Renal Artery Perfusion Research Articles

Acute Renal Artery Stent Thrombosis With a Solitary Functioning Kidney

A 55-year-old woman with a history of hypertension, bilateral renal artery disease with a left renal artery stent, and a chronically occluded right renal bypass graft presented with anuria and acute renal failure. Diagnostic studies showed high-grade renal artery in-stent stenosis with thrombotic occlusion of the main left renal artery distal to the stent. Catheter-directed thrombolysis and stent-in-stent placement within the left renal artery were successful at restoration of renal artery perfusion and function. Acute renal artery thromboembolic events are rare but can be devastating when these occur bilaterally or within a solitary functioning kidney. Timely diagnosis and therapy can often restore renal function and prevent dialysis dependence. The evolution of therapy for acute renal thromboembolism is discussed in this study. Recurrent stenosis within a stented renal artery is not uncommon and can be dependent on certain risk factors. Routine surveillance duplex ultrasound after endovascular therapy is essential for prevention of restenosis or thrombotic stent occlusion. The optimal therapy for in-stent restenosis is not defined; however, restenosis rates are lower with repeat stent-in-stent procedures as opposed to balloon angioplasty alone.

Renal Artery Implantation Angles in Thoracoabdominal Aneurysms and Their Implications in the Era of Branched Endografts

To determine the renal artery to aorta relationship in the setting of thoracoabdominal aortic aneurysm (TAAA) in order to help strategize preoperative stent-graft planning, device design, and deployment technicalities. The preoperative computed tomography (CT) studies of 147 patients who underwent TAAA repair between 2005 and 2008 were retrospectively reviewed. The Crawford classification of the TAAA, the renal artery implantation angle (RAIA), and the maximal aortic diameter were determined using 3-dimensional imaging analysis (centerline of flow). RAIAs were determined to be positive or negative as a function of their relative position above or below the plane perpendicular to the centerline of flow at the level of the renal ostia. RAIAs and maximum aortic diameters were compared between types II/III TAAA (n = 72) and type IV TAAA (n = 75), stratified by side, and examined for correlation. Maximal aortic diameter was not significantly different between the 2 groups: 67.5+/-13.4 mm for type II/III versus 65.3+/-12.5 mm for type IV (p = 0.3). There was no correlation between the maximal aortic diameter and the RAIAs. RAIAs in type II/III TAAAs were commonly orthogonal to the aortic centerline (mean -5.7 degrees +/-19.1 degrees on the right and -2.8 degrees +/-22.4 degrees on the left, respectively), while type IV TAAAs had downward pointing renal arteries (mean -24.1 degrees +/-18.4 degrees and -20.4 degrees +/-18.8 degrees for the right and left, respectively). There was a significant difference between the two groups regarding RAIAs on both sides (p<0.00001). The primary location of longitudinal aortic growth will drive the RAIA in a cranial or caudal direction. When the disease process is largely located below the renal ostia, infrarenal aortic lengthening drives the renal ostia cranially, forcing the implantation angle of the renal ostia to be caudally directed. The opposite occurs in type II or III TAAAs, where the bulk of disease is above the renal arteries, driving the ostia down to create RAIAs that are nearly orthogonal to the centerline of flow. Utilization of this data could result in endovascular grafts designed with branches replacing fenestrations for renal artery perfusion.

