Renal Pedicle Clamping Research Articles

Pretreatment with sodium selenite alleviates inflammatory responses in renal ischemia-reperfusion injury by suppressing the expression of NF-κb and miR-494

Background/objectivesInflammation and oxidative stress play a significant role in renal ischemia-reperfusion injury (RIRI). This study aimed to investigate the possible protective effects of pretreatment with sodium selenite on RIRI, emphasizing anti-inflammatory effects. MethodA total of 24 male Wistar rats (200±20 g) were divided into four groups (six per each): 1- Sham (surgery without renal pedicle clamping), 2- Sham-Se (0.5 mg/kg sodium selenite for 7 consecutive days, ip), 3- RIRI (ischemia was induced by clamping the renal pedicle for 45 min), and 4- IRIR-Se (0.5 mg/kg sodium selenite for 7 consecutive days before I/R induction). All animals were sacrificed under anesthesia 24 h after I/R induction. Blood and tissue sample were collected for biochemical and histological analyses. ResultsThe results showed that sodium selenite pretreatment significantly reduced the changes induced by the ischemia-reperfusion injury, including the reduction of serum Cr and BUN, decreased the renal tissue content of NF-κB, TNF-α, IL-1β, and miR-494, and increased IL-10 and GPx content of kidney (P< 0.05). Also, sodium selenite pretreatment significantly reduced renal ischemia-reperfusion-induced histopathological changes. ConclusionPretreatment with sodium selenite significantly improved ischemia-reperfusion-induced renal dysfunction and mitigated RIRI, probably regarding its potent anti-inflammatory and antioxidant effects.

Predictors of renal function deterioration at one year after off-clamp non-renorrhaphy partial nephrectomy.

Preservation of renal function is an important goal in renal cell carcinoma-related surgery. Although several case-dependent techniques for renal pedicle clamping and hemostasis have been used, their effects on long-term renal function are controversial. The clinical records of 114 patients who underwent off-clamp non-renorrhaphy open partial nephrectomy at our hospital were retrospectively reviewed. Perioperative estimated glomerular filtration rate (eGFR) preservation was calculated, and predictors of eGFR decline 12 months post-surgery and overtime deterioration of renal function were identified using a multivariate regression analysis. The median patient age was 65 years, and the median tumor size was 27 mm. The mean eGFR preservation at 1, 3, and 12 months post-surgery were 90.1%, 89.0%, and 86.9%, respectively. eGFR decline at 1 and 3 months were associated with poor eGFR preservation at 12 months with the odds ratio (95% confidence interval (CI)) of 1.97 and 3.157, respectively. Multivariate regression analyses revealed that tumor size was an independent predictor of eGFR decline at 12 months. Among 65 patients with eGFR preservation over 90% at 1 month post-surgery, eGFR value of 28 patients deteriorated below 90% at 12 months post-surgery compared with preoperative eGFR. Tumor size and eGFR preservation at 1 month were independent predictors of long-term renal function deterioration. Tumor size predicted eGFR decline 12 months post-surgery. Only a mild decline in eGFR was observed between 3 and 12 months after open partial nephrectomy. Tumor size and eGFR preservation at 1 month predicted the deterioration of renal function over time.

Obesity exacerbates ischemia-reperfusion injury and senescence in murine kidneys and perirenal adipose tissues.

Obesity is a major worldwide health problem and can be related to cellular senescence. Along with the rise in obesity, the comorbidity of renal ischemia-reperfusion (IR) injury is increasing. Whether obesity accelerates the severity of IR injury and whether senescence contributes to these conditions remain unclear. We studied the degree of injury and cellular senescence in the IR kidneys and perirenal adipose tissues of high-fat-diet-induced obese mice. C57BL/6 mice fed standard chow or a high-fat diet for 16 weeks were randomized to renal IR or sham group (n = 6-10 each). Renal IR was performed by unilateral clamping of the right renal pedicle for 30 minutes. Six weeks after surgery, renal function, perirenal fat/renal senescence, and histology were evaluated ex vivo. Obese mice showed more renal tubular damage and fibrosis in IR injury than control mice, even though the degree of ischemic insult was comparable. Renal expression of senescence and its secretory phenotype was upregulated in either IR injury or with a high-fat diet and was further increased in the IR kidneys of obese mice. Fat senescence and the expression of tumor necrosis factor alpha were also increased, especially in the perirenal depot of the IR kidneys, with a high-fat diet. A high-fat diet aggravates IR injury in murine kidneys, which is associated, at least in part, with perirenal fat senescence and inflammation. These observations support the exploration of therapeutic targets of the adipo-renal axis in injured obese kidneys.

