The development of diabetes mellitus (DM) after living donor kidney transplantation (KT) is a risk factor for worsening transplant kidney function, cardiac disease, and cerebrovascular disease, which ...may affect prognosis after KT. At our institution, all patients’ glucose tolerance is evaluated perioperatively by oral glucose tolerance tests (OGTTs) at pre-KT, and 3, 6, and 12 month (mo.) after KT. We analyzed the insulinogenic index (ISI) and homeostasis model assessment beta cell (HOMA-β) based on the immunoreactive insulin (IRI) levels to determine how glucose tolerance changed after KT in 214 patients who had not been diagnosed with DM before KT. In addition, we analyzed the body mass index (BMI) which may also influence glucose tolerance after KT. The concentration of tacrolimus (TAC) in blood was also measured as the area under the curve (AUC) to examine its effects at each sampling point. The preoperative-OGTTs showed that DM was newly diagnosed in 22 of 214 patients (10.3%) who had not been given a diagnosis of DM by the pre-KT fasting blood sugar (FBS) tests. The glucose tolerance was improved in 15 of 22 DM patients at 12 mo. after KT. ISI and IRI deteriorated only at 3 mo. after KT but improved over time. There was a trend of an inverse correlation between HOMA-β and TAC-AUC. We also found inverse correlations between IRI and an increase in BMI from 3 to 12 mo. after KT. Early corticosteroid withdrawal or the steroid minimization protocol with tacrolimus to maintain a low level of diabetogenic tacrolimus and BMI decrease after KT used by our hospital individualizes lifestyle interventions for each patient might contribute to an improvement in post-KT glucose tolerance.
•Recipients’ feelings of guilt for donors were associated with depressive symptoms.•Recipients with feelings of guilt showed the cognitive aspects of depression.•Findings may be helpful to prevent or ...reduce recipients’ depression before surgery.
Recipient depression before kidney transplantation needs to be treated to reduce poor posttransplant outcomes. For recipients who receive living kidney transplantation, feelings of guilt for potential donors may be factors related to the presence of depressive symptoms. This study aimed to examine the association between recipients’ feelings of guilt for the donor and depressive symptoms before living kidney transplantation.
Participants included 178 patients in Sapporo City General Hospital, Hokkaido, Japan, who completed a questionnaire before having living kidney transplantation from April 2009 to May 2016. Feelings of guilt for the donor, depressive symptoms using the Beck Depression Inventory-II (BDI-II), relationship to the donor, dialysis period, and socio-demographic characteristics were assessed via a questionnaire. Multivariate regression analyses were performed to examine the association between feelings of guilt for the donor and BDI-II score after multiple imputations.
The results showed that feelings of guilt for donors were associated with depressive symptoms, especially cognitive factors.
These findings indicate that medical staff needs to address recipients’ feelings of guilt for donors before living kidney transplantation.
Objectives
To evaluate the risk for urological complications after kidney transplantation at a single medical center in Japan.
Methods
In the present study, 408 kidney recipients (255 men, 153 women) ...were enrolled. There were 349 living and 59 deceased donors. The average age of the recipients was 42.5 ± 13.5 years, and the average pretransplant dialysis period was 71.8 ± 88.2 months. Ureteroneocystostomy was carried out on 347 patients, and ureteroureterostomy on 61 patients. We investigated the relationship between pretransplant duration of dialysis and bladder capacity, and examined the risk factors for urological complication. We also evaluated the incidence of vesicoureteral reflux in 191 recipients who underwent ureteroneocystostomy during transplantation.
Results
The preoperative duration of dialysis therapy showed a significant negative correlation with bladder capacity (R2 = 0.33, P < 0.001). The overall urological complication rate was 3.4% (14 patients), including urinary leakage (12 patients) and ureteral stricture (two patients). Univariate analysis showed that atrophic bladder, long‐term dialysis therapy, deceased donor and ureteroureterostomy were associated with a higher incidence of urological complications (odds ratio 8.05, 4.43, 3.42 and 3.35; P < 0.01, P = 0.01, P = 0.04 and P = 0.04, respectively). Furthermore, multivariate analysis showed that atrophic bladder was the only significant factor associated with urological complications (odds ratio 10.37; P = 0.01). Among 191 recipients, vesicoureteral reflux was observed in 32 (16.8%). The incidence of vesicoureteral reflux was significantly higher in patients with atrophic bladder.
Conclusions
Bladder atrophy in renal transplant recipients after long‐term dialysis therapy is associated with a higher risk of urological complications.
