Urological and Biochemical Aspects of Transplantation Biology
Anthony R. Mundy, John M. Fitzpatrick, David E. Neal, Nicholas J. R. George in The Scientific Basis of Urology, 2010
Because of the increasing shortage of kidneys for donation, there is a need to increase the pool of organs. Therefore, the option of non–heart beating donoration, which had been utilized before brain death legislation, was explored again. These donors have been subjected to a varying amount of primary warm ischemia, during the time between cardiac arrest and perfusion with cold preservation solution. Different categories can be defined (Maastricht), which have implications for the degree of warm ischemia, simply these are controlled (awaiting cardiac arrest, Maastricht III and IV) and uncontrolled (failed resuscitation in the emergency setting, Maastricht I and II) (2). Because there is damage to the organs after cardiac arrest (warm ischemia), care must be taken to establish which kidneys are safe to transplant (3). If such steps are taken and the kidneys are used, delayed graft function is common (4). However, after a time, the function recovers, and the long-term outlook is the same as for kidneys transplanted from brain-dead donors (4, 5) Livers and pancreata have all been transplanted from such donors, but greater care must be taken, as delayed graft function, if it occurs, in a liver transplant is usually fatal (6).
Cellular and Molecular Mechanisms of Ischemic Acute Renal Failure and Repair
Robin S. Goldstein in Mechanisms of Injury in Renal Disease and Toxicity, 2020
We found that verapamil and nifedipine did not protect isolated non-contracting heart cells (Cheung, et al., 1984) or kidney tubules (unpublished) against injury associated with 30 to 40 min of anoxia. When anoxic cardiac myocytes were paced to contract, verapamil and nifedipine protected by decreasing the cellular contractile activity (Cheung, et al., 1984). Ca2+ channel blockers have been used to try to decrease acute renal failure in the renal allograft. They have been administered to both donor and recipient with resultant reduction in the incidence of acute renal failure accounting for delayed graft function. It is possible that these agents are working on the vasculature to enhance blood flow to the renal tubular cells. The recipients also received cyclosporine, which results in vasoconstriction. Thus the calcium channel blocker may have blocked the vasoconstriction that is likely responsible, at least in part, for cyclosporine toxicity (Dawidson and Rooth, 1990; Wagner, et al., 1987).
Development and Optimization of Preservation Solutions
John J. Lemasters, Constance Oliver in Cell Biology of Trauma, 2020
This basic gluconate perfusate was successfully used clinically12 and appeared to give better results than CPP. However, it was not suitable for longer-term kidney preservation. McAnulty et al.13 studied the effects of continuous perfusion of dog kidneys on mitochondrial functions and found that the presence of 0.5 mM calcium in the gluconate perfusate was optimal for maintaining both mitochondrial function and successful five-day dog kidney preservation. Calcium appears necessary to stabilize membrane structures and maintain the structural integrity of the organ. This perfusion fluid is now used clinically with excellent results,14,15 and the delayed graft function rate is only about 5 to 9%. In addition, this perfusate is suitable for three-day liver perfusion as tested in the dog.16
Transcriptional profile changes after treatment of ischemia reperfusion injury-induced kidney fibrosis with 18β-glycyrrhetinic acid
Published in Renal Failure, 2022
Yamei Jiang, Chengzhe Cai, Pingbao Zhang, Yongsheng Luo, Jingjing Guo, Jiawei Li, Ruiming Rong, Yi Zhang, Tongyu Zhu
According to a 2017 global epidemiological survey, the worldwide prevalence of chronic kidney disease (CKD) is about 9.1%. Death caused by CKD or impaired renal function accounted for 4.6% of all deaths in 2017, and CKD was the twelfth leading cause of death [1]. The immense public health burden of CKD has aroused great interest in research into the mechanism and potential therapy of this disease worldwide. In clinical settings, kidney ischemia and reperfusion (I/R) injury leaded acute kidney injury is a common complication of major surgery such as cardiac surgery (accounting for 20%) and abdominal surgery [2,3]. Furthermore, it is also a common reason for delayed graft function after kidney transplantation [4]. I/R injury eventually results in serious adverse outcome of progressing to CKD [5]. Renal fibrosis with deposition of collagens and other extracellular matrix proteins is the basic feature of CKD. Targeting cytokines, transcription factors, developmental, and signaling pathways has been shown to ameliorate kidney fibrosis in preclinical studies [6]. In addition, experts in various fields have collaborated to provide insights into novel strategies to prevent and treat CKD through animals and biomimetic studies [7]. In the current post-genomic era, the application of systems biology enables in-depth analysis of CKD at the molecular and subcellular level [8]. It is imperative to explore promising effective therapeutic strategies for CKD.
A review of imlifidase in solid organ transplantation
Published in Expert Opinion on Biological Therapy, 2021
Review of the patients transplanted thus far point to some important limitations and opportunities for improvement. In these studies, deceased donor allografts ultimately accrued prolonged cold ischemic times; in part due to the time required to perform two prospective crossmatches. Extensive cold ischemia time invariably increases the likelihood of delayed graft function (DGF), which proved to be particularly challenging in these cases. When DGF overlapped with the rebound of DSA, the lack of a clinical marker (creatinine or urine output) to cue concern for the development of AMR was problematic. Since DSA rebound did not invariably equate to AMR in these cases, a pathologic diagnosis of AMR on biopsy was obtained prior to the initiation of treatment. It is interesting to note that in the NYU series, only patients with DGF had AMR, and all patients with DGF had AMR. This co-incidence of DGF with AMR is not entirely surprising as ischemia-reperfusion injury is a known risk factor for AMR post-transplant [45]. Ultimately, cold ischemic time is a modifiable risk factor in these cases, one that could be minimized with systematic improvements. Whether reducing organ ischemia correlates with reduced rates of AMR in these cases remains to be determined, but it is conceivable.
Experimental Rat Model for Brain Death Induction and Kidney Transplantation
Published in Journal of Investigative Surgery, 2020
Majid Esmaeilzadeh, Mahmoud Sadeghi, Hans E. Heissler, Roland Galmbacher, Ali Majlesara, Shadi Al–Afif, Arianeb Mehrabi
An intracranial balloon catheter has commonly been used to induce BD in animal models. Increasing the intracranial pressure by inflating saline immediately induces a short period of hypertension and bradycardia which been followed by release of catecholamine and cardiovascular responses [1]. BD induces neurogenic shock in the potential organ donor, which can affect organ function for example, by increasing hypotension after kidney transplantation [4]. Maintaining normotension by administering fluid and vasoactive drugs plays a vital clinical role in donor management [4]. Although our BD model does not reveal the hemodynamic changes which normally were observed in human donor studies, we do believe that it narrowly mimics the clinical situation. As mentioned, BD induction was induced slowly in this study. Hoeksma et al. [16] induced fast and slow BD induction in rats by an inflation of 0.45 and 0.015 ml/min, respectively. They reported that after slow brain death induction, increase of serum malondialdehyde levels and plasma creatinine levels, increase of superoxide production, decrease of glutathione levels, and increase of inducible nitric oxide synthase were more noticeable. It could lead to decreased rate of delayed graft function.
Related Knowledge Centers
- Chronic Kidney Disease
- Immunosuppressive Drug
- Abdomen
- Organ Transplantation
- Kidney
- Kidney Dialysis
- Transplant Rejection
- Renal Biopsy
- Creatinine
- Heart Transplantation