Intervention treatment reducing cellular senescence inhibits tubulointerstitial fibrosis in diabetic mice following acute kidney injury.

Senescence of kidney tubules leads to tubulointerstitial fibrosis (TIF). Proximal tubular epithelial cells undergo stress-induced senescence during diabetes and episodes of acute kidney injury (AKI), and combining these injuries promotes the progression of diabetic kidney disease (DKD). Since TIF is crucial to progression of DKD, we examined the therapeutic potential of targeting senescence with a senolytic drug (HSP90 inhibitor) and/or a senostatic drug (ASK1 inhibitor) in a model of TIF in which AKI is superimposed on diabetes. After 8 weeks of streptozotocin-induced diabetes, mice underwent bilateral clamping of renal pedicles to induce mild AKI, followed by 28 days of reperfusion. Groups of mice (n=10-12) received either vehicle, HSP90 inhibitor (alvespimycin), ASK1 inhibitor (GS-444217), or both treatments. Vehicle-treated mice displayed tubular injury at day 3 and extensive tubular cell senescence at day 10, which remained unresolved at day 28. Markers of senescence (Cdkn1a and Cdkn2a), inflammation (Cd68, Tnf, and Ccl2), and TIF (Col1a1, Col4a3, α-Sma/Acta2, and Tgfb1) were elevated at day 28, coinciding with renal function impairment. Treatment with alvespimycin alone reduced kidney senescence and levels of Col1a1, Acta2, Tgfb1, and Cd68; however, further treatment with GS-444217 also reduced Col4a3, Tnf, Ccl2, and renal function impairment. Senolytic therapy can inhibit TIF during DKD, but its effectiveness can be improved by follow-up treatment with a senostatic inhibitor, which has important implications for treating progressive DKD.

Transmission of high arterial pressure into renal microvessels during venous-clamping augments ischaemia/reperfusion-induced acute kidney injury in anaesthetized rats.

In two recent studies, we observed that a 30-min renal vein clamping caused formation of interstitial haemorrhagic congestion in ischaemic and ischaemic/reperfused kidney along with the development of severer acute kidney injury (AKI) than renal artery or pedicle clamping. It was suggested that the transmission of high arterial pressure into renal microvessels during vein occlusion probably causes the occurrence of interstitial haemorrhagic congestion that augments AKI. The present investigation aimed to evaluate this suggestion by reducing renal perfusion pressure (RPP) during renal venous occlusion. Anaesthetized male Sprague-Dawley rats were divided into three groups (n = 8), which underwent a 2-h reperfusion period following 30-min bilateral renal venous clamping along with reduced RPP (VIR-rRPP group) or without reduced RPP (VIR group) and an equivalent period after sham-operation (Sham group). The VIR-rRPP group compared with VIR group had lower levels of kidney malondialdehyde and tissue damages as epithelial injuries of proximal tubule and thick ascending limb, vascular congestion, intratubular cast and oedema, along with the less reductions in renal blood flow, creatinine clearance, Na+ -reabsorption, K+ and urea excretion, urine osmolality and free-water reabsorption. Importantly, the formation of intensive interstitial haemorrhagic congestion in the VIR group was not observed in the VIR-rRPP group. These results indicate that the transmission of high arterial pressure into renal microvessels during venous occlusion leads to rupturing of their walls and the formation of interstitial haemorrhagic congestion, which has an augmenting impact on ischaemia/reperfusion-induced renal structural damages and haemodynamic, excretory and urine-concentrating dysfunctions.

