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.

Nefopam as an adjunct to intravenous patient-controlled analgesia after renal transplantation: a randomised trial.

BACKGROUND: Nefopam has been used as an adjuvant to opioid analgesia after operation. We investigated the efficacy of nefopam as an adjunct to fentanyl-based intravenous patient-controlled analgesia (IV PCA) on post-operative pain relief in patients undergoing renal transplantation. METHODS: Ninety-eight patients undergoing elective renal transplantation were randomised into two groups: nefopam or control groups. The former received nefopam (160 mg in 200 ml at a rate of 4 ml/h) whereas the latter received normal saline during the first 48 h after reperfusion of grafted kidney. Pain intensity scores, cumulative dose of fentanyl, and the incidence of adverse events were assessed at 1, 6, 12, 24, and 48 h post-operatively. Serum creatinine and estimated glomerular filtration rate were evaluated on post-operative days 1, 2, 4, and 7. RESULTS: The cumulative fentanyl consumption during the first 48 h after operation was 19% less in the nefopam group than that in the control group (1005 ± 344 µg vs. 1246 ± 486 µg, mean ± SD; P = 0.006). Pain intensity scores at rest and on coughing were significantly lower in the nefopam group throughout the first 12 and 48 h after operation, respectively. Adverse events and early graft function were comparable between the groups, except a significantly lower incidence of drowsiness observed in the nefopam group (4% vs. 21%, P = 0.027). CONCLUSION: In combination with fentanyl PCA, nefopam reduced post-operative fentanyl consumption with superior analgesia after renal transplantation.

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.

Functional improvement of pig islet with exocrine encapsulation.

Porcine-specific obstacles in islet isolation frequently result from the low purity or contamination with exocrine tissues. We implemented a new technique involving as capsulation of islets with excess exocrine tissue as a beneficial material to address those difficulties. Pig islets were hand-picked as high purity (HI) or low purity (LO) islets containing significant amounts of exocrine tissue. We performed static (ST) or shaking (SK) cultures of HI and LO islets. Islet function was examined after 24 hours by a glucose challenge test. Insulin secretion into the culture media was continuously measured using ELISA during a 6-day culture period. Islet function after 24 hours exhibited better maintenance under SK than ST culture as assessed by a stimulation index. The ideal islet morphology was seen in LO islets at 3 days of SK culture with typical islet shapes of a smooth surface and a spherical configuration. In contrast, typical islet morphology was not observed in HI islets under SK culture; maintenance of typical spherical appearances was difficult. Insulin secretion from LO islets under SK culture was higher than under other conditions during the 6-day period. Under SK culture conditions, exocrine-encapsulated LO islets showed enhanced islet function by condensing loose islet aggregates into firm spheroids with native exocrine tissues as a natural scaffold.

Molecular mechanisms of cell death of mycophenolic acid-treated primary isolated rat islets: implication of mitogen-activated protein kinase activation.

Optimal immunosuppression after pancreas islet transplantation has not yet been established to achieve long-term graft survival. Mycophenolic acid (MPA) is widely used as an immunosuppressive drug after transplantation including among recipients of pancreas islet cells. Previously, we reported MPA-induced islet apoptosis in the HIT-T15 cell line. In this study, we confirmed the effects of MPA on cell death and its potential implications on the mitogen-activated protein kinase (MAPK) family expression levels in primary isolated rat islets. Lewis islets isolated by collagenase digestion were purified by the density gradient method. Cell death was analyzed by methylthiazoletetrazolium assay. Activation of MAPK kinase 4 (MKK4), c-jun N-terminal protein kinase (JNK), p38 MAPK, and caspase-3 cleavage was examined by Western blot analyses. MPA treatments (> 25 micromol/L) increased cell death significantly at 24 hours and in a dose-dependent manner activated MKK4, JNK, and p38 MAPK at 20 hours. Caspase-3 cleavage was also increased by MPA treatment. These results suggested that MPA induced significant cell death among primary isolated rat islets by activation of MKK4, JNK, and p38 MAPK, as well as caspase-3 cleavage.

Effects of inosine monophosphate dehydrogenase inhibition on high glucose-induced cellular reactive oxygen species in mesangial cells.

Mesangial cell extracellular matrix (ECM) synthesis plays an important role in chronic renal diseases including chronic renal allograft dysfunction and diabetic nephropathy. Although inosine monophosphate dehydrogenase 2 (IMPDH2), as a target of mycophenolic acid (MPA), is important for de novo guanosine synthesis in lymphocytes, mesenchymal cells are not wholly dependent on it. To explore the importance of IMPDH2 on the inhibitory effects of MPA in mesangial cells (MC), we compared the effects of MPA and IMPDH2 siRNA on high glucose (HG)-induced fibronectin secretion and cellular reactive oxygen species (ROS). Mouse mesangial cells (MMC) were stimulated with HG (30 mmol/L D-glucose) in the presence or absence of MPA pretreatment or IMPDH2 siRNA transfection. Fibronectin secretion was measured by Western blot analysis, and dichlorofluorescein (DCF)-sensitive cellular ROS assessed by flow cytometry. HG increased fibronectin secretion by 1.8-fold at 24 hours and DCF-sensitive cellular ROS by 1.5-fold at 1 hour. MPA at 10 micromol/L totally inhibited HG-induced fibronectin secretion and cellular ROS in MMC. However, IMPDH2 siRNA only partially suppressed HG-induced fibronectin secretion and cellular ROS. These results suggested that MPA may inhibit HG-induced fibronectin secretion partially through inhibiting cellular ROS and the inhibition of IMPDH2 may be partially involved in the mechanism of MPA.

