BACKGROUND: The glucose derivative 3-O-methyl-D-glucose (OMG) is used as a cryoprotectant in freezing cells. However, its protective role and the related mechanism in static cold storage (CS) of organs are unknown. The present study aimed to investigate the effect of OMG on cod ischemia damage in cold preservation of donor kidney.
METHODS: Pretreatment of OMG on kidney was performed in an isolated renal cold storage model in rats. LDH activity in renal efflux was used to evaluate the cellular damage. Indicators including iron levels, mitochondrial damage, MDA level, and cellular apoptosis were measured. Kidney quality was assessed via a kidney transplantation (KTx) model in rats. The grafted animals were followed up for 7 days. Ischemia reperfusion (I/R) injury and inflammatory response were assessed by biochemical and histological analyses.
RESULTS: OMG pretreatment alleviated prolonged CS-induced renal damage as evidenced by reduced LDH activities and tubular apoptosis. Kidney with pCS has significantly increased iron, MDA, and TUNEL+ cells, implying the increased ferroptosis, which has been partly inhibited by OMG. OMG pretreatment has improved the renal function (p <0.05) and prolonged the 7-day survival of the grafting recipients after KTx, as compared to the control group. OMG has significantly decreased inflammation and tubular damage after KTx, as evidenced by CD3-positive cells and TUNEL-positive cells.
CONCLUSIONS: Our study demonstrated that OMG protected kidney against the prolonged cold ischemia-caused injuries through inhibiting ferroptosis. Our results suggested that OMG might have potential clinical application in cold preservation of donor kidney.

BACKGROUND: Mitochondrial dysfunction results in poor organ quality, negatively affecting the outcomes of lung transplantation. Whether hydrogen benefits mitochondrial function in cold-preserved donors remain unclear. The present study assessed the effect of hydrogen on mitochondrial dysfunction in donor lung injury during cold ischemia phase (CIP) and explored the underlying regulatory mechanism.
METHODS: Left donor lungs were inflated using 40% oxygen + 60% nitrogen (O group), or 3% hydrogen + 40% oxygen + 57% nitrogen (H group). Donor lungs were deflated in the control group and were harvested immediately after perfusion in the sham group (n = 10). Inflammation, oxidative stress, apoptosis, histological changes, mitochondrial energy metabolism, and mitochondrial structure and function were assessed. The expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) were also analyzed.
RESULTS: Compared with the sham group, inflammatory response, oxidative stress, histopathological changes, and mitochondrial damage were severe in the other three groups. However, these injury indexes were remarkably decreased in O and H groups, with increased Nrf2 and HO-1 levels, elevated mitochondrial biosynthesis, inhibition of anaerobic glycolysis and restored mitochondrial structure and function compared with the control group. Moreover, inflation using hydrogen contributed to stronger protection against mitochondrial dysfunction and higher levels of Nrf2 and HO-1 when comparing with O group.
CONCLUSIONS: Lung inflation using hydrogen during CIP may improve donor lung quality by mitigating mitochondrial structural anomalies, enhancing mitochondrial function, and alleviating oxidative stress, inflammation, and apoptosis, which may be achieved through activation of the Nrf2/HO-1 pathway.