Robust Rat and Mouse Models of Bilateral Renal Ischemia Reperfusion Injury.

Acute and chronic kidney diseases are a major contributor to morbidity and mortality worldwide, with no specific treatments currently available for these. To enable understanding the pathophysiology of and testing novel treatments for acute and chronic kidney disease, a suitable in vivo model of kidney disease is essential. In this article, we describe two reliable rodent models (rats and mice) of efficacious kidney injury displaying acute to chronic kidney injury progression, which is also reversible through novel therapeutic strategies such as ischemic preconditioning (IPC). We utilized adult male Lewis rats and adult male wildtype (C57BL/6) mice, performed a midline laparotomy, and induced warm ischemia to both kidneys by bilateral clamping of both renal vascular pedicles for a set time, to mimic the hypoxic etiology of disease commonly found in kidney injury. Bilateral ischemia reperfusion injury caused marked structural and functional kidney injury as exemplified by histology damage scores, serum creatinine levels, and kidney injury biomarker levels in both rodents. Furthermore, this effect displayed a dose-dependent response in the mouse model. These rodent models of bilateral kidney IRI are reliable, reproducible, and enable detailed mechanistic study of the underlying pathophysiology of both acute and chronic kidney disease. They have been carefully optimised for single operator use with a strong track record of training both surgically trained and surgically naïve operators.

Nanoselenium attenuates renal ischemia-reperfusion injury in rats.

Using selenium (Se) nanoparticles has received attention in recent years because of their therapeutic benefits due to their anticancer, antioxidant, anti-inflammatory, and anti-diabetic effects. This research was conducted to evaluate the possible protective impact of nano-Se on renal unilateral ischemia/reperfusion injury (uIRI) in adult male Wistar rats. Using clamping of the left renal pedicle within 45 min uIRI was induced. The animals were randomly divided into nine groups of control, nano-Se (0.25, 0.5, and 1 mg/kg bw/day) alone, uIRI control, and uIRI rats administrated with nano-Se. At 30 days after treatment, the animals were sacrificed to be assessed biochemically and histopathologically. Nano-Se in uIRI groups have significantly decreased serum creatinine, urea levels, renal histological damage, and increased antioxidant status. Also, our findings demonstrated that the administration of nano-Se caused a significant decrease in the immunoreactivity level of the epidermal growth factor (EGF) and EGFR expression (EGF receptor) in the renal tissue of the uIRI rats. Therefore, nano-Se possesses renoprotective effects, and this effect might be attributable to its antioxidant and free radical scavenger effects. These renoprotective effects may depend on the decreased EGF immunoreactivity level and EGFR expression in the kidney tissue and improve the structure of the kidney tissue. Thus, our research provided biochemical and histological data supporting the potential clinical use of nano-Se for the treatment of certain kidney disorders.

Impaired NRF2 Inhibits Recovery from Ischemic Reperfusion Injury in the Aging Kidney.

Deteriorating kidney function is frequently observed in the elderly population, as well as vulnerability to acute kidney failure, such as ischemic/reperfusion injury (IRI), and inadequate recovery from IRI is one of the mechanisms of kidney dysfunction in the elderly. The potential mediators in the progression of kidney dysfunction in the aging kidney have not yet been clearly revealed. In this study, we investigated the role of nuclear factor erythroid 2-related factor 2 (NRF2), which is an essential regulator of cellular redox homeostasis, in restoring kidney function after IRI in the aging kidney. NRF2 expression decreased significantly in the kidneys of old mice, as well as histologic and functional renal recovery after IRI; 45-min renal pedicle clamping was retarded in old compared with young mice. Persistent renal injury during the recovery phase after IRI was aggravated in NRF2 knockout (KO) mice compared to wild-type mice. Oxidative stress occurred in NRF2 KO old mice during the IRI recovery phase along with decreased expression of mitochondrial OXPHOS-related proteins and a reduction in mitochondrial ATP content. In vitro, hypoxia/reoxygenation (H/R) injury was aggravated in senescent human proximal tubuloepithelial cells after NRF2 restriction using NRF2 siRNA, which also increased the level of oxidative stress and deteriorated mitochondrial dysfunction. Treating the mice with an NRF2 activator, CDDO-Me, alleviated the injury. These results suggest that NRF2 may be a therapeutic target for the aging kidney.

