Association Between the Fertile Period and Live Birth Post-Kidney Transplantation: A Retrospective Single-Center Cohort Study.

BACKGROUND: Despite restoration of fertility after kidney transplantation, the benefit is limited in female kidney recipients. Our objective is to determine the reasons for this discrepancy. METHODS: We evaluated 315 women who underwent kidney transplantation from 1983 to 2015 (a median of age at transplantation [10th-90th percentile] of 32 years [7-55 years]); 230 recipients between the ages of 15 to 49 years old as of March 2016 were observed. RESULTS: We experienced 10 abortions and 21 live births from our 23 recipients and 2 abortions and 7 live births in 7 recipients from other transplant center. The live birth rate was 8.9 per 1000 female transplant recipients of childbearing age. Seven recipients received either treatments of artificial insemination or in vitro fertilization. Average age at pregnancy was 33.2 ± 3.2 years old, and the fertile period post-transplantation was longer in recipients with live births than those without live births (14.1 ± 7.1 vs 9.9 ± 7.3 years, P < .05). In 42.9% of recipients with live birth, pregnancy-induced hypertension was observed in the last trimester. The gestational age and the average birth weight were 32.8 ± 5.0 months and 2184 ± 632 g, respectively. During follow-up of 14.5 years, there was one case of graft loss, which is a rate of 2.5 per 1000 female recipients. CONCLUSION: Although pregnancy complications are often observed in kidney recipients, graft survival is less influenced by pregnancy. Importantly, kidney disease at childbearing age disrupts pregnancy even after kidney transplantation.

Cancer Moonshot Connecting International Liquid Biopsy Efforts Through Academic Partnership.

The Kuhn Laboratory at the University of Southern California and the Dive Laboratory at the Cancer Research UK's Manchester Institute are teaming up to apply new cancer cell detection technology to identify patients who will progress after initial treatment. Researchers will take a simple blood sample to identify early those patients whose cancer has returned, while analyzing circulating tumor cells (CTCs) in great detail, providing new clues on the most effective therapy for the patient's cancer.

Pharmacokinetic Profile of Twice- and Once-daily Tacrolimus in Pediatric Kidney Transplant Recipients.

BACKGROUND: The aim of this study was to assess the differences in pharmacokinetic (PK) profiles after the 1:1 ratio-based conversion from a twice-daily to a once-daily tacrolimus formulation (TD-TAC and OD-TAC, respectively) in pediatric recipients of kidney transplants. METHODS: TD-TAC was initially administered to 29 pediatric patients who underwent kidney transplantations between April 2010 and September 2015 and were then subsequently switched to OD-TAC. The switch dose ratio was 1:1, and the 24-hour complete PK parameter assessment was performed before and after the regimen was changed from TD-TAC to OD-TAC. RESULTS: The mean total daily dose at baseline was 5.5 ± 2.9 mg (0.18 ± 0.10 mg/kg body weight). Consecutive PK studies revealed no significant difference in the mean time to achieve maximum concentrations and the area under the concentration-time curve from 0 to 24 hours (AUC0-24) of both drug formulations. However, the mean trough concentration (Cmin) and the maximum concentration of OD-TAC were 22% and 6% lower and higher, respectively, than those of TD-TAC. Therefore, a better correlation was observed between the AUC0-24 and Cmin of OD-TAC than between those of TD-TAC. CONCLUSIONS: After the change from TD-TAC to OD-TAC, the AUC0-24 values were equivalent despite a 22% reduction in Cmin. Cmin may therefore be an excellent predictor in the therapeutic drug monitoring of OD-TAC because of its superior correlation with AUC0-24.

Similar Anemic Control Between Chronic Kidney Diseases in Patients With and Without Transplantation on Entry to Dialysis.

