Experience of Lymphangiography as a Therapeutic Tool for Lymphatic Leakage After Kidney Transplantation.

INTRODUCTION: Lymphatic leakage after kidney transplantation is a relatively frequent complication but sometimes resistant to treatment, and there is no fixed treatment algorithm. The effectiveness of therapeutic lymphangiography for postoperative lymphatic or chyle leakage has been reported, but few reports are available regarding patients who have undergone kidney transplantation. In this study, we report our experience with lymphangiography as a therapeutic tool for lymphatic leakage after kidney transplantation. PATIENTS AND METHODS: Intranodal lymphangiography for lymphatic leakage was performed in 4 patients (3 male, 1 female; age range, 38 to 70 years old) after living kidney transplantation at the Osaka City University Hospital in Japan. The amount of drainage before lymphangiography was 169 to 361 mL/day. The procedure for intranodal lymphangiography was as follows: the inguinal lymph node was punctured under ultrasound guidance, and the tip of the needle was instilled at the junction between the cortex and the hilum, after which Lipiodol was slowly and manually injected. RESULTS: Lymphangiography was technically successful in 3 out of the 4 patients. In all successful cases, the amount of drainage decreased and leakage finally stopped without additional therapy such as sclerotherapy or fenestration. In 2 cases, we were able to directly detect the leakage site using lymphangiography. The time between lymphangiography and leakage resolution ranged from 8 to 13 days. There were neither complications of lymphangiography nor recurrence of lymphatic leakage in the successful cases. CONCLUSIONS: Intranodal lymphangiography may be not only a diagnostic tool but also an effective, minimally-invasive, and safe method for treatment of lymphatic leakage resistant to drainage after kidney transplantation.

Beneficial Effects of High-Dose Mizoribine on ABO-Incompatible Living-Related Kidney Transplantation: Two-Year Results by a Japanese Multicenter Study.

BACKGROUND: Mizoribine (MZ) has been developed as an immunosuppressive agent in Japan, but it has a less-potent immunosuppressive effect up to 3 mg/kg/d. In the previous study, a Japanese multicenter study, we reported that high-dose MZ, at 6 mg/kg/d, with a calcineurin inhibitor was effective and safe in reducing the frequency of cytomegalovirus (CMV)-related events in ABO-incompatible (ABO-i) living-related kidney transplantation (LKT). In the present study, therefore, we investigated the effects of high-dose MZ with a CNI in ABO-i LKT recipients in a Japanese multicenter study. METHODS: A total of 37 patients were treated with high-dose MZ (6 mg/kg), a CNI (cyclosporine [CsA] or tacrolimus [Tac]), basiliximab (Bas), rituximab (Rit), and corticosteroids. CsA was started at a dose of 7 mg/kg to maintain blood levels [200 ng/mL (C0), 6000 ng-h/mL (AUC 0-9)]. Tac was started at a dose of 0.2 mg/kg to maintain blood levels [8-10 ng/mL (C0), 100 ng-h/mL (AUC 0-9)]. Bas (20 mg/body) was administrated on day 0 and day 4 after transplantation. Rit (100-200 mg/body) was administrated on day -14 and day -7 before transplantation. MZ was adjusted to maintain target C0 levels of 1.5 to 2.0 µg/mL. RESULTS: Patient and graft survival rates for 2 years were 100% in the CsA group (n = 22) and 93.3% in the Tac group (n = 15) (not significant, NS). Overall incidence of acute rejection for 2 years was 22.7% in the CsA group and 26.7% in the Tac group. Mean serum creatinine levels at 2 years were 1.29 ± 0.2 mg/dL in the CsA group and 1.21 ± 0.34 mg/dL in the Tac group (NS). The incidence of CMV disease was 0% in both groups, and positive rates of CMV antigenemia were 50.0% and 26.7% in the CsA and Tac groups, respectively (NS). Mean serum uric acid levels were 5.5 ± 1.3 mg/dL and 6.4 ± 1.2 mg/dL at 2 years (NS) in the CsA and Tac groups, respectively. CONCLUSIONS: A high-dose MZ regimen including calcineurin inhibitor (CsA or Tac), Bas, Rit, and steroids was effective and safe in reducing the frequency of CMV-related events in ABO-i LKT.

