Changing pattern and safety of pretransplant malignancy in kidney transplant recipients.

BACKGROUND: Cancer rates are increasing not only in the general population but also in patients with end-stage renal disease. We investigated the changing pattern of pretransplant malignancy in kidney transplant recipients over 5 decades. METHODS: We reviewed 3,748 kidney transplant recipients between 1969 and 2016. We divided patients into three groups (1969-1998, 1999-2006, 2007-2016) based on the era of the cancer screening system used throughout the nation. We analyzed the incidence and pattern of pretransplant malignancy among the three groups. We also evaluated recurrent and de novo malignancy in these patients compared to patients without pretransplant malignancy. RESULTS: A total of 72 patients exhibited pretransplant malignancy (1.9%). There were no cases of pretransplant cancer until 1998, but the rate of pretransplant malignancy gradually increased to 1.1% during 1999-2006 and further increased to 4.3% thereafter. The most frequent types of pretransplant malignancy changed from the bladder, liver, and stomach cancers to thyroid cancer and renal cell carcinoma. There were no de novo cases, but there were three cases of recurrent cancer in patients with pretransplant malignancy; the recurrence rate among kidney transplant recipients with pretransplant malignancy was not significantly different from the incidence rate of de novo malignancy among kidney transplant recipients without pretransplant malignancy (4.2% vs. 6.9%, P = 0.48). CONCLUSION: The incidence of pretransplant malignancy in kidney transplantation candidates is gradually increasing, and recent increases were accompanied by changes in cancer types. Pretransplant malignancy may not be a hindrance to kidney transplantation because of the low incidence of posttransplant recurrence and de novo malignancy.

Exposure to Hyperchloremia Is Associated with Poor Early Recovery of Kidney Graft Function after Living-Donor Kidney Transplantation: A Propensity Score-Matching Analysis.

The effects of hyperchloremia on kidney grafts have not been investigated in patients undergoing living-donor kidney transplantation (LDKT). In this study, data from 200 adult patients undergoing elective LDKT between January 2016 and December 2017 were analyzed after propensity score (PS) matching. The patients were allocated to hyperchloremia and non-hyperchloremia groups according to the occurrence of hyperchloremia (i.e., ≥110 mEq/L) immediately after surgery. Poor early graft recovery was defined as estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 during the first 48 hours after surgery. After PS matching, no significant differences in perioperative recipient or donor graft parameters were observed between groups. Although the total amount of crystalloid fluid infused during surgery did not differ between groups, the proportions of main crystalloid fluid type used (i.e., 0.9% normal saline vs. Plasma Solution-A) did. The eGFR increased gradually during postoperative day (POD) 2 in both groups. However, the proportion of patients with eGFR > 60 mL/min/1.73 m2 on POD 2 was higher in the non-hyperchloremia group than in the hyperchloremia group. In this PS-adjusted analysis, hyperchloremia was significantly associated with poor graft recovery on POD 2. In conclusion, exposure to hyperchloremia may have a negative impact on early graft recovery in LDKT.

Prevalence of the Factor XIII Val34Leu Polymorphism in Korean Patients with Deep Vein Thrombosis.

OBJECTIVE: According to recent reports, a common polymorphism resulting in Val to Leu substitution, located 3 amino acids (Val34Leu) upstream of the thrombin cleavage site of FXIII A, has been related to a lower incidence of deep vein thrombosis (DVT). And, a different expression pattern has been shown across nations and races. However, the frequency of FXIII polymorphism expression in Koreans has not been reported in normal individuals or DVT-patient groups. DESIGN: Case-control study in Korean population. METHODS: We investigated the distribution of factor XIII Val34Leu polymorphisms in Korean patients of DVT (50 cases) and Korean healthy controls (100 cases), using real-time polymerase chain reaction for single nucleotide polymorphism genotyping. RESULTS: With regard to the frequency of the FXIII polymorphism in DVT patients and in the general control group, all 50 cases in the patient group and 100 cases in the control group were found to be Val34 homozygotes. CONCLUSIONS: The Val34Leu polymorphism of FXIII was not found in Korean people, and compared with Caucasians, a noticeably low incidence of DVT was shown. Thus, the preventive effect of the Val34 allele of FXIII on the formation of thrombi was shown.

Use of Reversed Iliac Leg Stent-Graft for the Treatment of Isolated Aneurysm of Internal Iliac Artery.

This is to report the technique of reversed iliac leg stent-graft in endovascular treatment for isolated internal iliac artery (IIA) aneurysm, which had significant size discrepancy between the common iliac artery (CIA) and external iliac artery (EIA) in 3 patients from different hospitals. Three patients were a 85- and two 82-year-old men. Treated were right IIA aneurysms, sized 6.5×6.2 cm, 5.0×4.0 cm, and 4.1 cm in longest diameter, respectively. The diameters of the right CIA and right EIA measured 21 mm/11 mm, 15 mm/11 mm, and 20 mm/10 mm, respectively. In all cases, reversed iliac leg stent-grafts were prepared on-site; unsheathed and mounted upside-down manually, and deployed in each right CIA. Post-stent-graft angiograms showed complete exclusion of the aneurysms, except for minimal type 1 endoleak in one case. This technique is a useful treatment option in patients with isolated IIA aneurysm.

