Dataset Information

Correlation of Glomerular Size With Donor-Recipient Factors and With Response to Injury.

ABSTRACT:

Background

Glomerular size in renal allografts is impacted by donor-recipient factors and response to injury. In serial biopsies of patients with well-functioning grafts, increased glomerular size correlates with better survival. However, no previous study has addressed the association of glomerular size at the time of a for-cause biopsy and clinical/histopathologic markers of injury, or effect on long-term graft outcome.

Methods

Two cohorts of kidney transplant recipients enrolled in the Deterioration of Kidney Allograft Function study were evaluated. The prospective cohort (PC, n = 581): patients undergoing first for-cause kidney biopsy 1.7 ± 1.4 (mean ± SD) y posttransplant; and the cross-sectional cohort (CSC, n = 446): patients developing new-onset renal function deterioration 7.7 ± 5.6 y posttransplant. Glomerular planar surface area and diameter were measured on all glomeruli containing a vascular pole. Kidney biopsy was read centrally in a blinded fashion according to the Banff criteria.

Results

Glomerular area was significantly higher in the CSC than the PC; time from transplant to indication biopsy was associated with glomerular area in both cohorts (P values ≤ 0.001). Glomerular area was associated with indices of microvascular inflammation (glomerulitis, peritubular capillary infiltrates; P values ≤ 0.001) and segmental glomerulosclerosis (P value < 0.0001). In the CSC, higher glomerular area was associated with higher estimated glomerular filtration rate (P value ≤ 0.001) and increased graft survival after accounting for microvascular inflammation (adjusted hazard ratio = 0.967; 95% confidence interval: 0.948-0.986; hazard ratio in biopsies without evidence of diabetes or antibody mediated rejection = 0.919, 95% confidence interval: 0.856-0.987).

Conclusions

Glomerular size is associated with histopathologic features present at the time of indication biopsy and with increased graft survival in the CSC.

SUBMITTER: Grande JP

PROVIDER: S-EPMC8166916 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Publications

Correlation of Glomerular Size With Donor-Recipient Factors and With Response to Injury.

Grande Joseph P JP Helgeson Erika S ES Matas Arthur J AJ

Transplantation 20211101 11

<h4>Background</h4>Glomerular size in renal allografts is impacted by donor-recipient factors and response to injury. In serial biopsies of patients with well-functioning grafts, increased glomerular size correlates with better survival. However, no previous study has addressed the association of glomerular size at the time of a for-cause biopsy and clinical/histopathologic markers of injury, or effect on long-term graft outcome.<h4>Methods</h4>Two cohorts of kidney transplant recipients enrolle ...[more]

PMID: 33273317

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Project description:Background and objectivesSmall donor and/or kidney sizes relative to recipient size are associated with a higher risk of kidney allograft failure. Donor and recipient ages are associated with graft survival and may modulate the relationship between size mismatch and the latter. The aim of this study was to determine whether the association between donor-recipient size mismatch and graft survival differs by donor and recipient age.Design, setting, participants, & measurementWe performed a retrospective cohort study of first adult deceased donor kidney transplantations performed between 2000 and 2018 recorded in the Scientific Registry of Transplant Recipients. We used multivariable Cox proportional hazards models to assess the association between donor-recipient body surface area ratio and death-censored graft survival, defined as return to dialysis or retransplantation. We considered interactions between donor-recipient body surface area ratio and each of recipient and donor age.ResultsAmong the 136,321 kidney transplant recipients included in this study, 23,614 (17%) experienced death-censored graft loss over a median follow-up of 4.3 years (interquartile range, 1.9-7.8 years). The three-way donor-recipient body surface area ratio by donor age by recipient age interaction was statistically significant (P=0.04). The magnitude of the association between severe size mismatch (donor-recipient body surface area ratio <0.80 versus ≥1.00) and death-censored graft survival was stronger with older donor age and recipient age. In all recipient age categories except the youngest (18-30 years), 5- and 10-year graft survival rates were similar or better with a size-mismatched donor aged <40 years than a nonsize-mismatched donor aged 40 years or older.ConclusionsThe association of donor-recipient size mismatch on long-term graft survival is modulated by recipient and donor age. Size-mismatched kidneys yield excellent graft survival when the donor is young. Donor age was more strongly associated with graft survival than size mismatch.

