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"apellidos" => "Territo" "email" => array:1 [ 0 => "territoangelo86@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">h</span>" "identificador" => "aff0040" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 10 => array:1 [ "colaborador" => "en representación del grupo de trabajo de trasplante renal de la sección de Jóvenes Urólogos Académicos (YAU) de la Asociación Europea de Urología (EAU)" ] ] "afiliaciones" => array:8 [ 0 => array:3 [ "entidad" => "Servicio de Urología, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Urología, Hospital San Luigi, Universidad de Turín, Turín, Italy" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Servicio de Urología, Trasplante Renal y Andrología, Hospital Universitario de Rangueil, Toulouse, France" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Servicio de Urología, Sección de Trasplante Renal y Urología Reconstructiva, Hospital Universitario Clínico San Carlos, Madrid, France" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Departamento de Urología, Facultad de Medicina, Universidad de Estambul, Estambul, Turkey" "etiqueta" => "e" "identificador" => "aff0025" ] 5 => array:3 [ "entidad" => "Unidad de Cirugía Robótica Urológica y Trasplante Renal, Universidad de Florencia, Hospital de Careggi, Florencia, Italy" "etiqueta" => "f" "identificador" => "aff0030" ] 6 => array:3 [ "entidad" => "Servicio de Urología y Trasplante Renal, Hospital Universitario de La Conception, Marsella, France" "etiqueta" => "g" "identificador" => "aff0035" ] 7 => array:3 [ "entidad" => "Servicio de Urología, Fundació Puigvert, Universidad Autónoma de Barcelona, Barcelona, Spain" "etiqueta" => "h" "identificador" => "aff0040" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Biomarcadores en el trasplante renal: ¿qué podemos esperar?" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Kidney transplantation (KT) stands as the treatment of choice for patients with end-stage renal disease, delivering superior outcomes in terms of morbidity, mortality and quality of life when compared to its alternative, dialysis.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> The increasing organs demand has been partially met through the utilization of “lower quality” donors, as “expanded criteria donors” and “donors after cardiac death”.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Clinicians still lack efficient and accurate tools for assessing kidney quality in order to avoid inferior quality kidney transplantation. Current methods for kidney quality evaluation, especially interesting in deceased donors, such as their comorbidities, serum creatinine and/or kidney biopsy (in selective cases), offer limited precision in predicting both short and long-term allograft outcomes. Moreover, diagnostic tools to identify any type of rejection are limited. Early recognition of rejections would help to achieve longer graft survival. Consequently, the transplant community is actively seeking new methods to overcome these issues. In this context, biomarkers emerge as a promising opportunity. Biomarkers are biological molecules present in body fluids (such as blood or urine) or tissues that can be used to monitor physiological processes and diseases. The ideal scenario involves the integration of biomarkers throughout the entire transplantation process, from the donor, through organ procurement preservation, and the recipient with the aim of predicting KT outcomes more effectively.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Donor’s perspective</span><p id="par0015" class="elsevierStylePara elsevierViewall">The quality of the allograft can be compromised due to numerous factors, including donor’s comorbidities, the cause of demise, the inflammatory environment associated with brain death, as well as hemodynamic instability and nephrotoxic insults during hospitalization, or potential damage during nephrectomy procedure, among others.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,3</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Regarding donor-related considerations, limited evidence exists in biomarkers. Donor urinary biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), IL-18, liver-type fatty acid binding protein (L-FABP) and urinary albumin, have been shown to be accurate markers of ischemic kidney injury in diverse experimental and clinical settings.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Other biomarkers, such as soluble 120-kDa transmembrane glycoprotein (sCD30) or B-cell interferon-gamma, have been investigated, finding no significant associations with acute rejection or kidney function.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Organ procurement perspective</span><p id="par0025" class="elsevierStylePara elsevierViewall">Within the realm of perfusate analysis, several biomarkers have undergone extensive investigation, with particular emphasis on glutathione S-transferase (GST), lactate dehydrogenase (LDH), and lactate levels. Among these biomarkers, GST and LDH have emerged as the most promising candidates for predicting short-term graft function. Elevated GST levels in urine has been correlated with renal injury and acute kidney injury (AKI) across diverse clinical scenarios. The accumulation of GST during the preservation within the machine systems could imply epithelial cell disruption and tubular damage. In contrast, LDH is a nonspecific marker of cell injury, influenced by factors such as circuit-dependent haemolysis.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Other research groups have explored inflammatory markers in perfusate liquid, with vascular cell adhesion molecule (VCAM) identified as a potential indicator of transplant health and an independent predictor of early kidney graft disfunction in brain-dead donors.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Notwithstanding the above, there is still lack of evidence in this field to accurately predict short- or long-term graft outcomes with biomarkers.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Recipients’ perspective</span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Pre-transplantation</span><p id="par0040" class="elsevierStylePara elsevierViewall">A recent study has underscored the significance of pretransplant plasma endotrophin to predict posttransplant allograft injury. Endotrophin, a derivative of pro-collagen type IV, capture attention through studies involving patients with chronic kidney disease and those with type 2 diabetes and microalbuminuria. A direct correlation between higher levels of endotrophin and elevated mortality rates have been shown. In KT field, there has been shown an association between elevated pretransplant plasma endotrophin in KT recipients and an increased incidence of acute allograft injury after transplantation in both living and deceased donor transplants. As a potentially modifiable factor, pretransplant endotrophin may be a new avenue for therapeutic interventions.