3
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: not found
      • Article: not found

      Kidney Structural Features from Living Donors Predict Graft Failure in the Recipient

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The quality of a kidney obtained from a living donor is often inferred from the donor’s age, risk factors, and kidney function. Little is known about the influence of a donated kidney’s structural features on the risk of death-censored graft failure in the recipient. In an analysis of 2293 kidney donor-recipient pairs, the authors identified subclinical nephrosclerosis, larger nephron size (but not nephron number), and smaller medullary volume as structural predictors of death-censored graft failure that were independent of both donor and recipient clinical characteristics. These findings provide important insights into the factors that define the “intrinsic quality” of the living kidney donor graft at the time of donation, and support use of intraoperative biopsies to identify donor kidneys that are at higher risk for failure. 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. 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. 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. 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.

          Related collections

          Most cited references18

          • Record: found
          • Abstract: found
          • Article: not found

          Belatacept and Long-Term Outcomes in Kidney Transplantation

          In previous analyses of BENEFIT, a phase 3 study, belatacept-based immunosuppression, as compared with cyclosporine-based immunosuppression, was associated with similar patient and graft survival and significantly improved renal function in kidney-transplant recipients. Here we present the final results from this study.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            The association between age and nephrosclerosis on renal biopsy among healthy adults.

            Chronic kidney disease is common with older age and is characterized on renal biopsy by global glomerulosclerosis, tubular atrophy, interstitial fibrosis, and arteriosclerosis. To see whether the prevalence of these histologic abnormalities in the kidney increases with age in healthy adults and whether histologic findings are explained by age-related differences in kidney function or chronic kidney disease risk factors. Cross-sectional study. Mayo Clinic, Rochester, Minnesota, from 1999 to 2009. 1203 adult living kidney donors. Core-needle biopsy of the renal cortex obtained during surgical implantation of the kidney, and medical record data of kidney function and risk factors obtained before donation. The prevalence of nephrosclerosis (> or =2 chronic histologic abnormalities) was 2.7% (95% CI, 1.1% to 6.7%) for patients aged 18 to 29 years, 16% (CI, 12% to 20%) for patients aged 30 to 39 years, 28% (CI, 24% to 32%) for patients aged 40 to 49 years, 44% (CI, 38% to 50%) for patients aged 50 to 59 years, 58% (CI, 47% to 67%) for patients aged 60 to 69 years, and 73% (CI, 43% to 90%) for patients aged 70 to 77 years. Adjustment for kidney function and risk factor covariates did not explain the age-related increase in the prevalence of nephrosclerosis. Kidney donors are selected for health and lack the spectrum or severity of renal pathologic findings in the general population. Kidney function and chronic kidney disease risk factors do not explain the strong association between age and nephrosclerosis in healthy adults. National Institutes of Health, U.S. Public Health Service.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Relationship between weight at birth and the number and size of renal glomeruli in humans: a histomorphometric study.

              The number of nephrons in humans varies considerably under normal circumstances, and retarded intrauterine growth has been reported to be associated with a significant reduction in nephron number. Low nephron number may be an independent risk factor for the development of hypertension. We therefore decided to evaluate the relationship between body weight at birth and the number and size of nephron units. We examined coronal sections of the kidneys of 35 neonates who died within two weeks of birth because of hyaline membrane, infectious complications, brain hemorrhage, or perinatal hypoxia and had no urinary congenital malformations. Nine of them (5 males and 4 females) were between 36 and 37 weeks of gestation, and the rest had 38 or more weeks of gestation. Eighteen neonates weighed less than 2500 g at birth [low birth weight (LBW); 9 females and 9 males], and 17 had weights above this value [normal birth weight (NBW); 8 females and 9 males]. In each section, glomeruli present in four sequential subcapsular microscopic fields, corresponding to 0.6 mm2, were counted; in addition, the area of each of 65 consecutive glomeruli was determined by a computerized measurement system. Glomerular volume was calculated from the glomerular area. Linear regression analysis was used to test the relationship between glomerular number and size and the weight at birth. The number of glomeruli per 0.6 mm2 of renal cortex was 92.9 +/- 4.85 in the LBW and 105.8 +/- 3.91 in NBW (P < 0.0001). Glomerular volume (micro(3) x 10(-3)) was 529.1 +/- 187.63 in the LBW group and 158.0 +/- 49.89 in the NBW group (P < 0.0001). The glomeruli occupied 8.59 +/- 1.38% of the kidney area under examination in the LBW group and 14.3 +/- 2.75% in the NBW group (P < 0.0001). There were significant direct correlations between the weight at birth and the number of glomeruli (r = 0.870, P < 0.0001) and area occupied by glomeruli (r = 0.935, P < 0.0001). There were inverse correlations between the number of glomeruli and the volume of the glomeruli (r = -0.816, P < 0.0001) and the weight at birth and glomerular volume (r = -0.848, P < 0.0001). These findings were independent of sex and race (black vs. white). Essential arterial hypertension existed in 38.9% of the mothers of children with LBW and in 5.9% of the mothers of children with NBW (P < 0.05). Smoking habits existed in 50% of the mothers of LBW children and in 11.8% of the mothers of NBW children (P < 0.05). There are strong correlations between glomerular number (direct) and size (inverse) with LBW in this cohort. Endowment with decreased nephron numbers may be a risk factor for hypertension and the rate of progression of renal disease.
                Bookmark

                Author and article information

                Journal
                Journal of the American Society of Nephrology
                JASN
                American Society of Nephrology (ASN)
                1046-6673
                1533-3450
                January 23 2020
                : ASN.2019090964
                Article
                10.1681/ASN.2019090964
                7003295
                31974271
                c87def6b-0a2a-4a91-8e9a-a8727b74fa98
                © 2020
                History

                Comments

                Comment on this article