Laparoscopic partial nephrectomy with hypothermic renal artery perfusion in situ

Objective To study a modified method of laparoscopic partial nephrectomy with hypothermic renal artery perfusion in situ.Methods Laparoscopic partial nephrectomy with hypothermic renal artery perfusion in situ was performed in 5 patients from March 2009 to May 2009.There were 3 males and 2 females,with an average age of 49 years (39 to 63 years).There were 3 tumors in the left kidney and 2 in the right kidney,with an average diameter of 5.6 cm (range,3.8 to 7.0 cm).There were 2 cases of chronic renal insufficiency,1 case of solitary kidney,1 case of contralateral renal atrophy and 1 case of larger benign tumor.The procedure of laparoscopic partial nephrectomy with hypothermic renal artery perfusion in situ was as follows:A catheter with balloon was placed in the renal artery with percutaneous approach through the femoral artery preoperatively.During the operation the balloon of the catheter was inflated with water in order to block the renal artery,and renal artery perfusion of about 200ml saline of 4 ℃ was conducted through the catheter under high pressure in order to achieve low temperature in situ kidney.The water of the balloon was extracted after the accomplishment of the laparoscopic partial nephrectomy.Results Laparoscopic partial nephrectomies with hypothermic renal artery perfusion in situ were carried out successfully in 5 cases.The average operative time was 102 min (80 to 120 min),the average renal artery occlusion time was 35 min (range,29 to 39 min),and the average amount of bleeding was 190 ml(50 to 300 ml).The temperature of skin,kidneys,and tumor after hypothermic perfusion dropped by an average of 0.6℃,10.0 ℃,and 9.8℃,respectively.The endogenous creatinine clearance rate was(84.7±16.9),(48.9±14.5),(52.1±12.4),(54.5±13.8),and(54.6±11.7)ml/min before and 1 day,3 days,5 days and 10 days after operation.There was significant difference among the 5 groups in endogenous creatinine clearance rate(P=0.001).There was significant difference between each 2 groups except that between the group at 5 days and 10 days after operaton,The endogenous creatinine clearance rate kept steady in 5 days after operation.Conclusions Laparoscopic partial nephrectomy with hypothermic renal artery perfusion in situ is feasible and safe in favor of the extension of renal ischemic time and the protection of renal function.And it has resolved 2 problems in laparoscopic partial nephrectomy,that is,the laparoscopic artery occlusion and the hypothermic perfusion. Key words: Hypothermia,induced; Renal artery; Laparoscopy; Nephrectomy

Targeting circulatory dysfunction in cirrhosis: Terlipressin and the hepatorenal syndrome

Hong Kong is adeveloped country with a relatively well-informed, highly literatesociety, so that levels of awareness regarding NAFLD are likely tobe much worse among less well-off populations with lower lit-eracy rates. This is worrying, given the magnitude of public healthproblems posed by NAFLD.NAFLD is one of the commonest, if not the commonest, liverdiseases in Western populations, affecting at least 24–42% ofadults.

A Simple Technique for In Situ Renal Artery Perfusion During Abdominal Aortic Aneurysm Repair

A Simple Technique for <i>In Situ</i> Renal Artery Perfusion During Abdominal Aortic Aneurysm Repair

Editorial Comment on: Assessing the Impact of Ischaemia Time During Partial Nephrectomy

[51] Lane BR, Gill IS. 5-year outcomes of laparoscopic partial nephrectomy. J Urol 2007;177:70–4. [52] Porpiglia F, Renard J, Billia M, et al. Is renal warm ischemia over 30 minutes during laparoscopic partial nephrectomy possible? One-year results of a prospective study. Eur Urol 2007;52: 1170–8. [53] Shekarriz B, Shah G, Upadhyay J. Impact of temporary hilar clamping during laparoscopic partial nephrectomy on postoperative renal function: a prospective study. J Urol 2004;172:54–7. [54] Nguyen MM, Gill IS. Halving the ischemia time during laparoscopic partial nephrectomy. J Urol 2008;179:627–32. [55] Bollens R, Rosenblatt A, Espinoza BP, et al. Laparoscopic partial nephrectomy with ‘‘on-demand’’ clamping reduces warm ischemia time. Eur Urol 2007;52:804–10. [56] Baumert H, Ballaro A, Shah N, et al. Reducing warm ischaemia time during laparoscopic partial nephrectomy: a prospective comparison of two renal closure techniques. Eur Urol 2007;52: 1164–9. [57] Gill IS, Abreu SC, Desai MM, et al. Laparoscopic ice slush renal hypothermia for partial nephrectomy: the initial experience. J Urol 2003;170:52–6. [58] Steffens J, Humke U, Ziegler M, Siemer S. Partial nephrectomy with perfusion cooling for imperative indications: a 24-year experience. BJU Int 2005;96:608–11. [59] Humke U, Uder M. Renovascular hypertension: the diagnosis and management of renal ischemia. BJU Int 1999;84:555–69. [60] Kemmer H, Siemer S, StockleM. Nephrectomy, work bench surgery, and autotransplantation: a case of a solitary left kidney with an extensive centrally located renal cell carcinoma and a tumour thrombus entering the vena cava. Eur Urol 2007;52:1518–20. [61] Janetschek G. Laparoscopic nephron sparing surgery: ischemic renal damage. Curr Opin Urol 2006;16:45–6. [62] Janetschek G, Abdelmaksoud A, Bagheri F, Al-Zahrani H, Leeb K, Gschwendtner M. Laparoscopic partial nephrectomy in cold ischemia: renal artery perfusion. J Urol 2004;171:68–71. [63] Landman J, Rehman J, Sundaram CP, et al. Renal hypothermia achieved by retrograde intracavitary saline perfusion. J Endourol 2002;16:445–9. [64] Landman J, Venkatesh R, Lee D, et al. Renal hypothermia achieved by retrograde endoscopic cold saline perfusion: technique and initial clinical application. Urology 2003;61:1023–5. [65] Orvieto MA, Zorn KC, Mendiola F, et al. Recovery of renal function after complete renal hilar versus artery alone clamping during open and laparoscopic surgery. J Urol 2007;177:2371–4.

