Warm Ischemic Kidney Research Articles

228.2: Efficacy of organ preservation at 22°C with extracellular-type preservation solutions in 2-hour warm ischemic kidney - Evaluation using a renal transplant model in MHC-inbred CLAWN miniature swine.

228.2: Efficacy of organ preservation at 22°C with extracellular-type preservation solutions in 2-hour warm ischemic kidney - Evaluation using a renal transplant model in MHC-inbred CLAWN miniature swine.

#1887 Comparison of the efficacy of preservation at 22°C versus 4°C in warm ischemic kidneys from MHC-inbred CLAWN miniature swine

Abstract Background and Aims Static cold preservation, the standard in transplantation, is primarily aimed at reducing metabolic and oxygen demand. Kidney transplantation from donors after cardiac death (DCD) addresses the shortage of donor organs, but these kidneys are susceptible to cold preservation. A previous study using small animal models demonstrated the potential benefits of preserving DCD kidneys at a warmer temperature of 22°C using extracellular-type solutions (Iwai S., PLoS One 2012). Based on this foundational research, our study aimed to evaluate the efficacy of preserving warm ischemic kidneys at temperatures of either 4°C or 22°C using preclinical large animal miniature swine models. Method After 2 hours of warm ischemia, the pig kidneys were preserved for 60 minutes at either 4°C or 22°C with extracellular-type solutions (ETK®). In Experiment 1, these preserved kidneys underwent ex-vivo perfusion for 120 minutes at 37°C with a mean arterial pressure of 85 mmHg. This perfusion used a Ringer's solution supplemented with red blood cells, aiming to determine the early functionality of kidneys subjected to 2-hour warm ischemia in transplantation and to assess whether preservation at 4°C or 22°C could maintain renal function during the acute postoperative period (n = 3 in each group). During this period, both physiological parameters (renal blood flow, intrarenal resistance, and urine output) and metabolic parameters (oxygen consumption) were evaluated. In Experiment 2, kidneys that underwent similar warm ischemia and preservation procedures were transplanted into MHC-matched recipients. These recipients received continuous tacrolimus treatment for 12 days to minimize rejection due to minor antigen differences. After transplantation, renal function was monitored and assessed by serum creatinine levels and renal biopsies for 14 days (n = 3 in each group). Results Experiment 1 demonstrated that kidneys subjected to 2 hours of warm ischemia and then preserved at 22°C had better physiological and metabolic indices during a subsequent 2-hour ex-vivo perfusion compared to those preserved at 4°C. The results were as follows: 22°C vs. 4°C—mean renal blood flow (27 ± 5 vs. 10 ± 0 ml/min), intrarenal resistance (3.5 ± 0.5 vs. 8.7 ± 0.1 mmHg/ml/min), total urine volume (14 ± 5 vs. 5 ± 4 ml), and oxygen consumption (224 ± 39 vs. 93 ± 16 ml/min/g). Importantly, there was no complete cessation of blood flow in either group, indicating the potential for long-term evaluation using a transplantation model. In Experiment 2, kidneys preserved at 22°C resulted in significantly lower peak post-transplant serum creatinine levels compared to those preserved at 4°C (3.9 ± 0.6 mg/dl vs 8.9 ± 0.3 mg/dl, p = 0.0015). There was a marked decrease in the area under the curve of creatinine from day 0 to day 14, with a 36% reduction from 61 mg/dL per day in the 4°C group to 39 mg/dL per day in the 22°C group. Renal biopsies performed on post-operative day 4 revealed extensive necrosis in the renal tubules of kidneys stored at 4°C. In contrast, kidneys preserved at 22°C showed more localized damage. In addition, PCNA staining indicated accelerated regeneration of the tubular epithelium in kidneys preserved at 22°C. Conclusion This study demonstrates that kidneys subjected to 2 hours of warm ischemia from MHC-inbred miniature swine are more effectively preserved at 22°C than at 4°C when using an extracellular-type solution. To our knowledge, this is the first report demonstrating the efficacy of organ preservation at 22°C in clinically relevant, large animal models. From the evaluation of ex-vivo perfusion of preserved kidneys, it was suggested that kidneys preserved at 22°C maintain better blood perfusion to severely ischemic kidneys immediately after transplantation, which leads to the rapid recovery of renal function of acute kidney injury. Future research will focus on elucidating the mechanisms underlying the superior outcomes associated with 22°C preservation. In addition, investigations will be conducted to determine whether similar benefits can be achieved using intracellular-type solutions, which are more commonly used in renal transplantation.

