Upregulation of HSP-72 in a Human Renal Allograft during Reflow

Abstract

Many types of renal injury, which are of potential relevance in transplantation medicine (such as extreme temperatures, ischemia, cytotoxic agents and cyclosporine), are known to induce the cellular stress response. Recently, we reported the first data on the 72-kD heat shock protein (HSP-72), a key player of the mammalian stress response, in a large number of nonperfused human donor kidneys (1). HSP-72 expression at both protein and mRNA levels remained low in the allografts at the time of engraftment regardless of pretransplant insults and posttransplant outcome. These data disqualified HSP-72 as a marker for allograft outcome in the clinical setting and suggested that constitutive HSP-72 expression does not play a role in graft protection. Herein, we report the findings on HSP-72 expression in a 10.5-year-old boy whose renal allograft was biopsied during early posttransplant reperfusion. His primary disease was chronic glomerulonephritis; the transplantation was performed after 12 months of peritoneal dialysis. The 52-year-old donor had died because of a cerebral insult. The creatinine at the time of explantation was 0.6 mg/dl, the donor was on low doses of pressors, cold ischemic time was 16 hours, and the mismatch was 2-2-0. The immunosuppressive regimen consisted of cyclosporine A, steroids, and mycophenolate mofetil. A routine donor kidney biopsy was performed immediately before engraftment, and a clinically indicated repeat biopsy was performed at 18 hours thereafter because of unexplained primary nonfunction. Immunohistochemical analysis of HSP-72 expression before and after engraftment is shown in Fig. 1.FIGURE 1.: HSP-72 expression in pre-transplant biopsy (upper panel) versus early re-perfusion (lower panel).Pretransplant biopsy demonstrated only weak and focal HSP-72 expression among different tubular segments (and thus failed to predict the complicated course). In strict contrast, the allograft biopsy during early reperfusion exhibited obvious overexpression of HSP-72 and thus suggested HSP-mediated cellular processes severe enough to produce a relevant in vivo stress response in the renal allograft. HSP-72 expression in the nonperfused donor kidney might have been insufficiently induced until the engraftment, and/or might have been prevented or even degraded during cold storage, despite significant expression at the time of harvest (2). At present, material from nonperfused organs constitutes the basis for most studies on posttransplant risk assessment. Data like ours should fuel discussions on strategies of early posttransplant biopsy procurement to improve clinical applicability of biomarkers. More importantly, this case provides the first direct evidence for the involvement of HSP-72 mediated cellular repair mechanisms in human renal allografts during reperfusion. These data corroborate a broad body of experimental evidence and support the potential of HSP-72 as a cytoprotective tool (3). Based on the recent finding of low pretransplant HSP-72 expression in the majority of donor kidneys, therapeutic interventions such as specific ex-vivo treatment of organs during cold storage fostering overexpression (and/or preventing degradation) of HSP-72 can be considered as an attractive concept in human transplant medicine. Regina Vargha Department of Pediatrics Medical University of Vienna Vienna, Austria Heinz Regele Department of Clinical Pathology Medical University of Vienna Vienna, Austria Christoph Aufrecht Department of Pediatrics Medical University of Vienna Vienna, Austria