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. 2025 Apr 15;20(4):e0321769.
doi: 10.1371/journal.pone.0321769. eCollection 2025.

The impact of ischemic reperfusion injury on contralateral kidneys and the determinants of renal prognosis after robot-assisted partial nephrectomy

Mitsunori Matsuo  1 , Kensei Taguchi  2 , Yunosuke Yokota  2 , Kei Fukami  2 , Tsukasa Igawa  1
Affiliations

The impact of ischemic reperfusion injury on contralateral kidneys and the determinants of renal prognosis after robot-assisted partial nephrectomy

Mitsunori Matsuo et al. PLoS One. .

Abstract

Robot-assisted laparoscopic partial nephrectomy (RAPN) is a safe and effective option for renal cell carcinoma (RCC). However, clamping of renal artery during RAPN sometimes causes ischemic reperfusion (IR) injury (IRI), which affects renal function at some later time. In the present study, we inserted catheters into the bilateral ureters from before RAPN until 24 hours after and analyzed urine biomarkers of renal injury excreted from both resected and contralateral kidneys to determine and investigated which biomarkers predict the future decline in renal function in patients with RCC and rodent IR model. Twenty-three patients diagnosed with RCC (66.4 ± 10.8 years old, eGFR: 73.6 ± 15.3 mL/min/1.73m2) were enrolled and ureteral catheters were inserted in both ureters. Urinary neutrophil gelatinase-associated lipocalin (NGAL), beta-2-microglobulin (β₂MG), N-acetyl-β-D-glucosaminidase were measured at several time points. Gene expression of injury markers in contralateral kidneys were analyzed in unilateral IR rodents. All the urinary markers were elevated 30 minutes after the clamping and sustained high until 24 hours in resected kidneys. Meanwhile, urinary NGAL and β2MG excreted from contralateral kidneys increased at 6 and 24 hours after the clamping. Warm ischemic time, estimated blood loss, and excised kidney weight were not associated with renal dysfunction; however, only contralateral urinary β2MG at 6 hours was correlated. Ngal and Il-6 mRNA in contralateral kidneys were upregulated in unilateral IR rodents. RAPN-related IRI induces contralateral kidney injury. Contralateral urinary β2MG can become a potent biomarker to predict the onset of kidney injury after RAPN.

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Conflict of interest statement

I have no competing interests regarding this paper.

Figures

Fig 1
Fig 1. Urinary renal injury markers before and after IR by RAPN in the resected kidney.
NGAL/Cr ratio (a), β2MG/Cr ratio (b), and NAG/Cr ratio (C). *** p<0.001, ** p<0.01 vs pre, ### p<0.001, # p<0.05 vs post 30 min. IR, ischemic reperfusion; RAPN, robot-assisted partial nephrectomy; NGAL, Neutrophil gelatinase-associated lipocalin; Cr, creatinine; β2MG, β2-microglobulin; NAG, N-acetyl-β-D-glucosaminidase.
Fig 2
Fig 2. Urinary renal injury markers before and after IR by RAPN in the contralateral kidney.
NGAL/Cr ratio (a), β2MG/Cr ratio (b), and NAG/Cr ratio (C). *** p<0.001, * p<0.05 vs pre, ### p<0.001, ## p<0.01 vs post 30 min. IR, ischemic reperfusion; RAPN, robot-assisted partial nephrectomy; NGAL, Neutrophil gelatinase-associated lipocalin; Cr, creatinine; β2MG, β2-microglobulin; NAG, N-acetyl-β-D-glucosaminidase.
Fig 3
Fig 3. Univariate regression analysis for the correlation between eGFR changes at 1 month and Urinaryβ2MG/Cr ratio. β2MG, β2-microglobulin; Cr, creatinine; eGFR, estimated glomerular filtration ratio.
Fig 4
Fig 4. Contralateral renal NGAL (a) and IL-6 (b) gene expressions and BUN (c) levels in IRI C57BL/6j mice.
*** p<0.001 vs sham, * p<0.05 vs Day 7. NGAL, Neutrophil gelatinase-associated lipocalin; lcn2, lipocalin 2; IL-6, interleukin-6; BUN, blood urea nitrogen; Gapdh, glyceraldehyde-3-phosphate dehydrogenase; UIRI, unilateral ischemic reperfusion injury.
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