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Post-transplantation</span><p id="par0045" class="elsevierStylePara elsevierViewall">Serum creatinine is currently the predominant biomarker employed in postoperative graft surveillance as it is the major tool used to monitor kidney function. However, it lacks the capacity to differentiate between distinct intra-graft pathologies. Attempts to use various blood biomarkers, including microRNA panels, whole blood mRNA expression of lymphocyte marker molecules, and even total cell-free DNA combined with procalcitonin, have yielded unsuccessful results.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> Soluble 120-kDa transmembrane glycoprotein (sCD30) is regarded as a marker of immune system activation, particularly in situations where T cells may damage the allograft. A recent systematic review and meta-analysis has unveiled a strong association between elevated sCD30 levels after transplantation and acute rejection. Nevertheless, factors such as living donor kidney transplantation, induction therapy and a shorter period of cold ischemia time could decrease sCD30 levels and consequently contribute to prolong allograft survival. Therefore, post-transplant sCD30 monitoring could serve as a predictive biomarker, aiding in the prevention of rejection.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Various urinary biomarkers, including kidney injury molecule-1 (KIM-1), NGAL, calprotectin, clusterin, IL-18, urinary tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) have been explored in post-transplantation to detect acute allograft injury.<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9,10</span></a> Elevated levels of urinary NGAL and IL-18 on the first day following kidney transplantation from deceased donor have been linked to higher rates of delayed graft function (DGF) and poorer allograft function at 12 months after kidney transplantation.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> NGAL has demonstrated accuracy in measuring acute kidney injury, DGF and acute rejection.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">When recipients experience tissue damage, whether from factors like ischemia, surgery, postoperative complications or due to patient’s comorbidities, the innate and adaptive immune system activate creating a proinflammatory environment which has an impact on early rejection events and even on transplantation’s outcomes.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> Additionally, immunological response to the graft has a drastic impact on the magnitude of this postoperative inflammatory environment.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> During this inflammatory process, early kidney injury is driven by immune cell infiltration and proinflammatory cytokine release, which likely enhance the alloimmune response, and could lead to interstitial fibrosis, tubular atrophy and glomerulosclerosis, resulting in functional kidney impairment and premature allograft failure.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Several studies tried to explore how to reduce the postoperative biological Systemic Inflammatory Response Syndrome (SIRS), which could theoretically, reduce the risk of graft loss. The minimal invasive approach (laparoscopic and robotic) has proved to be associated with a significant reduction in inflammatory markers compared with the open approach. This fact is mainly attributed to smaller skin incisions, less tissue manipulation and the immunomodulatory effect of CO<span class="elsevierStyleInf">2</span> infused in the peritoneal cavity.<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13,14</span></a> In general population, this inflammatory environment reduction is associated with better and faster patient recovery. However, in KT population, when comparing open versus robotic approach, the outcomes were similar between the two techniques. Thus, clinical relevance of postoperative SIRS is unknown in this population.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">Furthermore, elevated serum inflammatory markers, such as tumor necrosis factor-alpha (TNF α) and IL-6, independently correlate with a heightened risk of all-cause mortality, death with a functioning graft, and graft loss.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">In conclusion, although correlations between different biomarkers (mainly post-transplantation biomarkers) and AKI or graft loss have been demonstrated, this evidence remains insufficient for guiding treatment decisions. To validate the clinical utility of these biomarkers, prospective well-designed clinical trials are essential to assess the impact of biomarkers on KT recipient’s outcomes.</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Funding</span><p id="par0070" class="elsevierStylePara elsevierViewall">None.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Conflict of interest</span><p id="par0075" class="elsevierStylePara elsevierViewall">None.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:6 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Donor’s perspective" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Organ procurement perspective" ] 2 => array:3 [ "identificador" => "sec0015" "titulo" => "Recipients’ perspective" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0020" "titulo" => "Pre-transplantation" ] 1 => array:2 [ "identificador" => "sec0025" "titulo" => "Post-transplantation" ] ] ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Funding" ] 4 => array:2 [ "identificador" => "sec0035" "titulo" => "Conflict of interest" ] 5 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:15 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Quality of life in patients with chronic kidney disease: focus on end-stage renal disease treated with hemodialysis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "P.L. 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Journal Information
Vol. 48. Issue 6.
Pages 407-409 (July - August 2024)
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Vol. 48. Issue 6.
Pages 407-409 (July - August 2024)
Editorial
Biomarkers in kidney transplantation: Where do we stand?
Biomarcadores en el trasplante renal: ¿qué podemos esperar?
Visits
7
A. López-Abada, A. Pianab, T. Prudhommec, B. Bañuelos Marcod, M.I. Dönmeze, A. Pecorarof, R. Boissierg, R. Campif, A. Bredah, A. Territoh,
, en representación del grupo de trabajo de trasplante renal de la sección de Jóvenes Urólogos Académicos (YAU) de la Asociación Europea de Urología (EAU)
Corresponding author
a Servicio de Urología, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain
b Servicio de Urología, Hospital San Luigi, Universidad de Turín, Turín, Italy
c Servicio de Urología, Trasplante Renal y Andrología, Hospital Universitario de Rangueil, Toulouse, France
d Servicio de Urología, Sección de Trasplante Renal y Urología Reconstructiva, Hospital Universitario Clínico San Carlos, Madrid, France
e Departamento de Urología, Facultad de Medicina, Universidad de Estambul, Estambul, Turkey
f Unidad de Cirugía Robótica Urológica y Trasplante Renal, Universidad de Florencia, Hospital de Careggi, Florencia, Italy
g Servicio de Urología y Trasplante Renal, Hospital Universitario de La Conception, Marsella, France
h Servicio de Urología, Fundació Puigvert, Universidad Autónoma de Barcelona, Barcelona, Spain
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