BACKGROUND: Nephrosclerosis, nephron size, and nephron number vary among kidneys transplanted from living donors. However, whether these structural features predict kidney transplant recipient outcomes is unclear. METHODS: Our study used computed tomography (CT) and implantation biopsy to investigate donated kidney features as predictors of death-censored graft failure at three transplant centers participating in the Aging Kidney Anatomy study. We used global glomerulosclerosis, interstitial fibrosis/tubular atrophy, artery luminal stenosis, and arteriolar hyalinosis to measure nephrosclerosis; mean glomerular volume, cortex volume per glomerulus, and mean cross-sectional tubular area to measure nephron size; and calculations from CT cortical volume and glomerular density on biopsy to assess nephron number. We also determined the death-censored risk of graft failure with each structural feature after adjusting for the predictive clinical characteristics of donor and recipient. RESULTS: The analysis involved 2293 donor-recipient pairs. Mean recipient follow-up was 6.3 years, during which 287 death-censored graft failures and 424 deaths occurred. Factors that predicted death-censored graft failure independent of both donor and recipient clinical characteristics included interstitial fibrosis/tubular atrophy, larger cortical nephron size (but not nephron number), and smaller medullary volume. In a subset with 12 biopsy section slides, arteriolar hyalinosis also predicted death-censored graft failure. CONCLUSIONS: Subclinical nephrosclerosis, larger cortical nephron size, and smaller medullary volume in healthy donors modestly predict death-censored graft failure in the recipient, independent of donor or recipient clinical characteristics. These findings provide insights into a graft's "intrinsic quality" at the time of donation, and further support the use of intraoperative biopsies to identify kidney grafts that are at higher risk for failure.
BACKGROUND:Nephrosclerosis, nephron size, and nephron number vary among kidneys transplanted from living donors. However, whether these structural features predict kidney transplant recipient outcomes is unclear. METHODS: Our study used computed tomography (CT) and implantation biopsy to investigate donated kidney features as predictors of death-censored graft failure at three transplant centers participating in the Aging Kidney Anatomy study. We used global glomerulosclerosis, interstitial fibrosis/tubular atrophy, artery luminal stenosis, and arteriolar hyalinosis to measure nephrosclerosis; mean glomerular volume, cortex volume per glomerulus, and mean cross-sectional tubular area to measure nephron size; and calculations from CT cortical volume and glomerular density on biopsy to assess nephron number. We also determined the death-censored risk of graft failure with each structural feature after adjusting for the predictive clinical characteristics of donor and recipient. RESULTS: The analysis involved 2293 donor-recipient pairs. Mean recipient follow-up was 6.3 years, during which 287 death-censored graft failures and 424 deaths occurred. Factors that predicted death-censored graft failure independent of both donor and recipient clinical characteristics included interstitial fibrosis/tubular atrophy, larger cortical nephron size (but not nephron number), and smaller medullary volume. In a subset with 12 biopsy section slides, arteriolar hyalinosis also predicted death-censored graft failure. CONCLUSIONS: Subclinical nephrosclerosis, larger cortical nephron size, and smaller medullary volume in healthy donors modestly predict death-censored graft failure in the recipient, independent of donor or recipient clinical characteristics. These findings provide insights into a graft's "intrinsic quality" at the time of donation, and further support the use of intraoperative biopsies to identify kidney grafts that are at higher risk for failure.
Authors: Andrew D Rule; Hatem Amer; Lynn D Cornell; Sandra J Taler; Fernando G Cosio; Walter K Kremers; Stephen C Textor; Mark D Stegall Journal: Ann Intern Med Date: 2010-05-04 Impact factor: 25.391
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Authors: Naim Issa; Brian Stephany; Richard Fatica; Saul Nurko; Venkatesh Krishnamurthi; David A Goldfarb; William E Braun; Vincent W Dennis; Peter S Heeger; Emilio D Poggio Journal: Transplantation Date: 2007-03-15 Impact factor: 4.939
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Authors: Aleksandar Denic; Marija Bogojevic; Aidan F Mullan; Moldovan Sabov; Muhammad S Asghar; Sanjeev Sethi; Maxwell L Smith; Fernando C Fervenza; Richard J Glassock; Musab S Hommos; Andrew D Rule Journal: J Am Soc Nephrol Date: 2022-08-03 Impact factor: 14.978
Authors: Aleksandar Denic; Hisham Elsherbiny; Aidan F Mullan; Bradley C Leibovich; R Houston Thompson; Luisa Ricaurte Archila; Ramya Narasimhan; Walter K Kremers; Mariam P Alexander; John C Lieske; Lilach O Lerman; Andrew D Rule Journal: J Am Soc Nephrol Date: 2020-09-16 Impact factor: 10.121
Authors: Panagiotis Korfiatis; Aleksandar Denic; Marie E Edwards; Adriana V Gregory; Darryl E Wright; Aidan Mullan; Joshua Augustine; Andrew D Rule; Timothy L Kline Journal: J Am Soc Nephrol Date: 2021-12-07 Impact factor: 10.121
Authors: Stan Benjamens; Saleh Z Alghamdi; Elsaline Rijkse; Charlotte A Te Velde-Keyzer; Stefan P Berger; Cyril Moers; Martin H de Borst; Riemer H J A Slart; Frank J M F Dor; Robert C Minnee; Robert A Pol Journal: J Clin Med Date: 2021-01-17 Impact factor: 4.241