Project description:BackgroundNephron endowment in renal transplantation is infrequently considered, but may have important implications for post kidney transplantation outcomes. In this population-cohort study, we analyzed the deceased-donor kidney transplant outcomes stratified by donor-to-recipient size ratios.MethodsData for all deceased-donor adult kidney transplantation recipients between 2003 and 2015 were extracted from the UK Transplant Registry. We used weight as a surrogate marker for kidney size and defined the following mismatch categories (donor weight/recipient weight × 100): less than 75% (small donor kidney), 75% to 125% (weight matched kidney), and greater than 125% (large donor kidney). Univariable and multivariable analyses were undertaken to assess the relationship between this marker and patient outcomes.ResultsOutcomes for 11 720 transplants were analyzed with weight mismatch stratified as follows; small donor kidney (n = 1608, 13.7%), weight matched kidney (n = 7247, 61.8%) and large donor kidney (n = 2865, 24.4%). On multivariable analysis, no significant differences were detected in overall (P = 0.876) or death-censored (P = 0.173) graft survival, or in rates of delayed graft function (P = 0.396) between these 3 groups. However, 12-month creatinine levels were found to decline progressively across the groups (P < 0.001), with adjusted averages of 144.2 μmol/L for recipients of small donor kidneys, 134.7 μmol/L in weight matched kidneys, and 124.9 μmol/L in recipients of large donor kidneys. In addition, patient survival was found to be significantly shorter in recipients of larger kidneys than those with weight matched kidneys (hazard ratio, 1.21; 95% confidence interval, 1.05-1.40; P = 0.009), which is inconsistent with the existing literature.ConclusionsOur data demonstrate that 12-month creatinine is influenced by donor-to-recipient difference in body weight, but that no such difference is observed for either delayed graft function or death-censored graft survival. However, we observed increased mortality in recipients receiving larger kidneys; an observation which conflicts with the existing literature and warrants further investigation.

Project description:Importance:The shortage of deceased donor kidneys for transplants is an ongoing concern. Prior studies support transplanting kidneys from deceased donors with acute kidney injury (AKI), but those investigations have been subject to selection bias and small sample sizes. Current allocation practices of AKI kidneys in the United States are not well characterized. Objectives:To evaluate the association of deceased donor AKI with recipient graft survival and to characterize recovery and discard practices for AKI kidneys by organ procurement organizations. Design, Setting, and Participants:Registry-based, propensity score-matched cohort study from January 1, 2010, to December 31, 2013, in the United States. The dates of analysis were March 1 to November 1, 2019. From 2010 to 2013, a total of 6832 deceased donors with AKI and 15 310 deceased donors without AKI had at least 1 kidney transplanted. This study used a 1:1, propensity score-matched analysis to match deceased donors with AKI to deceased donors without AKI and investigated outcomes in their corresponding kidney recipients. Exposure:Deceased donor AKI, defined as at least 50% or 0.3-mg/dL increase in terminal serum creatinine level from admission. Main Outcomes and Measures:Recipients were assessed for the time to death-censored graft failure and the following secondary outcomes: delayed graft function, primary nonfunction, and the time to all-cause graft failure. Results:Ninety-eight percent (6722 of 6832) of deceased donors with AKI were matched to deceased donors without AKI. The mean (SD) age of the 13 444 deceased donors was 40.4 (14.4) years, and 63% (8529 of 13 444) were male. A total of 25 323 recipients were analyzed (15 485 [61%] were male), and their mean (SD) age was 52.0 (14.7) years. Recipients were followed up for a median of 5 (interquartile range, 4-6) years. Deceased donor AKI status had no association with death-censored graft failure (hazard ratio, 1.01; 95% CI, 0.95-1.08) or all-cause graft failure (hazard ratio, 0.97; 95% CI, 0.93-1.02). The results were consistent after examining by AKI stage and adjusting for recipient and transplant characteristics. More recipients of AKI kidneys developed delayed graft function (29% vs 22%, P < .001). Few recipients (120 of 25 323 [0.5%]) developed primary nonfunction regardless of deceased donor AKI status. Recovery and transplantation of AKI kidneys varied by organ procurement organization; most (39 of 58) had high recovery and high discard of AKI kidneys. Conclusions and Relevance:Deceased donor AKI kidneys transplanted in the study period had recipient graft survival comparable to that of non-AKI kidneys. This study's findings suggest that the transplant community should evaluate whether currently discarded AKI kidneys from donors without substantial comorbidities can be used more effectively.

Dataset Information

Correlation of Glomerular Size With Donor-Recipient Factors and With Response to Injury.

Background

Methods

Results

Conclusions

Publications

Correlation of Glomerular Size With Donor-Recipient Factors and With Response to Injury.

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