Mannitol Infusion Within 15 Min of Cross-Clamp Improves Living Donor Kidney Preservation

Abstract

Background Optical coherence tomography (OCT) revealed that cells lining proximal convoluted tubules of living donor kidneys (LDK) procured by laparoscopic procedures were very swollen in response to the brief period of ischemia suffered between the time of arterial vessel clamping and flushing the excised kidney with cold preservation solution. Damage to the tubules as a result of this cell swelling resulted in varying degrees of acute tubular necrosis (ATN) that slowed the recovery of the donor kidneys during the first two weeks following their transplant. Methods In order to prevent this cell damage during LDK procurement, we changed the protocol for intravenous administration of mannitol (i.e., 12.5 or 25 g) to the donor. Specifically, we reduced the time of mannitol administration from 30 to 15 minutes or less prior to clamping the renal artery. Result OCT revealed that this change in the timing of mannitol administration protected the human donor proximal tubules from normothermic induced cell swelling. An evaluation of post-transplant recovery of renal function showed that patients treated with this modified protocol returned to normal renal function significantly faster than those treated with mannitol 30 or more minutes prior to clamping the renal artery. Conclusion Since slow graft recovery in the first weeks following transplantation represents a risk factor for long-term graft function and survival, we believe that this change in pretreatment protocol will improve renal transplants in patients receiving LDK.

Optical coherence tomography and computer-aided diagnosis of a murine model of chronic kidney disease

“…16 In vivo imaging of human kidney has been reported during kidney transplantation procedures, 17 and clinical studies have indicated that the openness of tubular lumens observed by OCT has a strong correlation with the posttransplant recovery of renal function. 18 These results suggest that OCT may be a useful tool in intraoperative monitoring and evaluation of transplant kidneys for predicting postgraft function after ischemia-reperfusion injury. OCT has been applied to other clinical studies, including assessing the morphological features of the endothelial and vascular injury induced by catheter-based renal nerve ablation, 19 and differentiating between normal renal parenchyma and renal cell carcinoma.…”

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“…[21][22][23][24] With the deterioration in renal function associated with aging being an important variable for determining suitability for transplant, 27,28 it is important to determine whether OCT also can access nephropathy associated with aging. In the present investigation, male Munich-Wistar rats exhibited characteristic age-related nephropathy over a 16-to 18-month lifespan.…”

“…Not only can it image depths up to 1 to 2 mm in most lightscattering tissues; OCT can provide 3-dimensional images in arbitrary planes. Finally, OCT can be performed using a thin flexible sterile endoscope or catheter [16][17][18] or even with a needle, 19,20 [21][22][23][24] Conversely, conventional excisional biopsies are invasive, damaging, can only sample a small region of the kidney, take time to process, and result in severe artifacts that are difficult to distinguish from ischemia and other injuries. 25 Because the morphology of the proximal convoluted tubules imaged by OCT correlates with the extent of acute tubular necrosis (ATN), 26 the information obtained by OCT is potentially useful in evaluating the status of donor kidneys.…”

Examining Mannitol Use in Kidney Cancer Surgery: A Cautionary Tale of Extrapolated Surgical Data

“…Significant variability in practice including dosing regimens was reported in a recent survey indicating that 49% and 30% of urologists use 25 and 12.5 g in PN, respectively [7], starkly reflecting the absence of clinically useful information on utility and application. Physiologic equivalence, meanwhile, has been suggested in clinical studies using either dose [31]. A number of clinical studies have examined the utility of mannitol during PN, including a phase 3, double-blind randomized control trial of 199 patients with estimated GFR (eGFR) > 45 ml/min/1.73 m 2 who underwent PN and were randomized to receive intravenous mannitol or saline placebo at the time of surgery.…”

“…The main source of evidence supporting that mannitol is for renal transplantation where graft function and failure are key concerns, particularly in the early post-engraftment period where renal dysfunction and ATN are often associated with rejection events or prolonged ischemia time [40]. Doses between 12.5 and 50 g mannitol with or without furosemide have been associated with decreased rates of ATN and longer-term renal preservation in renal grafts [31,41]. As described previously and for uncertain mechanisms, mannitol appeared to be more effective if initiated <15 min prior to arterial clamping, with no lower limit of time being established [31].…”