Relationship Between Stress Coping Mechanisms and Depression in Kidney Transplant Recipients.

BACKGROUND: It has been reported that transplant recipients are exposed to physical and psychosocial stresses even after transplant surgery and exhibit psychological disorders such as depression. PURPOSE: In this study, we extracted trends concerning how recipients of kidney transplants cope with stress, and we also examined how they cope with depression and its countermeasures. METHOD: We administered questionnaire surveys to 109 kidney transplant recipients. These included items on personal attributes, medical information, depression, and stress-coping type scales. Statistical analysis was performed using factor analysis and multiple regression analysis. RESULTS: Fifteen out of 109 (13.8%) were found to be high-risk patients for depression based on responses to the questionnaire using the depression scale. We extracted 2 factors of stress-coping type, namely Factor 1, "Directly coping with the problem," of patients who try to directly resolve the problem in a positive manner and Factor 2, "Stress-release while avoiding the problem," for those who relieve their feelings in response to the stress without resolving the problem itself. When multiple regression analysis was conducted with the depression scale as the dependent variable and the stress-coping factor as the independent variable, Factor 1 tended to be associated with reduced depression and Factor 2 with increased depression. CONCLUSIONS: Results showed that to improve the mental health of those who receive kidney transplants, it is necessary to examine the depression and stress-coping types of such patients at an early stage and carry out education on stress-coping, focusing on resolving the actual problem.

Severe Phlebitis Accompanying Vascular Rejection Type Acute T Cell-Mediated Rejection in Renal Transplantation.

PURPOSE: Renal transplant patients with vascular rejection type acute T cell-mediated rejection (ATCMR) grade II have a poor prognosis. Vascular lesions in those cases are thought to randomly occur, thus we searched for a novel pathological marker related to vascular rejection in kidney transplantation. METHODS: We determined pathological characteristics in 14 ATCMR grade II patients treated during an acute phase from 2004 to 2013. We then examined whether those findings appeared in transplant kidney biopsy specimens, except for cases of vascular rejection, in patients examined from 2010 to 2014. RESULTS: In 9 of the 14 ATCMR grade II patients, phlebitis was accompanied by inflammatory cells that formed polypoid projections in the venous lumen and partial disappearance of vascular endothelium. Further investigation showed those inflammatory cells to be T cells and macrophages. Histological findings revealed coexisting phlebitis in 2 of 13 patients with ATCMR grade I, 3 of 24 with borderline changes, and none with normal findings. Phlebitis occurred at a significantly greater rate than the other findings in cases of vascular rejection (P < .05). However, there was no significant difference in regard to graft survival between patients with and without phlebitis (P = .1829). CONCLUSION: Our results suggest severe phlebitis as a novel finding associated with the pathology of vascular rejection in patients with a renal allograft.

Comparison of Sensitivity of Immunocomplex Capture Fluorescence Analysis for Detecting Donor-specific Anti-HLA Class II Antibodies in Kidney Transplant Patients.

BACKGROUND: Immunocomplex capture fluorescence analysis (ICFA) detects donor-specific antihuman leukocyte antigen (HLA) antibodies (DSA), but the detection sensitivity of HLA class II antibodies using conventional ICFA is as low as 57%. The aim of the study was to improve the detection sensitivity of HLA class II antibodies by ICFA, and compare the ICFA results with the Luminex single-antigen bead test. METHODS: Six DSA-negative kidney transplant donors and recipient pairs and 10 HLA class II DSA-positive pairs were included in the study. The detection sensitivity of modified ICFA was compared with conventional ICFA, and the ICFA results were compared with the Luminex single-antigen bead test. RESULTS: The index value of modified ICFA was higher than that of conventional ICFA. The cutoff value of conventional ICFA was 30,686 (MFI), which was improved to 19,405 using modified ICFA. Regarding the HLA-DQ antibody, 5 samples found to be positive by Luminex single-antigen bead testing were all negative using modified ICFA. The reason for this discrepancy could be related to: (1) the difference in detection sensitivity; (2) the difference in HLA antigen surface expression between naive lymphocytes and synthetic beads; or (3) the structure of synthetic HLA DQ antigen on the Luminex single-antigen beads. CONCLUSION: The index value of the modified ICFA was higher than that of conventional ICFA, and the detection sensitivity of HLA class II antibodies was improved by modified ICFA. Further assessment is necessary to clarify the reasons for divergence between ICFA and Luminex single-antigen bead test results.

