Differentiation between Chondrosarcoma and Synovial Chondromatosis of the Temporomandibular Joint Using CT and MR Imaging.

BACKGROUND AND PURPOSE: Chondrosarcoma and synovial chondromatosis of the temporomandibular joint share overlapping clinical and histopathologic features. We aimed to identify CT and MR imaging features to differentiate chondrosarcoma from synovial chondromatosis of the temporomandibular joint. MATERIALS AND METHODS: The CT and MR images of 12 and 35 patients with histopathologically confirmed chondrosarcoma and synovial chondromatosis of the temporomandibular joint, respectively, were retrospectively reviewed. Imaging features including lesion size, center, enhancement, destruction/sclerosis of surrounding bone, infiltration into the tendon of the lateral pterygoid muscle, calcification, periosteal reaction, and osteophyte formation were assessed. A comparison between chondrosarcoma and synovial chondromatosis was performed with a Student t test for quantitative variables and the Fisher exact test or linear-by-linear association test for qualitative variables. Receiver operating characteristic analysis was performed to determine the diagnostic performance for differentiation of chondrosarcoma and synovial chondromatosis based on a composite score obtained by assigning 1 point for each of 9 imaging features. RESULTS: High-risk imaging features for chondrosarcoma were the following: lesion centered on the mandibular condyle, destruction of the mandibular condyle, no destruction/sclerosis of the articular eminence/glenoid fossa, infiltration into the tendon of the lateral pterygoid muscle, absent or stippled calcification, periosteal reaction, internal enhancement, and size of ≥30.5 mm. The best cutoff value to discriminate chondrosarcoma from synovial chondromatosis was the presence of any 4 of these high-risk imaging features, with an area under the curve of 0.986 and an accuracy of 95.8%. CONCLUSIONS: CT and MR imaging features can distinguish chondrosarcoma from synovial chondromatosis of the temporomandibular joint with improved diagnostic performance when a subcombination of 9 imaging features is used.

Imaging features of synovial chondromatosis of the temporomandibular joint: a report of 34 cases.

AIM: To investigate the imaging features of synovial chondromatosis of the temporomandibular joint (TMJ), which is a rare benign arthropathy with cartilaginous proliferation. MATERIALS AND METHODS: Computed tomography and magnetic resonance imaging examinations of 34 patients with histopathologically confirmed primary synovial chondromatosis of the TMJ were reviewed retrospectively. Imaging features including the lesion epicentre, destruction/sclerosis of surrounding bone, calcification, periosteal reaction, osteophyte, lesion size, and joint space dimensions were assessed. RESULTS: Thirty-one of thirty-four patients (91.2%) showed the superior joint space as the lesion epicentre. For the mandibular condyle, more than one-third of patients (14/34; 41.2%) showed no destruction, and more than half of patients (19/34; 55.9%) showed no sclerosis. Conversely, >70% of patients showed destruction and sclerosis of the articular eminence/glenoid fossa, while >80% of patients (28/34; 82.4%) presented with various calcifications, including the ring-and-arc (9/34; 26.5%) and popcorn (13/34; 38.2%) types. The mean joint space on the affected side was significantly larger than that of the unaffected side (p<0.001). More than three-fourths of patients (76.9%) experienced no interval increase in lesion size during an average of 1.6 years of follow-up. CONCLUSION: Synovial chondromatosis of the TMJ demonstrated several imaging features, including the lesion centre being located in the superior joint space, resultant articular eminence/glenoid fossa-oriented bone changes, ring-and-arc and popcorn calcification, joint space widening, and self-limiting growth. These imaging features may be helpful in differentiating synovial chondromatosis from other lesions of the TMJ.

Imaging features of chondrosarcoma of the temporomandibular joint: report of nine cases and literature review.