Amazonia Phytotherapy Reduces Ischemia and Reperfusion Injury in the Kidneys.

Acute kidney injury (AKI) is defined as a sudden decrease in kidney function. Phytomedicines have shown positive effects in the treatment of AKI worldwide. The aim of this study was to evaluate the effect of Abuta grandifolia on the renal function of rats submitted to AKI. A phytochemical study of the plant was performed through liquid chromatography coupled with mass spectrometry (CL-EM) and DPPH and ABTS antioxidant tests. Renal function tests were performed in 20 male adult Wistar rats weighing from 250 to 300 g distributed in the following groups: SHAM (submitted to laparotomy with simulation of renal ischemia); ABUTA (animals that received 400 mg/kg of AG, orally-VO, once a day, for 5 days, with simulation of renal ischemia); I/N (animals submitted to laparotomy for clamping of bilateral renal pedicles for 30 min, followed by reperfusion); ABUTA + I/R (animals that received AG-400 mg/kg, 1× per day, VO, for 5 days, submitted to renal ischemia after treatment with herbal medicine). The results suggest that the consumption of Abuta grandifolia promoted renoprotection, preventing the reduction of renal function induced by ischemia, oxidizing activity, and deleterious effects on the renal tissue, confirmed by the decrease of oxidative metabolites and increase of antioxidants in the animals' organisms.

The safety and efficacy of laparoscopic microwave ablation-assisted partial nephrectomy: a new avenue for the treatment of cystic renal tumors

Purpose Clinically, the management of cystic renal masses is tricky. The study aims to evaluate the safety and efficacy of laparoscopic microwave ablation-assisted partial nephrectomy (LMAPN) for cystic renal tumors. Methods and materials Between November 2017 and January 2022, LMAPN was performed on 43 patients (29 men and 14 women; age range: 22–80 years; median age 54 years) with Bosniak category III (n = 15) or IV (n = 28) cystic renal tumors (size range: 1.2–5.0 cm; mean size 2.8 cm). The median follow-up period was 26 months (range: 7–56 months). Baseline and perioperative data, pathological features, renal function, postoperative complications and oncologic outcomes were collected and evaluated. Results Forty-three cystic renal tumors were successfully managed by LMAPN. The mean operating time was 79 min (range: 40–130 min). The mean time of renal pedicle clamping was 19 min (range: 12–25 min). Mean intraoperative blood loss was 28.4 mL (range: 10–80 mL). The mean postoperative hospitalization duration was 4 days (range: 2–6 days). Negative surgical margins were diagnosed in all cases. During the follow-up, no patient appeared with distant metastasis, wound or peritoneal cavity implantation. No major but minor complications of Clavien–Dindo grade I were encountered after the operation. The 1-, 3- and 4-year overall survival rate was 100%, 96.6% and 88.5%, respectively. Conclusion This is the first study focusing on LMAPN for cystic renal tumors, demonstrating its favorable feasibility, safety and disease control. Long-term follow-up is necessary to draw conclusions on the preference and advantages of the new therapeutic approach.

Different Acute Kidney Injury Patterns after Renal Ischemia Reperfusion Injury and Extracorporeal Membrane Oxygenation in Mice.

