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Defining cellular and molecular identities within the kidney is necessary to understand its organization and function in health and disease. Here we demonstrate a reproducible method with minimal artifacts for single-nucleus Droplet-based RNA sequencing (snDrop-Seq) that we use to resolve thirty distinct cell populations in human adult kidney. We define molecular transition states along more than ten nephron segments spanning two major kidney regions. We further delineate cell type-specific expression of genes associated with chronic kidney disease, diabetes and hypertension, providing insight into possible targeted therapies. This includes expression of a hypertension-associated mechano-sensory ion channel in mesangial cells, and identification of proximal tubule cell populations defined by pathogenic expression signatures. Our fully optimized, quality-controlled transcriptomic profiling pipeline constitutes a tool for the generation of healthy and diseased molecular atlases applicable to clinical samples.

Introduction: Laparoscopic partial nephrectomy has emerged as a standard of care for small renal masses. Nevertheless, there remains concern over the potential for irreversible insult to the kidney as a result of exposure to warm ischemia. We aim to investigate the utility of selective segmental arterial clamping as a means to reduce the potential for ischemic damage to a solitary kidney during laparoscopic partial nephrectomy utilizing a porcine model., Materials and Methods: A total of 20 domestic swine were randomized into four equal groups. Each subject underwent laparoscopic radical nephrectomy to create the condition of a solitary kidney. On the contralateral side, a laparoscopic lower pole partial nephrectomy was performed, employing either selective or nonselective vascular clamping for either 60 or 90 minutes. Postoperatively, clinical status and serial serum studies were closely monitored for 1 week., Results: There were no intraoperative complications. The 90-minute nonselective clamping produced devastating effects, resulting in rapid deterioration into florid renal failure within 72 hours. The 60-minute nonselective clamping group experienced modest but significant rises in both blood urea nitrogen and creatinine. Both 60- and 90-minute selective clamping groups performed well, with no significant rises in creatinine over a 7-day period, and no instances of renal failure., Conclusions: Selective arterial clamping is a safe and feasible means of vascular control during laparoscopic partial nephrectomy. In the porcine model, selective clamping appears to improve functional outcomes during prolonged periods of warm ischemic insult. Prospective evaluation of the technique in humans is necessary to determine if selective arterial control confers long-term functional benefits in patients with limited renal reserve.

Background: Controversy exists about the impact of ischemia on renal function. We evaluated the creatinine clearance of patients having undergone laparoscopic renal extirpative and ablative surgery., Study Design: The records of patients undergoing laparoscopic procedures for renal masses from February 2000 to March 2004 were examined. Creatinine clearance (CrCl) for each patient was determined using the Cockcroft-Gault equation and ideal body weight. We compared CrCl changes of patients undergoing laparoscopic partial nephrectomy (without renal ischemia [LPN-none], with warm ischemia [LPN-warm], and with cold ischemia [LPN-cold]) with patients undergoing laparoscopic radical nephrectomy (LRN) and laparoscopic cryoablation. Patients predisposed to medical renal disease were substratified and evaluated., Results: All patients who underwent LRN or LPN-warm sustained a significant drop in CrCl on the first postoperative day, compared with patients who had LPN without ischemia or cryoablation (p < 0.01). The CrCl decrease correlated directly with warm ischemia time. Six months postoperatively, CrCl changes were no longer significant. Patients with medical renal disease risk factors were more likely to sustain longterm (1 year postoperatively) renal damage if they had renal ischemia, trending toward statistical significance., Conclusions: Ischemia causes acute renal damage, which is apparently reversible in patients without evidence of medical renal disease. Patients with known medical renal disease have substantial longterm changes in renal function associated with unilateral renal ischemia. Considering the insensitivity of creatinine-based renal function metrics, only eliminating ischemic time will realize the goal of maximal nephron preservation, particularly in patients with preexisting medical renal disease.

Background and Objectives: Traditional trocar tip design for laparoscopic access incorporates cutting blades to penetrate the body wall. More recently, trocars applying tissue dilation have been used that create a smaller defect, seldom requiring fascial wound closure. Four 12-mm commercially available single-use trocar designs were evaluated for postoperative pain., Methods: The 4-trocar types included 2 cutting (single or pyramidal bladed) and 2 dilating trocars (radially or axially dilating) type. Fifty-six patients undergoing transperitoneal laparoscopic renal surgery were randomized and blinded to one of the 4 trocar types. In each case, trocars were placed in a standard "diamond" configuration: three 12-mm study trocars and a lateral 5-mm trocar that served as a reference point for normalizing patients' pain scores. Postoperative pain based on a visual analog scale and complications were assessed., Results: No statistically significant difference existed in pain scores between different trocar types or trocar sites at 3-hour, 24-hour, and 1-week postoperative assessment time points. Eight (4.8%) minor complications occurred: bleeding in 7 (4.2%) and 1 (0.6%) wound infection. The radially dilating trocar had more device malfunction (P<0.05) than did the others., Conclusion: All 4 disposable trocars, muscle cutting or dilating type, were safe and yielded similar postoperative pain scores with or without the fascial wound closure after renal laparoscopy.

