Renal Warm Ischemia Research Articles

Oxygen Consumption by Warm Ischemia-Injured Porcine Kidneys in Hypothermic Static and Machine Preservation

Static cold storage (SCS) and hypothermic machine perfusion (HMP) are currently standard methods for renal grafts clinical preservation. Both methods are predominantly implemented without the active delivery of oxygen, even for donation after circulatory death-like kidneys. However, even under severe hypothermia (4°C-6°C), kidneys can consume oxygen and produce ATP. What is not established, though, is to what extent and how SCS and HMP compare in terms of oxygen. Using a porcine preclinical model of renal warm ischemia (WI) to compare SCS and HMP methods, we continuously monitored and quantified oxygen level and consumption along preservation; we also determined prepreservation and postpreservation cortical ATP level; values were given as median and [min; max] range. One-hour WI reduced ATP by ∼90% (from 3.3 [1.7; 4.5] mmol/L tissue in Controls). Oxygen consumption (QO2, μmol/min per 100 g) was determined from initial solution PO2 decrease (SCS and HMP) and from arterio-venous difference (HMP). In SCS and HMP, PO2 decreased rapidly (t1/2 ∼1 h) from atmospheric levels to 52.9 [38.0; 65.9] and 8.2 [3.0, 16.0] mmHg, respectively. In HMP, QO2 was 2.7 [0.4; 3.9] versus 0.5 [0.0; 1.3] in SCS (P < 0.05); postpreservation ATP amounted to 5.8 [3.2; 6.5] in HMP versus 0.1 [0.0; 0.2] in SCS. Despite hypothermic conditions in SCS or HMP, donation after circulatory death-like renal grafts require oxygen. Increased oxygen consumption, restored ATP level, and improved histological profile in HMP might explain the established HMP superiority over SCS. These results establish a rational basis for the use of oxygen in hypothermic preservation. Optimal levels required for preservation and graft-type variants remain to be determined.

Normobaric hyperoxia ameliorates renal ischemia reperfusion injury in rats

IntroductionAcute kidney injury (AKI) represents an ever‐increasing clinical problem with high morbidity and mortality. The kidney, due to its inhomogeneous blood flow, is particularly susceptible to changes in oxygen delivery. Renal hypoxia constitutes a common hallmark of AKI, and in the progression to chronic kidney disease (CKD). However, the role of hypoxia per se in the acute phase of renal injury remains largely unclear. The present study investigated 1) the role of systemic hypoxia in the acute progression and recovery of AKI, and 2) if normobaric global hyperoxia following AKI improves renal outcome.MethodsAnaesthetized (thiobutabarbital 120mg/kg i.p.) adult male Sprague‐Dawley rats were subjected to unilateral complete warm renal ischemia for 45 minutes followed by 2 hours of reperfusion under normoxic (21% inspired oxygen, n=10), hypoxic (10% inspired oxygen, n=10), and hyperoxic (60% inspired oxygen n=10) conditions. Kidney function, renal hemodynamics, intrarenal tissue oxygen tension (PO2), and renal oxygen consumption were estimated before and after the ischemic insult.ResultsAll investigated parameters were similar between groups at baseline. Animals subjected to 10% inspired oxygen developed intrarenal tissue hypoxia, whereas animals subjected to 60% inspired oxygen presented with increased intrarenal PO2 demonstrating that the approach to manipulate intrarenal tissue oxygen availability was successful. Furthermore, GFR at baseline were independent of renal tissue oxygenation.IR per se caused a steep decline in GFR in all groups (−97 ± 1, −87 ± 3, and −70 ± 11% for hypoxic, normoxic and hyperoxic animals, respectively), although renal blood flow and renal vascular resistance were similar before and after the ischemic insult. However, following IR there was a linear relationship between GFR and cortical PO2 when analysing all animals in all groups (Fig 1, linear regression P&lt;0.05).ConclusionThis study demonstrates that renal function following IR is dependent on intrarenal oxygen availability. Furthermore, normobaric hyperoxia‐treatment initiated at the time of the ischemic insult has the potential to protect kidney function.Support or Funding InformationThis study was supported by the Swedish Research Council Medicine and Health.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Sutureless laparoscopic partial nephrectomy using fibrin gel reduces ischemia time while preserving renal function.