Salvaging donated kidneys from prolonged warm ischemia during ex vivo hypothermic oxygenated perfusion

Prolonged warm ischemic is the main cause discarding donated organs after cardiac death. Here, we identified that prolonged warm ischemic time induced disseminated intravascular coagulation and severe capillary vasospasm after cardiac death of rat kidneys. Additionally, we found a significant accumulation of fibrinogen in a hypoxic cell culture of human umbilical vein epithelial cells and in isolated kidneys exposed to prolonged warm ischemic following flushing out of blood. However, pre-flushing the kidney with snake venom plasmin in a 90-minute warm ischemic model maximized removal of micro thrombi and facilitated the delivery of oxygen and therapeutic agents. Application of carbon monoxide releasing CORM-401 during ex vivo hypothermic oxygenated perfusion achieved multipath protective effects in prolonged warm ischemic kidneys. This led to significant improvements in perfusion parameters, restoration of the microcirculation, amelioration of mitochondrial injury, oxidative stress, and apoptosis. This benefit resulted in significantly prolonged warm ischemic kidney recipient survival rates of 70%, compared with none in those receiving ex vivo hypothermic oxygenated perfusion alone. Significantly, ex vivo hypothermic oxygenated perfusion combined with cytoprotective carbon monoxide releasing CORM-401 treatment meaningfully protected the donated kidney after cardiac death from ischemia-reperfusion injury by reducing inflammation, oxidative stress, apoptosis, and pathological damage. Thus, our study suggests a new combination treatment strategy to potentially expand the donor pool by increasing use of organs after cardiac death and salvaging prolonged warm ischemic kidneys.

Evaluation of the safety of retroperitoneal laparoscopic partial nephrectomy by investigating the perioperative indicators.

In recent years, open nephron sparing partial nephrectomy (OPN) has been gradually applied and generally accepted. Recent statistical data show that PN not only can safely and effectively preserve the functional nephron, but also has fewer complications, low local recurrence rate and no significant difference in long-term survival rate compared with nephrectomy/radical nephrectomy, which has gradually become a routine treatment for small renal cell carcinoma. Therefore, how to maximize the protection of postoperative residual renal function (RRF) and reduce the risk of CKD while achieving the ideal local and overall tumor control effect is the key to the treatment of renal cancer, and is also the focus of attention of urologists and nephrologists. To evaluate the safety of retroperitoneal laparoscopic partial nephrectomy (RLPN) by investigating the perioperative indicators and postoperative follow-up. A total of 40 hospitalized patients in our hospital from December 2019 to December 2021 were selected and followed up for a long time. Patients with renal tumors less than 4cm in diameter and exogeneous or partial exogeneity were randomly divided into 2 groups. Patients in retroperitoneal laparoscopic group (n = 20) were treated with nephron sparing partial nephrectomy (0.5-1cm). Twenty patients underwent retroperitoneal laparoscopic radical nephrectomy (LRN).The time of removal of drainage tube, drainage volume, time of feeding activity and postoperative hospital stay were recorded, and the safety of the operation was evaluated. nephron sparing partial nephrectomy is suitable for patients with localized renal carcinoma or benign tumor <4cm. RLPN can be applied to all indications of open nephron sparing partial nephrectomy (OPN), with good safety, and can preserve residual renal function to the greatest extent. The operative vascular occlusion time was controlled within 40 minutes, and the use of renal function protection measures during the operation was safe and controllable in reducing the prevention of warm ischemic kidney damage, with good safety. The renal tumor capsule with 0.5cm~1cm margin was complete by postoperative pathology. In the process of tumor resection and suture collection system in the RLPN group, we improved the previous operation of "resection before hemostasis" to "resection while hemostasis" and "knot-free suture" technology, which saved the operation time of intracavity suture knotting. Reduced cortical tear caused by vertical pull during knot tying. The combined effect of biological clip and hemostatic gauze can stimulate the granulation proliferation of renal cortical wound and accelerate the repair. With the combination of knot-free suture and renal segment vascular occlusion, hot ischemic kidney damage is reduced. In the RLPN group, there were no complications of urinary fistula and bleeding, and no abnormal changes in renal function during follow-up. The safety of RLPN group is worthy of affirmation. The perioperative safety and short-term postoperative renal function recovery of RLPN are good, and the overall safety of this operation is worthy of affirmation.