BACKGROUND: Transplant recipients are supposedly in a more anemic, catabolic, and even inflammatory state at re-entering hemodialysis due to chronic rejection. The goal of this study was to clarify how transplant recipients can re-enter dialysis safely by focusing on control of anemia. METHODS: From 2012 to 2014, a total of 29 transplant recipients re-entered hemodialysis because of chronic rejection (ie, the chronic kidney disease with transplant [CKDT] group). At the same time, in 2014, a total of 30 patients with chronic kidney disease without transplantation entered dialysis as the control group (ie, the CKD group). CKDT recipients (mean ± standard deviation age, 41.9 ± 11.8 years; 18 male subjects, 10 female subjects; frequency of diabetes, 10%; duration of graft survival, 12.5 ± 4.3 years) were younger and fewer had diabetes compared with the CKD group (age, 53.2 ± 10.5 years; 21 male subjects, 9 female subjects; frequency of diabetes, 36%). Patient characteristics at entering dialysis in both groups were analyzed according to retrospective chart review. RESULTS: At entering dialysis, there were no significant differences between the CKD and CKDT groups in terms of the following: dose of darbepoetin; concentrations of hemoglobin, albumin, and C-reactive protein; cardiothoracic ratio; blood urea nitrogen and creatinine levels; estimated glomerular filtration rate; initial ultrafiltration; and duration of hospitalization for initiation of dialysis. The only difference between groups was mean weight at entry to dialysis (CKDT group, 58.5 ± 15.1 kg; CKD group, 67.1 ± 14.8 kg; P = .03). The darbepoetin dose per kilogram of weight did not differ between groups (CKDT, 2.28 ± 2.03 µg/kg; CKD, 2.12 ± 1.6 µg/kg; P = .95) in the final month before entry to dialysis. CONCLUSIONS: Safe re-initiation of dialysis is important for recipient survival. Although anemia is supposedly higher in transplant recipients due to immunosuppression, this single-center analysis found no difference in anemia in CKD with or without transplantation, caused by good use of erythropoietin-stimulating agents in both groups.

Successful Kidney Transplantation in Epstein Syndrome With Antiplatelet Antibodies and Donor-specific Antibodies: A Case Report.

An autosomal dominant hereditary disease, Epstein syndrome (ES) is characterized by sensorineural hearing impairment, macrothrombocytopenia, and hereditary nephritis, and can progress to end-stage kidney disease after puberty. Generally, kidney transplantation is difficult to perform in Epstein syndrome owing to the high risk of perioperative bleeding. Additionally, due to previous platelet transfusions, ES patients sometimes have antihuman leukocyte antigen (HLA) antibodies, including antiplatelet antibodies and donor-specific anti-HLA antibodies (DSA), which may result in refractoriness to platelet transfusion and antibody-mediated rejection (AMR). We report a case of successful kidney transplantation in a patient with ES who had DSA and antiplatelet antibodies. To prevent AMR, we used a desensitization protocol (a combination of plasmapheresis, rituximab, and basiliximab induction). Surveillance biopsy performed at 4 months and 1 year after transplantation showed no pathological findings suggesting AMR. To prevent perioperative bleeding complications, we infused the patient with HLA-matched platelets, thereby maintaining the platelet count at >10.0 × 10(4)/µL, and no postoperative episodes of bleeding occurred.

A Japanese multicenter study of high-dose mizoribine combined with cyclosporine, basiliximab, and corticosteroid in renal transplantation (the fourth report).

We examined the efficacy and safety of 4-drug combination therapy using high-dose mizoribine (MZR) (8 mg/kg/d), cyclosporine (CsA), basiliximab (BXM), and steroid (STR) in 39 renal transplant recipients. Acute rejection episodes (ARE), which occurred in 9 (23.1%) patients, correlated with lower blood levels of MZR (trough levels ≥ 2 µg/mL). In addition, lower MZR concentrations tended to be associated with a higher incidence of rejection episodes in children aged ≤ 10 years than in those aged ≥ 11 years. The area under the received operating characteristics (ROC) curve of MZR trough level to pred ARE was 0.825 (95% confidence interval, 0.690-0.962; P = .002). Based on the ROC analysis, are MZR cut-off of 1.6 µg/mL showed a sensitivity of 81.8% and a specificity of 75.0%. Adverse events were observed in 23 patients, including infections in 11 (7 patients positive for cytomegalovirus [CMV] antigen and 4 treated with anti-CMV drugs). The MZR trough levels seemed to be higher among patients with adverse events than in those free of them, but it was no significant. All patients experienced successful engraftment except 1 who died of unknown cause with a functioning graft. In conclusion, our study showed that low MZR trough levels correlated with the incidence of ARE. No serious adverse effects were encountered with this therapy.