Altered expression of microRNA during fracture healing in diabetic rats.

OBJECTIVES: Diabetes mellitus (DM) is known to impair fracture healing. Increasing evidence suggests that some microRNA (miRNA) is involved in the pathophysiology of diabetes and its complications. We hypothesized that the functions of miRNA and changes to their patterns of expression may be implicated in the pathogenesis of impaired fracture healing in DM. METHODS: Closed transverse fractures were created in the femurs of 116 rats, with half assigned to the DM group and half assigned to the control group. Rats with DM were induced by a single intraperitoneal injection of streptozotocin. At post-fracture days five, seven, 11, 14, 21, and 28, miRNA was extracted from the newly generated tissue at the fracture site. Microarray analysis was performed with miRNA samples from each group on post-fracture days five and 11. For further analysis, real-time polymerase chain reaction (PCR) analysis was performed at each timepoint. RESULTS: Microarray analysis showed that there were 14 miRNAs at day five and 17 miRNAs at day 11, with a greater than twofold change in the DM group compared with the control group. Among these types of miRNA, five were selected based on a comparative and extended literature review. Real-time PCR analysis revealed that five types of miRNA (miR-140-3p, miR-140-5p, miR-181a-1-3p, miR-210-3p, and miR-222-3p) were differentially expressed with changing patterns of expression during fracture healing in diabetic rats compared with controls. CONCLUSIONS: Our findings provide information to further understand the pathology of impaired fracture healing in a diabetic rat model. These results may allow the potential development of molecular therapy using miRNA for the treatment of impaired fracture healing in patients with DM.Cite this article: S. Takahara, S. Y. Lee, T. Iwakura, K. Oe, T. Fukui, E. Okumachi, T. Waki, M. Arakura, Y. Sakai, K. Nishida, R. Kuroda, T. Niikura. Altered expression of microRNA during fracture healing in diabetic rats. Bone Joint Res 2018;7:139-147. DOI: 10.1302/2046-3758.72.BJR-2017-0082.R1.

Diffusion Tensor Imaging MRI With Spin-Echo Sequence and Long-Duration Measurement for Evaluation of Renal Fibrosis in a Rat Fibrosis Model.

BACKGROUND: Renal fibrosis (RF) is a well-known marker for chronic kidney disease (CKD) progression, including chronic renal injury after renal transplantation. However, invasive biopsy is an available examination for evaluation of RF. Diffusion MRI was once recognized as a promising option for RF. However, it is now controversial for RF evaluation in a unilateral ureteral obstruction (UUO) model. METHODS: To seek an optimal imaging method applicable for RF in UUO model kidneys, we attempted a series of MRI methods, including proton density-weighted imaging, T1-weighted imaging, T2-weighted imaging, T2*-weighted imaging, diffusion-weighted imaging, and diffusion tensor imaging (DTI). RESULTS: We identified DTI MRI by spin-echo sequence plus a special kidney attachment as the best option for evaluation of renal UUO fibrosis, compared with normal kidney on the opposite side. To confirm these results, we applied this technique to a rat UUO therapeutic model with the anti-fibrotic reagent Fasudil. Fractional anisotropy values calculated from DTI MRI showed statistically significant linear correlation with the RF area measured by use of Sirius red or Masson trichrome staining of the positive area [cortex (r = 0.6397, P = .0283) and outer stripe of the outer medulla (r = 0.7810, P = .0039)]. CONCLUSIONS: By use of the DTI MRI with spin-echo sequence, it may be possible to accurately evaluate RF in CKD.

Induction Immunosuppressive Therapy With Everolimus and Low-Dose Tacrolimus Extended-Release Preserves Good Renal Function at 1 Year After Kidney Transplantation.