Extracellular histone release by renal cells after warm and cold ischemic kidney injury: Studies in an ex-vivo porcine kidney perfusion model.

Extracellular histones are cytotoxic molecules involved in experimental acute kidney injury. In patients receiving a renal transplant from donors after circulatory death, who suffer from additional warm ischemia, worse graft outcome is associated with higher machine perfusate extracellular histone H3 concentrations. We now investigated temperature-dependent extracellular histone release in an ex vivo porcine renal perfusion model, and subsequently studied histone release in the absence and presence of non-anticoagulant heparin. Seven pairs of ischemically damaged porcine kidneys were machine perfused at 4°C (cold ischemia) or 28°C (warm ischemia). Perfusate histone H3 concentration was higher after warm as compared to cold ischemia (median (IQR) = 0.48 (0.20-0.83) μg/mL vs. 0.02 (0.00-0.06) μg/mL; p = .045, respectively). Employing immune-electron microscopy (EM), histone containing cytoplasmic protrusions of tubular and endothelial cells were found after warm ischemic injury. Furthermore, abundant histone localization was detected in debris surrounding severely damaged glomerular cells, in a "buck shot" pattern. In vitro, histones were cytotoxic to endothelial and kidney epithelial cells in a temperature-dependent manner. In a separate ex vivo experiment, addition of heparin did not change the total histone H3 levels observed in the perfusate but revealed a continuous increase in the level of a lower molecular weight histone H3 variant. Our findings show that ischemically damaged kidneys release more extracellular histones in warm ischemia, which by EM was due to histone release by renal cells. Blocking of histone-mediated damage during transplantation may be beneficial in prevention of renal injury.

Impact of Warm Ischemia on Acute Kidney Injury After Robotic Partial Nephrectomy Stratified by Baseline Kidney Function.

Objectives: To evaluate the differences in baseline chronic kidney disease (CKD) status in correlations between warm ischemic time (WIT) and acute kidney injury (AKI) or acute/chronic renal function change after robot-assisted partial nephrectomy (RAPN). Methods: This study retrospectively recruited 1290 patients from a multi-institutional RAPN database. The patients were grouped into four preoperative CKD categories: CKD Group 1 (CKDG1), CKD Group 2 (CKDG2), CKD Group 3a (CKDG3a), and CKD Group 3b (CKDG3b). The correlation between WIT and the probability of AKI was assessed according to the baseline CKD grade, together with changes in serum creatinine (sCr) at the postoperative maximum and chronic renal function. Results: AKI was not observed in the CKDG1 group. The probability of AKI at WIT = 30 minutes was 5.6% for CKDG2, 8.5% for CKDG3a, and 11.6% for CKDG3b (all p < 0.05). WIT was an independent predictor of AKI occurrence in the multivariate model for these three CKD groups. Significant weak correlations were observed between WIT and sCr change for all four groups, with R2 = 0.22 for CKDG1, R2 = 0.16 for CKDG2, R2 = 0.03 for CKDG3a, and R2 = 0.09 for ≥CKDG3b. For chronic renal function, correlations were significant in CKDG2, CKDG3a, and ≥CKDG3b, yet R2 was considered small in all cases (<0.1). Conclusions: The association between extended WIT and the probability of AKI increased in patients with more severe baseline CKD. The correlation between WIT and renal function was significant, yet clinically modest.

Effectiveness of a machine perfusion preservation system, developed by industry-academic collaboration for warm ischemic porcine kidney

Effectiveness of a machine perfusion preservation system, developed by industry-academic collaboration for warm ischemic porcine kidney

Effects of Static Subnormothermic Preservation on Extended Warm Ischemic Porcine Kidneys Assessed by Normothermic Machine Perfusion and Renal Transplantation

Effects of Static Subnormothermic Preservation on Extended Warm Ischemic Porcine Kidneys Assessed by Normothermic Machine Perfusion and Renal Transplantation

598 Is a short pulsatile hypothermic perfusion just before the transplant beneficial for the graft in the setting of warm ischemic kidneys?

598 Is a short pulsatile hypothermic perfusion just before the transplant beneficial for the graft in the setting of warm ischemic kidneys?