Aortic transection and diverting bypass as treatment of repetitive recurrent abdominal aortic false aneurysm rupture in a patient with Behcet's disease.

Abdominal aortic false aneurysms in patients with Behcet's disease have been reported frequently and repaired successfully by various procedures; however, anastomotic false aneurysms have often been reported to occur after the operation. In this article, we report a case of four-time repetitive, recurrent suprarenal abdominal aortic false aneurysm ruptures that lasted for 7 years. The location of this aneurysm was not easy to repair not only by open surgical procedures but by endovascular stent because the aortic defect was too close to the visceral arterial branches. The last operation consisted of primary repair of aortic defect, transection of abdominal aorta at the level of supraceliac aorta with end closure, and a thoracic aorta to abdominal aorta bypass with Dacron graft. An 8-year follow-up revealed no more abdominal aortic aneurysm recurrence.

MAPKs (ERK1/2, p38) and AKT can be phosphorylated by shear stress independently of platelet endothelial cell adhesion molecule-1 (CD31) in vascular endothelial cells.

PECAM-1 (CD31) is a member of the Ig superfamily of cell adhesion molecules and is expressed on endothelial cells (EC) as several circulating blood elements including platelets, polymorphonuclear leukocytes, monocytes, and lymphocytes. PECAM-1 tyrosine phosphorylation has been observed following mechanical stimulation of EC but its role in mechanosensing is still incompletely understood. The aim of this study was to investigate the involvement of PECAM-1 in signaling cascades in response to fluid shear stress (SS) in vascular ECs. PECAM-1-deficient (KO) and PECAM-reconstituted murine microvascular ECs, 50 and 100% confluent bovine aortic EC (BAEC), and human umbilical vein EC (HUVEC) transfected with antisense PECAM-1 oligonucleotides were exposed to oscillatory SS (14 dynes/cm2) for 0, 5, 10, 30 or 60 min. The tyrosine phosphorylation level of PECAM-1 immunoprecipitated from SS-stimulated PECAM-reconstituted, but not PECAM-1-KO, murine ECs increased. Although PECAM-1 was phosphorylated in 100% confluent BAEC and HUVEC, its phosphorylation level in 50% confluent BAECs or HUVEC was not detected by SS. Likewise PECAM-1 phosphorylation was robust in the wild type and scrambled-transfected HUVEC but not in the PECAM-1 antisense-HUVEC. ERK(1/2), p38 MAPK, and AKT were activated by SS in all cell types tested, including the PECAM-1-KO murine ECs, 50% confluent BAECs, and HUVEC transfected with antisense PECAM-1. This suggests that PECAM-1 may not function as a major mechanoreceptor for activation of MAPK and AKT in ECs and that there are likely to be other mechanoreceptors in ECs functioning to detect shear stress and trigger intercellular signals.

Transcription factor Sp1 phosphorylation induced by shear stress inhibits membrane type 1-matrix metalloproteinase expression in endothelium.

Membrane type 1-matrix metalloproteinase (MT1-MMP) plays a key role in endothelial cell migration, matrix remodeling, and angiogenesis. Previous studies demonstrated that a mechanical force, cyclic strain, increases MT1-MMP expression by displacing Sp1 with increased Egr-1 expression and binding to the promoter site. However, the effect of shear stress (SS) on MT1-MMP expression is poorly understood. Although Egr-1 mRNA transcription and protein was induced (7.6-fold) in response to SS (n = 5, 0-8 h, p < 0.05), SS decreased MT1-MMP mRNA transcription and protein levels in a time-dependent fashion (10, 50, and 90% reduction at 1, 4, and 8 h, respectively; n = 5, p < 0.05). Egr-1 protein was increased after SS and cyclic strain, but Sp1 was serine-phosphorylated only after SS. SS increased Sp1 DNA binding (3.8-, 5.8-, and 2.4-fold increase at 1, 4, and 8 h, respectively; n = 5, p < 0.05) that was inhibitable by calf intestinal phosphatase. Thus, SS inhibits MT1-MMP expression despite Egr-1 up-regulation by inducing the serine phosphorylation of Sp1, which in turn increases its binding affinity for its site on the MT1-MMP promoter, reducing the ability of Egr-1 to displace it. These data illustrate the complex control of microvascular endothelial cell MT1-MMP expression in response to distinct environmental stimuli (cyclic strain versus shear stress), consisting of both the modulation of specific transcription factor expression (Egr-1) as well as transcription factor post-translational modification (serine phosphorylation of Sp1).