Non-invasive longitudinal monitoring of angiogenesis in a murine full-thickness cutaneous wound healing model using high-resolution three-dimensional ultrasound imaging.

BACKGROUND/PURPOSE: The aim of this study was to evaluate the longitudinal monitoring of angiogenesis in a murine full-thickness cutaneous wound healing model using high-resolution three-dimensional (3D) ultrasound imaging. METHODS: Two C57BL/6 mice were used. Two-dimensional (2D) ultrasound images with the Color Doppler mode were acquired at regular spatial intervals on day 9, 11, and 14 after wounding. 3D ultrasound images were processed by reconstructing the 2D ultrasound image sequences. The wounds were harvested on day 14 and serial sections were immunohistologically stained with an anti-CD31 antibody. RESULTS: 3D ultrasound imaging with the Color Doppler mode showed the distribution of microvascular growth on days 9, 11, and 14 after wounding (44.6%, 51.5%, and 27.3% in wound 1, 55.8%, 38.1%, and 35.1% in wound 2, 60.6%, 62.6%, and 63.1% in wound 3, and 15.8%, 42.0%, and 31.9% in wound 4, respectively). A correlation was observed between % vascularity measured by paired 2D ultrasound imaging with the Color Doppler mode and sections immunohistologically stained for the anti-CD31 antibody (r=0.927, 0.871, 0.717, and 0.913 for wounds 1, 2, 3, and 4, respectively. P<.01). CONCLUSION: These results indicate that high-resolution 3D ultrasound imaging is useful for longitudinally evaluating the distribution of microvascular growth over the course of healing.

Regional Survey of Tissue Donation Among the General Public and Medical Staffs Around Osaka, Japan.

BACKGROUND: Because tissue transplantation (TTx) has not been familiar to the general public or even to medical staffs in Japan, awareness of TTx is very important to increase tissue donation. Our primary aim was to describe the current status of awareness of TTx in medical staffs and in the general public around Osaka. METHODS: Between July 2014 and February 2015, 1015 general public citizens, 203 medical staff members working in emergency hospitals, and 168 cardiothoracic surgeons were invited to complete a letter or web-based survey through the use of a self-designed questionnaire. RESULTS: In the general public citizens, only 25.1% knew about TTx, whereas 54.7% knew about organ transplantation (OTx); 25.4% agreed to donate their organs or tissues and 17.3% disagreed to donate their organs or tissues. In medical staff members working in emergency hospitals, 58.7% knew about TTx; 82.3% agreed to support organ or tissue procurement and 10.8% disagreed to do so. Among cardiothoracic surgeons, 78.7% knew about TTx; 33.2% had used valve or vascular homografts and 57.4% wanted to use them if possible. CONCLUSIONS: According to these surveys, public awareness of TTx has been less than that of OTx, but willingness to donate tissue was not different from that of donating organs. Awareness of TTx in medical staffs in emergency hospitals was higher but still not satisfactory. To increase tissue donation in Japan, the East and West Japan Tissue Transplant Network, in collaboration with cardiothoracic surgeons, should make more effort to carry out dissemination and awareness regarding TTx to the general public and to medical staffs.

Efficacy and Safety of High-Dose Mizoribine Combined With Cyclosporine, Basiliximab, and Corticosteroids in Renal Transplantation: A Japanese Multicenter Study.

Mizoribine (MZR) is an immunosuppressive agent that exhibits a less potent immunosuppressive effect at doses up to 3 mg/kg/d. We investigated whether high-dose MZR is effective and safe for renal transplant patients in conjunction with cyclosporine (CsA), basiliximab, and corticosteroids. Ninety Japanese renal transplant patients were administered MZR (6 mg/kg/d), CsA (7 mg/kg/d), prednisolone (maintenance dose, 10 mg/d), and basiliximab (20 mg/body). They were compared with a control group of 81 renal transplant patients who received mycophenolate mofetil (MMF; 1500 mg/d), CsA, prednisolone, and basiliximab. The 2-year patient and graft survival rates were 98.9% and 97.8% in the MZR group and 98.8% and 97.5% in the MMF group, respectively. The rejection rate within 2 years after transplantation was 21.1% in the MZR group and 16.0% in the MMF group; the difference was nonsignificant. None of the MZR group developed cytomegalovirus (CMV) disease, whereas 12.3% of the MMF group contracted CMV (P < .0001). CMV viremia developed in 28.9% of the MZR group vs 46.9% of the MMF group (P < .0001); their peak antigen levels were 20.4 ± 44.1 and 252.8 ± 527.0 (P < .01). Furthermore, the incidence of gastrointestinal disorder, hyperlipidemia, and blood disorder was significantly lower in the MZR group than in the MMF group. The combination of high-dose MZR with CsA, basiliximab, and corticosteroids not only provides satisfactory immunosuppression but is also associated with a low incidence of CMV infection and gastrointestinal and blood disorders.