Beneficial Effect of Short Pretransplant Period of Hypothermic Pulsatile Perfusion of the Warm-Ischemic Kidney after Cold Storage: Experimental Study.

Warm ischemia (WI) produces a significant deleterious effect in potential kidney grafts. Hypothermic machine perfusion (HMP) seems to improve immediate graft function after transplant. Our aim was to analyze the effect of short pretransplant periods of pulsatile HMP on histology and renal injury in warm-ischemic kidneys. Twelve minipigs were used. WI was achieved in the right kidney by applying a vascular clamp for 45 min. After nephrectomy, autotransplant was performed following one of two strategies: cold storage of the kidneys or cold storage combined with perfusion in pulsatile HMP. The graft was removed early to study renal morphology, inflammation (fibrosis), and apoptosis. Proinflammatory activity and fibrosis were less pronounced after cold storage of the kidneys with HMP than after cold storage only. The use of HMP also decreased apoptosis compared with cold storage only. The detrimental effects on cells of an initial and prolonged period of WI seem to improve with a preservation protocol that includes a short period of pulsatile HMP after cold storage and immediately before the transplant, in comparison with cold storage only.

Assessment of eGFR and One-Hour Biopsy Using In-Situ-Cooling Double-Balloon Catheters in Deceased Kidney Transplants.

Introduction and Objectives:The shortage of deceased donor kidneys for transplantation has become a worldwide issue in the past decades. However, both availability and feasibility of marginal deceased donor kidneys are still problematic. To increase donor pool, we created a specially designed in-situ cooling system. The purpose of this study was to estimate availability of deceased donor kidneys, analyze donor one-hour biopsy, and better evaluate methods to estimate donor/recipient kidney function other than using donor Cr, comparing with living related transplants. Materials and Methods:We studied 129 deceased renal transplant recipients (DD) who received kidneys from non-heart-beating donors beginning in 1984. Donors were in Maastricht Donor Categories III and IV and to minimize warm ischemic kidney damage we performed in situ cooling with specially designed double-balloon catheters. Twenty-nine living-related transplants (LD) were a control group. Results:In the DD group average donor Cr and eGFR levels at admission were 0.3-2.1mg/dl (ave. 1.0) and 24-138 ml/min/1.73 (ave. 67) and levels before death were 0.3-15.9 (2.7) and 4-164 (34). Average recipient Cr and eGFR levels at discharge were 0.3-5.3 (1.8) and .10-133 (39). To define kidney function after transplant, the DD were classified according to recipient eGFR at discharge: <25 for the poor function group (PF: n=32) and >25 for the good function group (GF: n=95). GF had higher eGFR levels at donor hospital admission than the PF (p=0.005). There was no statistically significant difference in Cr levels of donor (at admission and before death) between those groups. Pathologically, the DD with less glomerular sclerosis of 1-hour biopsies had better graft survival than damaged subjects (p=0.015). Other histological scores were not associated with kidney survival. Conclusion:Deceased kidney transplants had excellent renal function with our double balloon catheter system. Compared with donor Cr levels, eGFR and 1-hour biopsy could be useful for donor evaluation and transplant renal function.

606 Beneficial effect of a short-period of hypothermic pulsatile machine perfusion of warm ischemic kidneys just before the transplant. Experimental study

606 Beneficial effect of a short-period of hypothermic pulsatile machine perfusion of warm ischemic kidneys just before the transplant. Experimental study

Assessment of eGFR and One-Hour Biopsy in Living-Related and Deceased Kidney Transplants with Using In-Situ-Cooling Double-Balloon Catheters