AIM: To investigate the imaging features of chondrosarcoma of the temporomandibular joint (TMJ) and review the literature. MATERIALS AND METHODS: Computed tomography (CT), magnetic resonance imaging (MRI), and integrated positron-emission tomography (PET)/CT images of nine patients with histopathologically confirmed chondrosarcoma of the TMJ were reviewed retrospectively. Imaging features regarding the direction of lesion growth, bone destruction, infiltration into the tendon of the lateral pterygoid muscle (LPM) in the pterygoid fovea, enhancement pattern, calcification, periosteal reaction, markedly hyperintense T2 signal area, and qualitative PET signal intensity were evaluated. RESULTS: Seven of nine patients (77.8%) presented with lesion growth that was outward from the medulla of the mandibular condyle. Infiltration into the tendon of LPM in the pterygoid fovea was observed in all cases, and 77.8% (7/9) of them demonstrated >50% infiltration. All the lesions showed a mixed peripheral and internal enhancement, and revealed a markedly hyperintense T2 signal intensity area, which showed no enhancement. Although five of nine cases demonstrated higher FDG uptake compared with that of the liver, the other four cases showed less FDG uptake than that of the liver. CONCLUSION: Chondrosarcoma of the TMJ demonstrated several imaging features, including outward growth from the mandibular condyle, resultant infiltration into the tendon of LPM in the pterygoid fovea, various patterns of internal enhancement, and a markedly hyperintense T2 signal intensity area. These imaging features may be helpful to differentiate chondrosarcoma from other lesions of the TMJ.

Coculture With Ischemia/Reperfusion-Preconditioned Hepatocytes Improves Islet Function and Survival.

In clinical islet transplantation, hepatic ischemia and insufficient neovascularization of transplanted islets are barriers to islet survival and function. However, hepatocytes have a potency to protect themselves against ischemia. We hypothesized that ischemia/reperfusion preconditioning (IRP) of hepatocytes might beneficially affect islet cells in a coculture system. Primary islets were cocultured with primary hepatocytes, and hepatocyte IRP was conducted by subjecting cells to hypoxic conditions for single 15-minute/30-minute hypoxia, or 2 tandem 15-minute/30-minute hypoxic treatments (hypoxic-normoxic-hypoxic). We show that gene expression levels of insulin-like growth factor 1 (IGF-1), hepatocyte growth factor (HGF), transforming growth factor-α (TGF-α), and TGF-ß1 in hepatocytes were increased by IRP. IRP hepatocytes secreted hepatocyte growth factor and insulin-like growth factor-1. Coculture of islets with IRP hepatocytes enhanced islet insulin secretion in glucose challenge test and expression of the survival-related gene Bcl-2 and the regenerating gene-1α (Reg-1α). Islets cocultured with the 30-minute double-IRP hepatocytes displayed significantly higher viability in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and terminal deoxynucleotidyl transferase dUTP nick end labeling stain compared with that of islets subjected to 30 minutes of hypoxia. These results suggest that islet coculture with IRP hepatocytes can improve islet survival and insulin secretion.

Impact of Korea Network for Organ Sharing Expanded Donor Criteria on Delayed Graft Fuction in Kidney Transplantation: A Single-Center Experience.

BACKGROUND: The shortage of donor organs has been a major challenge in transplantation. In an effort to reduce the donor shortage, kidney transplantation (KT) using expanded criteria donors (ECD) was encouraged. In Korea, transplantation centers used the Korea Network for Organ Sharing (KONOS) ECD criteria, which is different from the United Network for Organ Sharing (UNOS) criteria. The aim of this study is to evaluate the predictive power of KONOS criteria on delayed graft function (DGF) in comparison to UNOS criteria. METHODS: A total of 376 recipients who underwent deceased donor kidney transplantation between January 2005 and December 2014 at Severance Hospital were retrospectively reviewed. Of these, 130 cases satisfied KONOS ECD, while the others followed KONOS standard criteria donor (SCD). RESULTS: Donor age and history of hypertension was significantly higher with KONOS ECD than with KONOS SCD. In KONOS subgroup analysis, donor characteristics were different than with UNOS criteria. The incidence of DGF was higher in the KONOS ECD group than in the KONOS SCD group. However, UNOS ECD showed a high incidence of DGF compared to UNOS SCD with the same KONOS criteria. UNOS ECD was an independent risk factor for DGF in multivariate analysis. However, KONOS ECD was not a risk factor for DGF. Although glomerular filtration rate was inferior in the KONOS ECD group compared to the KONOS SCD group, the UNOS SCD group within the KONOS ECD group showed similar graft function compared to the KONOS SCD group. CONCLUSION: KONOS criteria have a lower predictive power for DGF than UNOS criteria.

Clinical Significance of Macrophage Polarization in Antibody-Mediated Rejection of Renal Allograft.