The use of extracorporeal membrane oxygenation (ECMO) is associated with acute kidney injury (AKI) in thoracic organ transplantation. However, multiple other factors contribute to AKI development after these procedures such as renal ischemia-reperfusion injury (IRI) due to hypo-perfusion of the kidney during surgery. In this study, we aimed to explore the kidney injury patterns in mouse models of ECMO and renal IRI. Kidneys of C57BL/6 mice were examined after moderate (35 min) and severe (45 min) unilateral transient renal pedicle clamping and 2 h of veno-venous ECMO. Renal injury markers, neutrophil infiltration, tubular transport function, pro-inflammatory cytokines, and renal heme oxygenase-1 (HO-1) expression were determined by immunofluorescence and qPCR. Both procedures caused AKI, but with different injury patterns. Severe neutrophil infiltration of the kidney was evident after renal IRI, but not following ECMO. Tubular transport function was severely impaired after renal IRI, but preserved in the ECMO group. Both procedures caused upregulation of pro-inflammatory cytokines in the renal tissue, but with different time kinetics. After ECMO, but not IRI, HO-1 was strongly induced in tubular cells indicating contact with hemolysis-derived proteins. After IRI, HO-1 was expressed on infiltrating myeloid cells in the tubulo-interstitial space. In conclusion, renal IRI and ECMO both caused AKI, but kidney damage after renal IRI was more pronounced including severe neutrophil infiltration and tubular transport impairment. Enhanced HO-1 expression in tubular cells after ECMO encourages limitation of hemolysis as a therapeutic approach to reduce ECMO-associated AKI.

Role of tRNA derived fragments in renal ischemia–reperfusion injury

Background Ischemia–reperfusion injury (IRI) is one of the major causes of acute kidney injury (AKI). tRNA derived fragments (tRFs/tiRNAs) are groups of small noncoding RNAs derived from tRNAs. To date, the role of tRFs/tiRNAs in renal IRI has not been reported. Herein, we aimed to investigate the involvement of tRFs/tiRNAs in the occurrence and development of ischemia–reperfusion-induced AKI. Methods Moderate/severe renal IRI mouse models were established by bilateral renal pedicle clamping. The tRF/tiRNA profiles of healthy controls and moderate/severe IRI-stressed kidney tissues were sequenced by Illumina NextSeq 500. Candidate differentially expressed tiRNAs were further verified by RT-qPCR. Biological analysis was also performed. Results Overall, 152 tRFs/tiRNAs were differentially expressed in the moderate ischemic injury group compared with the normal control group (FC > 2, p < 0.05), of which 47 were upregulated and 105 were downregulated; in the severe ischemic injury group, 285 tRFs/tiRNAs were differentially expressed (FC > 2, p < 0.05), of which 157 were upregulated, and 128 were downregulated. RT-qPCR determination of eight abundantly expressed tiRNAs was consistent with the sequencing results. Gene Ontology analysis for target genes of the tRFs/tiRNAs showed that the most enriched cell components, molecular functions and biological processes were Golgi apparatus, cytoplasmic vesicles, protein binding, cellular protein localization and multicellular organism development. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that these target genes were mainly involved in the natural killer cell mediated cytotoxicity pathway, citrate cycle, and regulation of actin cytoskeleton signaling pathway. Conclusion Our results indicated that tRFs/tiRNAs were involved in renal IRI. These tRFs/tiRNAs may be effective partly via regulation of renal immunity, inflammation and metabolism processes. Candidate genes, including tiRNA-Gly-GCC-003, tiRNA-Lys-CTT-003, and tiRNA-His-GTG-002, might be potential biomarkers and therapeutic targets of ischemia–reperfusion injury-induced acute kidney injury.

IDF21-0098 Curcumin prevents renal aggravation by ischemia and reperfusion in diabetes mellitus

Background: Diabetes Mellitus (DM) increases the susceptibility to ischemia and reperfusion (I/R). I/R and DM share common physiopathological mechanisms, like inflammation and oxidation. Curcumin, present in Curcuma longa l., is a natural anti-inflammatory and antioxidant, used as a medicine for the treatment of osteoarticular diseases and usually found as a food, in view of its regulation of practical use, it is considered to be used in the prevention of acute chronic kidney disease. Aim: The aim of this study was to evaluate the effect of previous Curcumin treatment on renal function, hemodynamics and oxidative profile of diabetic rats submitted to I/R. Method: Wistar male rats (250–290 g), randomized into four groups: Citrate- received citrate buffer, i.v., on 1st day; DM: received 65 mg/kg streptozotocin (STZ), i.v., diluted in citrate buffer, on 1st day; DM+I/ R: diabetic animals that on 26th day were submitted bilateral renal pedicle clamping for 30 min; DM+I/R+ Curcumin: diabetic animals that received Curcumin 30mg/kg/day, gavage, 17th until the 27th day, and on the 26th day were submitted I/R. The renal function (inulin clearance- InCl, urinary flow- UF, serum creatinine- SCr), renal hemodynamics (renal blood flow -RBF, renal vascular resistance- RVR) and oxidative profile (urinary peroxides- UP, urinary nitrate- UN, thiobarbituric acid reactive substances- TBARS and thiols in renal tissue) were assessed. Results: Curcumin treatment in diabetic animals submitted to I/R insult resulted in increased InCl and decreased SCr, accompanied by increased RBF and decreased RVR with a reduction in UP, UN, TBARS and increase in thiol renal. Discussion: Curcumin prevented renal function decline in diabetic rats submitted to I/R with beneficial repercussions on renal hemodynamics and renal oxidative profile compared with control rats.