BACKGROUND: Utilization of everolimus (EVR) has been increasing in recent years for patients undergoing renal transplantation to reduce calcineurin inhibitor (CNI) levels. However, an optimum regimen has yet to be established. METHODS: We retrospectively examined 12 renal transplant recipients who underwent an induction immunosuppressive protocol; the protocol comprises 5 agents, including EVR plus low-dose tacrolimus extended-release (TAC-ER) treatment. We compared those findings from those of 14 patients who underwent a conventional protocol without EVR. Clinical outcome and pathologic changes were assessed by using protocol graft biopsy findings obtained at 3 months and 1 year after transplantation. RESULTS: The estimated glomerular filtration rate was significantly higher for the EVR group at both 3 months and 1 year compared with the conventional group (P < .01 and P = .03, respectively). TAC-ER trough levels were also significantly lower at 3 months and 1 year (both, P < .01). Histologic findings of the 3-month protocol biopsy samples in the EVR group revealed 4 cases of borderline change and 2 of acute cellular-mediated rejection. The findings from the 1-year biopsy samples revealed 10 cases with normal findings with no evidence of CNI toxicity. Patients in the EVR group developed subclinical borderline change and acute cellular-mediated rejection after 3 months at a significantly higher rate than the conventional group (P = .02). CONCLUSIONS: Use of the present therapeutic strategy successfully maintained the trough of each drug at a lower level, and it also kept renal function stable up to 1 year after transplantation.

Post-Transplant Anemia Has Strong Influences on Renal and Patient Outcomes in Living Kidney Transplant Patients.

BACKGROUND: Post-transplant anemia (PTA) is a risk factor for mortality and graft loss in kidney transplant patients. METHODS: In all, 172 patients were included in this study. PTA was defined as hemoglobin <13.0 g/dL in men and 12.0 g/dL in women. The primary outcome of interest was the renal outcome, defined as a 50% increase in serum levels of creatinine, a return to chronic dialysis, and subsequent kidney transplantation (KTx). The secondary outcome was a composite of the primary outcome and death. RESULTS: At baseline, 75 patients (43.6%) had PTA. During follow-up of a median of 7.3 years, 52 patients (30.2%) had 2-fold higher creatinine levels than at baseline, 24 patients (14.0%) had to return to chronic dialysis or subsequent KTx, and 11 patients (6.4%) died; 8 (4.7%) of the deceased patients had functioning allografts. Univariate regression analyses showed that a lower hemoglobin level and positive proteinuria were significantly associated with both outcomes. After adjusting for important clinical variables, a lower hemoglobin level remained a strong predictor for both outcomes. Restricted cubic splines showed an almost linear inverse association with a hemoglobin level ≥12 g/dL. The risk of the outcomes increased with decreasing tertiles of the baseline hemoglobin level for both men and women, but the associations in women were much weaker than those in men, suggesting a different prognostic value of the hemoglobin level between men and women. CONCLUSIONS: PTA strongly influenced the renal and patient outcomes in living kidney transplant patients.

Adherence to Dietary Recommendations in Maintenance Phase Kidney Transplant Patients.

OBJECTIVES: Current adherence to dietary recommendations for chronic kidney disease was evaluated in kidney transplant patients in the maintenance phase. METHODS: A total of 268 maintenance phase kidney transplant patients were included in the study. Estimated daily intakes of oral protein and salt were calculated from 24-h urinary excretion of nitrogen and sodium, respectively. Dietary recommendations for chronic kidney disease, as issued in 2014 by the Japanese Society of Nephrology, were used as the basis for assessing diet. RESULTS: The study included 114 female patients and 154 male patients. The mean age, posttransplantation years, body mass index, estimated glomerular filtration rate, and 24-h urinary excretion of protein were 56.3 years, 11.2 years, 22.0 kg/m(2), 42.6 mL/min/1.73 m(2), and 321 mg/d, respectively. Estimated daily protein and salt intakes were 0.98 ± 0.26 g/kg/d and 9.3 ± 3.9 g/d. Only 47 patients (17.5%) in the case of salt intake and 105 patients (39.2%) in the case of protein intake were within reference values. The 24-h urinary protein excretion of the daily salt intake-adherent group (<6 g) was significantly less than that of the nonadherent group (≥6 g) (P = .021). CONCLUSIONS: The adherence rate to dietary recommendations for chronic kidney disease in kidney transplant patients was low. The 24-h urinary protein excretion of the daily salt intake-adherent group was significantly less than that of the nonadherent group. Dietary therapy for these patients may have the potential to improve kidney graft function and survival.

Practices for Supporting and Confirming Decision-Making Involved in Kidney and Liver Donation by Related Living Donors in Japan: A Nationwide Survey.

