Use of biomarkers to improve immunosuppressive drug development and outcomes in renal organ transplantation: A meeting report

Mannon, Roslyn B.; Morris, Randall E.; Abécassis, Michaël; Axelrod, David A.; Bala, Shukal; Friedman, Gary S.; Heeger, Peter S.; Lentine, Krista L.; Loupy, Alexandre; Murphy, Barbara; Nickerson, Peter; Sarwal, Minnie M.; O’Doherty, Inish; Spear, Nicole; Karpen, Stephen R.

doi:10.1111/ajt.15833

Cited by 16 publications

(20 citation statements)

References 17 publications

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“…80,81 Incorporation of novel biomarkers into posttransplant surveillance may help identify which patients have lower immunologic risk and could benefit from immunosuppression minimization to reduce complications without increasing risk of rejection. 82…”

Section: Recommendationsmentioning

confidence: 99%

A Roadmap for Innovation to Advance Transplant Access and Outcomes: A Position Statement From the National Kidney Foundation

Lentine

Pastan

Mohan

et al. 2021

American Journal of Kidney Diseases

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Over the past 65 years, kidney transplantation has evolved into the optimal treatment for patients with kidney failure, dramatically reducing suffering through improved survival and quality of life. However, access to transplant is still limited by organ supply, opportunities for transplant are inequitably distributed, and lifelong transplant survival remains elusive. To address these persistent needs, the National Kidney Foundation convened an expert panel to define an agenda for future research. The key priorities identified by the panel center on the needs to develop and evaluate strategies to expand living donation, improve waitlist management and transplant readiness, maximize use of available deceased donor organs, and extend allograft longevity. Strategies targeting the critical goal of decreasing organ discard that warrant research investment include educating patients and clinicians about potential benefits of accepting nonstandard organs, use of novel organ assessment technologies and real-time decision support, and approaches to preserve and resuscitate allografts before implantation. The development of personalized strategies to reduce the burden of lifelong immunosuppression and support "one transplant for life" was also identified as a vital priority. The panel noted the specific goal of improving transplant access and graft survival for children with kidney failure. This ambitious agenda will focus research investment to promote greater equity and efficiency in access to transplantation, and help sustain long-term benefits of the gift of life for more patients in need.As this article reflects the official position of the National Kidney Foundation (NKF) and because it was reviewed and approved by NKF, it was not peer reviewed by AJKD. This article was prepared by a work group comprising the authors and chaired by Dr Krista Lentine. It was reviewed and approved by the NKF Scientific Advisory Board and the NKF Executive Committee.Complete author and article information provided before references.

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Section: Recommendationsmentioning

confidence: 99%

A Roadmap for Innovation to Advance Transplant Access and Outcomes: A Position Statement From the National Kidney Foundation

Lentine

Pastan

Mohan

et al. 2021

American Journal of Kidney Diseases

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“…2. Dynamics of IGF-1 blood levels in pediatric recipients who received different tacrolimus (TAC) doses one year after liver transplantation, * -p = 0.001 Современные методы оценки эффективности иммуносупрессии на основе Т-клеточного ответа отличаются сложностью и длительностью проведения анализа [8,9]. Определение концентрации ИФР-1 в крови с помощью иммуноферментного метода занимает около 6 часов и является приемлемым по сложности и длительности методом для клинической трансплантологии.…”

Section: корреляция уровня гормона роста (гр) в плазме крови с концентрацией такролимуса (тас) в крови и его дозой в различные сроки послunclassified

“…число исследований, показатели эффективности иммуносупрессии не нашли своего применения в клинической практике в силу ряда причин, таких как длительность и сложность проведения анализа или его недостаточная точность и воспроизводимость [8,9].…”

Section: Introductionunclassified

Correlation between insulin-like growth factor 1 levels and tacrolimus dose in pediatric liver recipients