Introduction: The worldwide shortage of deceased donor kidneys for transplantation has become a serious issue in the past decade and marginal donor kidneys have been studied. However, both availability and feasibility of marginal deceased donor kidneys are still problematic. Some kidney donor candidates have been rejected because of increased creatinine(Cr) levels prior to death, while some transplants have had good renal function in spite of the high Cr levels of the donors. In order to reduce the discarded donor kidney rate, we performed specially designed in-situ cooling system. The aim of the present study was to estimate availability of deceased donor kidney with using our in-situ-cooling system, analyze donor one-hour biopsy, and find better evaluation method to estimate donor kidney function rather than using donor Cr, comparing with living related transplants. Methods: We studied 129 deceased renal transplant recipients (DD) who received kidneys from non-heart-beating donors beginning in 1984. Calcineurin Inhibitors were given to all transplants. Donors were in Maastricht Donor Categories III and IV and to minimize warm ischemic kidney damage we performed in situ cooling with specially designed double-balloon catheters. One-hour biopsies were analyzed with Remuzzi's evaluation system, and were scored for glomerulosclerosis, tubular atrophy, interstitial fibrosis and vascular narrowing. Twenty-nine living-related transplants (LD) were a control group. Results: In the DD group average donor Cr and eGFR levels at admission were 0.3-2.1 mg/dl (ave. 1.0) and 24-138 ml/min/1.73 (ave. 67) and levels before death were 0.3-15.9 (2.7) and 4-164 (34). Average recipient Cr and eGFR levels at discharge were 0.3-5.3 (1.8) and .10-133 (39). Although average donor Cr levels before death were high, the DD had good function using our catheter system. To define kidney function after transplant, the DD were classified according to recipient eGFR at discharge: < 25 ml/min/1.73 for the poor function group (PF: n=32) and >25 for the good function group (GF: n=95). GF had higher eGFR levels at donor hospital admission than the PF (p=0.005). There was no statistically significant difference in Cr levels of donor (at admission and before death) between those groups. Pathologically, the DD with less glomerular sclerosis of 1-hour biopsies had better graft survival than damaged subjects (p=0.015). Other histological scores were not associated with kidney survival. In mild-damaged histological scores, discharge-eGFR levels of DD and LD were the same with no statistically significant difference, although DD had poorer function than LD in less-damaged scores. Conclusions: Deceased kidney transplants had excellent renal function with our double balloon catheter system. Donor Cr levels were not a useful measurement for our analysis, but eGFR and 1-hour biopsy should be used for donor evaluation and transplant renal function.

2266 ASSESSMENT OF EGFR AND ONE-HOUR BIOPSY USING IN-SITU-COOLING DOUBLE-BALLOON CATHETERS IN DECEASED KIDNEY TRANSPLANTS

You have accessJournal of UrologyTransplantation & Vascular Surgery: Renal Transplantation, Vascular Surgery II1 Apr 20122266 ASSESSMENT OF EGFR AND ONE-HOUR BIOPSY USING IN-SITU-COOLING DOUBLE-BALLOON CATHETERS IN DECEASED KIDNEY TRANSPLANTS Kazuo Mizutani, Ryohei Hattori, Tsuneo Kinukawa, Osamu Kamihira, and Momokazu Gotoh Kazuo MizutaniKazuo Mizutani Nagoya, Aichi, Japan More articles by this author , Ryohei HattoriRyohei Hattori Nagoya, Japan More articles by this author , Tsuneo KinukawaTsuneo Kinukawa Nagoya, Japan More articles by this author , Osamu KamihiraOsamu Kamihira Komaki, Japan More articles by this author , and Momokazu GotohMomokazu Gotoh Nagoya, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.2444AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The shortage of deceased donor kidneys for transplantation has become a worldwide issue in the past decades. However, both availability and feasibility of marginal deceased donor kidneys are still problematic. To increase donor pool and improve results, we created a specially designed in-situ cooling system. The purpose of this study was to estimate availability of deceased donor kidneys, analyze donor one-hour biopsy, and better evaluate methods to estimate donor/recipient kidney function other than using donor Cr, comparing with living related transplants. METHODS We studied 129 deceased renal transplant recipients (DD) who received kidneys from non-heart-beating donors beginning in 1984. Calcineurin Inhibitors were given to all transplants. Donors were in Maastricht Donor Categories III and IV and to minimize warm ischemic kidney damage we performed in situ cooling with specially designed double-balloon catheters. One-hour biopsies were analyzed with Remuzzi's evaluation system, and were scored for histological assessment. Twenty-nine living-related transplants (LD) were a control group. RESULTS In the DD group average donor Cr and eGFR levels at admission were 0.3-2.1mg/dl (ave. 1.0) and 24-138 ml/min/1.73 (ave. 67) and levels before death were 0.3-15.9 (2.7) and 4-164 (34). Average recipient Cr and eGFR levels at discharge were 0.3-5.3 (1.8) and .10-133 (39). Although average donor Cr levels before death were high, the DD had good function using our catheter system. To define kidney function after transplant, the DD were classified according to recipient eGFR at discharge: <25 ml/min/1.73 for the poor function group (PF: n=32) and >25 for the good function group (GF: n=95). GF had higher eGFR levels at donor hospital admission than the PF (p=0.005). There was no statistically significant difference in Cr levels of donor (at admission and before death) between those groups. Pathologically, the DD with less glomerular sclerosis of 1-hour biopsies had better graft survival than damaged subjects (p=0.015). Other histological scores were not associated with kidney survival. In mild-damaged histological scores, discharge-eGFR levels of DD and LD were the same with no statistically significant difference, although DD had poorer function than LD in less-damaged scores. CONCLUSIONS Deceased kidney transplants had excellent renal function with our double balloon catheter system. Donor Cr levels were not a useful measurement for our analysis, but eGFR and 1-hour biopsy should be used for donor evaluation and transplant renal function. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e914 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kazuo Mizutani Nagoya, Aichi, Japan More articles by this author Ryohei Hattori Nagoya, Japan More articles by this author Tsuneo Kinukawa Nagoya, Japan More articles by this author Osamu Kamihira Komaki, Japan More articles by this author Momokazu Gotoh Nagoya, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Intravenous Sildenafil as a Preconditioning Drug Against Hemodynamic Consequences of Warm Ischemia-Reperfusion on the Kidney