Time-resolved MRA using sliding window reconstruction for evaluation of renal arterial anatomy and perfusion

Time-resolved MRA using sliding window reconstruction for evaluation of renal arterial anatomy and perfusion

Balloon occlusion and hypothermic perfusion of the renal artery in laparoscopic partial nephectomy

We describe our initial experience with renal arterial catheterization for temporary balloon occlusion of renal artery and hypothermic perfusion during laparoscopic partial nephectomy and compare the preoperative and postoperative nephron function. Fifteen patients received laparoscopic partial nephrectomy from September 2005 to December 2006. During the operations, the balloons of the arterial catheters were filled with distilled water to achieve pedicle control. Chilled Ringers lactate was continuously infused into the catheters for renal hypothermia. Postoperative Tc-99m diethylenetriamine pentaacetic acid (DTPA) renal scintigraphies were carried out to estimate differential renal function. The volumes of the renal tumors, tumor-bearing and contralateral kidneys from CT scans were measured using commercial software. Estimated creatinine clearance was calculated with Cockroft Gault formula. All procedures were successfully completed. Mean tumor size was 18.4 mL (range 2.14 to 59.0). Estimated mean intraoperative blood loss was 287 mL (range minimal to 1200). Mean estimated creatinine clearance per unit volume of functional renal parenchyma did not change statistically after the operation. Multiple regression analysis revealed that ischemic time was a significant variable which correlated with the value of lost total estimated creatinine clearance of the tumor bearing kidney. The initial experience shows that renal arterial catheterization for temporary balloon occlusion and hypothermic perfusion of the renal artery in laparoscopic partial nephectomy is safe, feasible and effective. The postoperative kidney function measured by mean estimated creatinine clearance per unit of functional renal volume was similar to the preoperative measurement.

Identification of Novel Endogenous Cytochrome P450 Arachidonate Metabolites with High Affinity for Cannabinoid Receptors

