Impact of donor-recipient size mismatch on post-transplant outcomes in kidney transplant recipients: A systematic review

Background

Donor-recipient size mismatch builds on the nephron dosing concept, but studies suggest unclear associations with kidney allograft outcomes.

Methods

We systematically searched, critically appraised, and summarized associations between donor-recipient size mismatch and primary outcome of death-censored graft failure, secondary outcomes of kidney function, all-cause graft failure, and mortality. The study protocol was registered a priori on PROSPERO (ID CRD42023455394). We searched MEDLINE, Embase, and Cochrane Databases from 1946 to 2025 for studies evaluating adult kidney transplant recipients. We excluded non-English or unavailable full texts, and studies with donors <16 years old. Risk of bias was assessed using Risk of Bias in Non-randomized Studies – of Exposure tool. Studies were narratively synthesized; marked heterogeneity precluded quantitative meta-analysis.

Results

From 1521 citations, 56 studies were included. Sample sizes ranged from 23 to 238,895 donor-recipient pairs (median 214, IQR [95, 807]), with follow-up from 1 week to >20 years. Studies varied in size mismatch definitions, exposure subgrouping, outcomes, patient populations, and follow-up period. Overall, 32 % demonstrated worse kidney allograft outcomes with unfavorable size mismatch, 9 % showed no association, and 59 % reported mixed findings. All studies had high or very high risk of bias.

Conclusions

Available studies do not provide strong evidence to support or reject the idea of nephron underdosing, however existing reports were generally of poor quality, with high or very high risk of bias. Due to data heterogeneity, quantitative meta-analysis was not performed. Well-designed studies with clear exposure definitions, standardized outcome assessments, appropriate confounder control, adequate follow-up, and robust statistical analyses remain a priority.