Goal-Directed Fluid Therapy Does Not Improve Early Glomerular Filtration Rate in a Porcine Renal Transplantation Model

Abstract

BACKGROUND: Insufficient fluid administration intra- and postoperatively may lead to delayed renal graft function (DGF), while fluid overload increases the risk of heart failure, infection, and obstipation. Several different fluid protocols have been suggested to ensure optimal fluid state. However, there is a lack of evidence of the clinical impact of these regimens. This study aimed to determine whether individualized goal-directed fluid therapy (IGDT) positively affects the initial renal function compared to a high-volume fluid therapy (HVFT) and to examine the effects on renal endothelial glycocalyx, inflammatory and oxidative stress markers, and medullary tissue oxygenation. The hypothesis was that IGDT improves early glomerular filtration rate (GFR) in pigs subjected to renal transplantation. METHODS: This was an experimental randomized study. Using a porcine renal transplantation model, animals were randomly assigned to receive IGDT or HVFT during and until 1 hour after transplantation from brain-dead donors. The kidneys were exposed to 18 hours of cold ischemia. The recipients were observed until 10 hours after reperfusion, which included GFR measured as clearance of chrom-51-ethylendiamintetraacetat (51Cr-EDTA), animal weight, and renal tissue oxygenation by fiber optic probes. The renal expression of inflammatory and oxidative stress markers as well as glomerular endothelial glycocalyx were analyzed in the graft using polymerase chain reaction (PCR) technique and immunofluorescence. RESULTS: Twenty-eight recipient pigs were included for analysis. We found no evidence that IGDT improved early GFR compared to HVFT (P = .45), while animal weight increased more in the HVFT group (a mean difference of 3.4 kg [1.96–4.90]; P < .0001). A better, however nonsignificant, preservation of glomerular glycocalyx (P = .098) and significantly lower levels of the inflammatory marker cyclooxygenase 2 (COX-2) was observed in the IGDT group when compared to HVFT. COX-2 was 1.94 (1.50–2.39; P = .012) times greater in the HVFT group when compared to the IGDT group. No differences were observed in outer medullary tissue oxygenation or oxidative stress markers. CONCLUSIONS: IGDT did not improve early GFR; however, it may reduce tissue inflammation and could possibly lead to preservation of the glycocalyx compared to HVFT.

To compare intraoperative goal directed fluid therapy by trans-oesophageal Doppler vis-à-vis FloTrac™ in patients undergoing living related renal transplantation-a prospective randomised controlled study

“…[ 28 29 ] In animal renal transplantation, individualised GDFT compared to high-volume therapy did not improve early GFR; however, it reduced tissue inflammation and led to preservation of the glycocalyx. [ 30 ]…”

Loss of Endothelial Glycocalyx During Normothermic Machine Perfusion of Porcine Kidneys Irrespective of Pressure and Hematocrit

“…In short, for the glycocalyx staining, a biotinylated lectin DBA (B-1035-5, Vector Laboratories Inc., Newark, CA) was used. 28,29 For the VEGFR-2 and fibrin stainings incubation with respectively a primary rabbit anti-human VEGFR-2 (antibody Cell Signaling Technology, MA D5B1, #9698S) and a rabbit anti-human fibrinogen (A0080, Dako, Glostrup, Denmark) antibodies was done. The ERG staining was performed using an anti-ERG rabbit monoclonal primary antibody (EPR3864; Abcam).…”

Anaesthetic Approach to Enhanced Recovery after Surgery for Kidney Transplantation: A Narrative Review

“…No significant difference in early glomerular filtration rate (GFR) was demonstrated when comparing IGDT and HVFT. However, the IGDT group had better preserved glycocalyx and lower levels of inflammatory markers [ 106 ].…”