Effects of mycophenolic Acid on high glucose-induced fibronectin secretion and cellular reactive oxygen species in rat vascular smooth muscle cells.

Vascular smooth muscle cell (VSMC) proliferation, migration, and matrix protein accumulation play important roles in the development and progression of vascular disease including diabetic vascular complications and chronic allograft vasculopathy. Mycophenolic acid (MPA) inhibits various mesenchymal cell proliferation and matrix protein accumulation and reactive oxygen species (ROS). In this study, we investigated the effects of MPA on high glucose (HG)-induced fibronectin secretion and the role of ROS in rat VSMCs. Primary cultured rat VSMCs from Sprague-Dawley rats were exposed for 1 hour before stimulation with media containing 5.6 mmol/L glucose (low glucose [LG]), 30 mmol/L mannitol (M), or 30 mmol/L glucose (HG) with or without MPA (0.1-10 micromol/L) or N-acetylcysteine (NAC; 5 mmol/L). Fibronectin secretion was measured by Western blot analysis and dichlorofluorescein (DCF)-sensitive cellular ROS by flow cytometry. HG significantly increased fibronectin secretion by 1.7-fold. The increment of DCF-sensitive cellular ROS was 1.5-fold at 1 hour by HG. MPA at concentrations above 1 micromol/L effectively inhibited HG-induced fibronectin secretion and cellular ROS in a dose-dependent manner. NAC at 5 mmol/L also inhibited HG-induced rat VSMC activation. These results suggested that MPA inhibits HG-induced VSMC activation partially through inhibiting cellular ROS.

Is the affinity column-mediated immunoassay method suitable as an alternative to the microparticle enzyme immunoassay method as a blood tacrolimus assay?

BACKGROUND: Tacrolimus is a potent immunosuppressive drug used in organ transplantation. Because of its substantial toxic effects, narrow therapeutic index, and interindividual pharmacokinetic variability, therapeutic drug monitoring of whole-blood tacrolimus concentrations has been recommended. We investigated the comparability of the results of 2 immunoassay systems, affinity column-mediated immunoassay (ACMIA) and microparticle enzyme immunoassay (MEIA), comparing differences in the tacrolimus concentrations measured by the 2 methods in relation to the hematologic and biochemical values of hepatic and renal functions. METHODS: A total of 154 samples from kidney or liver transplant recipients were subjected to Dimension RxL HM with a tacrolimus Flex reagent cartilage for the ACMIA method and IMx tacrolimus II for the MEIA method. RESULTS: Tacrolimus concentrations measured by the ACMIA method (n = 154) closely correlated with those measured by the MEIA method (r = 0.84). The Bland-Altman plot using concentration differences between the 2 methods and the average of the 2 methods showed no specific trends. The tacrolimus levels determined by both the MEIA method and the ACMIA method were not influenced by hematocrit levels, but the difference between the 2 methods (ACMIA - MEIA) tended to be larger in low hematocrit samples (P < .001). CONCLUSION: The ACMIA method used for a tacrolimus assay is precise and has advantages, including the lack of a required pretreatment procedure. Furthermore, it is only slightly influenced by the hematologic or biochemical status of the samples.

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.

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.

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.

Risk factors for changes in bone mineral density and the effect of antiosteoporosis management after renal transplantation.

Using the pretransplant bone mineral density (BMD) data records of renal recipients, we retrospectively examined risk factors affecting posttransplant changes in BMD and the effect of antiosteoporosis management. For 294 kidney transplant recipients from January 1996 to September 2003, BMD values were expressed as spine and femur T-scores. Gender, age, pretransplant diabetes, blood type compatibility, mode and duration of dialysis, and previous transplantation were considered to be variables affecting BMD changes. T-test or ANOVA was used to compare risk factors. At the time of transplantation, mean spine T-scores were significantly lower among the retransplant group. Mean femur T-scores were significantly lower among the retransplant group, older patients (older than 45 years), and female recipients. Prolonged hemodialysis (>12 months) and retransplant were risk factors for BMD loss during the first year posttransplant. Early application of antiosteoporosis management was effective to ameliorate posttransplant BMD loss. However, antiosteoporosis management after 1 year posttransplant was relatively ineffective. Pretransplant evaluation of BMD and the possibility of significant BMD loss during the first posttransplant year should not be overlooked. Prophylaxis against bone loss and treatment should be started as soon as possible after transplantation for recipients with either normal or abnormal pretransplant BMD.