Outcomes of pediatric ABO-incompatible kidney transplantations are equivalent to ABO-compatible controls.

BACKGROUND: Due to the profound shortage of suitable deceased allografts, much effort has been made to investigate whether successful kidney transplantation (KT) is possible across the ABO blood group barrier even for pediatric recipients. METHODS: We reviewed 52 consecutive ABO incompatible (ABOic) transplantation performed between September 1989 and March 2011. The mean age at transplantation was 10.6 ± 3.9 years (range, 4.4-19.7), with 35 boys and 17 girls. The donor-to-recipient ABO blood antigen incompatibility was as follows: A1/O (n = 17); B/O (n = 13); A1/B (n = 6); B/A1 (n = 1); A1B/B (n = 9); and A1B/A (n = 6). As a control group, data were collected from 271 pediatric ABO compatible (ABOc) living donor KT in the same period. RESULTS: Overall acute rejection episodes (ARE) among the ABOic group were significantly higher than those of the ABOc group (44% vs 26%; P < .02). However, there was no difference in glomerular filtration rate (GFR) at 1 year after transplantation: 86 ± 31 mL/min for ABOic vs 99 ± 37 mL/min for ABOic, respectively. The 1-y, 5-y, and 10-year patient survival rates were 98%, 92%, and 92% in the ABOic group, respectively, and 99%, 98%, and 97% in the ABOc group, respectively (P = not significant [NS]). The overall 1-, 5-, 10-, and 15-year graft survival rates were 94%, 88%, 86%, and 86% in the ABOic group, respectively, and 95%, 92%, 88%, and 78% in the ABOc group, respectively. CONCLUSION: ABOic KT provided long-term allograft and patient survivals equivalent to ABOc live donor transplantations.

Antiatherogenic effects of S-nitroso-N-acetylcysteine in hypercholesterolemic LDL receptor knockout mice.

BACKGROUND: The pathophysiology of the NO/NO synthase system and dysfunctional changes in the endothelium in the early phases of the atherogenic process are incompletely understood. In this study, we investigated the effects of the nitrosothiol NO donor S-nitroso-N-acetylcysteine (SNAC) in the early prevention of plaque development in the hypercholesterolemic LDLr-/- mice as well as the changes in endothelium-dependent relaxation and NO synthase expression. METHODS AND RESULTS: LDLr-/- mice were fed a 1.25% cholesterol-enriched diet for 15 days. Plasma cholesterol/triglyceride levels increased and this increase was accompanied by the development of aortic root lesions. Aortic vasorelaxation to acetylcholine was increased, although endothelium-independent relaxation in response to sodium nitroprusside did not change, which suggest stimulated NO release enhanced. This dysfunction was associated with enhanced aortic superoxide production and with increased levels of constitutive NOS isoform expression, particularly neuronal NOS. SNAC (S-nitroso-N-acetylcysteine) administration (0.51 micromol/kg/day i.p. for 15 days) decreased the extent of the plaque by 55% in hypercholesterolemic mice, but had no effects on vasomotor changes. It did, however, lead to a decrease in constitutive NOS expression. The SNAC induced only minor changes in plasma lipid profile. CONCLUSION: The present study has shown that, in early stages of plaque development in LDLr-/- mice, specific changes in NO/NO synthase system develop, that are characterized by increased endothelium-dependent vasorelaxation and increased constitutive NOS expression. Since the development of plaque and the indicator of endothelial cell dysfunction were prevented by SNAC, such treatment may constitute a novel strategy for the halting of progression of early plaque.