BACKGROUND: The significance of proinflammatory M1 (classically activated) and profibrotic M2 (alternatively activated) macrophages in antibody-mediated rejection (ABMR) after kidney transplantation has not been investigated. METHODS: Fifty-five biopsy-confirmed ABMR samples were stained with MRP 8/14 (a marker of M1 macrophages) and CD163 (a marker of M2 macrophages), and positive cells were counted in glomeruli and the tubulointerstitium, respectively. Patients were classified into M1 and M2 polarization groups according to the glomerular and tubulointerstitial M1:M2 ratio, and the results were compared with Banff scores, serum creatinine level, estimated glomerular filtration rate (eGFR), and graft survival. RESULTS: The glomerular M2 polarization group showed significantly higher chronic glomerulopathy scores, serum creatinine levels, and lower eGFR at the time of biopsy (P = .019 and P = .015, respectively) and 3-month postbiopsy (P = .016 and P = .032, respectively) than the M1 polarization group. The tubulointerstitial M2 polarization group had significantly lower glomerulitis, arteritis, peritubular capillaritis, and glomerulitis + peritubular capillaritis scores than the M1 polarization group, but there was no significant difference in renal function. Long-term graft survival was not associated with macrophage polarization. CONCLUSION: Glomerular M2 polarization in ABMR biopsy samples is associated with chronic glomerular injury and poorer graft function, but without graft survival.

Long-term Follow-up of Living Kidney Donors With Chronic Kidney Disease at 1 Year After Nephrectomy.

BACKGROUND: Although renal function recovery of living kidney donors has been reported in a number of studies, many patients show poor recovery, and the long-term prognosis of these patients has not been well studied. In this investigation we explored the long-term prognosis of renal function in patients with chronic kidney disease (CKD) at 1 year after nephrectomy. METHODS: Patients who underwent donor nephrectomy during the period from March 2006 to April 2014, with a follow-up creatinine study at 1 year postoperatively and more than 3 years of follow-up, were included in the study. Creatinine and estimated glomerular filtration rate (eGFR, using the Modification of Diet in Renal Disease formula) before and after surgery were studied. Age, sex, history of hypertension or diabetes, body mass index, blood pressure, complete blood count, preoperative routine serum chemistry, and urine study results were reviewed. RESULTS: Among 841 patients who had donor nephrectomy, 362 were included in the study. There were 111 patients (30.6%) with eGFR <60 mL/min/1.73 m2 at 1 year postsurgery, and the median follow-up period was 62.8 months (interquartile range [IQR] 42.0-86.3 months). The maximum eGFR after 3-year follow-up was studied, and 48 patients (43.2%) never recovered eGFR to >60 mL/min/1.73 m2. Age, history of hypertension, preoperative eGFR, and eGFR at 1 year were predictive factors at univariate analysis. Multivariate analysis of these factors was studied, and age (52.5 [IQR 47-55.7] vs 47 [IQR 7-53] years, odds ratio [OR] 1.1, 95% confidence interval [CI] 1.02-1.15, P = .007), history of hypertension (16.7% vs 1.6%, OR 10.0, 95% CI 1.09-92.49, P = .042), and eGFR at 1 year (53.9 [IQR 50.3-56.0] vs 57.0 [IQR 54.2-58.4] mL/min/1.73 m2, OR 0.8, 95% CI 0.72-0.92, P = .002) remained as significant risk factors. CONCLUSION: Of all living donors, 15.7% had CKD after >3 years of follow-up. Close observation is warranted when donors have CKD after 1 year follow-up, as 43.2% fail to recover renal function. Patients who are older, have a history of hypertension, and have low eGFR at 1-year follow-up are especially at risk.

Delayed Recovery of Renal Function After Donor Nephrectomy.