We evaluated the efficacy of sutureless laparoscopic partial nephrectomy (LPN), using a fibrin gel in order to minimize renal ischemia time and preserve kidney function. Nineteen patients (mean age 58.3 ± 7.1) undergoing sutureless LPN using a fbrin gel were compared with a control group consisting of 21 patients (mean age 57.9 ± 7.5) subjected to LPN with standard suturing. Intraand post-operative data for the two groups were compared. The following parameters were recorded: patient demographics, Charlson Comorbidity Index, tumor characteristics according to the RENAL score, warm ischemia and operative times, estimated blood loss, mean hospital stay, post-operative complications referring to the Clavien-Dindo classification, renal function parameters pathologic and follow-up data. The main outcome measure was renal ischemia time and maintenance of kidney function. Median warm ischemia time was 13 minutes (range 11-19) in the group treated with fibrin gel and 19 (range 17- 29) in the control group, with a statistically significant difference (p < 0.001). The two groups were homogeneous in terms of the Charlson Comorbidity Index (4.6 vs 4.8) and RENAL score (9.6 vs 9.4). Median operative time differed significantly in the two groups, 183 minutes (range 145-218) in the group treated with fibrin gel and 201 (range 197-231) in the control group (p < 0.001). A negative surgical margin was reported in 18 patients (94.7%) in the group treated with fibrin gel and in 21 patients (100%) in the control group. No difference in renal function was found between the two groups. Sutureless LPN with fibrin gel can reduce warm ischemia and total operative time while preserving kidney function.

The effect of zinc acexamate on oxidative stress, inflammation and mitochondria induced apoptosis in rat model of renal warm ischemia.

Zinc has proved its efficacy in many models of ischemia reperfusion (I/R) injury. In this study, we used zinc acexamate (ZAC) as an exogenous source of zinc against renal I/R injury and we investigated whether its protective effects are mediated by the decrease of oxidative stress, inflammation, and mitochondria induced-apoptosis. Rats were orally pretreated with vehicle or ZAC (10 or 100 mg/kg) 24 h and 30 min prior to 1 h of bilateral renal warm ischemia and 2 h of reperfusion. Our data showed that 10 mg/kg of ZAC, but not 100 mg/kg, improved renal architecture and function. Also, the low dose of ZAC up-regulated antioxidant enzymes activities and glutathione level and decreased lipids and proteins oxidation. Interestingly, the use of ZAC resulted in a significant reduce of pro-inflammatory cytokines (IL-1ß, IL-6 and MCP-1), enhanced mitochondria integrity and decreased expression of the pro-apoptotic protein caspase-9. We conclude that renal I/R induced oxidative stress, inflammation and apoptosis and that the use of ZAC at 10 mg/kg, but not 100 mg/kg, protects rat kidneys from I/R injury by down-regulating these processes.