Renoprotective effect of vinpocetine against ischemia/reperfusion injury: Modulation of NADPH oxidase/Nrf2, IKKβ/NF-κB p65, and cleaved caspase-3 expressions.

Ischemia/reperfusion injury (IRI) during kidney transplantation is a serious clinical problem with a high mortality rate and a lack of therapy. Therefore, there is a need to improve the ability of the kidney to tolerate IRI during transplantation. This study aimed to investigate the possible protective effect of vinpocetine; a derivative of vincamine alkaloid; against renal IRI in rats with the elucidation of the involved mechanisms. Vinpocetine (25 mg/kg; i.p.) was administered for 10 successive days before the induction of ischemia by bilateral clamping of both renal pedicles for 45 min followed by 24 h of reperfusion. Blood and renal tissue samples were then collected for biochemical, molecular, and histopathological investigations. Vinpocetine significantly reduced serum creatinine and blood urea nitrogen levels in rats subjected to IRI. It also reduced mRNA expression of NADPH oxidase and renal content of malondialdehyde, while enhanced Nrf2 protein expression and renal content of reduced glutathione. The suppression of the provoked inflammatory response was evident by the downregulation of IKKβ and NF-κB p65 protein expressions, as well as their downstream inflammatory markers; tumor necrosis factor-α, interleukin-6, and myeloperoxidase. In addition, vinpocetine reduced protein expression of the apoptotic executioner cleaved caspase-3. These nephroprotective effects were confirmed by the improvement in histopathological features. Collectively, the protective effect of vinpocetine against IRI could be attributed to modulation of NADPH oxidase/Nrf2, IKKβ/NF-κB p65, and cleaved caspase-3 expressions. Thus, vinpocetine could improve oxidant/antioxidant balance, suppress triggered inflammatory response, and promote renal cell survival after IRI.

The Protective Effect of Anethole against Renal Ischemia/Reperfusion: The Role of the TLR2,4/MYD88/NFκB Pathway.

Background: Anethole is the principle essential oil component of anise and fennel. Renal ischemia/reperfusion (RIR) is one of the utmost imperative reasons for acute kidney injury and often associated with high mortality rate. The aim of this study is to investigate the protective effect of anethole on RIR status, exploring the involved mechanisms. Methods: RIR was accomplished by bilateral renal pedicle clamping for 45 min, after which the clamps were removed to achieve the reperfusion phase. Rats were randomized into five groups; Sham, Sham + anethole, RIR, and finally RIR + anethole (125 mg/kg or 250 mg/kg) groups. Animals were given anethole (in specified groups in doses) for 14 days before RIR. Results: RIR-experienced animals developed renal injury evidenced by diminished renal function and histopathological alteration. RIR induced severe oxidative, inflammatory, and apoptotic status within renal tissue. Pre-RIR management with anethole enhanced renal morphology and improved renal function. Anethole amplified GSH content and SOD, CAT, and GPx activities and lowered MDA. Anethole reduced gene and protein expression levels of HMGB1, TLR2, TLR4, MYD88, and NFκB. Anethole distinctly dropped TNF-α, IFN-γ, and MCP-1 levels, increased IL-10, and diminished caspase 3 and 9, reflecting its anti-inflammatory and anti-apoptotic actions. Conclusion: Anethole displayed anti-inflammatory, anti-oxidant, and anti-apoptotic actions against RIR-induced injury. Anethole exhibited renal protective actions, which could be through inhibiting the HMGB1/TLR2, 4/MYD88/NFκB pathway. These results could suggest anethole as a protective agent against RIR.