Introduction: Clinical studies have shown beneficial role of oral alpha-blockers for ureteral stent-related morbidity. However, the in vivo effects of oral alpha-blockers on a stented ureter are unclear. We evaluated the effects of alpha-blockade on ureteral dynamics in a stented porcine ureter. Methods: Twenty-seven female pigs were used in this study. Fourteen pigs received oral alpha-blocker medication (silodosin, 8 mg daily), and 13 pigs received no medication. Under cystoscopic guidance, a 5F ureteral catheter was positioned in the renal pelvis and attached to a pressure monitor. A Foley catheter was placed in the bladder along with a bladder pressure transducer. A lumbotomy was performed, and the ureter was identified. A magnetic sensor was placed on the extraluminal surface of the ureter to monitor ureteral peristalsis. We measured renal pelvic and bladder pressures, urine output, and ureteral peristalsis every hour for 10 minutes for a total of 5 hours. The pigs were then euthanized. Results: The mean weight was 42.5 kg in the drug group and 45.9 kg in the nondrug group ( p = 0.008). Mean hourly urine output was 140 mL in the drug group and 144 mL in the nondrug group ( p = 0.76). Mean baseline renal pressure was 13.2 and 13.8 mm Hg ( p = 0.69) in the drug and nondrug groups, respectively. Mean peristaltic renal pelvic pressure was 19.1 mm Hg in the drug group and 19.2 mm Hg in the nondrug group ( p = 0.97). Mean number of peristalsis was 11/10 and 14/10 minutes ( p = 0.03) in the drug and nondrug groups, respectively. Conclusions: Alpha-blockade in an in vivo stented porcine ureter resulted in no significant effect on renal pelvic pressure but a significant decrease in the number of ureteral peristalsis. Further investigation of the effects of alpha-blocker on ureteral dynamics is required to better understand its effects on stent-related symptoms. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: To report the development of a novel, simple-to-use method for laparoscopic deployment of fine-quality saline ice slush by way of a 10-mm end-effector for laparoscopic parenchymal hypothermia. Methods: A mechanism for making fine ice slush was created, and a 10-mm laparoscopic end-effector was designed and constructed for deployment of the ice slush. The novel ice slush deployment system was tested in a porcine model and compared with that of standard open ice slush cooling. After atraumatic hilar clamping, the cortical and medullary temperatures in the upper, middle, and lower poles were measured with thermocouples. Results: Six pigs were evaluated in each group. In all cases, the kidneys were successfully cooled to our goal temperature of 15° to 25°C within 10 minutes and were maintained at the target temperature for 1 hour. The core body temperature for the slush group was decreased by 3°C but did not change in the open group. The renal temperatures quickly returned to normal on unclamping of the renal hilum. One pig in the open group died of acidosis and another in the same group experienced thrombosis of the renal artery. No complications occurred in the laparoscopic group. Conclusions: We describe a novel, simple-to-use mechanism for producing and delivering fine ice slush in a laparoscopic setting. The technique achieves optimal parenchymal hypothermia expeditiously. [Copyright &y& Elsevier]

Abstract: Objectives: To evaluate the utility of the porcine and canine models for collecting system closure after partial nephrectomy involving violation of the renal collecting system. Advanced surgical technologies and novel techniques for performing laparoscopic partial nephrectomy are frequently evaluated in an animal model. Methods: After evaluation of the upper urinary tract with retrograde pyelography, laparoscopic partial nephrectomy, including violation of the renal collecting system, was performed in 8 domestic pigs (group 1) and 2 dogs (group 2) with documented normal upper urinary tract physiology. No collecting system closure was performed. Subsequently, in an attempt to generate an adequate model for renal collecting system closure, 6 pigs (group 3) underwent partial obstruction of the proximal ureter before laparoscopic partial nephrectomy without collecting system closure. After 3 weeks, the animals underwent evaluation, including retrograde pyelography, and were killed for histopathologic evaluation of the upper urinary tracts. Results: Despite documented transection of major calices in all animals, none with physiologically normal upper urinary tracts developed urinomas. After partial occlusion of the proximal ureter, all pigs had hydronephrosis, but only one of six developed a urinoma. Conclusions: The porcine and canine models are inadequate for evaluating renal collecting system closure after partial nephrectomy. Our high-pressure partial occlusion model was similarly inadequate. The limitations of these animal models should be considered when reviewing published data regarding technologies for partial nephrectomy. Future data regarding novel technologies for partial nephrectomy should also be carefully considered before clinical application. [Copyright &y& Elsevier]