V06-11 ROBOTIC RADICAL ADRENALECTOMY FOR PHEOCHROMOCYTOMA ASSOCIATED WITH ADRENAL AND RENAL VEIN TUMOR THROMBECTOMY

You have accessJournal of UrologyAdrenal, Testis, UTUC Oncology & More1 Apr 2018V06-11 ROBOTIC RADICAL ADRENALECTOMY FOR PHEOCHROMOCYTOMA ASSOCIATED WITH ADRENAL AND RENAL VEIN TUMOR THROMBECTOMY Chirag Doshi, Parth Patel, and Gopal Gupta Chirag DoshiChirag Doshi More articles by this author , Parth PatelParth Patel More articles by this author , and Gopal GuptaGopal Gupta More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.1590AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Venous tumor thrombus due to an adrenal mass is rare, with published reports limited to individual cases and majority of them associated with adrenal cortical carcinoma. An adrenal and renal vein tumor thrombus due to a pheochromocytoma is exceedingly rare. To our knowledge, there have been no prior reports of a pheochromocytoma with adrenal and renal vein tumor thrombus managed robotically. Here we describe our technique of adrenal and renal vein tumor thrombectomy during a robotic left radical adrenalectomy. METHODS A 38 year-old gentleman presented with a left adrenal mass. Imaging studies revealed a left adrenal mass with left adrenal and renal vein tumor thrombus. Metabolic studies were suggestive of a pheochromocytoma. He was taken to the operating room for a robotic left radical adrenalectomy with renal vein tumor thrombectomy. Intraoperative ultrasound was used to delineate the extent of tumor thrombus into the left renal vein. The left renal artery, proximal and distal aspect of left renal vein and left gonadal vein were briefly controlled with vascular clamps. The adrenal vein was incised close to the renal vein and the tumor thrombus was removed en bloc with the left radical adrenalectomy specimen. The venotomy was repaired using 4-0 Prolene and the kidney was revascularized. RESULTS Renal warm ischemia time was 26 minutes, estimated blood loss was 800cc, operative time was 4.4 hours. Pathology revealed a 6.5cm pheochromocytoma with vein tumor thrombus. Surgical and vein margins were negative. Intra-operatively there were no uncontrolled or sustained hypertensive episodes. CONCLUSIONS Robotic assisted radical adrenalectomy is a feasible option for patients with associated adrenal or renal vein tumor thrombus without compromising oncologic outcome. Fundamental technical steps include use of intraoperative ultrasound, renal vascular control and renal venotomy repair. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e664 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Chirag Doshi More articles by this author Parth Patel More articles by this author Gopal Gupta More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

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

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.

Молекулярные и клеточные механизмы повреж-дения ренальной паренхимы при тепловой ишемии почки

Молекулярные и клеточные механизмы повреж-дения ренальной паренхимы при тепловой ишемии почки

Technical Intraoperative Maneuvers for the Management of Inferior Vena Cava Thrombus in Renal Cell Carcinoma.

Renal vein or inferior vena cava (IVC) invasion by neoplastic thrombus in patients with renal cell carcinoma (RCC) is not an obstacle for radical oncological treatment. The aim of this study is to present our technical maneuvers for complete removal of the intracaval thrombus without compromising hemodymanic stability of the patient. Between 2000 and 2014, 15 RCC patients with IVC involvement of levels I-III were treated with curative intent and were prospectively studied. The operative technique varied according to thrombus extent. For type I, extraction of the thrombus is facilitated by a 2-3 cm longitudinal incision on the IVC that begins at the level of the renal vein and extends cranially, encompassing a vessel wall rim of the orifice of the resected renal vein. For type II cases, the IVC is clamped above the neoplastic thrombus, and for type III, the IVC clamping is combined with hepatic blood flow control with "Pringle maneuver." For type IV, the IVC is clamped above the diaphragm, or if the thrombus extends into the right atrium cardiothoracic input is appropriate. The main operative steps include preparation and control of the renal vessels and the IVC. Occasionally, for type III tumor thrombi, the patient becomes hemodynamically unstable when IVC is clamped suprahepatically. In such a case, a novel operative maneuver of milking the thrombus below the orifice of the hepatic veins, and subsequently the IVC clamp also beneath the hepatic veins, allowing release of the "Pringle maneuver" is performed. This operative step restores hepatic blood flow and hemodynamic stability and is based on the floating nature of the thrombus into the IVC. Mean operative time was 120 min (range from 90 to 180 min), and average liver and renal warm ischemia time was 20 min (range from 15 to 35 min). Postoperative overall hospital stay ranged from 7 to 13 days. The technical solutions employed in the current study allow successful removal of neoplastic thrombi from the IVC in most cases, associated with minimal perioperative complication rate even for patients who due to multiple comorbidities would be considered otherwise inoperable.

Off-clamp robot-assisted partial nephrectomy does not benefit short-term renal function: a matched cohort analysis.