BACKGROUND: Many living kidney donors are still at risk of chronic kidney disease (CKD) 1 year after nephrectomy. Although some donors still experience poor renal function, many exhibit delayed recovery of renal function afterwards. We studied the factors related to delayed recovery of renal function in patients with CKD at 1 year after nephrectomy. METHODS: Patients who underwent donor nephrectomy from March 2006 to April 2014 with a follow-up creatinine study at 1 month, 6 months, 1 year, and after 3 years of follow-up were included in the study. Age, sex, history of hypertension or diabetes, body mass index, blood pressure, complete blood cell count, preoperative routine serum chemistry, and urine study results were reviewed. RESULTS: Among 275 donors, 83 (30.2%) who had an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 at 1 year of follow-up were included in the study, and the eGFR was observed during a median follow-up of 62.0 months (interquartile range [IQR], 48.9-83.1 months). Those who had improvements in eGFR of >5 mL/min/1.73 m2 were included in the recovery group (n = 48 [57.8%]), and those who did not were included in the nonrecovery group (n = 35 [42.2%]). The preoperative and 1-year follow-up eGFR did not differ significantly between the 2 groups, and the maximum eGFR after 3 years was higher in the recovery group (68.68 mL/min/1.73 m2 [IQR, 61.81-75.64 mL/min/1.73 m2] vs 55.63 mL/min/1.73 m2 [IQR, 51.73-58.29 mL/min/1.73 m2]; P < .001). The recovery group was more likely to have a history of hypertension (4.2% vs 20%; P = .032), a lower body mass index (24.11 kg/m2 [IQR, 22.04-25.20 kg/m2] vs 25.25 kg/m2 [IQR, 23.23-26.44 kg/m2]; P = .01), and a lower preoperative uric acid level (4.7 mg/dL [IQR, 3.8-5.4 mg/dL] vs 5.3 mg/dL [IQR, 4.4-6.2 mg/dL]; P = .031). After multivariate logistic regression analysis, history of hypertension (odds ratio, 0.131; P = .022) and uric acid level (odds ratio, 0.641; P = .036,) remained as significant factors. CONCLUSIONS: Although 30.2% of donors had CKD at 1 year after nephrectomy, 57.8% reported improved renal function. Those with a history of hypertension and high preoperative uric acid levels were less likely to have improvements in renal function and required close follow-up.

Impact of Cigarette Smoking on Living Kidney Donors.

BACKGROUND: Smoking is known to result in a decline in renal allograft function and survival of recipients; however, the effect of smoking on living kidney donors remains unknown. In this study we evaluated the impact of cigarette smoking on renal function of kidney donors. METHODS: Among 1056 donors who underwent nephrectomy, 612 completed the 6-month follow-up protocol and were enrolled in the study. The association of smoking status, including pack-years smoking history, and postoperative renal function was evaluated. RESULTS: Among donors, 68.1% had never smoked, 8% were former smokers, and 23.9% were current smokers. Donors who never smoked were older than former and current smokers (42.3 ± 11.8, 41.9 ± 11.1, and 38.3 ± 10.9 years, respectively; P < .001). There was no difference in preoperative renal function between groups; however, postoperative estimated glomerular filtration rate (eGFR) was lower in former and current smokers than in those who never smoked (64.6 ± 13.8, 64.7 ± 12.3, and 67.8 ± 13.1 mL/min/1.73 m2, respectively; P = .023). In former and current smokers, pack-years smoking history was negatively associated with pre- and postoperative eGFR (r = -0.305 and -0.435, P < .001), and correlated with postoperative percent eGFR decline (r = 0.248, P < .001). Smoking history was associated with postoperative development of chronic kidney disease (CKD). Especially in former smokers, a smoking history of more than 12 pack-years was strongly associated with development of CKD (odds ratio = 7.5, P = .003). CONCLUSION: Even if they no longer smoke, donors with a smoking history require close observation due to increased risk of CKD development after kidney donation. A detailed pack-years smoking history should be obtained, and smoking cessation strategies should be implemented in kidney donors.

Usefulness of Multi-Detector Computed Tomography Scanning as a Replacement for Diethylenetriamine Pentaacetic Acid.