We designed an experimental model of renal ischemia-reperfusion to evaluate the preemptive effect of intravenous sildenafil according to the dose administered (0.7 vs 1.4 mg/kg) and the time of administration (30 minutes before ischemia or during ischemia). A total of 20 minipigs were divided into groups of 4 each, including group 1-control, group 2-sildenafil 0.7 mg/kg intravenously 30 minutes before vascular clamping, group 3-sildenafil 0.7 mg/kg intravenously during warm ischemia, group 4-sildenafil 1.4 mg/kg intravenously 30 minutes before vascular clamping and group 5-sildenafil 1.4 mg/kg intravenously during warm ischemia. The ischemia-reperfusion model was applied using laparotomy and right kidney vascular clamping for 30 minutes, followed by unclamping and reperfusion for 45 minutes. Renal vascular flow and systemic mean arterial pressure were recorded for 45 minutes after unclamping. Mean values were compared using Student t test with significance considered at p <0.05. Sildenafil led to a decrease in arterial pressure compared to that in controls, especially at the dose of 1.4 vs 0.7 mg/kg, including 113.77, 109.76, 106.12, 97.41 and 82.85 mm Hg in groups 1 to 5, respectively. Renal vascular flow was significantly higher in groups 2 and 3 than in groups 1, 4 and 5 (112.82 and 111.33 vs 88.25, 87.91 and 84.37 ml per minute, respectively, p = 0.000). The effect of intravenous sildenafil as a preemptive drug against the hemodynamic effects of renal ischemia-reperfusion is dose dependent. The 0.7 mg/kg dose significantly increased reperfusion renal vascular flow with a small decrease in arterial pressure compared to the 1.4 mg/kg dose.

2244 EGFR AND ONE-HOUR BIOPSY: BETTER PREDICTORS OF DECEASED KIDNEY TRANSPLANTS WITH USING IN-SITU-COOLING DOUBLE-BALLOON CATHETERS SYSTEM