Purpose: Cold ischemia-reperfusion injury (CIRI) is one of the most serious complications following renal transplantation. The current study investigated the feasibility of Intravoxel Incoherent Motion (IVIM) imaging and blood oxygenation level-dependent (BOLD) in the evaluation of different degrees of renal cold ischemia-reperfusion injury in a rat model. Methods: Seventy five rats were randomly divided into three groups (N = 25 for each group): T0: sham-operated group, T2/T4: CIRI groups with different cold ischemia hours (2, 4 h, respectively). The rat model of CIRI group was established by left kidney cold ischemia with right nephrectomy. All the rats received a baseline MRI before the surgery. Five rats in each group were randomly selected to undergo an MRI examination at 1 h, day 1, day 2 and day 5 after CIRI. The IVIM and BOLD parameters were studied in the renal cortex (CO), the outer stripe of the outer medulla (OSOM), and the inner stripe of the outer medulla (ISOM) followed by histological analysis to examine Paller scores, peritubular capillary (PTC) density, apoptosis rate and biochemical indicators to obtain the contents of serum creatinine (Scr), blood urea nitrogen (BUN), superoxide dismutase (SOD) and malondialdehyde (MDA). Results: The D, D*, PF and T2* values in the CIRI groups were lower than those in the sham-operated group at all timepoints (all p < 0.05). The prolonged cold ischemia times resulted in gradually lower D, D*, PF and T2* values (all p < 0.05). The D and T2* values of cortex and OSOM in Group T0 and T2 returned to the baseline level (all p > 0.05) except Group T4. The D* and PF values of cortex, OSOM and ISOM in Group T2 and T4 still remained below the normal levels (all p < 0.05) except Group T0. D, D*, PF and T2* values were strongly correlated with histopathological (Paller scores, PTC density and apoptosis rate) and the biochemistry indicators (SOD and MDA) (|r|>0.6, p < 0.001). D*, PF and T2* values were moderately to poorly correlated with some biochemistry indicators (Scr and BUN) (|r|<0.5, p < 0.05). Conclusion: IVIM and BOLD can serve as noninvasive radiologic markers for monitoring different degrees of renal impairment and recovery after renal CIRI.

With rapid development of liver transplantation technology, the demand for transplants have reached beyond the supply of organs, and thus development of effective strategies to reduce cold ischemia injury in fatty liver is important. Here, we explored the potential effect of SGLT-2 inhibitor in cold ischemia injury, fatty livers from 2 weeks methionine and choline deficient diet (MCD) rats were administered. After one week of intragastric administration of Sodium-dependent glucose transporters (SGLT-2) inhibitor empagliflozin (EMPA) or NaCI, liver were stored for 24 h. The results showed that EMPA could significantly reduce the cold ischemic injury in the mitochondria of fatty liver. To explore the mechanism, signal transducers and activators of transcription 3(STAT3) inhibitor AG490 group was used in a similar manner. We detected the changes in p-signal transducers and activators of transcription 3 (P-STAT3), alcohol-dehydrogenase 2 (ALDH2) and degree of apoptosis in three distinct groups. The results suggested that the protein expression of P-STAT3 and ALDH2 was higher in the EMPA group than in other two groups, whereas extent of apoptosis in the EMPA group was lower than other two groups. The data suggested that SGLT2 inhibitors could alleviate cold ischemia damage of mitochondria in fatty liver, which may be related to the inhibition of apoptosis and the activation of P-STAT3 and ALDH2.

In recent years, dual-kidney transplant has become an established method to overcome the inferior quality of donor organs and to allow the recovery of discarded human kidneys. However, in some cases, 1 of the 2 donor kidneys is unsuitable for transplant because of severe pathological changes, and the remaining marginal kidney is often discarded regardless of whether it meets criteria for dual-kidney transplant. Here, we report the use of marginal kidneys from 2 different donors, both of whom had missed kidney donation as a result of the serious pathological changes in their contralateral kidney. We combined the 2 donors\' marginal kidneys for dual-kidney transplant, which were implanted into the right iliac fossa of the recipient after cold ischemia times of 13 hours 40 minutes and 30 hours 30 minutes, respectively. The recipient had fully recovered and showed favorable renal function without complications at discharge and at the 1.5-year follow-up. To the best of our knowledge, this is the first case report of successful unilateral dual-kidney transplant of discarded kidneys from 2 expanded criteria donors.

Acute kidney injury (AKI) is the main reason for the bad outcome of the donation of circulatory death (DCD) kidney after transplantation. Prolonged cold storage (CS) is a risk factor for the occurrence of the delayed graft function in DCD kidney. The protein NLR-domain containing receptor 3 (NLRP3) plays a crucial role in renal ischemia reperfusion injury by triggering inflammasome formation. Herein, we investigated whether the NLRP3 signal participate in the CS-induced damage of DCD kidney in rat kidney transplantation models.
DCD kidney and living donor (LD) kidney of SD rats were preserved in UW solution at 4 °C for 2 h or 18 h, and then transplanted into syngeneic recipient. Thus, the animals were randomly divided into 4 groups: 2-h LD group, 2-h DCD group, 18-h LD group and 18-h DCD group. The renal function and pathological changes were determined. The expressions of NLRP3 and inflammatory factor IL-1β were assessed. The concentration of ferrous iron (Fe2+) was analyzed both in kidneys and in the preservation solution. The renal morphological changes were examined by hematoxylin eosin staining.
Our results showed that the levels of Cr and BUN were higher in 18-h LD group as compared to the 2-h LD group, which were remarkably increased in 18-h DCD group. The expression levels of NLRP3 and IL-1β were increased by 18-h CS compared to 2-h CS in both LD kidney and DCD kidney. In addition, the Fe2+ concentration has significantly increased in 18-h LD group than that in 2-h LD group, and the elevation of Fe2+ was more remarkable in DCD kidneys.
In conclusion, our study demonstrated that prolonged hypothermic storage of DCD kidney deteriorated the graft function via the increased Fe2+ concentration, which was associated with the upregulation of NLRP3 expression.