In the interest of renal functional preservation, partial nephrectomy has supplanted radical nephrectomy as the preferred treatment for T1 renal masses. This procedure usually involves the induction of renal warm ischemia by clamping the hilar vessels prior to tumor excision. Performing robot-assisted partial nephrectomy (RAPN) "off-clamp" can theoretically prevent renal functional loss associated with warm ischemia. We describe our institutional experience and compare perioperative and renal functional outcomes using a propensity score matched cohort. We conducted a retrospective comparison from a prospectively maintained database of all patients who underwent RAPN from 2009 to 2015. Of those patients, 143 underwent off-clamp RAPN. Fifty off-clamp RAPN patients were propensity score matched with fifty clamped RAPN patients based on renal function, tumor size, and R.E.N.A.L. nephrometry score. The cohorts were compared across demographics, operative information, perioperative outcomes, and renal functional outcomes. For all off-clamp RAPN patients, mean nephrometry score was 7.1, mean estimated blood loss (EBL) was 236.9mL, perioperative complication rate was 7.7%, and mean decrease in estimated glomerular filtration rate (eGFR) was 7.1% at a median follow-up of 9.2months. In the propensity score matched cohorts, off-clamp RAPN resulted in a shorter mean operative time (172.0 versus 196.0min, p=0.025) and a lower mean EBL (179.7 versus 283.2mL, p=0.046). A lower complication rate of 6.0% in the off-clamp group compared with 20.0% in the clamped group approached significance (p=0.071). Mean preoperative eGFR was similar in both cohorts. Importantly, there was no significant difference in decrease in eGFR between the clamped cohort (9.8%) and off-clamp cohort (11.9%) at a median follow-up of 9.0months (p=0.620). Off-clamp RAPN did not result in improved renal functional preservation in our experience. Surprisingly, the off-clamp cohort experienced lower intraoperative blood loss, shorter operative times, and fewer complications.

Overexpression of Human CD55 and CD59 or Treatment with Human CD55 Protects against Renal Ischemia-Reperfusion Injury in Mice.

Deficiency in the membrane-bound complement regulators CD55 and CD59 exacerbates renal ischemia-reperfusion injury (IRI) in mouse models, but the effect of increasing CD55 and CD59 activity has not been examined. In this study, we investigated the impact of overexpression of human (h) CD55 ± hCD59 or treatment with soluble rhCD55 in a mouse model of renal IRI. Unilaterally nephrectomised mice were subjected to 18 (mild IRI) or 22 min (moderate IRI) warm renal ischemia, and analyzed 24 h after reperfusion for renal function (serum creatinine and urea), complement deposition (C3b/c and C9), and infiltration of neutrophils and macrophages. Transgenic mice expressing hCD55 alone were protected against mild renal IRI, with reduced creatinine and urea levels compared with wild type littermates. However, the renal function of the hCD55 mice was not preserved in the moderate IRI model, despite a reduction in C3b/c and C9 deposition and innate cell infiltration. Mice expressing both hCD55 and hCD59, on the other hand, were protected in the moderate IRI model, with significant reductions in all parameters measured. Wild type mice treated with rhCD55 immediately after reperfusion were also protected in the moderate IRI model. Thus, manipulation of CD55 activity to increase inhibition of the C3 and C5 convertases is protective against renal IRI, and the additional expression of hCD59, which regulates the terminal complement pathway, provides further protection. Therefore, anti-complement therapy using complement regulatory proteins may provide a potential clinical option for preventing tissue and organ damage in renal IRI.

The relationship between renal warm ischemia time and glomerular loss. An experimental study in a pig model

To investigate the glomerular number after different warm ischemia times. Thirty two pigs were assigned into four groups. Three groups (G10, G20, and G30) were treated with 10, 20, and 30 minutes of left renal warm ischemia. The sham group underwent the same surgery without renal ischemia. The animals were euthanized after 3 weeks, and the kidneys were collected. Right kidneys were used as controls. The kidney weight, volume, cortical-medullar ratio, glomerular volumetric density, volume-weighted mean glomerular volume, and the total number of glomeruli per kidney were obtained. Serum creatinine levels were assessed pre and postoperatively. Serum creatinine levels did not differ among the groups. All parameters were similar for the sham, G10, and G20 groups upon comparison of the right and left organs. The G30 group pigs' left kidneys had lower weight, volume, and cortical-medullar ratio and 24.6% less glomeruli compared to the right kidney. A negative correlation was found between warm ischemia time and glomerular number. About one quarter of glomeruli was lost after 30 minutes of renal warm ischemia. No glomeruli loss was detected before 20 minutes of warm ischemia. However, progressive glomerular loss was associated with increasing warm ischemia time.