You have accessJournal of UrologyTransplantation & Vascular Surgery: Renal Transplantation, Vascular Surgery1 Apr 20112244 EGFR AND ONE-HOUR BIOPSY: BETTER PREDICTORS OF DECEASED KIDNEY TRANSPLANTS WITH USING IN-SITU-COOLING DOUBLE-BALLOON CATHETERS SYSTEM Kazuo Mizutani, Ryohei Hattori, Tsuneo Kinukawa, Osamu Kamihira, and Momokazu Gotoh Kazuo MizutaniKazuo Mizutani Nagoya, Aichi, Japan More articles by this author , Ryohei HattoriRyohei Hattori Nagoya, Aichi, Japan More articles by this author , Tsuneo KinukawaTsuneo Kinukawa Nagoya, Aichi, Japan More articles by this author , Osamu KamihiraOsamu Kamihira Komaki, Japan More articles by this author , and Momokazu GotohMomokazu Gotoh Nagoya, Aichi, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.2486AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The worldwide shortage of deceased donor kidneys for transplantation has become a serious issue in the past decade and marginal donor kidneys have been studied. However, both the availability and feasibility of kidneys from deceased donors is still unclear. The aim of the present study was to estimate availability of deceased donor kidney with using our in-situ-cooling system, analyze donor one-hour biopsy, and find better evaluation method to estimate donor kidney function rather than using donor Cr. METHODS We studied 129 deceased renal transplant recipients who received kidneys from non-heart-beating donors beginning in 1984. Cyclosporine or Tacrolimus were given to all transplants. Those donors were in Maastricht Donor Categories III and IV and, in order to minimize warm ischemic kidney damage, we performed in situ cooling with specially designed double-balloon catheters. One-hour biopsies were analyzed with Remuzzi′s evaluation system. RESULTS The average donor Cr levels at admission were 0.3–2.1mg/dl (Average 1.0) and those level before death were 0.3–15.9 (Average 2.7). The average recipient Cr levels at discharge were 0.3–5.3 (Average 1.8). Although the average donor Cr levels before death were high levels, transplanted kidneys had good function with using our catheter system. To define the best measure of kidney function after transplant, recipients were classified according to estimated donor glomerular filtration rate (eGFR) at discharge: <25 ml/min/1.73 for the poor function group (n=32) and >25, the good function group (n=95). There was no statistically significant difference in Cr levels of donor (at admission and before death) between those groups. And both groups had no statistically significant difference in ischemic time of organ procurements. However, the good function group had higher eGFR levels at admission to the hospitals than the poor function group (p=0.005), although there was no statistically significant difference in eGFR levels before death. Pathologically, the good function group had less glomerular global sclerosis, tubular atrophy, and arterial/arteriolar narrowing than the poor function group in one-hour biopsies. (p=0.0000001, 0.003, 0.0002) . Histological scores of interstitional fibrosis was not associated with kidney function. CONCLUSIONS In conclusion, our kidney transplants had excellent renal function with double balloon catheter system. Although donor Cr levels were not a useful measurement for our analysis, eGFR was and should be used for donor evaluation. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e900 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kazuo Mizutani Nagoya, Aichi, Japan More articles by this author Ryohei Hattori Nagoya, Aichi, Japan More articles by this author Tsuneo Kinukawa Nagoya, Aichi, Japan More articles by this author Osamu Kamihira Komaki, Japan More articles by this author Momokazu Gotoh Nagoya, Aichi, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Sildenafil as a protecting drug for warm ischemic kidney transplants: experimental results

Editorial Comment This is an interesting experimental study in pigs, on which the authors tested the intra-arterial injection of reverse thermoplastic polymer LeGoo-XL that allows temporary selective vascular occlusion. The polymer was used with the intend of facilitate hemostasis for laparoscopic partial nephrectomy of the lower (caudal) pole. The perfusion hemostasis was not reliable in achieving occlusion while when using a local plug formation for hemostasis the results were consistent, with occlusion time from 13 to 30 minutes. The authors performed 2 robotic partial nephrectomies and concluded that the technique allowed minimal blood loss. Nevertheless, the authors did not take into account previous studies on intra-renal anatomy in pigs. While the collecting system anatomy is very similar to that of humans (1), the arterial (2) and venous (3) intra-renal anatomy in pigs is different from that of humans in many aspects that would be interesting to be discussed. Also, there are many important differences in the upper and lower pole vascular anatomy, being the upper pole vessels much more complex in distribution. Although we cannot transpose the results to clinical setting, the study opened new avenue to enhance the possibility of partial nephrectomy.

Sildenafil as a Protecting Drug for Warm Ischemic Kidney Transplants: Experimental Results

