate psychosocial outcomes, which are important considerations for living donors. Overall, while providing useful data, the retrospective study design and lack of long-term comprehensive follow-up are clear limitations of this analysis.

In conclusion, this retrospective study by Chauhan et al. provides valuable insights into the usage of implantation biopsy to identify MSC in kidney donors with varied characteristics. Although they did not detect patterns to support specific changes in their acceptance criteria, certain subgroups of donors might benefit from close follow-up.

Moving forward, it is important to conduct larger multi-center prospective studies with long-term follow-up are needed to more definitively evaluate the clinical implications of histological findings on implantation biopsies among living kidney donors. Such studies should incorporate comprehensive assessments of psychosocial assessments and potential risk factors rather than age and blood pressure. While this retrospective study suggests a relatively low prevalence of MSC in carefully screened donors, continued optimization of donor selection criteria is important.

1. Collins, A. J., Foley, R. N., Herzog, C., Chavers, B. M., Gilbertson, D., Ishani, A., … & Agodoa, L. (2010). Excerpts from the US renal data system 2009 annual data report. American journal of kidney diseases, 55(1), A6-A7.
2. Saran, R., Marshall, S. M., Madsen, R., Keavey, P., & Tapson, J. S. (1997). Long-term follow-up of kidney donors: a longitudinal study. Nephrology, dialysis, transplantation: official publication of the European Dialysis and Transplant Association-European Renal Association, 12(8), 1615-1621.
3. Fehrman-Ekholm, I., Dunér, F., Brink, B., Tydén, G., & Elinder, C. G. (2001). No Evidence of Accelerated Loss of Kidney Function in Living Kidney Donors: Results From A Cross-Sectional Follow-Up1. Transplantation, 72(3), 444-449.



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