Effects of Granulocyte and Monocyte Adsorptive Apheresis in Renal Transplantation Recipients With Concomitant Cytomegalovirus Infection.

BACKGROUND: Granulocyte and monocyte adsorptive apheresis (GMAA) is widely used as a treatment for active ulcerative colitis (UC) in Japan. Much attention has been paid to the possibility of GMAA for the treatment and control of cytomegalovirus (CMV) reactivation in patients with refractory UC and concomitant CMV infection. In this study, the effects of the combination of GMAA and antiviral therapy were examined in renal transplant recipients with concomitant CMV infection. METHODS: Combination therapy of GMAA and antiviral drugs was performed 9 times in 7 renal transplant recipients with concomitant CMV infection. Four of the cases were positive for CMV-IgG, and 3 were negative. The clinical presentation of CMV infection was viremia in 6 cases and disease (CMV retinitis) in 1 case. CMV infection was diagnosed by using an antigenemia assay (C7-HRP). GMAA session was performed once, and the duration of the session was 120 min. Immediately after the GMAA session, ganciclovir was administered at 5 mg/kg/body weight. CMV infection was monitored based on C7-HRP and CMV-DNA in the peripheral blood samples. RESULTS: All cases became negative for C7-HRP and CMV-DNA within 21 days (median, 14 days; range, 3-21 days) and 17 days (median, 6 days; range, 3-17 days), respectively, after starting the combination therapy. No side effects of GMAA were observed. CONCLUSIONS: This case series found that GMAA in combination with antiviral drugs may shorten the duration of treatment against CMV infection in renal transplant recipients. Further studies in a larger number of patients are required to confirm these results.

Tissue characterization of progressive cardiac allograft vasculopathy in patients with everolimus therapy compared with donor-transmitted atherosclerosis assessed using serial intravascular imaging: a case report.

Using serial intravascular ultrasound (IVUS), integrated-backscatter IVUS, and optical coherence tomography, we observed rapidly progressive cardiac allograft vasculopathy (CAV) and donor-transmitted plaque in the left anterior descending artery. Late-phase everolimus-resistant CAV had a rapidly progressive course (maximal intimal thickness [MIT] increased by 0.5 mm between years 3 and 4 after cardiac transplantation, from MIT growth<0.5 mm at year 1). Conversely, the donor-transmitted plaque grew slowly (0.1 mm increase during the same period). Tissue characteristics in the 2 segments were also different; CAV had eccentric, noncalcified, and lipid-rich components and was associated with macrophage accumulation, whereas donor-transmitted atherosclerosis presented with typical features of atherosclerosis (ie, fibrocalcific plaque). CAV with late-phase progression involves everolimus resistance and features of vulnerable plaques seen in nontransplantation patients and is independent of donor-transmitted atherosclerosis.

Structural changes in dermal collagen and oxidative stress levels in the skin of Japanese overweight males.