Heat shock protein 90 (HSP90), a molecular chaperone associated with the activation of client proteins, was recently reported to play an important role in immunologic reactions. To date, the role of ...HSP90 in solid organ transplantations has remained unknown. The aim of this study was to evaluate the relationship between serum HSP90α levels and acute allograft rejection after organ and tissue transplantation using serum samples from kidney allograft recipients, an in vitro antibody-mediated rejection model, and a murine skin transplantation.
Serum HSP90α levels were significantly higher in kidney recipients at the time of acute rejection (AR) than in those with no evidence of rejection. In most cases with AR, serum HSP90 decreased to baseline after the treatment. On the other hand, serum HSP90α was not elevated as much in patients with chronic rejection, calcineurin inhibitor nephrotoxicity, or BK virus nephropathy as in AR patients. In vitro study showed that HSP90α concentration in the supernatant was significantly higher in the supernatant of human aortic endothelial cells cocultured with specific anti-HLA IgG under complement attack than in that of cells cocultured with nonspecific IgG. In mice receiving skin transplantation, serum HSP90α was elevated when the first graft was rejected and the level further increased during more severe rejection of the second graft.
The results suggest that HSP90α is released into the serum by cell damage due to AR in organ and tissue transplantation, and it is potentially a new biomarker to help detect AR in kidney recipients.
Urinary extracellular vesicles (EV) could be promising biomarkers for urological diseases. In this retrospective feasibility study, we conducted biomarker screening for early stage bladder cancer ...using EV mRNA analysis.
Biomarker candidates were identified through RNA-seq analysis of urinary EV from patients with non-muscle invasive bladder cancer (N=3), advanced urothelial cancer (N=3), no residual tumor after TURBT (N=2), and healthy and disease controls (N=4). Diagnostic performance was evaluated by RT-qPCR in a larger patient group including bladder cancer (N=173), renal pelvis and ureter cancer (N=33), no residual tumor and non-cancer disease control (N=36).
Urinary EV
,
and
were overexpressed in pT1 and higher stage bladder cancer by 20.6-fold, 18.2-fold and 29.5-fold, respectively. These genes allowed detection of non-muscle invasive bladder cancer (AUC: 0.56 to 0.64 for pTa, 0.62 to 0.80 for pTis, and 0.82 to 0.86 for pT1) as well as pT2 and higher muscle invasive bladder cancer (AUC: 0.72 to 0.90). Subgroup analysis indicated that these markers could be useful for the detection of cytology-negative/-suspicious and recurrent bladder cancers.
Three urinary EV mRNA were discovered to be elevated in bladder cancer. Urinary EV mRNA are promising biomarkers of urothelial cancer and worth further investigation.
Non-invasive, prompt, and proper detection tools for kidney graft injuries (KGIs) are awaited to ensure graft longevity. We screened diagnostic biomarkers for KGIs following kidney transplantation ...using extracellular vesicles (EVs; exosomes and microvesicles) from the urine samples of patients.
One hundred and twenty-seven kidney recipients at 11 Japanese institutions were enrolled in this study; urine samples were obtained prior to protocol/episode biopsies. EVs were isolated from urine samples, and EV RNA markers were assayed using quantitative reverse transcription polymerase chain reaction. Diagnostic performance of EV RNA markers and diagnostic formulas comprising these markers were evaluated by comparison with the corresponding pathological diagnoses.
EV CXCL9, CXCL10, and UMOD were elevated in T-cell-mediated rejection samples compared with other KGI samples, while SPNS2 was elevated in chronic antibody-mediated rejection (cABMR) samples. A diagnostic formula developed through Sparse Logistic Regression analysis using EV RNA markers allowed us to accurately (with an area under the receiver operator characteristic curve AUC of 0.875) distinguish cABMR from other KGI samples. EV B4GALT1 and SPNS2 were also elevated in cABMR, and a diagnostic formula using these markers was able to distinguish between cABMR and chronic calcineurin toxicity accurately (AUC 0.886). In interstitial fibrosis and tubular atrophy (IFTA) urine samples and those with high Banff chronicity score sums (BChS), POTEM levels may reflect disease severity, and diagnostic formulas using POTEM detected IFTA (AUC 0.830) and high BChS (AUC 0.850).
KGIs could be diagnosed with urinary EV mRNA analysis with relatively high accuracy.
A TLR5 agonist inhibits acute renal ischemic failure Fukuzawa, Nobuyuki; Petro, Marianne; Baldwin, 3rd, William M ...