Analysis of endophytic renal tumor growth characteristic on the outcomes of robot-assisted laparoscopic partial nephrectomy

Objective To analyze the effect of endophytic renal tumor growth characteristic on the short-term outcomes of robot-assisted laparoscopic partial nephrectomy (RALPN). Methods From March 2015 to October 2016, 23 RALPN cases of endophytic renal masses and 68 RALPN cases of intermediate and exophytic renal tumors were retrospectively analyzed. There were no significant differences in age, gender, tumor side, history of abdominal surgery, benign and malignant cases of the two groups of patients (P>0.05). Patients with a completely endophytic mass had smaller tumors [(2.4±0.5)cm vs.(3.9±1.1)cm], and higher overall R. E.N.A.L. score (P<0.05). The differences of perioperative period and postoperative follow-up results were analyzed. Results All 91 RALPN cases were successfully done without conversion to open or radical nephrectomy. There were no significant differences in intraoperative blood loss, postoperative Hb decrease, intraoperative and postoperative blood transfusion rate, hospital days, positive tumor margins, and the incidence of Clavien-Dindo grade Ⅲ or above in the two groups (P>0.05). The endophytic group showed longer operative time[(95.6± 19.4)min vs.(75.3±16.9)min ], and longer renal warm ischemia [(25.2±5.4)min vs.(17.6±7.0)min]. In the postoperative follow-up of 3 months to 22 months, all patients got disease-free survival. Conclusions RALPN for completely intraparenchymal renal tumors can be safely and effectively performed in experienced institutes. However, the long-term period of follow-up is still missing. Key words: Endophytic renal masses; Robot-assisted laparoscopic; Partial nephrectomy

Glomerular loss after arteriovenous and arterial clamping for renal warm ischemia in a swine model.

To evaluate the glomerular loss after arteriovenous or arterial warm ischemia in a swine model. Twenty four pigs were divided into Group Sham (submitted to all surgical steps except the renal ischemia), Group AV (submitted to 30 minutes of warm ischemia by arteriovenous clamping of left kidney vessels), and Group A (submitted to 30 minutes of ischemia by arterial clamping). Right kidneys were used as controls. Weigh, volume, cortical volume, glomerular volumetric density (Vv[Glom]), volume-weighted glomerular volume (VWGV), and the total number of glomeruli were measured for each organ. Group AV showed a 24.5% reduction in its left kidney Vv[Glom] and a 25.4% reduction in the VWGV, when compared to the right kidney. Reductions were also observed when compared to kidneys of sham group. There was a reduction of 19.2% in the total number of glomeruli in AV kidneys. No difference was observed in any parameters analyzed on the left kidneys from group A. Renal warm ischemia of 30 minutes by arterial clamping did not caused significant glomerular damage, but arteriovenous clamping caused significant glomerular loss in a swine model. Clamping only the renal artery should be considered to minimize renal injury after partial nephrectomies.

Ouabain Contributes to Kidney Damage in a Rat Model of Renal Ischemia-Reperfusion Injury.

