Inulin Clearance During Ex vivo Normothermic Machine Perfusion as a Marker of Renal Function

Abstract

Normothermic machine perfusion (NMP) offers a unique opportunity to objectively assess donor organ quality. This study describes the evaluation of inulin clearance as a potential marker for the ex vivo function of porcine kidneys during NMP. The function assessment was performed in both kidneys from slaughterhouse pigs (n = 20) and kidneys from pigs in a laboratory setting (n = 28). The kidneys were exposed to different warm ischemia times (WIT). After a period of static cold storage, the kidneys underwent a 4-hour NMP with autologous whole blood. Inulin clearance, hemodynamic parameters, and urine output were measured. Based on the inulin excretion behavior laboratory pig kidneys were assigned to three classes (functional, limited functional, and nonfunctional), slaughterhouse pig kidneys to two classes (limited functional and nonfunctional), respectively. Contrary to the marginal kidneys of the slaughterhouse pigs, the functional variation of kidneys of the laboratory pigs was associated with the WIT. A correlation between functional kidneys and a WIT less than 25 min was shown. Because none of the slaughterhouse pig kidneys could be assigned to the functional class, only the laboratory pig kidneys were used for examinations with functional markers. Renal blood flow and urine output during NMP correlated significantly (p < 0.01) with ex vivo kidney function. This study demonstrated that inulin is a marker of high quality for the evaluation of suggested kidney function after NMP with whole blood. Furthermore, surrogate markers measured during NMP can be used to describe and predict the physiologic behavior of kidneys before transplantation.

Hyperspectral Imaging during Normothermic Machine Perfusion—A Functional Classification of Ex Vivo Kidneys Based on Convolutional Neural Networks

“…This exploratory analysis aimed to perform a functional classification of ex vivo kidneys by CNN models based on tissue-related properties obtained by HSI. For this purpose, HSI data recorded during a previously published study [ 18 ] were analyzed. Kidneys from healthy laboratory pigs were removed and perfused ex vivo with NMP for four hours.…”

“…The NMP method including the description of blood and organ retrieval, the ex vivo normothermic machine perfusion device, the experimental protocol, and the inulin clearance analysis has been described in detail previously [ 18 ]. In brief, kidneys (n = 28) were collected from laboratory pigs of different races, sexes, and body weights after nonabdominal surgical training.…”

“…In the above studies, markers are measured during NMP and their predictive value is assessed after transplantation. In contrast, our recently published study on renal preservation suggests new possibilities for organ evaluation with respect to inulin clearance, which is the gold standard for determining glomerular filtration rate (GFR) in vivo and thus renal function [ 18 ]. Knowledge about the ability of the kidneys to filter inulin during NMP allows assessment of functional renal status ex vivo and, if postoperative renal function is also confirmed, may be a promising approach for the development of new preoperative strategies to evaluate renal function [ 18 ].…”

“…In contrast, our recently published study on renal preservation suggests new possibilities for organ evaluation with respect to inulin clearance, which is the gold standard for determining glomerular filtration rate (GFR) in vivo and thus renal function [ 18 ]. Knowledge about the ability of the kidneys to filter inulin during NMP allows assessment of functional renal status ex vivo and, if postoperative renal function is also confirmed, may be a promising approach for the development of new preoperative strategies to evaluate renal function [ 18 ]. For the first time, perfusion characteristics during NMP (renal blood flow, mean arterial pressure, intrarenal resistance, total urine output) could be correlated with renal function before transplantation [ 18 ].…”

“…Knowledge about the ability of the kidneys to filter inulin during NMP allows assessment of functional renal status ex vivo and, if postoperative renal function is also confirmed, may be a promising approach for the development of new preoperative strategies to evaluate renal function [ 18 ]. For the first time, perfusion characteristics during NMP (renal blood flow, mean arterial pressure, intrarenal resistance, total urine output) could be correlated with renal function before transplantation [ 18 ]. The consequent next step is to expand the assessment strategy and investigate other markers or analytical methods that would provide a more comprehensive measure of organ quality and thus ensure an objective, systematic classification of kidneys according to their function.…”