Arachidonic acid is an essential constituent of cell membranes that is esterified to the sn-2-position of glycerophospholipids and is released from selected lipid pools by phospholipase cleavage. The released arachidonic acid can be metabolized by three enzymatic pathways: the cyclooxygenase pathway forming prostaglandins and thromboxanes, the lipoxygenase pathway generating leukotrienes and lipoxins, and the cytochrome P450 (cP450) pathway producing epoxyeicosatrienoic acids and hydroxyeicosatetraenoic acids. The present study describes a novel group of cP450 epoxygenase-dependent metabolites of arachidonic acid, termed 2-epoxyeicosatrienoylglycerols (2-EG), including two regioisomers, 2-(11,12-epoxyeicosatrienoyl)glycerol (2-11,12-EG) and 2-(14,15-epoxyeicosatrienoyl)glycerol (2-14,15-EG), which are both produced in the kidney and spleen, whereas 2-11,12-EG is also detected in the brain. Both 2-11,12-EG and 2-14,15-EG activated the two cannabinoid (CB) receptor subtypes, CB1 and CB2, with high affinity and elicited biological responses in cultured cells expressing CB receptors and in intact animals. In contrast, the parental arachidonic acid and epoxyeicosatrienoic acids failed to activate CB1 or CB2 receptors. Thus, these cP450 epoxygenase-dependent metabolites are a novel class of endogenously produced, biologically active lipid mediators with the characteristics of endocannabinoids. This is the first evidence of a cytochrome P450-dependent arachidonate metabolite that can activate G-protein-coupled cell membrane receptors and suggests a functional link between the cytochrome P450 enzyme system and the endocannabinoid system.

Tailoring Technique of Laparoscopic Partial Nephrectomy to Tumor Characteristics

We use a tailored approach to laparoscopic partial nephrectomy based on tumor depth of penetration and proximity to the renal sinus. We evaluated differences in perioperative outcomes to determine the value of this paradigm. The surgical approach to hilar clamping and tumor bed management during laparoscopic partial nephrectomy included no clamp or suture, clamp with no suture, and clamp and suture. The end points assessed retrospectively were differences in perioperative, pathological and complication outcomes among these groups. Our surgical paradigm was used in 174 patients, including no clamp or suture in 36, clamp with no suture in 25, and clamp and suture in 113. Compared to the other patients those with a clamp and suture procedure were older with larger and deeper tumors that were closer to the renal sinus-collecting system and more likely to be malignant. Operative time was shortest in the no clamp or suture group and in the 2 clamp groups warm ischemia and operative times were shorter than in the no suture group. Estimated blood loss, hospital stay, surgical margins, complications and recurrences did not differ among the groups. A creatinine increase of 0.3 mg/dl or greater was seen in 33 patients (19%) following surgery, which was attributable to conversion to nephrectomy in 4, contralateral nephrectomy or partial nephrectomy in 3 and underlying medical renal disease in 1. In the remaining 25 patients no other cause was apparent except renal hilar clamping and tumor resection. A tailored approach based on tumor location and proximity to the renal sinus-collecting system can limit operative and ischemia times, and technically simplify the procedure without adversely impacting morbidity, convalescence and oncological outcomes.

Repair of a pararenal abdominal aortic aneurysm with bilateral renal artery stenosis using a rapid infusion pump for renal perfusion: Report Of a case

A 73-year-old man with a history of hypertension and drug-induced hepatitis underwent surgical treatment of an enlarging pararenal abdominal aortic aneurysm (PRAAA) with bilateral renal artery stenosis, found on enhanced computed tomography (CT). His preoperative renal function was normal. We divided the right renal artery and used a 6-mm expanded polytetrafluoroethylene (ePTFE) tube graft for the anastomosis. Renal artery perfusion was achieved by a rapid infusion pump set at 200 ml/min. The left renal artery was reconstructed and perfused in the same way. The abdominal aorta was cross-clamped just distal to the superior mesenteric artery and a Y-graft was anastomosed. The ePTFE grafts were connected to the Y-graft and bilateral renal artery circulation was re-established. The renal ischemic time was 1 h 25 min and the urine output during reconstruction was 80 ml. Postoperatively, his serum blood urea nitrogen and serum creatinine levels increased slightly, but normalized within 3 days. This case report shows that this method of renal artery perfusion could prove useful for complex renal artery reconstructions.