OBJECTIVE: It has been reported that obese people have poorly organized dermal collagen structure because of the degradation of collagen fibers, which is caused by an increase in oxidative stress levels associated with the hypertrophy of subcutaneous adipose cells. However, it is unclear whether an increase in oxidative stress levels caused by the accumulation of subcutaneous adipose tissue and a change in the dermal structure also occur in overweight and obese Japanese people. The objectives of this study are to identify structural changes that occur in the dermis and to measure the levels of oxidative stress in Japanese overweight males. METHODS: The overweight group included 43 Japanese male volunteers aged between 25 and 64 years and with a body mass index (BMI) of ≥25 and <30. The control group included 47 male volunteers aged between 22 and 64 years and with BMI of <25. The 20-MHz Dermascan C® ultrasound scanner with software for image analyses was used. Echogenicity of the upper and lower dermis was measured. The mRNA expression level of heme oxygenase-1 (HMOX1) in hair follicles was quantitatively analyzed by real-time reverse transcription polymerase chain reaction (RT-PCR) and was used as a marker of oxidative stress. Ultrasonographic imaging and collection of hair follicles were performed at the same site on the thigh, abdomen, and upper arm. RESULTS: The HMOX1 mRNA expression level in the abdomen and thigh was significantly lower in the overweight group than in the control group. Moreover, the echogenicity of the upper dermis of the abdomen and the lower dermis of the abdomen and thigh was significantly lower in the overweight group than in the control group. CONCLUSION: We detected an increase in oxidative stress levels and a decrease in the density of dermal collagen at the same site on the thigh, abdomen, and upper arm of Japanese overweight males. These findings suggest the fragility of the dermis of Japanese overweight males, which might have been caused by the accumulation of subcutaneous adipose tissue.

Poor glycemic control and decreased renal function are associated with increased intrarenal RAS activity in Type 2 diabetes mellitus.

AIMS: The renin-angiotensin system (RAS) plays an important role in the pathogenesis of diabetic nephropathy. The aim of the present study was to investigate intrarenal RAS activity in patients with type 2 diabetes (T2DM). METHODS: We measured urinary angiotensinogen, a reliable biomarker of intrarenal RAS activity, in 14 controls without T2DM, 25 T2DM patients without nephropathy, 11 chronic kidney disease (CKD) patients without T2DM and 46 CKD patients with T2DM. Associations between urinary angiotensinogen and clinical parameters were examined. RESULTS: Compared with the controls, urinary [angiotensinogen:creatinine] were significantly higher in T2DM patients without nephropathy (4.70 ± 2.22 vs. 8.31 ± 5.27 µg/g, p=0.037). Age, hemoglobin A1c (HbA1c) and fasting plasma glucose correlated significantly and positively with the log{urinary [angiotensinogen:creatinine]} (r=0.632, p=0.007; r=0.405, p=0.027; r=0.583, p=0.003, respectively) in T2DM patients without nephropathy. In contrast, the urinary [angiotensinogen:creatinine] were not significantly different between CKD patients with and without T2DM (22.7 ± 27.8 vs. 33.5 ± 40.8 µg/g, p=0.740); although they were significantly higher when compared with non-CKD patients. In the CKD patients with T2DM systolic blood pressure, serum creatinine, estimated glomerular filtration rate and urinary [albumin:creatinine] correlated significantly with the log{urinary [angiotensinogen:creatinine]} (r=0.412, p=0.004; r=0.308, p=0.037; r=-0.382, p=0.001; r=0.648, p<0.001, p<0.001, respectively). CONCLUSIONS: Our findings indicate that poor glycemic control is significantly associated with intrarenal RAS activity in T2DM patients without nephropathy, and that decreased renal function is significantly associated with intrarenal RAS activity in CKD patients with T2DM.

Importance of early appropriate intervention including antibiotics and wound care for device-related infection in patients with left ventricular assist device.

INTRODUCTION: A left ventricular assist device (LVAD) is essential for treating patients with advanced heart failure. However, LVAD-related infection is a significant cause of mortality and morbidity, with bloodstream infection (BSI) especially associated with high mortality. We investigated the incidence of infectious complications in patients who received an LVAD and evaluated the effects of early and appropriate intervention for LVAD-related infection. METHOD: We retrospectively reviewed 27 consecutive patients who underwent continuous-flow LVAD (CF-LVAD; n = 16) or pulsatile-flow LVAD (PF-LVAD; n = 11) implantation at the National Cerebral and Cardiovascular Center between April 2011 and March 2013. Incidences of LVAD-related infections, such as drive-line infection in patients with CF-LVAD, cannula infection in patients with PF-LVAD, and BSI in patients with both types, were examined (follow-up period, 342 ± 229 days). The mandatory antibiotic prophylaxis protocol at our institution includes teicoplanin (400 mg) 2 days before LVAD implantation and doripenem (1000 mg) within 1 hour of skin incision. In addition, the driveline exit sites undergo sterile cleansing with diluted hydrogen peroxide and placement of an antimicrobial occlusive dressing for wound care, with dressing changes performed 2-3 times per day. RESULTS: More than 90% of all patients suffered from a drive-line infection within 12 months after LVAD implantation. However, BSI developed in only 12.5% of CF-LVAD and 10% of PF-LVAD patients within 12 months (log-rank test; P = .875). CONCLUSIONS: LVAD-related infections, such as drive-line and cannula infections, were common, whereas the incidence of BSI was low in our LVAD-implanted patients. Our results highlight the importance of early and appropriate intervention including antibiotics and wound care for device-related infections for reducing the incidence of potentially fatal BSI.

