Gadolinium-enhanced MRI visualizing backflow at increasing intra-renal pressure in a porcine model

PLOS ONE RESEARCH ARTICLE Gadolinium-enhanced MRI visualizing backflow at increasing intra-renal pressure in a porcine model Søren Kissow Lildal ID1*, Esben Søvsø Szocska Hansen2, Christoffer Laustsen ID2, Rikke Nørregaard3, Lotte Bonde Bertelsen2,3, Kirsten Madsen4, Camilla W. Rasmussen ID2, Palle Jörn Sloth Osther5,6, Helene Jung5,6 a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 1 Department of Urology, Aarhus University Hospital, Aarhus, Denmark, 2 Department of Clinical Medicine, MR Research Centre, Aarhus University, Aarhus, Denmark, 3 Department of Clinical Medicine, Aarhus University, Aarhus, Denmark, 4 Department of Clinical Pathology, Odense University Hospital, Odense, Denmark, 5 Department of Regional Health Research, University of Southern Denmark, Odense, Denmark, 6 Department of Urology, Vejle Hospital–a part of Lillebaelt Hospital, University Hospital of Southern Denmark, Vejle, Denmark * Abstract OPEN ACCESS Citation: Lildal SK, Hansen ESS, Laustsen C, Nørregaard R, Bertelsen LB, Madsen K, et al. (2023) Gadolinium-enhanced MRI visualizing backflow at increasing intra-renal pressure in a porcine model. PLoS ONE 18(2): e0281676. https://doi.org/10.1371/journal.pone.0281676 Editor: Kartikeya Rajdev, University of Pittsburgh Medical Center Pinnacle Health Medical Services, UNITED STATES Introduction Intrarenal backflow (IRB) is known to occur at increased intrarenal pressure (IRP). Irrigation during ureteroscopy increases IRP. Complications such as sepsis is more frequent after prolonged high-pressure ureteroscopy. We evaluated a new method to document and visualize intrarenal backflow as a function of IRP and time in a pig model. Received: October 3, 2022 Methods Accepted: January 27, 2023 Studies were performed on five female pigs. A ureteral catheter was placed in the renal pelvis and connected to a Gadolinium/ saline solution 3 ml/L for irrigation. An occlusion balloon-catheter was left inflated at the uretero-pelvic junction and connected to a pressure monitor. Irrigation was successively regulated to maintain steady IRP levels at 10, 20, 30, 40 and 50 mmHg. MRI of the kidneys was performed at 5-minute intervals. PCR and immunoassay analyses were executed on the harvested kidneys to detect potential changes in inflammatory markers. Published: February 16, 2023 Peer Review History: PLOS recognizes the benefits of transparency in the peer review process; therefore, we enable the publication of all of the content of peer review and author responses alongside final, published articles. The editorial history of this article is available here: https://doi.org/10.1371/journal.pone.0281676 Copyright: © 2023 Lildal et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the paper and its Supporting Information files. Results MRI showed backflow of Gadolinium into the kidney cortex in all cases. The mean time to first visual damage was 15 minutes and the mean registered pressure at first visual damage was 21 mmHg. On the final MRI the mean percentage of IRB affected kidney was 66% after irrigation with a mean maximum pressure of 43 mmHg for a mean duration of 70 minutes. Immunoassay analyses showed increased MCP-1 mRNA expression in the treated kidneys compared to contralateral control kidneys. PLOS ONE | https://doi.org/10.1371/journal.pone.0281676 February 16, 2023 1 / 13 PLOS ONE Funding: The authors received no specific funding for this work. Competing interests: The authors have declared that no competing interests exist. Gadolinium-enhanced MRI visualizing backflow at increasing intra-renal pressure in a porcine model Conclusions Gadolinium enhanced MRI provided detailed information about IRB that has not previously been documented. IRB occurs at even very low pressures, and these findings are in conflict with the general consensus that keeping IRP below 30–35 mmHg eliminates the risk of post-operative infection and sepsis. Moreover, the level of IRB was documented to be a function of both IRP and time. The results of this study emphasize the importance of keeping IRP and OR time low during ureteroscopy. Introduction Indications for ureteroscopy have expanded dramatically during recent years, and although ureteroscopy in general is considered a safe procedure, serious complications and even deaths do occur, and these are most often related to sepsis [1]. To understand this, we must focus on how ureteroscopy may push upper urinary tract physiology to pathophysiology [3, 10]. When advancing a ureteroscope to the upper urinary tract and using saline irrigation, which is necessary for vision, the intrarenal pressure will increase significantly [5, 6], and when exceeding certain thresholds, intrarenal backflow may occur: backflow of urine and irrigation fluid to the renal tubules and the venous system. We have studied intrarenal pressure during ureteroscopy quite extensively during recent years [3, 6, 10]; however, our understanding on the relation between intrarenal pressure (IRP) and intrarenal backflow (IRB), which is the likely event immediately before sepsis, is still deficient; and the objective of this study was to approach this knowledge gap. The specific aim was to evaluate and visualize IRB dynamically as a function of intrarenal pressure and time using MRI in a porcine model with a Gadolinium tracer in the irrigation fluid. Materials and methods Experimental animals The animal protocol was approved by The National Animal Experiments Inspectorate (Copenhagen, Denmark). Studies were performed on 5 anaesthetized female pigs weighing 45 kg (Påskehøjgård, Ølsted, Denmark). The pigs were fed a standard diet during breeding. Before the study they had access to water but were fasting 12 hours prior to anaesthesia. After premedication with azaperone (4mg/kg) and midazolam (4 mg/kg), anaesthesia was induced by propofol (4–20 mg/kg) and maintained with sevoflurane (1.2 MAC) and fentanyl (0.03 mg/kg/h). The pigs were orotracheally intubated and mechanically ventilated (GE Healthcare S5 Avance). Hydration was maintained by administration of saline (9 g/l sodium chloride; 10 ml/kg/h) at a temperature of 37˚C through an ear vein. A cystoscope was inserted through the urethra into the bladder. A ureteral catheter (Selectip1, Bard Medical, Covington, USA) was placed in the distal part of the ureter and a retrograde pyelography was performed to visualize the anatomy of the upper urinary tract. A guide wire (Sensor1, Boston Scientific, Marlborough, MA, USA) was placed via the ureteral catheter, through the ureter, to the renal pelvis, and the cystoscope was removed. Over the guide wire, and under fluoroscopic guidance, a dual lumen catheter (Cook Medical, Bloomington, IN, USA) was inserted to (...truncated)