Hypothermic Renal Protection Using Cold Histidine–Tryptophan–Ketoglutarate Solution Perfusion in Suprarenal Aortic Surgery

We examined data of 21 patients who were treated with selective perfusion of both renal arteries with 500 mL of 8 degrees C histidine-tryptophan-ketoglutarate (HTK) solution each for renal protection during aortic surgery. Only the data from aortic surgeries with unavoidable suprarenal aortic cross-clamping for juxtarenal or suprarenal abdominal aortic aneurysms (AAAs) or high Leriche syndrome accompanied with stenosis of renal arteries are presented. Five patients underwent immediate surgery because of perforation of an AAA; the other 16 patients went through elective surgeries. In three cases (14%) stenosis of the renal arteries was diagnosed; nevertheless, implantation of an aortorenal bypass was necessary in seven patients. In total, 14 aortorenal bypasses were implanted (five venous grafts and nine prosthesis grafts). Four (19%) patients needed catecholaminergic support to establish stable circulatory conditions; in two (9%) of these cases additional ischemia of the colon was observed and sigmoidectomy was performed. All of these four patients underwent immediate surgery, and one died after surgery because of severe sepsis. In four cases postsurgical renal insufficiency was observed. Three of these patients were admitted for emergency surgery because of their hemodynamic situation due to perforation of the AAA. None of the patients needed chronic dialysis after surgery. Whereas in all patients who underwent elective surgery the renal function remained stable as judged by postoperative serum creatinine values, in five out of seven patients with aortorenal bypass surgery the renal function improved. Perfusion with cold HTK solution offers an additional procedure to protect renal function in patients undergoing elective surgery with suprarenal cross-clamping of the aorta.

Partial Nephrectomy Using Renal Artery Perfusion for Cold Ischemia: Functional and Oncologic Outcomes

We present our series on the safety and long-term oncologic and functional outcomes of laparoscopic partial nephrectomy using renal artery perfusion for cold ischemia. Of 94 patients who underwent laparoscopic partial nephrectomy at our center between August 2000 and September 2006, 28 procedures were performed using cold ischemia and are included in this review. Mean age was 57.8 years (range 22-80 yrs). Mean tumor size was 2.67 cm (range 1.5-5 cm). Five patients had an imperative indication for partial nephrectomy. Eight tumors were hilar. Cold ischemia was achieved through renal artery catheterization followed by intraoperative artery clamping and perfusion with 4 degrees C lactated Ringer solution with mannitol. Mean ischemia time was 40.8 min (range 25-101 min). Mean estimated blood loss was 241 mL (range 50-1000 mL). Three patients underwent conversion to open surgery, but their procedures were still completed under cold perfusion. Segmental artery penetration and venous penetration took place in one patient each. Two postoperative complications occurred, including pancreatitis and pulmonary embolism; none were related to the cold perfusion. Oncologic outcome revealed 100% disease-specific survival for 45 months median followup. Functional studies showed a mild decrease in renal creatinine clearance with improvement 1 month after surgery. Nuclear scans showed functional kidney moiety in all but one patient. Intraoperative cold ischemia for laparoscopic partial nephrectomy using arterial perfusion is safe and feasible. It constitutes a viable alternative for complex tumors when ischemia time is expected to exceed 30 minutes. We provide proof of principle confirming the protective effect of cold perfusion to prevent parenchymal damage.