暂无摘要。

With the increasing incidence of end-stage renal disease (ESRD), patients\' life span and life quality are significantly reduced. Kidney transplantation has gradually become the ideal method for treating ESRD, and the shortage of organ sources has become the main problem. In recent years, China has successfully realized the transformation of organ sources. Voluntary donation after the death of citizens has increased year by year, and the number of kidney transplantations has increased, which alleviates the organ shortage to a certain extent, but compared with the past, the increasing proportion of aged donors has also become an inevitable global problem. At the same time, due to the sudden and widespread distribution of voluntary donation, most donor kidneys have the problem of longer cold ischemic time (CIT). The probability of adverse events, such as delayed renal function recovery after transplantation, was also significantly increased. At present, there is little research on the effect of donor\'s aging and long CIT on the prognosis of renal transplantation. This paper reviews the literature in recent years and explore this problem from 2 aspects: the elderly donor and the long CIT.

Traditional liver transplant strategies with cold preservation usually result in ischemia-reperfusion injury (IRI) to the donor liver. Regular normothermic machine perfusion (NMP) donor livers suffer IRI twice. Here, we aimed to introduce a novel technique called continuous NMP without recooling to avoid a second IRI and its application in livers from extended criteria donors.
Seven donor livers transplanted following continuous NMP without recooling, 7 donor livers transplanted following standard NMP, and 14 livers under static cold storage (SCS) were included in this study. Perioperative outcomes were recorded and analyzed between groups.
During the NMP without a recooling procedure, all livers cleared lactate quickly to normal levels in a median time of 100 min (interquartile range, 60-180) and remained stable until the end of perfusion. In the NMP without recooling and standard NMP groups, posttransplant peak aspartate aminotransferase and alanine aminotransferase levels were both significantly lower than those in the SCS group (P = 0.0015 and 0.016, respectively). The occurrence rate of early allograft dysfunction was significantly lower in the NMP without recooling group than in the SCS group (P = 0.022), whereas there was no difference in the NMP group with or without recooling (P = 0.462).
Our pilot study revealed a novel technique designed to avoid secondary IRI. This novel technique is shown to have at least a comparable effect on the standard NMP, although more data are needed to show its superiority in the future.

UNASSIGNED: Kidneys obtained from deceased donors increase the incidence of delayed graft function (DGF) after renal transplantation. Here we investigated the influence of the risk factors of donors with DGF, and developed a donor risk scoring system for DGF prediction.
UNASSIGNED: This retrospective study was conducted in 1807 deceased kidney donors and 3599 recipients who received donor kidneys via transplants in 29 centers in China. We quantified DGF associations with donor clinical characteristics. A donor risk scoring system was developed and validated using an independent sample set.
UNASSIGNED: The incidence of DGF from donors was 19.0%. Six of the donor characteristics analyzed, i.e., age, cause of death, history of hypertension, terminal serum creatinine, persistence of hypotension, and cardiopulmonary resuscitation (CPR) time were risk factors for DGF. A 49-point scoring system of donor risk was established for DGF prediction and exhibited a superior degree of discrimination. External validation of DGF prediction revealed area under the receiver-operating characteristic (AUC) curves of 0.7552.
UNASSIGNED: Our study determined the deceased donor risk factors related to DGF after renal transplantation pertinent to the Chinese cohort. The scoring system developed here had superior diagnostic significance and consistency and can be used by clinicians to make evidence-based decisions on the quality of kidneys from deceased donors and guide renal transplantation therapy.