Mannitol reduces nephron loss after warm renal ischemia in a porcine model

Abstract

BackgroundMannitol has been employed to ameliorate renal warm ischemia damage during partial nephrectomy, however, there is limited scientific evidence to support the use of mannitol during partial nephrectomy. The objective of the present study was to investigate the glomerular number after renal warm ischemia, with and without the use of mannitol in a Pig Model.MethodsTwenty-four male pigs were assigned into three groups. Eight animals were allocated to the sham group that was subjected to laparoscopic dissection of the left renal hilum, without renal ischemia. Eight animals were allocated to the ischemia group that had the left renal hilum clamped for 30 min through laparoscopic access. Eight animals received mannitol (250 mg/kg) before the occlusion of renal hilum for 30 min. The kidneys were collected after the euthanasia of the pigs 21 days post surgery. The right kidney was utilized as a self-control for each animal. Serum creatinine, urea levels, the weight and volume of the kidneys were measured. Glomerular volumetric density, volume-weighted glomerular volume, and cortical volume were quantified through stereological methods and employed to determine the number of nephrons per kidney. Student’s t test and ANOVA were used for statistical analysis.ResultsIn the ischemia group, the left kidney recorded a reduction of 24.6% (290, 000 glomeruli) in the number of glomeruli in comparison to the right kidney. Kidneys subjected to ischemia also displayed decreased weight and volume in comparison to the sham and mannitol groups. No difference was observed between the left and right kidneys from the sham and mannitol groups. Further, no distinction in serum creatinine and urea among the groups was observed.ConclusionThe use of mannitol significantly reduces nephron loss during warm ischemia in pigs.

Mannitol for the Prevention of Peri-Operative Acute Kidney Injury: A Systematic Review

“…14,17 In a recent study, Damasceno-Ferreira et al demonstrated in a pig model that mannitol could prevent glomerular loss during warm ischaemia. 19 Clinical parameters, including urea and creatinine concentrations, did not change significantly. 19 Moreover, mannitol was proposed to act as an oxygen free radical scavenger attenuating ischaemia reperfusion injury.…”

“…19 Clinical parameters, including urea and creatinine concentrations, did not change significantly. 19 Moreover, mannitol was proposed to act as an oxygen free radical scavenger attenuating ischaemia reperfusion injury. 20e22 Haraldsson et al and Khoury et al could observe an effect of mannitol on direct and indirect renal ischaemia reperfusion injury in animals.…”

Examining Mannitol Use in Kidney Cancer Surgery: A Cautionary Tale of Extrapolated Surgical Data

“…Similar to the effects of urea, decreased renal tubular swelling has also been described when mannitol is given after reperfusion, although this observed feature is of unknown physiologic significance [28]. A differential impact of contralateral renal effects can also confound studies, whereas solitary kidney models may demonstrate a different pre-existing renal physiology and mannitol response in ischemia models [20,29]. Finally, it is notable that preclinical study results demonstrate only short-term physiologic shifts without a correlation to long-term functional benefits suggesting transient, artificial changes, as previously noted [30].…”

“…Mathematical models have estimated that a 50% decrease in GFR requires a four-fold reduction in glomeruli from baseline [37]. This was demonstrated in an animal model with mannitol, in which IRI led to a decrease of 1.14-0.89 million glomeruli without measurable change in GFR [29]. Solitary kidney models may offer some insight into renal compensatory change.…”

Antioxidants as Renoprotective Agents for Ischemia during Partial Nephrectomy

“…Histological evaluation of kidneys demonstrates that mannitol significantly decreased tubular necrosis and inflammatory infiltration [81]. A recent study used the porcine model of I/R with positive results: kidneys subjected to ischemia displayed decreased weight, volume, and number of glomeruli in comparison to the sham operated and mannitol groups and concluded that using this antioxidant significantly reduces nephron loss during warm ischemia in this animal model [107].…”