Can remote ischemic preconditioning counteract the renal functional deterioration attributable to partial nephrectomy under warm ischemia? Results of an animal study

Abstract

Background: To investigate if remote ischemic preconditioning (RIPC) can offer any renoprotective value by counteracting the deleterious effect of partial nephrectomy (PN) under warm ischemia on renal function.

Methods: Four groups, each with 5 Wistar albino rats, were constructed; RIPC + PN, PN, RIPC and sham. Right nephrectomy was performed to constitute a solitary kidney model. RIPC denoted sequential clamping/declamping of the femoral artery/vein complex. PN was performed under warm-ischemia following RIPC. Blood samples were collected on multiple occasions until euthanasia on day 7. Immunoassays were conducted to measure the serum and tissues levels of kidney injury markers. Kidneys were examined histologically and morphometric analyzes were performed using digital scanning.

Results: IL-33 levels did not differ significantly between the groups. Serum levels of KIM-1, NGAL, and aldose reductase in RIPC + PN, PN and RIPC groups were significantly lower than that of sham group. Tissue biomarker levels were similar across groups. The observed trend in mean necrosis area of PN group was higher than that of RIPC + PN group (p > 0.05). The transitional zone between necrosis and healthy tissue showed a trend towards increasing width in the rats subjected to RIPC before PN vs. those who underwent PN without RIPC (p > 0.05).

Conclusion: RIPC failed to counteract the renal functional consequences of PN under warm ischemia in a solitary kidney animal model. The supportive but marginal histological findings in favor of RIPC's renoprotective potential were not supplemented with the changes in serum and tissue biomarker levels.

Keywords: Biomarker; Function; Ischemia; Kidney; Preconditioning; Remote.

Fig. 1

a Macroscopic view of the left kidney s/p PN. Red-encircled area is showing the resultant parenchymal defect. b Clamping phase of the RIPC cycle. Femoral blood flow (artery and vein) was temporarily interrupted by bulldog clamp

Fig. 2

The study protocol: Four groups, each with 5 Wistar albino rats, were constructed; RIPC + PN, PN, RIPC, and sham. Right nephrectomy was performed in all groups except the sham group. Three days later, PN was performed in the PN and RIPC + PN groups. PN was performed under warm ischemia following RIPC. Blood samples were collected on multiple occasions until euthanasia on day 7

Fig. 3

a One of the rat kidneys in PN group showing focal infarct (depicted by *) at the resection bed (H-E x 15). b Zone of severe ischemia (depicted by **) between regions of infarct (depicted by *) and unaffected renal parenchyma (depicted by ***) (Left: PAS x 100; Right: PAS x 200). c and d Calculations done by the image analysis program. Panel C shows the encircled and measured area of necrosis, while panel D demonstrates the thickness readings of ischemic zone through the perpendicular lines drawn 1 mm apart throughout the entire lesion (A: H-E x 30; B: PAS x 90). e Area of necrosis in PN and RIPC + PN groups (each blue bar indicating a rat belonging to the groups being compared, p= 0.14). f The thickness of ischemic zone in PN and RIPC + PN groups (each red bar indicating a rat belonging to the groups being compared, p= 0.24)

Fig. 4

Changes in IL-33, NGAL, KIM-1, aldose reductase, and creatinine values with respect to time across study groups