BACKGROUND: Diethylenetriamine pentaacetic acid (DTPA) and multi-detector computed tomography (MDCT) can predict postoperative estimated glomerular filtration rate (eGFR) in a live kidney donor. Accordingly, we compared predicted eGFR measured by use of DTPA and MDCT. METHODS: From January 2013 to May 2015, 264 live kidney donors were enrolled. All donors underwent preoperative DTPA and MDCT, and bilateral renal cortex volume was measured by use of MDCT. We estimated DTPA-eGFR [remaining split renal function (%) × preoperative eGFR] and Vol-eGFR [remaining renal volume/total renal volume (%) × preoperative eGFR] and analyzed DTPA-eGFR, Vol-eGFR, and Modification of Diet in Renal Disease (MDRD)-eGFR during week 1 and in months 1, 3, and 6. Additionally, we compared DTPA-eGFR and Vol-eGFR by use of the formula ΔeGFR (maximum eGFR minus minimum eGFR during 6 months). RESULTS: The mean DTPA-eGFR and Vol-eGFR values (mL/min/1.73 m2) were 52.97 ± 10.32 and 51.26 ± 10.26, respectively. Predictions of the dominant side did not agree in 113 of 303 (37.3%) cases. Postoperative MDRD-eGFR exhibited a statistically significant correlation with total renal volume, DTPA-eGFR, and Vol-eGFR (P < .0001). A significant correlation was found between ΔeGFR and total renal volume, DTPA-eGFR, and Vol-eGFR (P < .0001). Receiver operating characteristic curves were generated to predict the possibility of eGFR <60 mL/min/1.73 m2 at 6 months, using DTPA-eGFR and Vol-eGFR, which indicated that DTPA-eGFR (area under the curve = 0.858; P < .0001) and Vol-eGFR (area under the curve = 0.878; P < .0001) could predict chronic kidney disease class III at 6 months. CONCLUSIONS: MDRD-eGFR, Vol-eGFR, and DTPA-eGFR were significantly correlated. Moreover, Vol-eGFR and DTPA-eGFR exhibited high predictive value for chronic kidney disease class III at 6 months, whereas Vol-eGFR was a good predictor of renal function recovery.

Reduction of Slit Diaphragm-associated Molecules by Sirolimus: Is it Enough to Induce Proteinuria?

Sirolimus (SRL), a mammalian target of rapamycin inhibitor, is widely used in transplantation, but the mechanisms whereby it induces adverse effects, such as proteinuria and edema, remain unclear. To determine whether isolated SRL induces proteinuria or not, the authors intraperitoneally injected C57BL/6 mice with different doses of SRL (0 mg/[kg·d], 3 mg/[kg·d], 10 mg/[kg·d], or 30 mg/[kg·d]) for 24 days. Urinary albumin excretion was then quantified using a double-sandwich enzyme-linked immunosorbent assay, and serum creatinine levels were measured using a single dry-film chemistry auto-analyzer. The mRNA expression levels of various genes were also measured by polymerase chain reaction. Urinary albumin was not detected in the SRL-treated mice, but serum creatinine levels were found to increase dose-dependently and were significantly higher in the animals treated with 30 mg/kg of SRL than in untreated controls. Glomerular mRNA expression profiling showed down-regulations of podocyte-related genes (Wilms tumor 1, synaptopodin, nephrin, CD2-associated protein, and podocin) and of transforming growth factor-beta (a marker of fibrosis) in sirolimus-treated mice. In addition, expressions of the antiapoptotic genes Bcl-2 and Bcl-xL were also down-regulated. Furthermore, the protein levels of these genes in mice kidney were also decreased by sirolimus. Although sirolimus treatment reduced the expressions of slit diaphragm-associated molecules and increased serum creatinine levels, it failed to induce proteinuria. Our findings indicate that proteinuria is not induced by isolated SRL treatment. Further studies are required to identify conditions in which sirolimus induces proteinuria.

Clinical Investigation Into Plasma Neutrophil Gelatinase-Associated Lipocalin and Body Adipose Tissue Associated With Remaining Renal Function in Living Kidney Donor.

OBJECTIVE: Plasma neutrophil gelatinase-associated lipocalin (pNGAL) is known to increase in proportion to the degree and period of renal damage. This study aimed to evaluate the clinical relevance of pNGAL and body adipose tissue to remaining renal function in living kidney donors. METHODS: Between July 2013 and February 2015, 75 live kidney donors were enrolled. Visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and VAT/SAT ratio were measured in preoperative CT scan which performed before surgery. We analyzed the correlation among the variables (VAT, SAT, and VAT/SAT ratio), eGFR and pNGAL. ΔpNGAL-max(=Maximum pNGAL-measures), ΔpNGAL-min(=Minimum pNGAL-measures), ΔeGFR-max(=Maximum eGFR-measures) and ΔeGFR-min(=Minimum eGFR-measures) were also analyzed. RESULTS: The highest value of pNGAL (207.46 ± 76 ng/mL) was observed on postoperative day 7, and the lowest value of eGFR (57.52 ± 11.20 mL/min/1.73 m2) was also measured on postoperative day 7. A significant correlation was found between ΔpNGAL, VAT, and VAT-to-SAT ratio. Moreover, a significant correlation between ΔpNGALmin and ΔeGFRmin was revealed. Also, VAT-to-SAT ratio was correlated with ΔeGFRmin during the all of the follow-up periods, and it was also correlated with ΔpNGALmin until postoperative day 3. CONCLUSION: There was a correlation between the elevation of pNGAL until postoperative day 5 and the decrease of eGFR after living donor nephrectomy. VAT-to-SAT ratio had a significant correlation with both ΔpNGALmin and eGFRmin. Given the metabolism of pNGAL, the increase of pNGAL seemed to be affected as a consequence of body adipose tissue.