Laparoscopic Partial Nephrectomy for Hilar Tumors: Technique and Results

BackgroundLaparoscopic partial nephrectomy for hilar tumors is a cutting edge procedure for which little data is available in the current literature. ObjectiveTo describe our technique and results of laparoscopic partial nephrectomy for renal hilar tumors. Design, Setting, and ParticipantsBetween April 2000 and September 2006, 94 partial laparoscopic nephrectomies were performed at our institution. A total of 18 (19.1%) patients had hilar tumors. A hilar tumor was defined as a lesion suspicious for renal cell carcinoma in contact with a major renal vessel on preoperative cross-sectional imaging. In 3 (16.7%) of the patients, the indication for nephron-sparing surgery was imperative. Mean tumor size was 3cm (range, 2–4.5). Eight (44.4%) surgeries were performed with renal artery perfusion for cold ischemia; the remaining surgeries were performed under warm ischemia. Intervention(s)After occluding the renal artery and controlling the renal vein by using separate rubber band tourniquets, we excised the tumor mass including delicate mobilization away from the blood vessels. Although we used to insert a ureteral stent at the beginning of our experience with laparoscopic partial nephrectomies, we no longer do so. All surgeries were performed by a single urologist (G.J.). MeasurementsOperative time, ischemia time, blood loss, renal function using the Cockroft formula as well as renal scans, operative and post-operative complications, pathology parameters. Results and LimitationsAll surgeries were completed laparoscopically. Mean surgical time was 238min (range, 150–420). Mean ischemia times were 42.5min (range, 27–63) and 34.1min (range, 24–56) for the cold and warm ischemia groups, respectively. Estimated intraoperative blood loss was 165ml (range, 50–500). There were two (11%) entries into major vessels during tumor excision, namely a segmental renal artery in one patient and a segmental renal vein in another. Both of these occurrences were managed laparoscopically. One patient necessitated laparoscopic reexploration for urine extravasation in the immediate postoperative period. All postoperative nuclear scans (available in 12 of 18 patients) showed functional kidney moiety. Mean split renal function was 38.6% (range, 24–50) on the operated side. Histopathological examination confirmed renal cell carcinoma in 14 (77.8%) of the patients. One (7.1%) patient had a positive surgical margin on the surface that was adjacent to the renal artery. In a median follow-up of 26 mo (range, 1–59), no local recurrence or systemic progression occurred. ConclusionLaparoscopic partial nephrectomy for hilar tumors is a feasible and safe procedure in the hands of experienced laparoscopic surgeons. Oncological results seem excellent, but further follow-up is needed for accurate long-term assessment of this surgical approach.

PARTIAL NEPHRECTOMY USING RENAL ARTERY PERFUSION FOR COLD ISCHEMIA: FUNCTIONAL AND ONCOLOGICAL OUTCOMES

Purpose: We present our series on the safety and long-term oncologic and functional outcomes of laparoscopic partial nephrectomy using renal artery perfusion for cold ischemia. Patients and Methods: Of 94 patients who underwent laparoscopic partial nephrectomy at our center between August 2000 and September 2006, 28 procedures were performed using cold ischemia and are included in this review. Mean age was 57.8 years (range 22–80 yrs). Mean tumor size was 2.67 cm (range 1.5–5 cm). Five patients had an imperative indication for partial nephrectomy. Eight tumors were hilar. Cold ischemia was achieved through renal artery catheterization followed by intraoperative artery clamping and perfusion with 4°C lactated Ringer solution with mannitol. Results: Mean ischemia time was 40.8 min (range 25–101 min). Mean estimated blood loss was 241 mL (range 50–1000 mL). Three patients underwent conversion to open surgery, but their procedures were still completed under cold perfusion. Segmental artery penetration and ven...

Acute renal haemodynamic effects of radiocontrast media in patients undergoing left ventricular and coronary angiography

Tubular toxicity and renal ischaemia have been implicated in the pathogenesis of radiocontrast media induced nephropathy (CIN), but their respective role remains unclear. Aims. In order to evaluate changes in renal blood flow in response to intra-arterial contrast media administration, we aimed to continuously measure renal arterial perfusion by means of renal blood flow velocity (RBFV) during left ventricular and coronary angiography and subsequent coronary intervention in patients with chronic kidney disease (CKD). Ten patients (7 males, 63.4 +/- 11.7 years) with serum creatinine (SCr) >1.5 mg/dl participated in the study. The first five patients received low-osmolar iopromide and the others iso-osmolar iodixanol contrast medium. RBFV was measured using a 0.014-inch Doppler guide wire, which was inserted through a separate contralateral femoral sheath via a 5 F Cobra diagnostic catheter into the renal artery. Data were recorded at 500 Hz to allow beat-to-beat analysis of RBFV and pressure. All patients were pre-treated with acetylcysteine and hydration. Immediately after left ventricular angiography no significant changes in RBFV were detected. Over time, however, following repeated administration of the additional contrast medium into the coronary arteries, RBFV decreased significantly from baseline until the end of the investigation, 28.4 (19.1/42.7) to 22.9 (16.9/30.6) cm/s (median and quartiles; P = 0.005), in the absence of significant changes in systemic arterial blood pressure. In individual patients the reduction in RBVF varied from 3.7% to 39.5%. On average the decline in RBFV was more pronounced in patients receiving iopromide (from 41.6 cm/s to 29.3 cm/s) than in those receiving iodixanol (from 19.3 to 17.8 cm/s; P = 0.008 for the difference of relative decline). However, in the iopromide treated patients, coronary intervention was more frequently performed (5/5 versus 2/5) and the median duration of the procedure tended to be longer [85 (32-150) min versus 38 (27-110) min; P > 0.2]. The administration of non-ionic low-osmolal contrast media has no immediate effect on renal perfusion in patients with CKD. However, during the course of coronary angiography a gradual decline in renal blood flow may occur, the extent of which varies, presumably depending on individual pre-disposition as well as on the amount of the contrast medium.