Regimen of tacrolimus-based immunosuppression with basiliximab, mycophenolate mofetil, and low-dose steroid reduces acute rejection in kidney transplants.

BACKGROUND: Acute rejection is a major problem in kidney transplantation. To reduce its likelihood, we investigated the efficacy and safety of an immunosuppressive regimen including tacrolimus, basiliximab, mycophenolate mofetil, and low-dose steroids. METHODS: Fifty-seven patients, including 14 pediatric patients, were enrolled in this study. The mean age at the time of transplantation was 33.5 years, and the mean observation period was 8.2 months. The mean trough concentrations of FK at 1, 6, and 12 months posttransplant were 10.2, 6.6, and 6.0 ng/mL, respectively. RESULTS: All recipients survived without graft loss. The cumulative incidence of acute rejection in adults was 2.3% and 8.4% at 6 and 12 months posttransplant, respectively. Of the adverse events, 11 recipients (19.3%) were positive for CMV antigenemia or had CMV infections. Four recipients (7.0%) exhibited mild hyperglycemia. CONCLUSIONS: Our immunosuppressive regimen demonstrated favorable results, reducing the incidence of acute rejection without causing severe adverse events, especially in adults.

Current status of ABO-incompatible kidney transplantation in children.

This article reviews the current status of ABO-incompatible kidney transplantation in the pediatric population. ABO blood type incompatibility between a donor and recipient was generally considered a contraindication to kidney transplantation because of the associated high risk for hyperacute rejection. However, due to a severe shortage of suitable cadaveric allografts, much effort has been made over the last decade to investigate whether successful and effective kidney transplantation is possible across the ABO blood group barrier. At present, ABO-incompatible kidney transplantation has been shown to be a valid alternative even for children with end stage renal disease. In this review, we will discuss protocols available for successfully performing ABO-incompatible kidney transplantation in children: (1) pre-transplant extracorporeal immunomodulation with removal of pre-existing anti-A and/or anti-B antibodies; (2) immunosuppressive therapy and anti-rejection therapy; (3) splenectomy and the associated infectious complication in asplenic children. Also, we will speculate regarding the mechanisms underlying accommodation following transplantation.

A prospective trial of steroid withdrawal after renal transplantation in children: results obtained 1990 and 2002.

Ten-year graft survival rate was 89% after immunosuppressive therapy with cyclosporine, methylprednisolone, and mizoribine in pediatric renal transplant recipients enrolled in our multicenter study. Adrenocorticosteroids, which cause growth retardation, were reduced by administration on alternate days in 67% and withdrawn in 23% of recipients. Acute rejection episodes occurred in 30% of patients after withdrawal of steroids. Graft function returned to prerejection levels after treatment with high-dose methylprednisolone. Catch-up growth occurred after alternate day administration and steroid withdrawal. Twenty-eight of 94 patients reached the final height of 156 cm in boys and 145 cm in girls, because of the gradually reduced growth rate. Management of growth retardation before transplantation, especially in patients with congenital renal diseases, and early reduction of the steroid dose after transplantation will increase the final height of children with chronic renal failure.

ABO-incompatible living-donor kidney transplantation in children.

