Preserving organ function of marginal donor kidneys

Niertransplantatie is de beste medische behandeling voor patiënten die lijden aan eindstadium nierfalen. De afgelopen decennia is de samenstelling van de overleden donorpool radicaal veranderd, zodanig dat er steeds meer organen beschikbaar komen van oudere donoren, die vaak al meerdere aandoeningen in de voorgeschiedenis hebben, of van zogenaamde non-heart beating donoren bij wie de orgaanuitname pas kan beginnen wanneer het hart al enkele minuten stil heeft gestaan. Zulke orgaandonoren worden ook wel marginale donoren genoemd. Dit proefschrift beschrijft de resultaten van klinische en pre-klinische studies op het gebied van niertransplantatie. In deze studies wordt de invloed die verscheidene karakteristieken van overleden orgaandonoren op het transplantatieresultaat hebben gekwantificeerd. Tevens wordt het effect onderzocht van interventies vóór of gedurende orgaanpreservatie, die zijn gericht op het beter conserveren van de orgaankwaliteit voorafgaand aan de transplantatie. Daarnaast beschrijft het proefschrift een studie waarin biomarkers worden gemeten in de orgaanpreservatievloeistof en een andere studie waarin de vasculaire weerstand wordt bepaald tijdens machinale preservatie van donornieren. Deze beide studies hebben als doel het voorspellen van de vitaliteit en de functie van het orgaan na transplantatie. Hoewel de resultaten van de studies in dit proefschift betrekking hebben op nieren afkomstig van alle typen overleden donoren, zijn ze het meest relevant voor marginale donornieren. Aangezien de functie en levensduur van zulke nieren na transplantatie vaak suboptimaal zijn, is extra informatie over hun kwaliteit nog vóór transplantatie belangrijk. Tevens zijn nieuwe interventies die de orgaanfunctie ná transplantatie verbeteren noodzakelijk

Reparative and Regenerative Effects of Mesenchymal Stromal Cells-Promising Potential for Kidney Transplantation?

Mesenchymal stromal cells (MSCs) possess reparative, regenerative and immunomodulatory properties. The current literature suggests that MSCs could improve kidney transplant outcome via immunomodulation. In many clinical domains, research has also focussed on the regenerative and reparative effects of therapies with MSCs. However, in the field of transplantation, data on this subject remain scarce. This review provides an overview of what is known about the regenerative and reparative effects of MSCs in various fields ranging from wound care to fracture healing and also examines the potential of these promising MSC properties to improve the outcome of kidney transplantations

Kidney Transplantation and Diagnostic Imaging:The Early Days and Future Advancements of Transplant Surgery

The first steps for modern organ transplantation were taken by Emerich Ullmann (Vienne, Austria) in 1902, with a dog-to-dog kidney transplant, and ultimate success was achieved by Joseph Murray in 1954, with the Boston twin brothers. In the same time period, the ground-breaking work of Wilhelm C. Röntgen (1895) and Maria Sklodowska-Curie (1903), on X-rays and radioactivity, enabled the introduction of diagnostic imaging. In the years thereafter, kidney transplantation and diagnostic imaging followed a synergistic path for their development, with key discoveries in transplant rejection pathways, immunosuppressive therapies, and the integration of diagnostic imaging in transplant programs. The first image of a transplanted kidney, a urogram with intravenous contrast, was shown to the public in 1956, and the first recommendations for transplantation diagnostic imaging were published in 1958. Transplant surgeons were eager to use innovative diagnostic modalities, with renal scintigraphy in the 1960s, as well as ultrasound and computed tomography in the 1970s. The use of innovative diagnostic modalities has had a great impact on the reduction of post-operative complications in kidney transplantation, making it one of the key factors for successful transplantation. For the new generation of transplant surgeons, the historical alignment between transplant surgery and diagnostic imaging can be a motivator for future innovations

Normothermic machine perfusion of ischaemically damaged porcine kidneys with autologous, allogeneic porcine and human red blood cells

In porcine kidney auto-transplant models, red blood cells (RBCs) are required for ex-vivo normothermic machine perfusion (NMP). As large quantities of RBCs are needed for NMP, utilising autologous RBCs would imply lethal exsanguination of the pig that is donor and recipient-to-be in the same experiment. The purpose of this study was to determine if an isolated porcine kidney can also be perfused with allogeneic porcine or human RBCs instead. Porcine kidneys, autologous and allogeneic blood were obtained from a local slaughterhouse. Human RBCs (O-pos), were provided by our transfusion laboratory. Warm ischaemia time was standardised at 20 minutes and subsequent hypothermic machine perfusion lasted 1.5–2.5 hours. Next, kidneys underwent NMP at 37°C during 7 hours with Williams’ Medium E and washed, leukocyte depleted RBCs of either autologous, allogeneic, or human origin (n = 5 per group). During perfusion all kidneys were functional and produced urine. No macroscopic adverse reactions were observed. Creatinine clearance during NMP was significantly higher in the human RBC group in comparison with the allogeneic group (P = 0.049) but not compared to the autologous group. The concentration of albumin in the urine was significantly higher in the human RBC group (P <0.001) compared to the autologous and allogeneic RBC group. Injury marker aspartate aminotransferase was significantly higher in the human RBC group in comparison with the allogeneic group (P = 0.040) but not in comparison with the autologous group. Renal histology revealed glomerular and tubular damage in all groups. Signs of pathological hyperfiltration and microvascular injury were only observed in the human RBC group. In conclusion, perfusion of porcine kidneys with RBCs of different origin proved technically feasible. However, laboratory analysis and histology revealed more damage in the human RBC group compared to the other two groups. These results indicate that the use of allogeneic RBCs is preferable to human RBCs in a situation where autologous RBCs cannot be used for NMP

Introduction of the Grayscale Median for Ultrasound Tissue Characterization of the Transplanted Kidney

Ultrasound examination is advised for early post-kidney transplant assessment. Grayscale median (GSM) quantification is novel in the kidney transplant field, with no systematic assessment previously reported. In this prospective cohort study, we measured the post-operative GSM in a large cohort of adult kidney transplant recipients (KTR) who consecutively underwent Doppler ultrasound directly after transplantation (within 24 h), compared it with GSM in nontransplanted patients, and investigated its association with baseline and follow-up characteristics. B-mode images were used to calculate the GSM in KTR and compared with GSM data in nontransplanted patients, as simulated from summary statistics of the literature using a Mersenne twister algorithm. The association of GSM with baseline and 1-year follow-up characteristics were studied by means of linear regression analyses. In 282 KTR (54 ± 15 years old, 60% male), the median (IQR) GSM was 55 (45-69), ranging from 22 to 124 (coefficient of variation = 7.4%), without differences by type of donation (p = 0.28). GSM in KTR was significantly higher than in nontransplanted patients (p < 0.001), and associated with systolic blood pressure, history of cardiovascular disease, and donor age (std. β = 0.12, -0.20, and 0.13, respectively; p < 0.05 for all). Higher early post-kidney transplant GSM was not associated with 1-year post-kidney transplant function parameters (e.g., measured and estimated glomerular filtration rate). The data provided in this study could be used as first step for further research on the application of early postoperative ultrasound in KTR