Date: Tuesday, June 5, 2018
Session Time: 4:30pm-6:00pm
Presentation Time: 4:42pm-4:54pm
Location: Room 4B
Introduction: Both indication and 10-yr surveillance biopsy data point to the important role of progressive glomerular disease in intermediate and long-term allograft outcomes. As all kidney transplants have podocyte detachment rates above native kidney controls (PMID:25388223) we looked for potential superimposed accelerators of this process. Given the association of DSA's with transplant glomerulopathy (TG) we first investigated the impact of circulating DSA's on allograft function and podocyte loss.
Methods: Urine pellet podocyte mRNA markers were analyzed in 57 kidney allograft recipients who had >1 urine sample collected (mean 4.7±2.6 years post transplant, range 2-15 urine samples per allograft) at greater than 1-year post-transplant. Clinical data was collected from patient charts. A tertile analysis was done by allograft loss of function.
Results: Urinary podocyte detachment rate (Urine Podocin mRNA to Creatininine ratio, UPodCR) was significantly elevated with a trend towards increased DSA+ve among allografts that were losing function (upper table). In a separate analysis, the rate of podocyte detachment was significantly elevated among patients with circulating DSA's (lower table). 3 patients had missing eGFR data.
|Rate of GFR decline analyzed by tertiles for urine samples collected >1 year post TP|
|Tertile||Lowest (n=18)||Intermediate (n=18)||Highest (n=18)||p value|
|eGFR decline (ml/min/year)||1.6±1.3||-1.9±0.8||-12.5±9.9||0.0001|
|U. Protein:Creatinine ratio||0.22±0.18||0.33±0.61||1.99±1.98||0.01|
|UPodCR||2.6e-05 ± 2.3e-05||3.1e-05±4.9e-05||1.2e-04±1.5e-04||0.002|
|DSA positive||5/17 (29%)||7/17 (41%)||9/13 (69%)||0.09|
|Allograft function decline and podocyte detachment by DSA|
|DSA negative (n=26)||DSA positive (n=21)||p value|
|eGFR decline (ml/min/yr)||-1.3 ± 4.1||-4.8±9.0||0.08|
|U. Protein:Creatinine ratio||0.62±1.4||0.84±1.49||0.6|
Conclusion: Recipients with circulating DSA's were more likely to have accelerated podocyte detachment and allograft loss of function. The directionality and mechanisms of the association between circulating DSA and podocyte loss needs further study.
CITATION INFORMATION: Naik A., Aqeel J., Cibrik D., Samaniego M., Wang S., Chowdhury M., Afshinnia F., Wiggins R. Presence of Donor Specific Antibodies is Associated with Accelerated Podocyte Detachment Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:Naik A, Aqeel J, Cibrik D, Samaniego M, Wang S, Chowdhury M, Afshinnia F, Wiggins R. Presence of Donor Specific Antibodies is Associated with Accelerated Podocyte Detachment [abstract]. https://atcmeetingabstracts.com/abstract/presence-of-donor-specific-antibodies-is-associated-with-accelerated-podocyte-detachment/. Accessed September 20, 2020.
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