*Purpose: Studies in healthy adults have shown that glomerular density slowly declines with older age (-0.5% per decade), and globally sclerotic glomeruli (GSG) slowly increase (+1.7% per decade). However, no study has examined the rate of decline of glomerular density in renal allografts. The goal of this study was to determine the changes in glomerular density in the same kidney, and how it associates with a glomerular volume, %GSG, and function in kidney recipients in the first decade after transplantation.

*Methods: For quantitative morphometric analysis, the PAS stained slides of implantation biopsies, and matched 10-year surveillance biopsies were scanned into high resolution images, and the cortex, non-sclerosed (NSG), and globally sclerosed glomeruli (GSG) were manually traced. From these measures we calculated NSG volumetric density and NSG volume using the Weibel and Gomez stereology models, and the percent of all GSG. From the glomerular densities at 10-year and implantation biopsies, we calculated % density decline, and divided it into quintiles. We excluded cases with biopsies that had less than 4 glomeruli.

*Results: We identified 256 renal allografts (80.9% living donors, 19.1% deceased donors) who had implantation and 10-year surveillance biopsies (total of 512 biopsies) and divided them into quintiles based on % density decline (Table). Non-sclerotic glomerular volume reflecting glomerular hypertrophy was increased in all groups from T0 to 10 years. Donor’s age was similar in all 5 quintiles. Quintiles 1-3 were considered similar given the variability of assessing glomerular density. However, quintiles 4 and 5 clearly showed decline in glomerular density that was greater than that predicted by either variability or age-related decline alone. The %GSG was increased only in the quintile 5 with declining glomerular density. While eGFR did not differ between 5 groups (likely due to compensatory glomerular hypertrophy), 24hr urinary protein at 10-years was higher in quintiles 4 and 5 (i.e. groups with declining glomerular density).

*Conclusions: Accelerated decline in glomerular density with increasing glomerulosclerosis after kidney transplantation is a previously unrecognized pathologic process that is associated with increasing proteinuria at 10 years. The causes are unclear, but the decline cannot be explained by aging of the kidney.

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