Investigation of urinary angiotensinogen in renal transplant recipients.

BACKGROUND: Recent studies have indicated that angiotensinogen (AGT) is also locally produced in the kidney and that urinary AGT is a marker of local renal renin-angiotensin system activation. Because urinary AGT levels are significantly higher in patients with chronic kidney disease (CKD) than in patients without CKD and correlate with urinary albumin and other levels, urinary AGT is increasingly recognized as a marker for CKD monitoring, prognosis, and treatment. In this study, we investigated urinary AGT levels in renal transplant recipients. METHODS: Among the patients who were treated as outpatients at the Department of Urology of Osaka City University Hospital from March 2012 to April 2013, 146 stable renal transplant recipients and 50 donors who gave informed consent were studied. Urinary AGT and creatinine (Cr) levels were measured. The urinary AGT-to-Cr ratio was calculated, and its correlation with clinical parameters was examined. RESULTS: The urinary AGT-to-Cr ratio of the renal transplant recipients was significantly higher than that of the renal transplant donors (P = .0143). Furthermore, the urinary AGT-to-Cr ratio had a significantly positive correlation with the urinary albumin-to-Cr ratio (ACR; r = 0.39, P < .0001), while on the other hand, it had a significantly negative correlation with estimated glomerular filtration rate (eGFR; r = -0.31, P = .0002). Multiple linear regression analysis of factors associated with eGFR showed that urinary AGT was a significant and independent factor after adjusting for age, sex, and ACR. CONCLUSIONS: Our results indicated that urinary AGT levels were elevated in renal transplant recipients. In addition, urinary AGT significantly correlated with renal function and degree of albuminuria.

Effects of conversion from a twice-daily tacrolimus to a once-daily tacrolimus on glucose metabolism in stable kidney transplant recipients.

INTRODUCTION: The adverse effects of tacrolimus are known to play major roles in new-onset diabetes after transplantation. The purpose of this study was to investigate the effects of conversion from a twice-daily tacrolimus (Tac-BID) to a once-daily tacrolimus (Tac-OD) on glucose metabolism in stable kidney transplant recipients. PATIENTS AND METHODS: Twenty-six patients were converted from Tac-BID to Tac-OD on a 1:1 mg basis and examined for its effects on glucose metabolism. Unless rejection or tacrolimus toxicity was suspected, we did not perform dose adjustments of Tac-OD or reconversion to Tac-BID until 4 weeks after conversion. Subsequent dose adjustments were allowed to maintain tacrolimus target trough concentration within the. Changes in clinical parameters were compared between baseline and 24 weeks after conversion. RESULTS: Conversion from Tac-BID to Tac-OD on a 1:1 mg basis resulted in a significant decrease in tacrolimus trough level at 4 weeks after conversion. Because dose adjustments were performed, the trough level did not differ significantly between baseline and 24 weeks after conversion. At 4 and 24 weeks after conversion, the homeostasis model assessment of pancreas ß-cell function (HOMA-ß) increased significantly. CONCLUSIONS: Although there was no change in tacrolimus trough level between baseline and 24 weeks after transplantation, HOMA-ß at 24 weeks after conversion was significantly higher than that at baseline. These results indicated that conversion from Tac-BID to Tac-OD may improve pancreas ß-cell function in kidney transplant recipients.

Physiological and appearance characteristics of skin maceration in elderly women with incontinence.