This nationwide survey investigated the actual practices for supporting and confirming the decision-making involved in related living-organ donations in Japan, focusing on organ type and program size differences. Answers to a questionnaire survey were collected from 89 of the 126 (71%) kidney and 30 of the 35 (86%) liver transplantation programs in Japan that were involved in living-donor transplantations in 2013. In 70% of the kidney and 90% of the liver transplantation programs, all donors underwent "third-party" interviews to confirm their voluntariness. The most common third parties were psychiatrists (90% and 83%, respectively). Many programs engaged in practices to support decision-making by donor candidates, including guaranteeing the right to withdraw consent to donate (70% and 100%, respectively) and prescribing a set "cooling-off period" (88% and 100%, respectively). Most donors were offered care by mental health specialists (86% and 93%, respectively). Third parties were designated by more of the larger kidney transplant programs compared with the smaller programs. In conclusion, the actual practices supporting and confirming the decision to donate a living organ varied depending on the organ concerned and the number of patients in the program.

Radiation protection issues on preparedness and response for a severe nuclear accident: experiences of the Fukushima accident.

Radiation protection issues on preparedness and response for a severe nuclear accident are discussed in this paper based on the experiences following the accident at Fukushima Daiichi nuclear power plant. The criteria for use in nuclear emergencies in the Japanese emergency preparedness guide were based on the recommendations of International Commission of Radiological Protection (ICRP) Publications 60 and 63. Although the decision-making process for implementing protective actions relied heavily on computer-based predictive models prior to the accident, urgent protective actions, such as evacuation and sheltering, were implemented effectively based on the plant conditions. As there were no recommendations and criteria for long-term protective actions in the emergency preparedness guide, the recommendations of ICRP Publications 103, 109, and 111 were taken into consideration in determining the temporary relocation of inhabitants of heavily contaminated areas. These recommendations were very useful in deciding the emergency protective actions to take in the early stages of the Fukushima accident. However, some suggestions have been made for improving emergency preparedness and response in the early stages of a severe nuclear accident.

Risk factors and incidence for lipid abnormalities in kidney transplant patients.

BACKGROUND: Lipid abnormalities (LA) are related to an increased risk for cardiovascular diseases in kidney transplantation patients. PATIENTS AND METHODS: Multivariable logistic regression models were used to estimate the risk of LA associated with potential risk factors, including immunosuppressant use, patient background characteristics, and laboratory data. RESULTS: In total, 386 patients who were undergoing kidney transplantation were included in the study. Statins were prescribed to 43% of patients. The LA composite outcome was defined as statin use and/or low density lipoprotein cholesterol level ≥120 mg/dL, and 229 patients (59.3%) developed LA as a result. LA was significantly related to everolimus, corticosteroid, age, and estimated glomerular filtration ratio in the multiple logistic regression analysis. The odds ratios were 2.264, 3.119, 1.186, and 0.870, respectively. Mycophenolate mofetil, mizoribine, azathioprine, cyclosporine (CYA), tacrolimus, proteinuria, body mass index, and male sex were not related to LA. DISCUSSION: CYA influenced lipid metabolism but was not related to LA in our study. The mean post transplantation period was 8.4 years, and the CYA dose decreased over time. The CYA blood concentration was 70.0 ng/mL, which is relatively low, but it decreased the susceptibility to LA. Serum lipid levels were well controlled by statins, and the estimated glomerular filtration rate was maintained stably. CONCLUSIONS: Everolimus and corticosteroid use, as well as a lower estimated glomerular filtration rate and higher age, were significant risk factors for LA. CYA is known for its adverse LA effects, but it was not a significant risk factor for LA in patients undergoing maintenance phase kidney transplantation.

Anti-huCD20 antibody therapy for antibody-mediated rejection of renal allografts in a mouse model.

We have reported that B6.CCR5(-/-) mice reject renal allografts with high serum donor-specific antibody (DSA) titers and marked C4d deposition in grafts, features consistent with antibody-mediated rejection (AMR). B6.huCD20/CCR5(-/-) mice, where human CD20 expression is restricted to B cells, rejected A/J renal allografts by day 26 posttransplant with DSA first detected in serum on day 5 posttransplant and increased thereafter. Recipient treatment with anti-huCD20 mAb prior to the transplant and weekly up to 7 weeks posttransplant promoted long-term allograft survival (>100 days) with low DSA titers. To investigate the effect of B cell depletion at the time serum DSA was first detected, recipients were treated with anti-huCD20 mAb on days 5, 8, and 12 posttransplant. This regimen significantly reduced DSA titers and graft inflammation on day 15 posttransplant and prolonged allograft survival >60 days. However, DSA returned to the titers observed in control treated recipients by day 30 posttransplant and histological analyses on day 60 posttransplant indicated severe interstitial fibrosis. These results indicate that anti-huCD20 mAb had the greatest effect as a prophylactic treatment and that the distinct kinetics of DSA responses accounts for acute renal allograft failure versus the development of fibrosis.

