Opportunities for Increasing the Rate of Preemptive Kidney Transplantation

Fishbane, Steven; Nair, Vinay

doi:10.2215/cjn.02480218

Cited by 18 publications

(13 citation statements)

References 10 publications

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“…9,[23][24][25][26][27] Similar to improving care for the general ESRD population, these factors likely involve earlier recognition of the need for repeat transplant as well as care coordination with community caregivers. 28,29 Interestingly, the current findings indicated higher incidence of preemptive care among women with graft failure, which is contrary to results demonstrating lower access to primary kidney transplantation among women. 11,30,31 Results further highlighted that the increased PRLT rates were apparent in younger but not older women.…”

Section: Discussioncontrasting

confidence: 99%

“…The degree to which these differences are based on timely referral and identification of failing graft function and are amenable to interventions targeting access to care among ESRD patients is important to evaluate . Similar to improving care for the general ESRD population, these factors likely involve earlier recognition of the need for repeat transplant as well as care coordination with community caregivers . Interestingly, the current findings indicated higher incidence of preemptive care among women with graft failure, which is contrary to results demonstrating lower access to primary kidney transplantation among women .…”

Section: Discussioncontrasting

confidence: 65%

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Modest rates and wide variation in timely access to repeat kidney transplantation in the United States

Schold

Augustine

Huml

et al. 2020

American Journal of Transplantation

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Success of transplantation is not limited to initial receipt of a donor organ. Many kidney transplant recipients experience graft loss following initial transplantation and the benefits of expedited placement on the waiting list and retransplantation extend to this population. Factors associated with access to repeat transplantation may be unique given experience with the transplant process and prior viability as a candidate. We examined the incidence, risk factors, secular changes, and center‐level variation of preemptive relisting or transplantation (PRLT) for kidney transplant recipients in the United States with graft failure (not due to death) using Scientific Registry of Transplant Recipients data from 2007 to 2018 (n = 39 557). Overall incidence of PRLT was 15% and rates of relisting declined over time. Significantly lower PRLT was evident among patients who were African American and Hispanic, males, older, obese, publicly insured, had lower educational attainment, were diabetic, had longer dialysis time prior to initial transplant, shorter graft survival, longer distance to transplant center, and resided in distressed communities. There was significant variation in PRLT by center, median = 13%, 10th percentile = 6%, 90th percentile = 24%. Cumulatively, results indicate that despite prior access to transplantation, incidence of PRLT is modest with pronounced clinical, social, and center‐level sources of variation suggesting opportunities to improve preemptive care among patients with failing grafts.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussioncontrasting

confidence: 65%

Modest rates and wide variation in timely access to repeat kidney transplantation in the United States

Schold

Augustine

Huml

et al. 2020

American Journal of Transplantation

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“…[1][2][3] Recently, PIs have been employed as a means to target nontransformed PCs that mediate autoimmune disease and HLA sensitization in organ transplantation, where pathogenic antibodies (Abs) play a major role. [5][6][7] It is now clear in kidney transplantation that Ab-mediated rejection (AMR) is the major cause of renal allograft loss, and HLA Abs also promote AMR in heart, lung, and pancreas transplantation. 4 Kidney transplantation is the treatment of choice for patients with end-stage renal disease (ESRD) as it is associated with improved patient survival and better quality-of-life.…”

Section: Introductionmentioning

confidence: 99%

“…4 Kidney transplantation is the treatment of choice for patients with end-stage renal disease (ESRD) as it is associated with improved patient survival and better quality-of-life. [5][6][7] It is now clear in kidney transplantation that Ab-mediated rejection (AMR) is the major cause of renal allograft loss, and HLA Abs also promote AMR in heart, lung, and pancreas transplantation. [8][9][10] HLA Abs, which arise from pregnancy, blood transfusion, or prior transplantation, present a significant and often impenetrable barrier to kidney transplantation, leading to increased morbidity and mortality.…”

