Poly[ADP-Ribose] Polymerase-1 Expression Is Related To Cold Ischemia, Acute Tubular Necrosis, and Delayed Renal Function In Kidney Transplantation

Cold ischemia time especially impacts on outcomes of expanded-criteria donor (ECD) transplantation. Ischemia-reperfusion (IR) injury produces excessive poly[ADP-Ribose] Polymerase-1 (PARP-1) activation. The present study explored the hypothesis that increased tubular expression of PARP-1 contributes to delayed renal function in suboptimal ECD kidney allografts and in non-ECD allografts that develop posttransplant acute tubular necrosis (ATN)

Comparative data among control kidneys (from expanded-criteria donors [ECD] and patients with stable renal function), preimplant kidneys from ECDs, and transplanted kidneys from patients with ATN.

<p>ECD: Expanded-criteria donor with ATN; ATN: Acute tubular necrosis. Values are expressed as mean ± standard deviation.</p>*<p>P = 0.0001 one-way ANOVA test and <i>post hoc</i> with Bonferroni test.</p>†<p>Transplant protocol biopsies with stable renal function; NS: Non-significant.</p

Clinical variables according to nuclear immunohistochemical expression of PARP-1 in human kidney biopsies.

<p>Values are expressed as mean ± standard deviation; NS: Non-significant.</p>*<p>Student's <i><u>t</u>-</i> test.</p

Representation of ROC curves using PARP-1 expression as state variable.

<p>Representation of ROC curves using PARP-1 expression as state variable.</p

PARP-1 expression in human kidneys using polymer peroxidase-based method.

<p>A) Absence of PARP-1 expression in tubular cell nuclei in transplant protocol biopsy of kidney with stable renal function and without ATN (×100). B) Moderate PARP-1 expression in tubular cells of ECD kidney biopsy with ATN (×200). C) Moderate PARP-1 expression in necrotic tubuli of posttransplant kidney biopsy with ATN (×200). D, E, F): Intense PARP-1 expression in various biopsies with severe ATN (D x200, and E, F ×400). G) Glomerular immunostaining in a case of severe ATN. Note nuclear immunostaining in capillary and Bowman's capsule (×400). H) Negative isotype control (x200).</p

Western-blot analysis of PARP-1 expression in kidney of C57BL/6 mice.

<p>A) Presence of PARP-1 expression in kidney of C57BL/6 Parp1^+/+ mice absence of PARP-1 in knockout mice; and evident increase in PARP-1 expression at 48 h of reperfusion. Note partial inhibition of PARP-1 after inoculation with 3-ABA at 6 h of reperfusion. B) Induction of protein poly(ADP-ribosyl)ation after renal IR and its total inhibition by PARP-1 with 3-ABA. +/+: C57BL/6 wild-type mouse; −/−: C57BL/6 Parp-1 knockout mouse; 3-ABA: 3-aminobenzamide; C: Control; IR: Ischemia-Reperfusion; R: Reperfusion.</p

Area under the ROC curve, statistical significance and p-values using dichotomous PARP-1 expression in human kidney biopsies as state variable.

*<p>95% Confidence Interval.</p