Permanent acceptance of mouse cardiac allografts with CD40 siRNA to induce regulatory myeloid cells by use of a novel polysaccharide siRNA delivery system.

The CD40/CD154 co-stimulatory pathway is crucial in alloimmune response. We developed a novel small interfering RNA (siRNA) delivery system with a poly-dA extension at the 5'-end of the siRNA sense strand that was stably incorporated into 1,3-ß-glucan (schizophyllan, SPG). This was captured and incorporated into dendritic cells (DCs) through its receptor, Dectin-1, specifically silencing CD40 genes (siCD40) to exert immunoregulatory activity. siCD40/SPG-treated CBA mice permanently accepted B10 fully mismatched cardiac allografts. Consistent with graft survival, the infiltration of CD4(+), CD8(+) T cells into the graft was lower, and that the numbers of CD40(low)CD11c(+) DCs cells and CD4(+)Foxp3(+)cells were increased in both the graft and in the recipient spleen. In addition, naive CBA recipients given an adoptive transfer of splenocytes from the primary recipients with siCD40/SPG accepted a heart graft from donor-type B10, but not third-party Balb/c mice. In conclusion, the treatment with siCD40/SPG targeting DCs could generate antigen-specific Tregs, resulting in the permanent acceptance of mouse cardiac allografts. These findings have important implications for clarifying the mechanism underlying the induction of tolerance in DCs, and also highlight the potential of immunomodulation and the feasibility of siRNA-based clinical therapy in the transplantation field.

Proceedings from an international consensus meeting on posttransplantation diabetes mellitus: recommendations and future directions.

A consensus meeting was held in Vienna on September 8-9, 2013, to discuss diagnostic and therapeutic challenges surrounding development of diabetes mellitus after transplantation. The International Expert Panel comprised 24 transplant nephrologists, surgeons, diabetologists and clinical scientists, which met with the aim to review previous guidelines in light of emerging clinical data and research. Recommendations from the consensus discussions are provided in this article. Although the meeting was kidney-centric, reflecting the expertise present, these recommendations are likely to be relevant to other solid organ transplant recipients. Our recommendations include: terminology revision from new-onset diabetes after transplantation to posttransplantation diabetes mellitus (PTDM), exclusion of transient posttransplant hyperglycemia from PTDM diagnosis, expansion of screening strategies (incorporating postprandial glucose and HbA1c) and opinion-based guidance regarding pharmacological therapy in light of recent clinical evidence. Future research in the field was discussed with the aim of establishing collaborative working groups to address unresolved questions. These recommendations are opinion-based and intended to serve as a template for planned guidelines update, based on systematic and graded literature review, on the diagnosis and management of PTDM.

Graft-derived CCL2 increases graft injury during antibody-mediated rejection of cardiac allografts.

The pathogenic role of macrophages in antibody-mediated rejection (AMR) remains unclear. Monocyte chemoattractant protein-1 (MCP-1/CCL2) is a potent chemotactic factor for monocytes and macrophages. The current studies used a murine model of AMR to investigate the role of graft-derived CCL2 in AMR and how macrophages may participate in antibody-mediated allograft injury. B6.CCR5−/−/CD8−/− recipients rejected MHC-mismatched WT A/J allografts with high donor-reactive antibody titers and diffuse C4d deposition in the large vessels and myocardial capillaries, features consistent with AMR. In contrast, A/J.CCL2−/− allografts induced low donor-reactive antibody titers and C4d deposition at Day 7 posttransplant. Decreased donor-reactive CD4 T cells producing interferon gamma were induced in response to A/J.CCL2−/− versus WT allografts. Consequently, A/J.CCL2−/− allograft survival was modestly but significantly longer than A/J allografts. Macrophages purified from WT allografts expressed high levels of IL-1ß and IL-12p40 and this expression and the numbers of classically activated macrophages were markedly reduced in CCL2-deficient allografts on Day 7. The results indicate that allograft-derived CCL2 plays an important role in directing classically activated macrophages into allografts during AMR and that macrophages are important contributors to the inflammatory environment mediating graft tissue injury in this pathology, suggesting CCL2 as a therapeutic target for AMR.