Impact of the Ratio of Visceral to Subcutaneous Adipose Tissue in Donor Nephrectomy Patients.

OBJECTIVE: It was reported that a metabolic syndrome affected the remaining renal function after living donor nephrectomy. However, the measurement of waist circumference is unclear because it cannot distinguish between visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). We investigate the clinical correlation between body adipose tissue and renal function recovery after living donor nephrectomy. METHODS: From July 2013 to February 2015, 75 living kidney donors were enrolled. The VAT and SAT were measured by preoperative computed tomography (CT) scan. Body mass index (BMI), VAT, SAT, and VAT-to-SAT ratio were analyzed according to a postoperative renal function recovery. Receiver operating characteristic (ROC) was performed to predict estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m2 at postoperative 6 months for BMI, VAT, SAT, and VAT-to-SAT ratio. RESULTS: The lowest value of eGFR (57.52 ± 11.20 mL/min/1.73 m2) was measured at postoperative day 7. There was no statistically significant difference in eGFR between 1 month and 3 months. BMI, VAT, SAT, and VAT-to-SAT ratio showed a statistically significant correlation with each other (Pearson correlation, P < .05). Also, the recovery time of eGFR was correlated with VAT-to-SAT ratio; it was significant at postoperative 1, 3, and 6 months. VAT-to-SAT ratio (0.654, 95% confidence interval 0.525-0.783, P = .024) had higher predictive value in ROC. CONCLUSION: We developed a new variable to predict the value of lower eGFR (less than 60 mL/min/1.73 m2) at a postoperative 6 months in living kidney donor. According to a CT scan, VAT-to-SAT ratio can predict renal function recovery.

Significance of Time-Zero Biopsy for Graft Renal Function After Deceased Donor Kidney Transplantation.

BACKGROUND: Donor organ quality from deceased donors affects graft survival after kidney transplantation. This study was performed to identify clinico-histological factors that affect early graft outcome, using time-zero biopsies of deceased donors. METHODS: Between December 2006 and July 2011, 135 recipients of deceased donor kidneys were included, and data concerning donor and recipient-related clinical characteristics and histological findings of time-zero biopsies categorized by use of the Banff 07 scoring system were included in the analysis. Mean donor age was 44.3 ± 12.3 years. Mean terminal serum creatinine level and cold ischemic time were 1.50 ± 0.96 mg/dL and 349 ± 166 minutes. Mean follow-up time after transplantation was 37 ± 16 months, and all recipients were followed for at least 1 year. RESULTS: Global glomerulosclerosis (38.5%), tubular atrophy (37.8%), arteriolar hyaline thickening (25.9%), interstitial fibrosis (23%), vascular fibrous intimal thickening (21.5%), and interstitial inflammation (20%) were the major pathologic findings of time-zero biopsies. The majority of pathologic scores were of mild degree. Among histological findings, arteriolar hyaline thickening and interstitial fibrosis were only significantly associated with early post-transplant renal function in multivariate analyses. CONCLUSIONS: Considerations of clinico-histological findings were found to be valuable for predicting early graft outcome after deceased donor kidney transplantation.

Outcomes of Kidney Recipients According to Mode of Pretransplantation Renal Replacement Therapy.