BACKGROUND: Due to a severe shortage of suitable cadaveric allografts for children awaiting kidney transplants, we have performed a series of ABO-incompatible living kidney transplantations (LKT) at our institution. METHODS: Between July 1989 and March 2000, 16 pediatric patients (3 female, 13 male) underwent ABO-incompatible LKT. The mean age at transplantation was 10.9+/-4.3 years (range 5.1-15.0 years). The donor to recipient ABO blood antigen incompatibility was as follows: A1-->O, 5 patients; B-->O, 6 patients; A1B-->B, 2 patients; and A1B -->B, A1-->B, or B-->A1, 1 patient each. The median pretransplantation anti-A1 titers of eight A-incompatible recipients were 1:128 (IgM, range 1:16 to 1:512) and 1:32 (IgG, range 1:2 to 1:128). Median anti-B titers of seven B-incompatible recipients were 1:32 (IgM, range 1:4 to 1:128) and 1:8 (IgG, range 1:2 to 1:64). All patients received three or four sessions of plasmapheresis (PP) and/or immunoadsorption (IA) to remove the anti-A and/or anti-B antibodies before transplantation. Immunosuppression initially consisted of cyclosporine, methylprednisolone, cyclophosphamide, and antilymphocyte globulin. Splenectomy was performed on all recipients at the time of transplantation. RESULTS: The patients were followed for 6 to 122 months with a mean follow-up of 63 months. All 16 recipients who underwent ABO-incompatible LKT achieved a pretransplant isoagglutinin titer less than 1:8 with 3-4 sessions of PP/IA treatment. Of 16 patients, 10 patients had rebound increase in their IgM and/or IgG anti-A/B titers to greater than 1:64 or predepletion levels within 10 days posttransplantation. In addition, nine patients developed renal dysfunction in association with the rebound increase in their anti-A/B. One patient lost his graft because of uncontrolled delayed hyperacute rejection, whereas eight other recipients recovered completely with pulse steroids and PP/IA therapy. After the third week posttransplant, there was no correlation between the occurrence of AR and their isoagglutinin titers. Moreover, no antibody-mediated rejection was observed, even in recipients with continued high titer anti-A and/or anti-B antibodies. Patient survival is 100% to date. The actuarial 1-year and 5-year graft survival rates are 87% and 85%, respectively. No fatal infectious complications occurred despite the combination of splenectomy and immunosuppressive drugs. CONCLUSIONS: We have demonstrated that with adequate pre- and posttransplant management, successful kidney transplantation across the ABO barrier is possible in the pediatric population. "Accommodation" of the allografts occurred within 2 weeks of transplantation. Subsequently, the long-term graft outcome of ABO-incompatible LKT was comparable to that of ABO-compatible LKT.

[The usefulness of two-step tuberculin skin testing in nosocomial infection cases].

The usefulness of the two-step tuberculin skin test in the preceding year for the contact investigation was reported, when a pulmonary tuberculosis patient was discovered in our hospital. Four persons showed stronger reaction than the results in two-step tuberculin skin test in the preceding year after nosocomial infection. One of them was diagnosed as pulmonary tuberculosis by chest radiograph, and antituberculosis chemotherapy was started. Other three started chemoprophylaxis. The chemoprophylaxis subjects might increase 4, if basic value of tuberculin reaction had not been available by two-step tuberculin skin test in the previous year. We could identify persons in whom tuberculin reaction became stronger by comparing the test results after exposure with the result of two-step tuberculin skin test in the preceding year. It is considered that two-step tuberculin skin test is very useful to efficiently execute the protective measure.

[Clinical evaluation of patients with pulmonary tuberculosis during the past 10 years in our hospital].

The background of patients who died of active pulmonary tuberculosis during 10 year's period (1989 to 1998). Of 973 tuberculosis patients, 76 patients died, of which 56 died of non-tuberculosis, and 20 died of tuberculosis. A total of 12 patients died within 3 months after being hospitalized. The period from hospitalization to death was significantly shorter in tuberculosis patients with independent gait failure, original treatment, without tuberculosis medical history, and no drug resistance. We considered that in tuberculosis death, severe tuberculosis itself is the cause of early death, and recurrence and drug resistance patients are the most serious problems in later deaths.

Invasive pulmonary aspergillosis with thrombosis in the left atrium.

