*Purpose: ESRD rates increase exponentially both after kidney donation and as the US population ages. Increases in ESRD rates from the first to the second postdonation decade were compared to increases in ESRD in unselected young adults in the US population over the same interval. Baseline rates in these cohorts are very similar. Rates of increase will determine long term risk.

*Methods: ESRD in the large UNOS database is reported as ESRD/10,000 donors/decade, which was converted to ESRD/million/year to reflect the average yearly rates in the first and the second post transplant decades. ESRD rates in the US population are reported as ESRD/million/year in five year age increments (USRDS 2018). The increase in ESRD rates from the first to the second postdonation decade was compared to the increase in young adults in the US population over the same interval.

The greatest increase in ESRD rates in the US population occurs in young adults. With age, ESRD rates increase less due to an increasing competing risk of death, e.g., in pre ESRD diabetic nephropathy. Unselected young adults most resemble donors at 0-10 years; they have low mortality and very similar ESRD rates.

*Results: ESRD increased more rapidly in donors. In the US population, ESRD appears at 76.5/million/year at ages 25-29 and 168/million/year at ages 35-39 (a 2.2 fold increase per decade) . Subsequent increases are somewhat smaller. In UNOs donors in the second decade Massie (JASN 2017) found a 4.7 fold increase (from 60 to 280/million/year). Wainright (AJT 2018) found a 3.9 fold increase (from 100 to 390/million/year). Anjum found a 7.5 fold increase over postdonation years 11-25 (AJT 2016). Matas (AJT 2018) reported a single-center increase from 30 to 480/million/year (16 fold) during the second decade.

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*Conclusions: Although absolute risks are small early on, early increases in ESRD after kidney donation are outpacing those at any point in the unselected US population. Hypothetically, if ESRD initially occurred at 70/million/year and continued to double each decade in the US population and quadruple in donors, by 40 years cumulative ESRD risks would approximate 1% vs 6%. About half of lifetime ESRD occurs after age 64. 25 year-old donors would be 65, with 6 times population risk and half their lifetime ESRD yet to come. Over any interval, increased donor ESRD could be due to loss of eGFR at nephrectomy, which decreases renal reserve when progressive post donation kidney diseases began (Muzaale JAMA 2014, Mjoen KI 2014). In the second post donation decade, this may outweigh the higher baseline risks in the unscreened population. Whatever the mechanism, the accelerated increase in donor ESRD may justify at least provisionally more scrutiny in the selection of young donor candidates (Steiner AJT 2014). Although dismaying, the rate of increase in postdonation ESRD is a long desired, real-time predictor of donor outcomes that merits more detailed attention.

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