Курабекова

Цирульникова

Гичкун

et al. 2021

RJTAO

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Introduction. To prevent post-transplant complications associated with unbalanced immunosuppression, objective indicators reflecting the state of the immune system and associated with the immunosuppressant dose are required. In pediatric liver transplantation, an important indicator of hepatocellular function and restoration of anthropometric characteristics is insulin-like growth factor 1 (IGF-1), which exhibits both nonspecific and selective immunomodulator properties.Objective: to assess the correlation between growth hormone and IGF-1 levels and tacrolimus dose and blood concentrations in pediatric liver recipients and to determine the possibility of using the IGF-1 level in selecting the drug dose required to achieve its target concentration in the blood. Materials and methods. We examined 156 children aged from 2 to 105 (median – 8) months with liver cirrhosis of various etiology, who received liver from a living related donor. The concentration of growth hormone and IGF-1 was determined in blood plasma before, one month, and one year after transplantation using the enzyme-linked immunosorbent assay. Tacrolimus residual concentration was measured in the patient’s whole blood by immunochemical method.Results. Growth hormone levels in the blood of pediatric liver recipients did not correlate with the dose or concentration of immunosuppressant tacrolimus one month or one year after transplantation, whereas the IGF-1 content was directly related to tacrolimus dose one year later (r = 0.41, p = 0.001), but not a month after surgery. The correlation coefficient was higher in uncomplicated post-transplant recipients (r = 0.51, p = 0.002) than in those with complications (r = 0.26, p = 0.17). The diagnostic efficiency of the IGF-1 level as an objective criterion for selecting the tacrolimus dose required to achieve its target blood concentration was 0.80 ± 0.11; 95% CI [0.58–1.00] (p = 0.007). In recipients with blood IGF-1 levels ≥115.7 ng/mL, the probability of prescribing a tacrolimus dose ≥0.25 mg/kg/day was 14 times higher than in children with lower blood IGF-1 levels. The estimated accuracy of the test was 83%, positive predictive value was 71%, and negative predictive value was 85%.Conclusion. The IGF-1 level was found to correlate with tacrolimus dose in liver transplant recipients one year after transplantation. The diagnostic efficiency of IGF-1 as a potential indicator for choosing the tacrolimus dose required to achieve its target blood concentration is 80%, which suggests further study of the test to assess the effectiveness of immunosuppression and selection of an individual immunosuppressant dose.

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“…Resulting in increased operational risks (e.g., costs, trial incompletion) for sponsors, they also pose a high operational burden on patients and physicians. The need for shorter term, clinically meaningful endpoints that are predictive of longer-term outcomes has been extensively described ( 5 – 7 ).…”

Section: Introductionmentioning

confidence: 99%

Demonstrating Benefit-Risk Profiles of Novel Therapeutic Strategies in Kidney Transplantation: Opportunities and Challenges of Real-World Evidence

et al. 2022

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While great progress has been made in transplantation medicine, long-term graft failure and serious side effects still pose a challenge in kidney transplantation. Effective and safe long-term treatments are needed. Therefore, evidence of the lasting benefit-risk of novel therapies is required. Demonstrating superiority of novel therapies is unlikely via conventional randomized controlled trials, as long-term follow-up in large sample sizes pose statistical and operational challenges. Furthermore, endpoints generally accepted in short-term clinical trials need to be translated to real-world (RW) care settings, enabling robust assessments of novel treatments. Hence, there is an evidence gap that calls for innovative clinical trial designs, with RW evidence (RWE) providing an opportunity to facilitate longitudinal transplant research with timely translation to clinical practice. Nonetheless, the current RWE landscape shows considerable heterogeneity, with few registries capturing detailed data to support the establishment of new endpoints. The main recommendations by leading scientists in the field are increased collaboration between registries for data harmonization and leveraging the development of technology innovations for data sharing under high privacy standards. This will aid the development of clinically meaningful endpoints and data models, enabling future long-term research and ultimately establish optimal long-term outcomes for transplant patients.

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Use of biomarkers to improve immunosuppressive drug development and outcomes in renal organ transplantation: A meeting report

Cited by 16 publications

References 17 publications

A Roadmap for Innovation to Advance Transplant Access and Outcomes: A Position Statement From the National Kidney Foundation

A Roadmap for Innovation to Advance Transplant Access and Outcomes: A Position Statement From the National Kidney Foundation

Correlation between insulin-like growth factor 1 levels and tacrolimus dose in pediatric liver recipients

Demonstrating Benefit-Risk Profiles of Novel Therapeutic Strategies in Kidney Transplantation: Opportunities and Challenges of Real-World Evidence

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