OBJECTIVE: To identify the physiological and appearance characteristics of skin maceration caused by urine and/or faeces and determine their suitability as risk indicators for incontinence-associated dermatitis. METHOD: This cross-sectional, comparative study involved sixty-nine elderly women with urinary and/or faecal incontinence who provided informed consent to participate. Exclusion criteria included serious medical problems, acute illness and the presence of damaged skin on the buttocks. The physiological and appearance characteristics of macerated skin on the buttocks of the patients were examined. Stratum corneum and dermis hydration levels, transepidermal water loss and skin pH were used to assess skin condition. Skin morphology (sulcus cutis) was confirmed using images at x15 magnification. The erythema index and white index were used to evaluate colour in the macerated skin areas. RESULTS: Forty-four patients exhibited skin maceration. Stratum corneum and dermis hydration levels were significantly greater in the maceration group than in the non-maceration group, as were transepidermal water loss, skin pH and differences in sulcus cutis interval between the buttock of interest and the subumbilical region. Furthermore, differences in the erythema and white indices between these two regions were significantly higher and lower, respectively, in the maceration group than in the non-maceration group. CONCLUSION: To our knowledge, this is the first report to note that there are interesting changes not only in the epidermal layer but also in the dermis layer in patients with skin maceration. This finding confirmed that skin maceration caused by incontinence is a severe condition. Moreover, the erythema index was the best index for identifying skin maceration caused by incontinence, indicating that it can be used for precise and easy identification of the condition in clinical practice.

Glucose intolerance is associated with increased intimal-medial thickness of the carotid artery and increased pulse-wave velocity in renal transplant recipients.

BACKGROUND: Although new-onset diabetes after transplantation has been demonstrated to have a significant negative impact on allograft and patient survival, the role of glucose intolerance (impaired fasting glucose [IFG] and/or impaired glucose tolerance [IGT], as asymptomatic hyperglycemia and borderline diabetes, has not been identified in renal transplant recipients. METHODS: We enrolled 32 renal transplant recipients (at least 1 year after transplantation) without prior evidence of diabetes at our institution in this study. Transplant recipients were divided into 2 groups (normal glucose tolerance group and glucose intolerance group) according to the results of their oral glucose tolerance test with 75 g of glucose. Glucose intolerance included IFG, IGT, and IFG/IGT. Normal glucose tolerance was detected in 19 patients, and glucose intolerance in 13: had 6 IGT, 2 IFG, and 5 IGT/IFG. Bilateral brachial-ankle pulse-wave velocity (baPWV) and intimal-media thickness (IMT) measured as markers of atherosclerosis were compared between the 2 groups. Insulin resistance was estimated with the homeostasis model assessment of insulin resistance (HOMA-R), and pancreatic ß-cell function evaluated by the homeostasis model assessment of ß-cell function and insulinogenic index. RESULTS: The patients in the glucose intolerance group showed significantly greater baPWV and IMT than those in the normal glucose tolerance group. HOMA-R in the glucose intolerance patients was significantly higher than in the normal glucose tolerance patients. Linear regression analysis showed the increased IMT in the renal transplant recipients to be significantly correlated with HOMA-R. CONCLUSIONS: Renal transplant recipients with glucose intolerance had increased IMT and baPWV, suggesting that glucose intolerance in renal transplant recipients may induce atherosclerosis and that the rise in insulin resistance may contribute to the increased IMT in renal transplant recipients.

Insulin resistance and insulin secretion in renal transplant recipients with hepatitis C.