Murine models of renal ischemia reperfusion injury: An opportunity for refinement using noninvasive monitoring methods.

BackgroundRenal ischemia reperfusion injury (R‐IRI) can cause acute kidney injury (AKI) and chronic kidney disease (CKD), resulting in significant morbidity and mortality. To understand the underlying mechanisms, reproducible small‐animal models of AKI and CKD are needed. We describe how innovative technologies for measuring kidney function noninvasively in small rodents allow successful refinement of the R‐IRI models, and offer the unique opportunity to monitor longitudinally in individual animals the transition from AKI to CKD.MethodsMale BALB/c mice underwent bilateral renal pedicle clamping (AKI) or unilateral renal pedicle clamping with delayed contralateral nephrectomy (CKD) under isoflurane anesthetic. Transdermal GFR monitoring and multispectral optoacoustic tomography (MSOT) in combination with statistical analysis were used to identify and standardize variables within these models.ResultsPre‐clamping anesthetic time was one of the most important predictors of AKI severity after R‐IRI. Standardizing pre‐clamping time resulted in a more predictably severe AKI model. In the CKD model, MSOT demonstrated initial improvement in renal function, followed by significant progressive reduction in function between weeks 2 and 4. Performing contralateral nephrectomy on day 14 enabled the development of CKD with minimal mortality.ConclusionsNoninvasive monitoring of global and individual renal function after R‐IRI is feasible and reproducible. These techniques can facilitate refinement of kidney injury models and enable the degree of injury seen in preclinical models to be translated to those seen in the clinical setting. Thus, future therapies can be tested in a clinically relevant, noninvasive manner.

Laparoscopic renal surgery using multi degree-of-freedom articulating laparoscopic instruments in a porcine model.

We evaluated the performance of a new multi-degree-of-freedom articulating laparoscopic instrument, ArtiSential, and compared it with that of a straight-shaped instrument and the da Vinci surgical system, in renal surgery using porcine model. Nine female Yorkshire pigs were equally divided into three groups. The three groups were compared at each surgical step in terms of objective and subjective parameters. The median operative times for renal pedicle clamping and ureter dissection were significantly shorter in ArtiSential group than robotic group (1.3 min vs. 4.7 min, p=0.002; 8.1 min vs. 11.1 min, p=0.015). The median operative time for bladder repair was significantly longer in ArtiSential group than robotic and straight-shaped groups (17.9 min vs. 5.5 min, p=0.002; 17.9 min vs. 9.3 min, p=0.026). There were no significant differences among groups in terms of blood loss or intraoperative complications. ArtiSential device was less useable for renorrhaphy (p=0.009) and bladder repair (p=0.002) compared to the robotic system. ArtiSential group was less accurate than robotic group in terms of tumor resection, renorrhaphy, and bladder repair. During ureter dissection, bladder cuff excision, and bladder repair, the surgeon experienced greater wrist discomfort but lesser back discomfort in ArtiSential group than robotic group. For most steps, ArtiSential performed as well as robotic and straight-shaped instruments. The development of specialized surgical techniques for ArtiSential will maximize the advantages of these instruments.

Effect of curcumin on acute chronic kidney disease due to ischemia-reperfusion syndrome.