Warm renal ischemia performed during partial nephrectomy has been found to be associated with kidney disease. Since endogenous ouabain (EO) is a neuro-endocrine hormone involved in renal damage, we evaluated the role of EO in renal ischemia-reperfusion injury (IRI). We measured plasma and renal EO variations and markers of glomerular and tubular damage (nephrin, KIM-1, Kidney-Injury-Molecule-1, α1 Na-K ATPase) and the protective effect of the ouabain inhibitor, rostafuroxin. We studied five groups of rats: (1) normal; (2) infused for eight weeks with ouabain (30 µg/kg/day, OHR) or (3) saline; (4) ouabain; or (5) saline-infused rats orally treated with 100 µg/kg/day rostafuroxin for four weeks. In group 1, 2–3 h after IRI, EO increased in ischemic kidneys while decreased in plasma. Nephrin progressively decreased and KIM-1 mRNA increased starting from 24 h. Ouabain infusion (group 2) increased blood pressure (from 111.7 to 153.4 mmHg) and ouabain levels in plasma and kidneys. In OHR ischemic kidneys at 120 h from IRI, nephrin, and KIM-1 changes were greater than those detected in the controls infused with saline (group 3). All these changes were blunted by rostafuroxin treatment (groups 4 and 5). These findings support the role of EO in IRI and suggest that rostafuroxin pre-treatment of patients before partial nephrectomy with warm ischemia may reduce IRI, particularly in those with high EO.

Allopurinol Protective Effect of Renal Ischemia by Downregulating TNF-α, IL-1β, and IL-6 Response

ABSTRACTAllopurinol is a well-known antioxidant that protects tissue against ischemia and reperfusion injury, blocking purine catabolism, and possibly reducing TNF-α and other cytokines. It also plays a significant role in reducing the inflammatory processes by inhibiting chemotaxis and other inflammatory mediators. The objective of this study was to define the role of allopurinol regarding kidney ischemic injury particularly as to its effect on inflammatory molecules such as TNF-α, IL-1β, and IL-6 response. One hundred and twenty five rats were subjected to warm renal ischemia. Five more animals were included as sham. Animal survival and plasma levels of lipid peroxidation, myeloperoxidase, lactate dehydrogenase, glutathione, urea, creatinine, and cytokines were determined. Inflammatory parameters (TNF-α, IL-1β, and IL-6) were measured in all groups by quantitative immunosorbent assay. Further, immunohistological and histopathological studies were carried out on animals treated prior to, or following reperfusion with 10 and 50 mg/kg of Allopurinol. The statistical analysis included ANOVA and Fisher test as well as χ2 test. Significance was reached at a p < 0.05. The results of this study indicated that Allopurinol protected against kidney ischemia–reperfusion injury since significantly better results of survival, biochemical analysis, and histopathological testing were observed in treated animals as compared to ischemic controls. In conclusion, Allopurinol protected ischemic kidneys through a mechanism associated with downregulation of TNF-α, IL-1 β, and IL-6, in addition to other well-known effects such as decreased lipid peroxidation and neutrophil activity. It also increased antioxidant capacity and diminished endogenous peroxidase stain in renal ischemic tissue. Therefore, this experiment showed an effectiveness of allopurinol protection against proteomic and morphological damage.

Efficacy of allogeneic mesenchymal stem cell administration in a model of acute ischemic kidney injury in cats

ObjectiveTo evaluate the effects of allogeneic mesenchymal stem cells (MSCs) in a model of ischemic acute kidney injury (AKI). Study designRandomized controlled trial. AnimalsAdult, purpose-bred research cats (n=15) and a historical reference group (n=3). MethodsCats underwent unilateral, in vivo, warm renal ischemia, then intravenous administration of 4 million adipose-derived MSCs, bone marrow-derived MSCs, or fibroblasts (n=5/treatment) 1h after reperfusion. Serum creatinine and blood urea nitrogen concentrations were measured at baseline and days 1 and 6. Urine specific gravity, urine protein to urine creatinine ratio, and glomerular filtration rate were measured at baseline and day 6. Both kidneys were harvested on day 6; histopathology was described and scored and smooth muscle actin was quantified with histomorphometry. A 2-way ANOVA was used to compare time and treatment. Chi square analysis was used to determine the % of cats with at least International Renal Interest Society (IRIS) Grade 1 AKI. ResultsTime, but not treatment, had a significant effect on renal function. No difference was noted in % of cats with IRIS AKI. Significantly fewer mitotic figures were observed in ischemic kidneys that received bone-marrow derived MSCs vs. fibroblasts. No differences in smooth muscle actin staining were noted. ConclusionsThis study did not support the use of allogeneic MSCs in AKI in the regimen described here. Type of renal injury, MSC dose, allogenicity, duration, and route or timing of administration could influence the efficacy MSCs.