A murine model of site-specific renal microvascular endothelial injury and thrombotic microangiopathy

Despite the importance of endothelial injury and healing for primary and secondary renal disease and the availability of genetically engineered mouse models, to date no generally applicable murine disease model with site-specific renal endothelial injury has been established. We induced specific microvascular renal injury via selective renal arterial perfusion of the lectin concanavalin A (Con A) followed by sheep anti-concanavalin A and harvested tissues after 4 h, 24 h, days 3 and 7. Compared to control kidneys, histological evaluation demonstrated endothelial cell injury with subsequent complement, and platelet activation and thrombosis by light and electron microscopy. Mouse kidneys showed histologic evidence of severe glomerular and peritubular microvascular thrombosis with acute tubular necrosis, proteinuria, increased BUN and presence of schistocytes. Initial cell death of intrinsic renal cells resulted in a decrease of the glomerular cell count by 50% after 4 h followed by a proliferative response of glomerular (day 3, P < 0.05), interstitial (day 3, P < 0.05) and tubular cells leading to increased total glomerular cell count by day 7. This study establishes the Con A anti-Con A model as specific endothelial injury model in the mouse kidney providing a novel tool for investigating endothelial injury and repair mechanisms as well as elucidating the role of platelets in genetically engineered mice.

Compartment-Specific Expression and Function of the Chemokine IP-10/CXCL10 in a Model of Renal Endothelial Microvascular Injury

The recruitment of inflammatory cells into renal tissue, mainly T cells and monocytes, is a typical feature of various renal diseases such as glomerulonephritis, thrombotic angiopathies, allograft rejection, and vasculitis. T cells predominantly infiltrate the tubulointerstitium, whereas monocytes are present in the tubulointerstitial and glomerular compartment. Because chemokines play a pivotal role in leukocyte trafficking under inflammatory conditions, this study investigated whether a differential expression of chemokines contributes to the precise coordination of leukocyte subtype trafficking in a rat model of renal microvascular endothelial injury. Renal microvascular endothelial injury was induced in rats by selective renal artery perfusion with an anti-endothelial antibody. Induction of the disease led to severe glomerular and tubulointerstitial endothelial injury with subsequent upregulation of chemokines followed by inflammatory cell recruitment. Among the analyzed chemokine mRNA, IP-10/CXCL10 (119-fold), acting via CXCR3 on activated T cells, and MCP-1/CCL2 (65-fold), acting via CCR2 on monocytes, were by far the most strongly upregulated chemokines. In situ hybridization revealed that IP-10/CXCL10 mRNA was selectively expressed by endothelial cells in the tubulointerstitial area, co-localizing with infiltrating T cells. Despite extensive damage of glomerular vasculature, no IP-10/CXCL10 expression by glomerular endothelial cells was detected. MCP-1/CCL2 mRNA in contrast was detectable in the glomerulus and the tubulointerstitium. Treatment with a neutralizing anti-IP-10/CXCL10 antibody significantly reduced the number of infiltrating tubulointerstitial T cells without affecting monocyte migration and led to an improved renal function. Our study demonstrates a role of IP-10/CXCL10 on T cell recruitment in a rat model of renal endothelial microvascular injury. Furthermore, a differential chemokine expression profile by endothelial cells in different renal compartments was found. These findings are consistent with the hypothesis that functional heterogeneity of endothelial cells from different vascular sites exists and provide an insight into the molecular mechanisms that may mediate compartment-specific T cell and monocyte recruitment in inflammatory renal disease.