Establishment of educational program for multiorgan procurement from deceased donors.

INTRODUCTION: Multiorgan procurement is not an easy procedure and requires special technique and training. Since sufficient donors are not available for on-site training in Japan, establishment of the educational program for multiorgan procurement is mandatory. MATERIALS AND METHODS: Development of e-learning and simulation using pigs are our main goals. E-learning contains three dimensional computer graphic (3DCG) animations of the multiorgan procurement, explanation of both donor criteria and procurement procedure, and self-assessment examination. To clarify the donor criteria, the risk factors to 3-month survival of the recipients were analyzed in 138 adult cases of liver transplantation. The 3DCG animation for liver procurement was developed, which was used in the lecture prior to the simulation on August 10, 2013. The results of the examination after this lecture (exam 2013) were compared with the results after the lecture without using animation in 2012 (exam 2012). The simulation was performed by 97 trainees divided into 9 teams, and the surveys were conducted. RESULTS: The risk factors for early outcome of the recipients were cold ischemia time (≥ 10 hours), Model for End-stage Liver Disease score (≥ 20), and donor age (≥ 55 years). Results of examination showed that overall percentage of the correct answers was significantly higher in exam 2013 than in exam 2012 (48.3% vs 32.7%; P = .0001). The survey after the simulation of multiorgan procurement revealed that most trainees thought that the simulation was useful and should be continued. CONCLUSION: The novel educational program could allow young surgeons to make precise assessments and perform the exact procedure in the multiorgan procurement.

Performance of the Japanese glomerular filtration rate equation based on standardized serum cystatin C in potential kidney donors.

BACKGROUND: It was reported that the glomerula filtration rate (GFR) equation based on serum creatinine underestimated the GFR in potential kidney donors. Recently, the Japanese GFR equation based on standardized serum cystatin C was reported. Therefore, we assessed the performance of the equation in potential kidney donors. METHODS: Forty-five potential kidney donors from 2 hospitals were included. GFR was measured (mGFR) using inulin renal clearance. Serum creatinine was measured using the enzymatic method. Serum cystatin C was measured using a nephelometric immunoassay (Siemens) and calibrated to the standardized value traceable to ERM-DA471/IFCC using an equation reported previously. The estimated GFR (eGFR) was calculated using the Japanese GFR equation based on serum creatinine (eGFRcreat) and the Japanese GFR equation based on serum cystatin C (eGFRcys). Bias (mGFR - eGFR) and accuracy (P30) of the equations were evaluated. RESULTS: Inulin clearance, eGFRcreat, and eGFRcys were 91.0 ± 18.2, 78.5 ± 18.8, and 93.3 ± 16.3 mL/min/1.73 m(2), respectively. Bias of eGFRcreat was 12.4 ± 15.8 mL/min/1.73 m(2) and significantly different from zero, indicating underestimation of GFR. Bias of eGFRcys was -2.3 ± 16.3 mL/min/1.73 m(2) and was not significantly different from zero, suggesting better performance. But, the precision (standard deviation [SD] of bias) and accuracy (P30: Percentage of participants with eGFR within 30% of mGFR) of eGFRcys were not better compared with eGFRcreat. Accuracies (P30) of eGFRcreat and eGFRcys were 87% (95% confidence interval [CI], 74-94) and 82% (95% CI, 69-91), respectively. CONCLUSION: Bias of eGFRcys was better compared with eGFRcreat. But, the precision (SD of bias) and accuracy of eGFRcys were not superior compared with eGFRcreat in potential kidney donors.

Beneficial effects of tonsillectomy for mesangial immunoglobulin A (IgA) deposition and clinical outcome in five kidney transplant patients with recurrent IgA nephropathy: case report.