The effects of pretransplantation dialysis modality on graft function are key issues in end-stage renal disease patients. The aim of this study was to evaluate post-transplantation outcomes according to pretransplantation renal replacement therapy modality in deceased-donor kidney transplantation. Among 444 deceased-donor kidney transplant recipients in Severance Hospital between April 1993 and Dec 2014, 275 who maintained a unique dialysis modality (hemodialysis [HD; n = 178] or peritoneal dialysis [PD; n = 97]) until transplantation were enrolled. There were no significant differences in sex, age, human leukocyte antigen mismatch, cold ischemic time, or duration of dialysis between groups. There was also no difference in 5-year graft survival between HD and PD groups (87.7% vs. 82.3%, respectively; P = .148). On multivariate Cox regression for risk factors affecting graft survival, renal replacement therapy modality was not found to be a risk factor. However, the rate of delayed graft function was higher in the HD group than in the PD group (32.0% vs. 19.6%, respectively; P = .028). In addition, graft function at 1 week after transplantation in the PD group was superior to that in the HD group. The pretransplantation dialysis modality was found to affect both delayed graft function and early graft function, although not graft survival.

Role of Thalidomide on the Expression of OX40, 4-1BB, and GITR in T Cell Subsets.

BACKGROUND: Thalidomide (TM) is known to have anti-cancer and anti-inflammatory properties; however, its mechanism on T cells is still unclear. We previously showed the immune modulatory effect of TM on T cells and its therapeutic effect on lupus nephritis models. Here we examined the changes in the expression of tumor necrosis factor receptor superfamilies (TNFRSFs), including OX40, 4-1BB, and glucocorticoid-induced TNFR-related protein (GITR) in T cell subsets by TM treatments. METHODS: Splenic naïve T cells (Tnaives) from C57BL/6 mice were sort-purified and cultured for CD4(+) T cell proliferation and regulatory T cells (Tregs) conversion with TM treatments. All samples were analyzed by flow cytometry after stained with anti-mouse CD4, Foxp3, OX40, 4-1BB, or GITR antibodies. RESULTS: Expressions of OX40, 4-1BB, and GITR on CD4(+) T cells showed a decreasing tendency by TM treatments. Especially, downregulation of these molecules on CD4(+)CFSE(low) T cells was significant in TM treatment groups. On the condition of Treg conversion, OX40 was downregulated significantly. In contrast, the expression of GITR was increased, and that of 4-1BB had shown no particular change under the condition of Treg. CONCLUSION: Considering these results, TM may have an immune modulatory role through the T cell subset-specific change of OX40, 4-1BB, and GITR expression. Further study is required to elucidate the effect of thalidomide on T cells.

Comparative Proteomic Analysis of Rapamycin Versus Cyclosporine Combination Treatment in Mouse Podocytes.

BACKGROUND: The mechanism of podocyte injury observed with the use of rapamycin (RPM) remains unclear. The conversion from calcineurin inhibitors (CNIs) to RPM in kidney transplant recipients has been associated with a higher incidence of proteinuria and renal injury. In this study, we performed proteomic analyses to investigate the alteration of protein expression in mouse podocytes treated with RPM in comparison with CNI/RPM combination. METHODS: Immortalized mouse podocytes were treated with 20 nmol/L RPM or 20 nmol/L RPM + 1 µg/mL cyclosporine. Podocyte proteins were separated by 2-dimensional polyacrylamide gel electrophoresis (2DE) and identified by matrix-assisted laser desorption time-of-flight (MALDI-TOF) mass spectrometry and peptide fingerprinting. Selected proteins were analyzed by means of Western blot assay. RESULTS: We identified 36 differently expressed proteins after isolated RPM or CNI/RPM combination treatment in cultured mouse podocytes. There are 3 distinct patterns of protein expression: (1) potentiated down- or upregulation of proteins by CNI/RPM treatment compared with isolated RPM treatment (n = 4); (2) partial offset of down-regulation by CNI/RPM in comparison with RPM treatment (n = 25); (3) no difference in down-regulation between RPM and CNI/RPM treatment (n = 5). We found a significant interplay between RPM and CNI on the expression of the selected proteins in mouse podocytes. This might explain the higher incidence of proteinuria by CNI/RPM combination in clinical settings. CONCLUSIONS: Further study is required to elucidate the target protein associated with RPM-induced podocyte injury.

Abdominal Aortic Calcification in Living Kidney Donors.