Putting the Brakes on Renin Release

Modulation of renin release from juxtaglomerular cells is critical for appropriate adjustments of the cardiovascular and renal systems to internal and external stresses, and dysregulation of renin release participates in the pathophysiology of hypertension, vascular disease, heart failure, and chronic renal disease. This justifies investments in research to elucidate the fundamental mechanisms regulating renin release. These investments have yielded, and continue to yield, high returns, as exemplified by Schweda et al1 in this issue of Hypertension , showing that A1 receptors mediate high perfusion pressure–induced inhibition of renin release, whereas prostaglandins (PGs) participate in low perfusion pressure–mediated stimulation of renin release. The purpose of this commentary is to discuss how Schweda et al’s findings confirm and challenge present-day models of renin release. As comprehensively reviewed by Davis and Freeman2 and Keeton and Campbell,3 investigators recognized early on that three systems, namely the sympathetic nervous system, the macula densa apparatus, and the intrarenal baroreceptor, are the primary physiological mechanisms regulating renin release from juxtaglomerular cells. A key development was the recognition that the two most important biochemical accelerators of renin release are catecholamines (mediating sympathetically induced renin release) and PGI2 (mediating macula densa–induced and intrarenal baroreceptor–stimulated renin release).4 Subsequently, a third autocoid, adenosine (acting via A1 receptors), was proposed to serve as a molecular brake on renin release and thereby to moderate the effects of catecholamines and PGI2 on renin secretion.5 Because cAMP is a critical second messenger mediating the exocytosis of renin from juxtaglomerular cells, adenylyl cyclase unifies these concepts because β-adrenoceptors and PGI2 receptors accelerate, whereas A1 receptors brake the rate of cAMP production. The results reported by Schweda et al corroborate the accelerator/brake model of renin release because they report that PGs mediate stimulation of renin release …

Partial nephrectomy with perfusion cooling for imperative indications: a 24‐year experience

To report our 24-year experience with open nephron-sparing surgery for renal tumours, using cold ischaemia achieved by renal artery perfusion, as partial nephrectomy for imperative indications is a surgical challenge. From 1980 to 2004, open partial nephrectomy was performed in 717 patients; of these, 65 (9.1%) with a solitary kidney, synchronous bilateral tumours or renal failure in the opposite kidney (imperative indication) had surgery under cold ischaemia, achieved by continuous perfusion of Ringer's lactate at 4 degrees C through the renal artery, which was clamped and cannulated. The tumour was resected in a bloodless field, with biopsies taken from the tumour bed. Focusing on patients with an imperative indication and cold perfusion, we report our perfusion technique, and the ischaemia time, complication rate and cancer-specific survival rate of these patients. The mean (SD, range) operative duration was 132 (103, 91-252) min and ischaemia time 49 (37, 31-71) min. The most common complications were postoperative haemorrhage in 19%, urinary fistula in 8% and acute renal failure in 6% of patients. There were no specific complications related to the perfusion technique (renal artery stenosis, renal artery or vein thrombosis). The mean (SD, range) long-term follow-up of 95 (71, 4.3-231) months showed increased but constant creatinine values (95 micromol/L before, 182 micromol/L after surgery; P < 0.05) with no need for long-term dialysis. The tumour-specific survival rate was 94%, 76% and 76% after 1, 5 and 10 years, respectively. Partial nephrectomy under cold ischaemia remains reserved for selected patients with renal tumours with an imperative indication. The technique provides excellent intraoperative visibility in an absolutely bloodless field, allows surgery with no pressure of time, and makes ex vivo workbench surgery with autotransplantation unnecessary. Perfusion cooling allows good tumour-specific long-term results, with stable residual kidney function sufficient to prevent dialysis.