The Journal of immunology (1950),
2011-Oct-01, 2011-10-01, 20111001, Letnik:
187, Številka:
7
Journal Article
Recenzirano
Odprti dostop
Reperfusion of ischemic organs induces a potent inflammatory response initiated by the generation of reactive oxygen species that directly damage tissue and promote leukocyte infiltration and ...activation that also mediate tissue injury. We recently found that radiation-induced tissue injury, which is caused by radiation-induced reactive oxygen species, is attenuated by administration of CBLB502, a pharmacologically optimized derivative of the TLR5 agonist flagellin. Therefore, we tested the ability of CBLB502 to attenuate injury in a murine model of acute ischemic renal failure. CBLB502 given 30 min before imposition of bilateral renal pedicle occlusion provided marked protection against the renal dysfunction and inflammation that follows reperfusion of ischemic kidneys, including marked decreases in leukocyte infiltration, proinflammatory cytokine production, and tubular injury. Importantly, CBLB502 given within 30 min after ischemic kidney reperfusion reproduced the protective effects of pretreatment with the TLR5 agonist, indicating a window following reperfusion in which CBLB502 administration abrogates acute renal ischemic failure. Bone marrow-reconstituted chimeras were used to show that the protective effects of CBLB502 could be delivered by intact MyD88 signaling on renal parenchymal cells. Consistent with this, Ab staining of kidney sections indicated that cells lining the renal vasculature expressed TLR5. Overall, these results indicate the use of TLR5 agonists as mitigators and protectants of acute renal ischemic failure.
Laparoscopic surgery has been a standard procedure of living donor nephrectomy (LDN). Transperitoneal hand-assisted laparoscopic LDN (HALDN) has been commonly reported by many centers with excellent ...outcome. However, there are few studies reporting retroperitoneoscopic LDN (RPLDN).
Four hundred four consecutive kidney donors (124 men, 280 women) were enrolled in this study. Age of the donors was 55.0 ± 10.7 years. RPLDN was performed for 294 donors, and HALDN for 110 donors. We compared perioperative donor outcome and early complication rates between RPLDN and HALDN to evaluate the safety and efficacy of RPLDN.
Intraoperative blood loss was significantly less in RPLDN than in HALDN (p < 0.05). The conversion rate to open surgery was similar between the two groups. The intraoperative complication rate was 1.0% (two vascular injuries and one bowel injury) in RPLDN and 0.9% (one vascular injury) in HALDN. The postoperative complication rate was 3.4% (six surgical site infections, two postoperative bleeding, one colon perforation, one ileus, one rhabdomyolysis) in RPLDN and 1.8% (two surgical site infections) in HALDN. Although warm ischemic time was significantly longer in RPLDN than in HALDN (p < 0.01), the incidence of delayed graft function was similar between the two groups. Furthermore, there was no difference in 1-year graft survival between the two groups.
Both RPLDN and HALDN procedures were well tolerated with minimal complication rates, and both procedures showed similar impact on recipient graft function. These results suggest that RPLDN could be a feasible option for LDN as well as HALDN.
Heat shock protein 90 (HSP90), a molecular chaperone associated with the activation of client proteins, was recently reported to play an important role in immunologic reactions. To date, the role of ...HSP90 in solid organ transplantations has remained unknown. The aim of this study was to evaluate the relationship between serum HSP90alpha levels and acute allograft rejection after organ and tissue transplantation using serum samples from kidney allograft recipients, an in vitro antibody-mediated rejection model, and a murine skin transplantation. Serum HSP90alpha levels were significantly higher in kidney recipients at the time of acute rejection (AR) than in those with no evidence of rejection. In most cases with AR, serum HSP90 decreased to baseline after the treatment. On the other hand, serum HSP90alpha was not elevated as much in patients with chronic rejection, calcineurin inhibitor nephrotoxicity, or BK virus nephropathy as in AR patients. In vitro study showed that HSP90alpha concentration in the supernatant was significantly higher in the supernatant of human aortic endothelial cells cocultured with specific anti-HLA IgG under complement attack than in that of cells cocultured with nonspecific IgG. In mice receiving skin transplantation, serum HSP90alpha was elevated when the first graft was rejected and the level further increased during more severe rejection of the second graft. The results suggest that HSP90alpha is released into the serum by cell damage due to AR in organ and tissue transplantation, and it is potentially a new biomarker to help detect AR in kidney recipients.
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