Donation, Not Disease! A Multiple-Hit Hypothesis on Development of Post-Donation Kidney Disease

Purpose of Review The risks following living kidney donation has been the subject of rigorous investigation in the past several decades. How to utilize the burgeoning new knowledge base to better the risk assessment, education, and health maintenance of donors is unclear. We review the physiologic and epidemiologic evidences on the post-donation state and submit a multiple-hit hypothesis to reconcile the finite elevation in risk of kidney disease after donation with the benign course of most kidney donors. Recent Findings The risk of end-stage kidney disease is higher in kidney donors compared to similarly healthy non-kidney donors. Nonetheless, post-donation kidney disease is uncommon and arises mostly in the setting of other "hits"-either a "first hit" present at birth or a "second hit" acquired later in life. Summary The transplant community's focus should be directed toward (1) personalized risk assessment to inform consent before donation and (2) preventing and treating development of "second hits" following kidney donation.