BACKGROUND: Several reports have suggested an association between hepatitis C virus (HCV) infection and new-onset diabetes after transplantation (NODAT). NODAT is a common complication after renal transplantation, and it has been associated with increased long-term morbidity and mortality. HCV-positive recipients may have abnormal glucose metabolism, even though NODAT has never been previously diagnosed. The aim of this study was to analyze the pathogenic factors responsible for glucose metabolism in a series of HCV-positive renal transplant recipients. METHODS: The study population comprised 16 renal transplant patients who received their grafts from deceased or living donors with anti-HCV antibodies. HCV-negative transplant recipients were individually matched with these HCV-positive recipients by year of transplantation, sex, age, serum creatinine levels, and type of calcineurin inhibitors. None of the patients had been diagnosed with diabetes. Insulin secretion and insulin resistance were determined by a 75-g oral glucose tolerance test (OGTT) and compared between the 2 groups. Categories of glucose tolerance were defined according to World Health Organization criteria. RESULTS: Glucose intolerance (impaired fasting glucose, impaired glucose tolerance, diabetes mellitus) as assessed by OGTT was detected in 7 of the HCV-positive recipients (43.8%) and 3 of the HCV-negative recipients. The homeostasis model assessment of insulin resistance was greater in the HCV-positive recipients than in the HCV-negative recipients. The homeostasis model assessment of ß-cell function was higher in the HCV-positive recipients than in the HCV-negative recipients. CONCLUSIONS: The frequency of glucose intolerance tended to be higher in HCV-positive recipients. Furthermore, insulin resistance was greater and insulin secretion higher in HCV-positive recipients, which indicated that the increase in insulin secretion compensated for insulin resistance observed in these patients. However, HCV-positive renal transplant recipients may ultimately develop NODAT as this compensation diminishes with time.

Conversion of stable kidney transplant recipients from a twice-daily prograf to a once-daily tacrolimus formulation: a short-term study on its effects on glucose metabolism.

BACKGROUND: The adverse effects of tacrolimus are known to play major roles in posttransplantation diabetes mellitus (PTDM). In the present study, we investigated the effects of conversion from a twice-daily (Tac BID) to a once-daily prolonged release of tacrolimus formulation (Tac OD) on glucose metabolism in stable kidney transplant recipients. PATIENTS AND METHODS: In this prospective study, 26 patients converted from Tac BID to the same milligram-milligram daily dose of Tac OD were examined for the effects on renal function, drug trough levels, and glucose metabolism over a 4-week period. RESULTS: Conversion from Tac BID to Tac OD on a 1:1 mg basis resulted in a significant decrease in tacrolimus trough levels, but no significant changes in renal function. At 4 weeks after conversion, a homeostasis model assessment of ß-cell function, and hemoglobin A1c (HbA1c) decreased significantly. CONCLUSIONS: This study demonstrated a significant reduction in tacrolimus trough levels after switching from Tac BID to Tac OD, which increased insulin secretion and decreased HbA1c, suggesting that it may decrease the frequency of PTDM among stable renal transplant recipients.

Excellent results with high-dose mizoribine combined with cyclosporine, corticosteroid, and basiliximab in renal transplant recipients: multicenter study in Japan.

We performed a multicenter study in Japan to assess the efficacy and safety of immunosuppressive therapy with high-dose mizoribine (MZR; 6 mg/kg) combined with basiliximab (Bas), cyclosporine (CyA), and a corticosteroid in 90 patients. MZR was adjusted to maintain a target trough level of 1 to 2 µg/mL. CyA was started at 7 mg/kg to maintain blood levels in the target therapeutic range of 200 ng/mL (trough [C0]), 1200 ng/mL (2-hour post-dose [C2]), and 6000 ng·h/mL (area under the curve(0-9)). Bas (20 mg/body weight) was administered on the day of transplantation and on postoperative day 4. Rejection was diagnosed by episode and protocol biopsies. Cytomegalovirus (CMV) antigenemia (direct immunological staining of leukocytes using peroxidase-labeled monoclonal antibody [C7-HRP]) levels were measured every 2 weeks for 6 months. At 12 months, all patients and grafts were surviving except for one death from infection: the 1-year patient and graft survival rate was 98.9%. The acute rejection rate was 21.1%. The mean serum creatinine level at 1 year was 1.51 ± 0.61 mg/dL. The incidence of CMV disease was 0% with 28.9%, CMV antigenemia and 5.6%, ganoyclovir treatment. The incidence of BK virus disease was 2.2%. The mean serum uric acid level was 7.15 ± 1.79 mg/dL at 1 month and 7.06 ± 1.78 mg/dL at 3 months. We observed that a high-dose MZR regimen in combination with CyA, Bas, and corticosteroid was safe and effective to reduce the frequency of CMV and BK virus-related events in renal transplant recipients.