We report a female patient with left atrial wall invasion from pulmonary aspergillosis. She had been treated for diabetes mellitus. Pulmonary aspergillosis extended to the left atrial wall via the left pulmonary vein and formed a polypoid lesion in the left atrium. The polypoid lesion was composed of thrombus, and the thrombus increased in size to become large, and it showed invagination into the mitral valve during diastole. We considered that the thrombus was formed on the injured endocardium. Severe invasive aspergillosis thus could occur in a mild systemic immunocompromised host.

Lipo prostaglandin E1 reduces the production of CXC chemokines in endotoxin-induced rat liver injury.

The present study attempted to assess the effect of prostaglandin E1 (PGE1) incorporated into lipid microspheres (Lipo PGE1) on chemokine production in endotoxin-induced rat liver injury. Male Wistar rats weighing 200-250 g were injected with 2 mg lipopolysaccharide (LPS) per kg intravenously. Lipo PGE1 was administered simultaneously at various concentrations (0.002, 0.02, 0.2, 2 µg/kg) in the tail vein. Blood samples and liver specimens were taken from the rats at 1, 3, 8, 12 and 24 h after injection with LPS alone or with LPS and Lipo PGE1. Serum macrophage inflammatory protein-2 (MIP-2) and cytokine-induced neutrophil chemoattractant (CINC) levels were measured by the enzyme-linked immunosorbant assay using the corresponding antibodies. Liver specimens were fixed, and the number of neutrophils that had infiltrated each liver section was determined under a microscope. Serum alanine aminotransferase (ALT) levels were significantly lower in the rats injected with LPS and Lipo PGE1 compared with those in the rats injected with LPS alone, and this difference was expressed in a PGE1 dose-dependent manner. Serum MIP-2 levels were significantly lower at 3 h (141.4+/-95.5 pg/ml) and 8 h (44.9+/-44.7 pg/ml) after injection with LPS and Lipo-PGE1 (2 µg/kg) than at the same times after injection with LPS alone (342.9+/-35.9 and 358.3+/-23.4 pg/ml, respectively). Similarly, serum CINC levels were significantly lower at 8 h (482.7+/-156.0 ng/ml) after injection with LPS and Lipo-PGE1 (2 µg/kg) than at the same time after injection LPS alone (723.3+/-29.0 ng/ml). No significant differences were observed at any time between serum tumor necrosis factor-alpha (TNF-alpha) levels in rats injected with LPS alone and in rats injected with LPS and Lipo-PGE1 (2 µg/kg). The number of neutrophils that had infiltrated the liver was significantly lower at 8 h after injection with LPS and Lipo PGE1 than at the same time after injection with LPS alone. This difference was expressed in a Lipo PGE1 dose-dependent manner. In conclusion, Lipo PGE1 reduces liver injury and serum levels of MIP-2 and CINC, but not TNF-alpha, in rats injected with LPS and also reduces the number of neutrophils that infiltrate in the liver.

[Desensitization therapy for antituberculous drugs].

We retrospectively evaluated the effectiveness of desensitization therapy for antituberculous drugs (Rifampicin and Isoniazid) in 28 cases (29 episodes) with adverse reactions to these drugs. Desensitization therapy for RFP was performed in 23 cases (24 episodes) with administration of a first dose of 1-150 mg and a final dose of 300-450 mg for 1-29 days. The success rate of this therapy was 79% (19 of 24 episodes). Desensitization therapy for INH was performed in 12 cases with administration of a first dose of 2.5-100 mg and a final dose of 200-400 mg for 3-25 days. The success rate of this therapy was 83% (10 of 12 cases). Based on a comparative study of cases between successful and unsuccessful desensitization to RFP and INH it was concluded that there were no significant differences with regard to allergic history, adverse effects and their periods of appearance, the first dose and final dose of administration and the interval of administration, starting periods of the desensitization therapy and the periods of appearance of adverse effects due to this therapy. We evaluated desensitization therapy for two antituberculous drugs (RFP and INH) for tuberculous patients for whom the use of such drugs was restricted because of adverse effects, and we found it is a useful treatment, showing a high rate of success (80%).