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Introduction: The utility of kidney procurement biopsies is controversial. Understanding the current landscape of how clinicians obtain and use biopsies in organ evaluation may help inform consensus-building efforts. Methods: An electronic survey was distributed to clinicians at US kidney transplant programs (April 22, 2021-June 30, 2021) to evaluate donor biopsy indications, frequency, processing and interpretation, and impact of findings on practices. Results: Responses from staff involved in organ acceptance (73% surgeons, 20% nephrologists, 6% coordinators) at 95 transplant centers were analyzed, representing 40% of US transplant centers and 50% of recent deceased donor kidney transplant volume. More than a third of centers (35%) reported obtaining procurement biopsies on most-to-all kidneys. Most clinicians decided when to biopsy jointly with the Organ Procurement Organization (OPO) (82%) based on formal criteria for the decision (72%), although 41% reported having requested a biopsy outside of the criteria. Most respondents used a semiquantitative scoring system for interpretation (57%). Many respondents reported rarely or never having access to renal specialty pathologists (37%) or to telepathology (59%). Most respondents reported that a favorable biopsy result would encourage them to accept a "marginal" donor kidney (72%); nearly half (46%) indicated that an unfavorable biopsy result would lead to decline of a standard criteria kidney. Conclusion: Procurement biopsies are commonly used in organ acceptance decisions despite inconsistent access to experienced renal pathologists and heterogeneous approaches to criteria, scoring, and interpretation. Ongoing study and consensus building are needed to direct procurement biopsy practice toward increasing organ utilization and reducing allocation inefficiency.
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Ischemia/reperfusion (I/R) injury unavoidably occurs during hepatic resection and transplantation. Aged livers poorly tolerate I/R during surgical treatment. Although livers have a powerful endogenous inhibitor of calpains, calpastatin (CAST), I/R activates calpains, leading to impaired autophagy, mitochondrial dysfunction, and hepatocyte death. It is unknown how I/R in aged livers affects CAST. Human and mouse liver biopsies at different ages were collected during in vivo I/R. Hepatocytes were isolated from 3-month- (young) and 26-month-old (aged) mice, and challenged with short in vitro simulated I/R. Cell death, protein expression, autophagy, and mitochondrial permeability transition (MPT) between the two age groups were compared. Adenoviral vector was used to overexpress CAST. Significant cell death was observed only in reperfused aged hepatocytes. Before the commencement of ischemia, CAST expression in aged human and mouse livers and mouse hepatocytes was markedly greater than that in young counterparts. However, reperfusion substantially decreased CAST in aged human and mouse livers. In hepatocytes, reperfusion rapidly depleted aged cells of CAST, cleaved autophagy-related protein 5 (ATG5), and induced defective autophagy and MPT onset, all of which were blocked by CAST overexpression. Furthermore, mitochondrial morphology was shifted toward an elongated shape with CAST overexpression. In conclusion, CAST in aged livers is intrinsically short-lived and lost after short I/R. CAST depletion contributes to age-dependent liver injury after I/R.