OBJECTIVE: This study assesses the association between abdominal aortic calcification (AAC) and renal function of living kidney donors and evaluate AAC as a surrogate marker for nephrosclerosis. METHODS: Between January 2010 and March 2013, 287 donors who underwent living donor nephrectomy were enrolled. We analyzed computed tomography angiographies and quantified AAC scores by calculating the Agatston score for the abdominal aorta. The donors were stratified into the non-AAC group (AAC score = 0; n = 238) and the AAC group (AAC score >0; n = 49). The relationship between AAC and perioperative estimated glomerular filtration rate was analyzed. For the 180 donors consenting to implantation biopsy, the nephrosclerosis score was defined as the sum of abnormalities, including glomerulosclerosis, tubular atrophy, interstitial fibrosis, and arteriosclerosis. RESULTS: The mean AAC score was 185.5 ± 263.3 in the AAC group. The AAC group was older than the non-AAC group (51.1 ± 6.1 vs 37.9 ± 11 years; P < .001). Perioperative renal function was not different between the 2 groups. However, among the AAC group, donors with an AAC score of >100 were associated with delayed renal function recovery (P = .035). Donors with AAC were more likely to have glomerulosclerosis (50.0% vs 29.1%; P = .022), tubular atrophy (62.5% vs 33.1%; P = .002), and a higher nephrosclerosis score (P = .002). CONCLUSIONS: Living donors with an AAC score of >100 require close observation because they have a higher probability of delayed renal function recovery after donation. AAC is associated with nephrosclerosis in healthy adults.

Plasma Neutrophil Gelatinase-associated Lipoprotein in Living Kidney Donors.

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) is a biomarker for acute kidney injury. This study was conducted to determine the clinical implications of perioperative plasma NGAL levels for renal function after living donor nephrectomy. METHODS: Between July 2013 and May 2014, 112 donors underwent live donor nephrectomy at our institution. Donor plasma NGAL levels were measured perioperatively for 6 months. The relationship between perioperative plasma NGAL and recovery of renal function was analyzed. Renal function was estimated with the Modification of Diet in Renal Disease formula. RESULTS: Mean preoperative NGAL was 62.1 ± 29.5 ng/mL. Plasma NGAL was most elevated 1 week postoperatively (218 ± 95.5 ng/mL), and stabilized after 1 month (122.9 ± 45.3 ng/mL). Preoperative plasma NGAL was not correlated with donor age or preoperative estimated glomerular filtration rates (eGFR), but was negatively correlated with 6-month eGFR (r = -0.458, P < .001). During the observation period, plasma NGAL at 1 week was most correlated with 6-month eGFR (r = -0.554, P < .001). An ROC curve analysis showed that age, preoperative eGFR, and 1-week postoperative plasma NGAL were highly predictive of developing of chronic kidney disease (CKD), defined as eGFR <60 mL/min/1.73 m(2), 6 months postoperatively (AUC = 0.91, P < .001). One-week postoperative plasma NGAL was also independently associated with CKD risk at 6 months (odds ratio: 1.13 for each 10 ng/mL increase, P = .013). CONCLUSION: Plasma NGAL becomes elevated after kidney donation and can provide information about acute kidney injury during the compensatory hyperfiltration period. Donors with increased perioperative plasma NGAL require close observation because their possibility of developing CKD after donation may be greater.

Health-Related Quality of Life of Kidney Transplantation Patients: Results from the KoreaN Cohort Study for Outcome in Patients With Kidney Transplantation (KNOW-KT) Study.

BACKGROUND: As patient and graft survival rates have been improving after kidney transplantation, health-related quality of life (HR-QOL) has become an important indicator of effective treatment. This study aimed to evaluate changes in HR-QOL after kidney transplantation. MATERIALS AND METHODS: The KoreaN cohort study for Outcome in patients With Kidney Transplantation (KNOW-KT) is a multicenter, observational, 9-year, cohort study. The HR-QOL of patients in the KNOW-KT study was assessed before transplantation and 2 years after transplantation using the Kidney Disease Quality of Life Short Form (KDQOL-SF) including chronic kidney disease targeted area and the Medical Outcome Study 36-item Short Form Health Survey (SF-36). Multivariate linear regression was used to identify significant factors associated with follow-up QOL scores. RESULTS: A total of 175 patients from 8 centers were analyzed. All QOL scores including the total QOL score, chronic kidney disease targeted score, and SF-36 at the 2-year follow-up were significantly increased compared to baseline values. Both physical and mental scale scores were improved after transplantation. CONCLUSION: The QOL scores for both the mental and physical scales were improved at 2 years after kidney transplantation. High glomerular filtration rate at 2 years, high baseline QOL score, and low body mass index were associated with good follow-up QOL scores. Kidney transplantation for an Asian population with end-stage renal disease can result in better QOL as well as better patient and graft survival.