To evaluate the effect of curcumin on renal function, hemodynamics, and renal oxidative profile of rats with chronic kidney disease (CKD) subjected to renal ischemia-reperfusion injury (IRI). Wistar rats, 250-300 g, distributed in four groups: Sham (n = 5), CKD simulation; CKD (n = 5), 5/6 renal ablation for CKD induction; CKD + IRI (n = 5), CKD and renal pedicle clamping for 30 minutes; and CKD + IRI+curcumin (n = 5), CKD + IRI, curcumin administration 30 mg/kg/day, orally, for 10 days. Renal function (inulin clearance, urine flow, plasma creatinine), hemodynamics (blood pressure), and oxidative profile (peroxides, TBARS, and urine nitrate, non-protein soluble thiols in renal tissue) were evaluated. The CKD + IRI + curcumin group showed increased inulin clearance and reduced plasma creatinine, decreased RVR and increased RBF, decreased oxidative metabolites in urine and increased thiols in renal tissue when compared with the CKD + IRI group. The treatment with curcumin preserved renal function and hemodynamics of animals with acute CKD, improving oxidative profile, with reduction of oxidants and preservation of antioxidant reserve.

Diffusion Weighted Imaging and T2 Mapping Detect Inflammatory Response in the Renal Tissue during Ischemia Induced Acute Kidney Injury in Different Mouse Strains and Predict Renal Outcome.

To characterize ischemia reperfusion injury (IRI)-induced acute kidney injury (AKI) in C57BL/6 (B6) and CD1-mice by longitudinal functional MRI-measurement of edema formation (T2-mapping) and inflammation (diffusion weighted imaging (DWI)). IRI was induced with unilateral right renal pedicle clamping for 35min. 7T-MRI was performed 1 and 14 days after surgery. DWI (7 b-values) and multiecho TSE sequences (7 TE) were acquired. Parameters were quantified in relation to the contralateral kidney on day 1 (d1). Renal MCP-1 and IL-6-levels were measured by qPCR and serum-CXCL13 by ELISA. Immunohistochemistry for fibronectin and collagen-4 was performed. T2-increase on d1 was higher in the renal cortex (127 ± 5% vs. 94 ± 6%, p < 0.01) and the outer stripe of the outer medulla (141 ± 9% vs. 111 ± 9%, p < 0.05) in CD1, indicating tissue edema. Medullary diffusivity was more restricted in CD1 than B6 (d1: 73 ± 3% vs. 90 ± 2%, p < 0.01 and d14: 77 ± 5% vs. 98 ± 3%, p < 0.01). Renal MCP-1 and IL-6-expression as well as systemic CXCL13-release were pronounced in CD1 on d1 after IRI. Renal fibrosis was detected in CD1 on d14. T2-increase and ADC-reduction on d1 correlated with kidney volume loss on d14 (r = 0.7, p < 0.05; r = 0.6, p < 0.05) and could serve as predictive markers. T2-mapping and DWI evidenced higher susceptibility to ischemic AKI in CD1 compared to B6.

Assessment of surgical outcomes of off-clamp open partial nephrectomy without renorrhaphy for ≥T1b renal tumours.

To assess the surgical outcomes of off-clamp open partial nephrectomy without renorrhaphy. In the era of robot-assisted surgeries, open partial nephrectomy remains a surgical option for ≥ T1b renal tumours. Although the necessity of renal pedicle clamping and renorrhaphy in open partial nephrectomy for larger tumours remains to be discussed, reports on this issue are rare. Twenty-seven open partial nephrectomies for ≥ T1b renal tumours were performed without renal pedicle clamping or renorrhaphy. A soft coagulation system was used to control bleeding from the resection bed. Surgical results, complications, and predictors of perioperative estimated glomerular filtration rate (eGFR) preservation at 1month and 3months after surgery were analysed. The median estimated volume of blood loss was 420mL. The rates of perioperative eGFR preservation were 88.9 and 87.3% at 1 and 3months after surgery, respectively. Tumour size was an independent predictor of perioperative eGFR preservation at 1month after surgery, whereas age and exophytic/endophytic properties of the tumour were independent predictors of perioperative eGFR preservation at 3months after surgery. Open partial nephrectomy without renal pedicle clamping or renorrhaphy could be safely performed for ≥ T1b renal tumours, even when tumours were entirely endophytic and located close to the renal pedicle. Mild perioperative eGFR reduction was observed. Although surgical indications should be carefully considered in these cases, off-clamp open partial nephrectomy without renorrhaphy is a feasible procedure for patients with ≥ T1b renal tumours.