Renal ischemia-reperfusion (IR) injury can lead to acute kidney injury, increasing the risk of developing chronic kidney disease. We hypothesized that mild therapeutic hypothermia (mTH), 34 °C, applied during ischemia could protect the function and structure of kidneys against IR injuries in mice. In vivo bilateral renal IR led to an increase in plasma urea and acute tubular necrosis at 24 h prevented by mTH. One month after unilateral IR, kidney atrophy and fibrosis were reduced by mTH. Evaluation of mitochondrial function showed that mTH protected against IR-mediated mitochondrial dysfunction at 24 h, by preserving CRC and OX-PHOS. mTH completely abrogated the IR increase of plasmatic IL-6 and IL-10 at 24 h. Acute tissue inflammation was decreased by mTH (IL-6 and IL1-β) in as little as 2 h. Concomitantly, mTH increased TNF-α expression at 24 h. One month after IR, mTH increased TNF-α mRNA expression, and it decreased TGF-β mRNA expression. We showed that mTH alleviates renal dysfunction and damage through a preservation of mitochondrial function and a modulated systemic and local inflammatory response at the acute phase (2–24 h). The protective effect of mTH is maintained in the long term (1 month), as it diminished renal atrophy and fibrosis, and mitigated chronic renal inflammation.

We are lacking tools to evaluate renal performance. In this review, we presented the current knowledge and potential future applications in nephrology of new magnetic resonance imaging (MRI) techniques, focusing on diffusion-weighted (DWI) MRI, blood oxygen level-dependent (BOLD) MRI, and magnetic resonance relaxometry (T1 and T2 mapping). These sequences are sensitive to early changes in biological processes such as perfusion, oxygenation, edema, or fibrosis without requiring contrast medium injection and avoids irradiation and nephrotoxicity. Combining these different sequences into the so-called “multiparametric MRI” enables noninvasive, repeated exploration of renal performance on each kidney separately. DWI MRI, which evaluates the movement of water molecules, is a promising tool for noninvasive assessment of interstitial fibrosis and the cortical restricted diffusion has a prognostic value for the deterioration of renal function in diabetic nephropathy. BOLD MRI is sensitive to changes in renal tissue oxygenation based on the paramagnetic properties of deoxyhemoglobin and is of particular interest in the setting of renal artery stenosis to assess tissue oxygenation in the post-stenotic kidney. This sequence can be used for predicting degradation of renal function in chronic kidney diseases (CKD) and might be useful in preclinical studies to assess nephroprotective and nephrotoxic effects of drugs in development. T1 and T2 relaxation times change with tissue water content and might help assessing renal fibrosis. A corticomedullary dedifferentiation in T1 has been observed in CKD and negatively correlates with glomerular filtration rate. Data on the significance of T2 values in renal imaging is more limited. Multiparametric MRI has the potential to provide a better understanding of renal physiology and pathophysiology, a better characterization of renal lesions, an earlier and more sensitive detection of renal disease, and an aid to personalized patient-centered therapeutic decision-making. Further data and clinical trials are needed to allow its routine application in clinical practice.

The consequences of partial nephrectomy (PN) compared to radical nephrectomy (RN) are less documented in patients with pre-existing chronic kidney disease (CKD) or with solitary kidney (SK). We assessed renal outcomes, and their determinants, after PN or RN in a retrospective cohort of patients with moderate-to-severe CKD (RN-CKD and PN-CKD) or SK (PN-SK). All surgical procedures conducted between 2013 and 2018 in our institution in patients with pre-operative estimated glomerular filtration rate (eGFR)<60 mL/min/1.73m² or with SK were included. The primary outcome was a composite criterion including CKD progression or major adverse cardio-vascular events (MACE) or death, assessed one year after surgery. Predictors of the primary outcome were determined using multivariate analyses. A total of 173 procedures were included (67 RN, and 106 PN including 27 SK patients). Patients undergoing RN were older, with larger tumors. Preoperative eGFR was not significantly different between the groups. One year after surgery, PN-CKD was associated with lower rate of the primary outcome compared to RN-CKD (43% vs 71% p = 0.007). In multivariate analysis, independent risk factors for the primary outcome were postoperative AKI (stage 1 to stage 3 ranging from OR = 8.68, 95% CI 3.23–23.33, to OR = 28.87, 95% CI 4.77–167.61), larger tumor size (OR = 1.21 per cm, 95% CI 1.02–1.45), while preoperative eGFR, age, sex, diabetes mellitus, and hypertension were not. Postoperative AKI after PN or RN was the major independent determinant of worse outcomes (CKD progression, MACE, or death) one year after surgery.

Cyclosporine A (CsA) preconditioning is known to target mitochondrial permeability transition pore and protect renal function after ischemia reperfusion (IR). The upregulation of heat-shock protein 70 (Hsp70) expression after CsA injection is thought to be associated with renal protection. The aim of this study was to test the effect of Hsp70 expression on kidney and mitochondria functions after IR. Mice underwent a right unilateral nephrectomy and 30 min of left renal artery clamping, performed after CsA injection and/or administration of the Hsp70 inhibitor. Histological score, plasma creatinine, mitochondrial calcium retention capacity, and oxidative phosphorylation were assessed after 24 h of reperfusion. In parallel, we used a model of hypoxia reoxygenation on HK2 cells to modulate Hsp70 expression using an SiRNA or a plasmid. We assessed cell death after 18 h of hypoxia and 4 h of reoxygenation. CsA significantly improved renal function, histological score, and mitochondrial functions compared to the ischemic group but the inhibition of Hsp70 repealed the protection afforded by CsA injection. In vitro, Hsp70 inhibition by SiRNA increased cell death. Conversely, Hsp70 overexpression protected cells from the hypoxic condition, as well as the CsA injection. We did not find a synergic association between Hsp70 expression and CsA use. We demonstrated Hsp70 could modulate mitochondrial functions to protect kidneys from IR. This pathway may be targeted by drugs to provide new therapeutics to improve renal function after IR.

Tissue perfusion and oxygenation, key factors of renal ischemia‐reperfusion injury (RIR), can be assessed using contrast‐enhanced ultrasound (CEUS) and photoacoustic (PA) imaging. We hypothesized that early changes in renal perfusion and oxygenation caused by IRI, or protection by mild therapeutic hypothermia (mTH), could be detected and correlate with fibrosis. C57BL6 mice underwent 15‐min unilateral renal ischemia, with or without mTH, followed by 1‐month reperfusion. They were assigned to sham ( n = 5), normothermic renal ischemia (IR‐37°C, n = 7), mTH renal ischemia (IR‐34°C, n = 7). The IR‐37°C and IR‐34°C groups had body temperature maintained at 37°C or 34°C during surgery. CEUS and PA were conducted at baseline, 20 min, and 1 month after reperfusion. Histological analysis was performed at 1 month. IRI induced renal atrophy and fibrosis at 1 month, prevented by mTH. CEUS revealed altered perfusion in IR‐37°C at 20 min, sustained at 1 month, compared to Sham, while perfusion was preserved with mTH in IR‐34°C. Oxygenation assessed by PA was not modified. However, oxygenation measured 20 min after IRI correlated with fibrosis at 1 month. CEUS and PA are promising tools for non‐invasive assessment of renal IRI. IRI induced early and sustained perfusion alterations, while early assessment of oxygenation correlated with fibrosis. mTH prevented these alterations.