In an experimental model we studied the protective effects of the phosphodiesterase-5 inhibitor sildenafil on kidney grafts autotransplanted after 45 minutes of warm ischemia by vascular clamping, nephrectomy and 60 minutes of isolated hypothermic pump perfusion. A total of 14 laboratory minipigs were divided into group 1-7 administered 100 mg sildenafil orally 1.5 hours preoperatively and group 2-7 in which no sildenafil was given. Right single nephrectomy was completed after 45 minutes of warm ischemia by complete vascular clamping. Before autotransplantation all kidneys underwent 60 minutes of hypothermic pulsatile perfusion. Renal flow, arterial pressure and renal vascular resistance were recorded in real time for 60 minutes after autotransplantation. Nitric oxide levels were determined in blood samples from the renal vein at predefined intervals. Optical and electronic microscopy was done in all organs at the end of the procedure. In group 1 vs 2 renal vascular flow was significantly higher (155.30 vs 29.04 ml per minute per 100 gm) and renal vascular resistance was significantly lower (0.59 vs 3.10 mm Hg/ml per minute, each p <0.01). No significant differences were observed in systemic arterial pressure between groups 1 and 2 (84.08 and 84.65 mm Hg, respectively, p >0.05). Nitric oxide levels were significantly higher for all periods in group 1 (49.94 vs 16.85 muM, p <0.01). No significant differences were observed in histological studies, although endothelial cell structure was better preserved in the sildenafil group. To our knowledge our study suggests for the first time in the literature a positive effect of sildenafil in the immediate posttransplantation outcome of warm ischemic kidneys without secondary systemic effects.

Trimetazidine reduces early and long-term effects of experimental renal warm ischemia: A dose effect study

Renal ischemia reperfusion (IR) injury (IRI) is an important mechanism of acute renal failure (ARF) and a crucial factor of tissue damage during vascular surgery. IR may lead to tissue destruction and influence the early and long-term outcome of organs. The anti-anginal medication trimetazidine (TMZ) is a drug, the protective effects of which have been already assessed during cold preservation and warm ischemia (WI). The objective of this dose-effect study was to assess the role of TMZ in severe renal WI model. We have used an established WI pig kidney model associated with a uninephrectomy condition and studied the dose-dependent role of TMZ (1, 5, and 10 mg/Kg, i.v. for 24 hours before WI) against deleterious effects of WI (60 minutes of WI followed by reperfusion) compared with sham-operated (control) and uninephrectomized animals (unif). Direct effect of TMZ was determined using different variables: renal function (creatinine clearance; C(cr)) and indirectly, the consequences on inflammation (cells infiltration), rate of apoptosis, fibrosis development, and renal epithelial cells change into myofibroblast, which defined epithelial to mesenchymal transition (alpha-smooth muscle actin [alpha-SMA] and vimentin expression). TMZ (5 or 10 mg/Kg) significantly increased C(cr) and reduced the inflammatory response prevalent in ischemic kidney injury and rate of apoptosis expression. In addition, the limitation of initial IRI was correlated with an earlier and greater expression of hypoxia-inducible transcription factor-1alpha (HIF-1alpha), which is a hypoxia marker during kidney regeneration. A reduction of the tubulointerstitial development of fibrosis and a limitation of the alpha-smooth muscle actin expression (alpha-SMA) was observed with TMZ treatment. At 3 months, vimentin expression was increased in WI groups without TMZ or low TMZ dose treatment compared with 5 or 10 mg/Kg treated groups. Collectively, these data suggest that TMZ made the warm ischemic kidneys more resistant to the deleterious impact of a single episode of IR and could have a role in preserving the ischemic kidney from long-term damage.

Sildenafil Improves Immediate Posttransplant Parameters in Warm-Ischemic Kidney Transplants: Experimental Study

Objective To evaluate in an experimental model the effects of the PDE5 inhibitor sildenafil on kidney grafts autotransplanted after a period of 45 minutes of warm ischemia and 60 minutes of hypothermic pump perfusion. Methods Nine laboratory large-white pigs were divided into two groups. Group A ( n = 4): oral dose of 100 mg sildenafil was administered 1 hour before the surgery. Group B ( n = 5): no sildenafil given. Right single nephrectomy was completed after a 45-minute period of warm ischemia by complete vascular clamping. Before the autotransplant, all kidneys were submitted to a 60-minute period of hypothermic pulsatile perfusion. Renal flow, arterial pressure, and renal vascular resistance were recorded in real time for 60 minutes after autotransplant. Nitric oxide levels were determined in blood samples of the renal vein at predefined intervals. Optical and electronic microscopy was performed on all organs at the end of the procedure. Results Renal vascular flow was significantly higher and renal vascular resistance significantly lower in the sildenafil group compared with the non-sildenafil group. No significant differences were observed in systemic arterial pressure values between both groups. Nitric oxide levels were significantly higher for all periods in the sildenafil group. No differences were observed in histological studies. Conclusion Our experimental work suggested a positive effect of sildenafil on the immediate posttransplant outcome of warm-ischemic kidneys without systemic secondary effects.