Section: Introductionmentioning

confidence: 99%

Proteasomal adaptations underlying carfilzomib-resistance in human bone marrow plasma cells

Woodle

Tremblay

Brailey³

et al. 2020

American Journal of Transplantation

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Donor-specific antibodies (DSAs) have a deleterious effect on allografts and remain a major immunologic barrier in transplantation. Current therapies to eliminate DSAs are ineffective in highly HLA-sensitized patients. Proteasome inhibitors have been employed as a strategy to target bone marrow plasma cells (BMPCs), the source of long-term antibody production; however, their efficacy has been limited by poorly defined drug-resistance mechanisms. Here, we performed transcriptomic profiling of CD138 + BMPCs that survived in vivo desensitization therapy with the proteasome inhibitor carfilzomib to identify mechanisms of drug resistance. The results revealed a genomic signature that included increased expression of the immunoproteasome, a highly specialized proteasomal variant. Western blotting and functional studies demonstrated that catalytically active immunoproteasomes and the immunoproteasome activator PA28 were upregulated in carfilzomib-resistant BMPCs.Carfilzomib-resistant BMPCs displayed reduced sensitivity to the proteasome inhibitors carfilzomib, bortezomib, and ixazomib, but enhanced sensitivity to an immunoproteasome-specific inhibitor ONX-0914. Finally, in vitro carfilzomib treatment of BMPCs from HLA-sensitized patients increased levels of the immunoproteasome β5i (PSMB8) catalytic subunit suggesting that carfilzomib therapy directly induces an adaptive immunoproteasome response. Taken together, our results indicate that carfilzomib induces structural changes in proteasomes and immunoproteasome formation. K E Y W O R D Sbasic (laboratory)

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“…According to recent studies, pre-emptive transplantation has many benefits, including improved patient and graft survival, and a less delayed graft function in comparison to transplantation after dialysis [10]. Other outcomes are improved, including a reduced overall cost of care, and improved patient employment status [11]. Despite the clearly defined benefits, the identification of a living donor is essential for successful pre-emptive transplantation.…”

Section: Discussionmentioning

confidence: 99%

Successful pre-emptive kidney transplantation in a cystinuria patient with nephrolithiasis-related end-stage renal disease

et al. 2019

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Background: Cystinuria is a rare autosomal recessive metabolic disorder that affects renal and intestinal cystine transport. Cystine stones are found in only 1-2% of all stone formers. Patients with cystinuria are at high risk for nephrolithiasis and subsequent morbidity. In spite of the various medical and surgical treatments that are currently available for cystinuria, some patients gradually develop kidney failure, with only a few reported cases regarding kidney transplantation (KTx) to treat end-stage renal disease (ESRD) secondary to cystinuria. Cystinuria is likely not to be a systemic disease; thus, renal replacement with transplantation seems a good therapeutic option for ESRD. However, few cystinuria patients have undergone KTx due to ESRD. Case presentation: We herein describe the case of a 49-year-old man with cystinuria, frequent stone events, and ESRD who underwent pre-emptive ABO-incompatible kidney transplantation. At 2 years and 6 months post-transplantation, the patient remains asymptomatic with no prophylactic therapy for cystinuria, and the allograft function has been preserved without evidence of rejection. Conclusions: In conclusion, a cystinuria patient with nephrolithiasis-related ESRD was successfully treated by transplantation. Although additional cases are required to confirm the efficacy of this approach, renal replacement may be useful for treating ESRD in patients with rare hereditary forms of kidney stone disease.

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Opportunities for Increasing the Rate of Preemptive Kidney Transplantation

Cited by 18 publications

References 10 publications

Modest rates and wide variation in timely access to repeat kidney transplantation in the United States

Modest rates and wide variation in timely access to repeat kidney transplantation in the United States

Proteasomal adaptations underlying carfilzomib-resistance in human bone marrow plasma cells

Successful pre-emptive kidney transplantation in a cystinuria patient with nephrolithiasis-related end-stage renal disease

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