Robot-assisted Laparoscopic Inferior Vena Cava Thrombectomy: Different Sides Require Different Techniques

BackgroundThe safety and feasibility of robot-assisted laparoscopic inferior vena cava (IVC) thrombectomy (RAL-IVCTE) have been investigated in limited reports. ObjectiveTo share our initial experience with RAL-IVCTE, as well as describe respectively the detailed techniques for RAL-IVCTE for left or right renal cell carcinoma (RCC). Design, setting, and participantsFrom May 2013 to July 2014, 17 patients with RCC involving IVC tumor thrombus were admitted to our hospital. Surgical procedureFor right RCC, the caudal IVC, left renal vein, and cephalic IVC were sequentially clamped. The IVC wall was cut, and the thrombus was removed. For left RCC, the left renal vein, which included the thrombus, was ligated with Endo-GIA. The caudal IVC, right renal artery, right renal vein, and cephalic IVC were sequentially clamped. MeasurementsThe detailed techniques for RAL-IVCTE for different sides were described and the perioperative outcomes recorded. Results and limitationsThe operations were successfully performed without open conversion. Median operation time was 131min (100–150min) and 250min (190–275min) for the right and left RCC, respectively. Median estimated blood loss was 240ml (145–320ml). Median IVC blocking time was 17min (12–25min). For left RCC, median warm ischemia time for the right kidney was 18min (14–22min). A grade IV complication—bleeding from tributaries of the IVC—developed in one case and was successfully resolved with intraoperative endoscopic suture. ConclusionsRAL-IVCTE is safe and feasible. For left RCC involving IVC thrombus, right renal warm ischemia time is necessary during the procedure, requiring a more advanced technical skill. The therapeutic effect and overall survival rate require further investigation with a larger sample size and longer follow-up. Patient summaryRobot-assisted laparoscopic inferior vena cava thrombectomy is technically challenging but safe and feasible. The therapeutic effect needs further investigation.

N-octanoyl dopamine treatment exerts renoprotective properties in acute kidney injury but not in renal allograft recipients.

N-octanoyl dopamine (NOD) treatment improves renal function when applied to brain dead donors and in the setting of warm ischaemia-induced acute kidney injury (AKI). Because it also activates transient receptor potential vanilloid type 1 (TRPV1) channels, we first assessed if NOD conveys its renoprotective properties in warm ischaemia-induced AKI via TRPV1 and secondly, if renal transplant recipients also benefit from NOD treatment. We induced warm renal ischaemia in Lewis, wild-type (WT) and TRPV1(-/-) Sprague-Dawley (sd) rats by clamping the left renal artery for 45 min. Transplantations were performed in allogeneic and syngeneic donor-recipient combinations (Fisher to Lewis and Lewis to Lewis) with a cold ischaemia time of 20 h. Treatment was instituted directly after restoration of organ perfusion. Renal function, histology and perfusion were assessed by serum creatinine, microscopy and magnetic resonance imaging (MRI) using arterial spin labelling (ASL). NOD treatment significantly improved renal function in Lewis rats after warm ischaemia-induced AKI. It was, however, not effective after prolonged cold ischaemia. The renoprotective properties of NOD were only observed in Lewis or WT, but not in TRPV1(-/-) sd rats. Renal inflammation was significantly abrogated by NOD. MRI-ASL showed a significantly lower cortical perfusion in ischaemic when compared with non-ischaemic kidneys. No overall differences were observed in renal perfusion between NOD- and NaCl-treated rats. NOD treatment reduces renal injury in warm ischaemia, but is not effective in renal transplant in our experimental animal models. The salutary effect of NOD appears to be TPRV1-dependent, not involving large changes in renal perfusion.