Excellent outcomes of ABO-incompatible kidney transplantation: a single-center experience.

INTRODUCTION: Due to the severe shortage of deceased donors in Japan, ABO-incompatible living donor kidney transplantation has been performed since the late 1980s. Excellent long-term outcomes have been achieved; the rates of graft survival among these patients are currently similar to those of recipients of ABO-compatible grafts. Our single-center experience describing the immunosuppressive protocols, complications, and grafts survivals is documented in this study. PATIENTS AND METHODS: Among 123 patients with end-stage renal disease who underwent living donor kidney transplantation between January 1999 and December 2010, 25 cases were ABO-incompatible grafts. All of these patients were followed until August 2011. Analyzing these patients, we focused on their immunosuppressive protocols, complications, and graft survivals. RESULTS: Patient and graft survival rates were 100%. One patient experienced antibody-mediated rejection and an intractable acute cellular rejection episode, 1 patient an antibody-mediated rejection, and 6 patients had acute cellular rejection episodes. However, there were no severe complications. CONCLUSION: Although ABO-incompatible kidney transplantation is a high-risk procedure, a short-term graft survival rate of 100% may be expected due to recent significant improvements in desensitization and recipient management.

The persistence of drug-induced fever by teicoplanin--a case report.

OBJECTIVE: It was reported that the drug-induced fever of teicoplanin tended to persist after cessation of treatment. It is considered that the long half-life of teicoplanin causes the phenomenon. However there was no detailed report regarding plasma concentration of teicoplanin during onset of drug induced-fever. Therefore we investigated the relation between persistence of drug-induced fever and plasma concentration of teicoplanin. CASE: A 38-year-old male patient on the Left Ventricular Assist System (LVAS) was treated with teicoplanin for methicillin-resistant Staphylococcus aureus (MRSA) and he experienced drug-induced fever. Plasma concentrations of teicoplanin were measured not only during the treatment with the drug but also after it was discontinued. As such, plasma concentration was measured even when the fever had subsided. RESULTS: On Day 9 of treatment, the dose was increased from 400 to 600 mg, but the patient had a fever of about 38 - 39 °C. When the treatment was discontinued, it took 9 days for the fever to subside to a temperature of about 37 °C. The half-life of elimination of teicoplanin in the elimination phase is about 108 h, which is long. The fever persisted until the plasma concentration decreased to below 10 µg/ml, which is the effective trough concentration, and subsided when the estimated blood concentration was 7.5 µg/ml. CONCLUSIONS: We suggest that there is the possibility that the drug-induced fever due to teicoplanin persisted until the plasma concentration had decreased adequately. Close monitoring of plasma concentration is necessary, particularly when teicoplanin clearance is decreased such as in patients with renal dysfunction.

Factors associated with silent cerebral microbleeds in hemodialysis patients.

BACKGROUND: The recent development of gradient-echo T2*-weighted magnetic resonance imaging (MRI) has enabled the highly accurate detection of prior cerebral microbleeds (CMBs), which might indicate a higher risk of future intracerebral hemorrhage (ICH) and be a marker of cerebral small-vessel disease in the general population. The present study investigated the clinical factors associated with the presence of CMBs in hemodialysis (HD) patients. METHODS: Cranial MRI, including T2*-weighted MRI, was performed on 179 HD patients without symptomatic cerebrovascular disease and 58 healthy control subjects, and we investigated the prevalence of CMBs and clinical factors associated with the presence of CMBs. We also investigated the relationship between CMBs and other cerebral small-vessel diseases. RESULTS: The prevalence of CMBs was significantly higher in the HD patients than in the healthy subjects (45 patients (25.1%) vs. none in the healthy controls (0%), p < 0.0001). Multiple logistic regression analysis showed that independent and significant factors associated with the presence of CMBs were age, systolic blood pressure, diastolic blood pressure and pulse pressure. Moreover, the presence of CMBs correlated significantly with the presence of lacunar infarcts, periventricular hyperintensity and deep and subcortical white matter hyperintensity. CONCLUSIONS: These findings indicated a high prevalence of CMBs among HD patients, and that older age and high blood pressure were strong factors associated with the presence of CMBs. Moreover, CMBs were closely associated with other cerebral small-vessel diseases.