Localization of renal oxidative stress and inflammatory response after lithotripsy

Abstract

OBJECTIVE To determine if the acute renal oxidative stress and inflammation after extracorporeal shock wave lithotripsy (ESWL), thought to be mediated by ischaemia, is most severe in the portion of the kidney within the focal zone of the lithotripter, and if these effects result primarily from ischaemic injury. MATERIALS AND METHODS Pigs (7-8-weeks old) received either 2000 shock waves at 24 kV to the lower-pole calyx of one kidney or unilateral renal ischaemia for 1 h. A third group (sham) received no treatment. Timed urine and blood samples were taken for analysis of lipid peroxidation and the inflammatory cytokines, tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). At 4 h after treatment, kidneys were removed and samples of cortex and medulla were frozen for analysis of cytokines and heme oxygenase-1 (HO-1). RESULTS ESWL did not affect urinary excretion of malondialdehyde, but did elicit an eight-fold induction of HO-1 in the portion of the renal medulla within the focal zone of the lithotripter (F2), while remaining unchanged elsewhere in the treated kidney. There was no induction of HO-1 in renal tissue after ischaemia-reperfusion. Urinary excretion of TNF-alpha increased from the lithotripsy-treated kidney by 1 h after treatment, but was unaffected by ischaemia-reperfusion. As with the HO-1 response after lithotripsy, IL-6 increased only in the renal medulla at F2. By contrast, ischaemia-reperfusion increased IL-6 in all samples from the treated kidney. CONCLUSION These findings show that the acute oxidative stress and inflammatory responses to ESWL are localized to the renal medulla at F2. Furthermore, the differing patterns of markers of injury for ESWL and ischaemia-reperfusion suggest that ischaemia is not the principal cause of the injury response after ESWL.

Figures

Fig. 1

Urine MDA excretion (A,B) from untreated and treated kidneys of sham and ESWL-treated pigs (six each). After the baseline MDA excretion, all other collections are timed from the end of ESWL. Values are the mean ± SEM.

Fig. 2

HO-1 in sham vs untreated kidney of ESWL-treated pigs. For cortex (A) the results are representative of two experiments with three pigs in each group (six pigs per group). For medulla (B) the results represent one experiment with three pigs per group. There was no significant difference for cortex or medulla. Values are the mean ± SD.

Fig. 3

HO-1 in untreated kidney, and opposite and treated poles (F2) of treated kidney of ESWL-treated pigs. (A) For cortex, the data are from one of two experiments with similar results. There was no significant difference between tissue regions. (B) For medulla, the images are from one of two experiments with similar results. The densitometry data includes values from two experiments with three pigs per group per experiment (total of six pigs): *P < 0.001 vs untreated kidney and opposite pole of treated kidney. Values are mean ± SD.

Fig. 4

HO-1 in the left lower pole medulla (treated pole of treated kidney, F2 for ESWL) in sham, ESWL- and IR-treated pigs. (A) Cortex; images and chart represent one experiment with three pigs for each treatment. (B) Medulla; images are from one of two experiments with similar results. The chart includes data from two experiments with three pigs per group per experiment (total of six pigs per group). *P < 0.01 vs sham; **P < 0.05 vs IR. The sham and IR groups were not significantly different. Values are means ± SD.

Fig. 5

(A) Plasma TNF-α levels in sham-, ESWL- and IR-treated pigs (10 or more). (B) Urine TNF-α excretion from untreated and treated kidneys of sham-, ESWL- and IR-treated pigs (eight or more). *P < 0.05 vs sham. (C) Tissue TNF-α levels of untreated and treated kidneys of sham-, ESWL and IR-treated pigs (six or more). Values are the mean ± SD.

Fig. 5

(A) Plasma TNF-α levels in sham-, ESWL- and IR-treated pigs (10 or more). (B) Urine TNF-α excretion from untreated and treated kidneys of sham-, ESWL- and IR-treated pigs (eight or more). *P < 0.05 vs sham. (C) Tissue TNF-α levels of untreated and treated kidneys of sham-, ESWL and IR-treated pigs (six or more). Values are the mean ± SD.

Fig. 5

(A) Plasma TNF-α levels in sham-, ESWL- and IR-treated pigs (10 or more). (B) Urine TNF-α excretion from untreated and treated kidneys of sham-, ESWL- and IR-treated pigs (eight or more). *P < 0.05 vs sham. (C) Tissue TNF-α levels of untreated and treated kidneys of sham-, ESWL and IR-treated pigs (six or more). Values are the mean ± SD.

Fig. 6

Tissue IL-6 levels of treated and contralateral kidneys of sham-, ESWL- and IR-treated pigs (six or more): *P < 0.05 vs sham. Values are the mean ± SEM.