Ischaemic conditioning reduces kidney injury in an experimental large-animal model of warm renal ischaemia

Ischaemic conditioning, using short repeated sequences of intermittent ischaemia, is a strategy that may ameliorate ischaemia-reperfusion injury. The aim of the study was to assess the effects of direct and remote ischaemic conditioning in a porcine model of renal warm ischaemia-reperfusion injury. Pigs (50 kg) underwent laparotomy and 60-min occlusion of the left renal pedicle followed by right nephrectomy. Animals were divided into three groups: untreated controls (n = 8); direct postconditioning involving six 15-s cycles of clamping then releasing of the left renal artery (n = 7); or remote periconditioning involving four 5-min cycles of clamping then releasing of the left common iliac artery (n = 8). After 7 days kidney tissue was harvested, and blood and urine samples were collected on postoperative days 1, 3 and 7. The direct postconditioning group had a lower area under the serum creatinine curve (mean(s.d.) 1378(157) versus 2001(1022) µmol/l · day respectively; P = 0.036) and peak creatinine level (316(46) versus 501(253) µmol/l respectively; P = 0.033) compared with values in control animals. There was a significant increase in serum levels of tumour necrosis factor α on day 1 in control animals but not in the conditioning groups (P = 0.013). Urinary levels of neutrophil gelatinase-associated lipocalin increased over the study period in both the control and remote groups (P = 0.001 for both), but not in the direct group (P = 0.176). There was no mortality and no complications related to either conditioning technique. In this in vivo large-animal model, direct renal artery ischaemic postconditioning protected kidneys against warm ischaemia injury. This straightforward technique could readily be translated into clinical practice. Surgical relevance Ischaemic conditioning has been shown to improve outcomes in both experimental studies and clinical trials in cardiac surgery. Evidence from small-animal and human studies assessing ischaemic conditioning techniques in renal transplantation have not yet established the optimal technique and timing of conditioning. In this study, a large-animal model of renal warm ischaemia was used to compare different conditioning techniques. Postconditioning applied directly to the renal artery was shown to reduce renal injury. Furthermore, new evidence is provided that shorter cycles of ischaemic postconditioning than previously described can protect against renal injury. Evidence from a large-animal model is provided for different conditioning techniques. The beneficial postconditioning technique described is straightforward to perform and provides an alternative method of conditioning following renal transplantation, with potential for application in clinical practice.

The effect of warm ischemia duration on renal function early after laparoscopic partial nephrectomy

Objective To assess the effect of variable durations of warm ischemia on renal function early after laparoscopic partial nephrectomy (LPN) and make the definite safety duration of renal warm ischemia. Methods The clinical data of 76 patients treated with LPN from October 2012 to June 2014 were retrospectively analyzed. The patients were divided into 3 groups based on warm ischemic time, namely group A (28 cases) with warm ischemia time less than 20 min, group B (34 cases) with warm ischemia time more than 20 min and less than 30 min, group C (14 cases) with warm ischemia time more than 30 min.LPN was performed with renal artery clamping alone in all the patients.Preoperative and postoperative renal scintigraphic scan was performed to access glomerular filtration rate (GFR) in all patients.The GFR values were compared among before, 1 week, 1 month and 3 months after operation.The factors predicting the early renal injury were assessed by multivariate regression analysis. Results The renal GFR of the kidney underwent LPN decreased 19.43(17.70, 22.06) ml/min at 1 week, 17.04(13.94, 20.70) ml/min at 1 month, 13.82(10.72, 18.73) ml/min at 3 months after the surgery in group C, respectively.In group A, the renal GFR of the operated-side decreased 12.07(10.91, 13.42) ml/min, 10.04(9.16, 11.75) ml/min, 8.44(7.07, 9.72) ml/min, respectively.In group B, the renal GFR of the operated-side decreased 13.64(12.48, 16.72) ml/min, 10.29(9.17, 14.27)ml/min, 9.63(7.85, 12.59) ml/min, respectively.The GFR decreased greater in group C than that in group A and B(P 0.05). The multivariate regression analysis revealed that warm ischemia duration was the independent risk factor of the early renal injury. Conclusions Warm ischemia duration is the major factor regarding the early renal recovery after LPN.Warm ischemia time more than 30 min may not only greatly affect the renal function but also the renal function recovery rate. Key words: Laparoscopes; Nephrectomy; Warm ischemia; Renal function