INTRODUCTION: Tonsillectomy has been applied for recurrent immunoglobulin (Ig)A nephropathy (IgAN) in kidney transplantation recipients, but allograft histologic changes after this treatment remain unclear. METHODS: Five patients with recurrent IgAN underwent tonsillectomy for persistent proteinuria (average, 397.2 mg/d; >6 months). Six repeated biopsies were taken 33.8 ± 17.1 months after treatment. Glomerular IgA deposition was detected by immunofluorescence staining on frozen tissue. Histologic and clinical data have been collected. RESULTS: An average of 11.2 months (range, 6-20) after tonsillectomy, proteinuria decreased to 60.8 ± 49.3 mg/d. Serum creatinine (SCr) slightly decreased (1.33 ± 0.31 before vs 1.24 ± 0.29 after treatment; P > .05). In 5 of the 6 repeated biopsy samples month after tonsillectomy, there was decreased mesangial IgA deposition. Glomerular crescent and endothelial proliferation were no longer found, although there was increased focal sclerosis and adhesion. After tonsillectomy, there were increased interstitial fibrosis and tubular atrophy, with no significant differences in Banff scores. CONCLUSIONS: Tonsillectomy can reverse not only persistent proteinuria, but also mesangial IgA deposition in patients with recurrent IgAN. Tonsillectomy may have both favorable clinical and histologic effects in recurrent IgAN after kidney transplantation.

Latent mesangial immunoglobulin A deposition in long-term functioning kidney does not correlate with disease progression and may exhibit fluctuating patterns.

BACKGROUND: Latent mesangial immunoglobulin (Ig)A deposition in long-term functioning kidney does not correlate with disease progression and may exhibit fluctuating patterns Mesangial IgA deposition without urinary abnormalities (latent mesangial IgA deposition) is occasionally observed in non-episode biopsies of kidney allografts. However, the histologic features of latent IgA deposition have not been fully characterized. METHODS: To better identify the clinicopathologic background of subclinical mesangial IgA deposition, we compared the clinical and histologic characteristics of long-term functioning kidney allografts with and without latent IgA deposition. RESULTS: Among 29 patients with a posttransplant duration of >10 years, 37.9% exhibited latent mesangial IgA deposition. Biopsies indicated that renal function at the time of and 5 years before subclinical mesangial IgA deposition was generally similar. HLA-DR4 and HLA-Bw51 showed a nonsignificant trend to be more frequent in the IgA-positive group. Histologic investigation demonstrated no changes in disease scores based on the Banff 2009 classification between groups. Immunofluorescence revealed co-deposition of C3 at >1+ intensity in 72% IgA-positive patients. Immunohistochemical analysis revealed that IgA deposition per se did not cause notable increases in intraglomerular α-smooth muscle actin (SMA)-positive cells. One patient with subclinical IgA deposition demonstrated a waxing and waning pattern in the amount of IgA deposition. CONCLUSION: This study suggests that subclinical IgA deposition in long-term functioning kidney allografts is not associated with progressive course in clinical and pathologic findings. Furthermore, the amount of subclinical IgA deposition may exhibit fluctuating patterns in some cases.

Obstacles of non-heart-beating donor kidney transplantation in Japan to date and future perspectives.

In Japan, multiple organ retrieval from brain-dead heart-beating donors has been gradually increasing since the law was adopted in 1997 and amended in 2009. However, almost more than 90% of total deceased donor kidney transplantation (DDKT) in Japan are still obtained from non-heart-beating donors (NHBD). The majority of NHBD are Maastricht categories IV and III. In category IV, we usually place a double balloon arterial and a venous drainage catheter via the femoral vessels after the diagnosis of clinical brain death and acquisition of informed consent from the family. After controlled cardiac arrest, the double balloons are inflated and in situ cold perfusion started as soon as possible to minimize warm ischemic time (WIT), seeking to achieve a zero to within a few minutes WIT in most cases. In category III, it is impossible to place the device prior to cardiac arrest. In these cases, after declaration of cardiac death, cardiopulmonary compression is accompanied by systemic heparinization, immediate laparotomy, and insertion of a cold perfusion catheter at the aortic and caval bifurcations to minimize WIT. NHBD kidney retrieval is critical; extirpation must be performed as rapidly as possible. The results of NHBD kidney transplantation in Japan are excellent, according to the advancement and utilization of in situ cannulation, organ perfusion, and sophisticated retrieval techniques. The patient and graft survival rates of DDKT at 1, 3, and 5 years in most recent 2001 to 2007 era were 95.4%, 92.2%, 89.1% (n = 945) and 89.2%, 83.7%, 77.8% (n = 919), respectively.