Nobuyuki Fukuzawa

A TLR5 agonist inhibits acute renal ischemic failure.

Reperfusion of ischemic organs induces a potent inflammatory response initiated by the generation of reactive oxygen species that directly damage tissue and promote leukocyte infiltration and activation that also mediate tissue injury. We recently found that radiation-induced tissue injury, which is caused by radiation-induced reactive oxygen species, is attenuated by administration of CBLB502, a pharmacologically optimized derivative of the TLR5 agonist flagellin. Therefore, we tested the ability of CBLB502 to attenuate injury in a murine model of acute ischemic renal failure. CBLB502 given 30 min before imposition of bilateral renal pedicle occlusion provided marked protection against the renal dysfunction and inflammation that follows reperfusion of ischemic kidneys, including marked decreases in leukocyte infiltration, proinflammatory cytokine production, and tubular injury. Importantly, CBLB502 given within 30 min after ischemic kidney reperfusion reproduced the protective effects of pretreatment with the TLR5 agonist, indicating a window following reperfusion in which CBLB502 administration abrogates acute renal ischemic failure. Bone marrow-reconstituted chimeras were used to show that the protective effects of CBLB502 could be delivered by intact MyD88 signaling on renal parenchymal cells. Consistent with this, Ab staining of kidney sections indicated that cells lining the renal vasculature expressed TLR5. Overall, these results indicate the use of TLR5 agonists as mitigators and protectants of acute renal ischemic failure.

Tonsillectomy ameliorates histological damage of recurrent immunoglobulin A nephropathy after kidney transplantation.

Recurrence of immunoglobulin A (IgA) nephropathy (IgAN) after renal transplantation is important as a cause of graft failure under improving rejection control. However, no specific therapy for recurrent IgAN is currently available. In this study, we evaluated the histological efficacy of tonsillectomy for allograft IgAN.

Long-term outcome of single institutional experience with conservative and surgical management for renal artery aneurysm.

BACKGROUND Spontaneous rupture risk of a renal artery aneurysm (RAA) is extremely low. Indications for surgical repair of RAA remain uncertain. OBJECTIVE Long-term outcomes of conservative therapy and surgical repair were evaluated. PATIENTS The study included 58 patients (17 males, 41 females) who were diagnosed with RAA during the last 21 years. Median age at the time of diagnosis was 62 (19-85) years, and the median follow-up 69 months (range 3-216). METHODS The patients were divided into two groups, conservative group (n = 30) who had been followed with blood pressure control, and treatment group (n = 29), who underwent an intervention. RESULTS Multiple efferent aneurysmal branches were observed in seven conservative and 16 treatment cases (P = .002). The median maximum diameter of the aneurysm was lower in the conservative than the treatment group (15 versus 25 mm, P = .005). Two conservative group cases showed increases in aneurysm size during follow-up. The hypertensive state showed essentially no change in either group during the follow-up. Renal function decreased with age similarly both in conservative and treatment groups. CONCLUSIONS Our conservative management criteria for RAA are justifiable and even too strict.

Successful kidney transplantation ameliorates arterial stiffness in end-stage renal disease patients.

PURPOSE Successful kidney transplantation (KTx) can ameliorate bodily damage caused by end-stage renal disease (ESRD). Arterial stiffness (AS) is one of the critical factors that shorten the survival of patients due to cardiovascular events. KTx may reduce AS as well; however, this has not been investigated well. We therefore conducted a retrospective study using noninvasive pulse wave velocity (PWV), which is a useful index of aortic damage. PATIENTS AND METHODS Fifty-eight consecutive kidney recipients (34 men, 24 women) were enrolled in this study. Mean age at transplantation was 40.5 ± 12.3 years and the dialysis period was 73.1 ± 95.8 months. The brachial-ankle PWV was measured preoperatively and 6 months postoperatively. First, we investigated the relationship between the PWV and the other parameters related to AS. Second, we studied the pre- to posttransplant change in PWV to evaluate the amelioration of AS after successful KTx. RESULTS PWV showed significant positive correlations with age, systolic blood pressure (BP), diastolic BP, and abdominal aortic calcification index. After successful KTx, PWV significantly decreased (P < .01). In addition, systolic and diastolic BP significantly decreased (P < .01 and P < .05, respectively). CONCLUSION Successful KTx ameliorates AS in ESRD patients. This might explain the improved cardiovascular prognosis of ESRD patients who undergo KTx.

Quadruple immunosuppression with basiliximab, tacrolimus, mycophenolate mofetil and prednisone is safe and effective for renal transplantation

Abstract:  Introduction:  Recent immunosuppression with tacrolimus and mycophenolate mofetil has improved the results of renal transplantation. In this study, we analyzed the effect and safety of basiliximab as an induction therapy.

High Renal Ischemia Temperature Increases Neutrophil Chemoattractant Production and Tissue Injury During Reperfusion Without an Identifiable Role for CD4 T Cells in the Injury

Various leukocyte populations, including neutrophils and CD4 T cells, have been implicated as mediators of acute renal ischemic injury. The influence of ischemic temperature on molecular and cellular mechanisms mediating this injury was tested in a mouse model. Wild-type C57BL/6, B6.CD4(-/-), B6.CD8(-/-), and B6.RAG-1(-/-) mice subjected to bilateral renal pedicle occlusion for 30 min at a higher (37 degrees C) but not a lower (32 degrees C) ischemic maintenance temperature had clear evidence of renal dysfunction and histopathology. Ischemia imposed at the higher temperature also increased CXCL1/KC and CXCL2/MIP-2 levels and neutrophils, but not T cells or macrophages, infiltrating into the ischemic kidneys. Depletion of neutrophils but not T cells attenuated the acute ischemic injury. These results indicate the influence of ischemic temperature and time on the production of neutrophil chemoattractants and subsequent neutrophil infiltration to mediate acute ischemic injury but fail to identify a role for adaptive immune components in this injury.

Heat Shock Protein 90α Is a Potential Serological Biomarker of Acute Rejection after Renal Transplantation.

Background Heat shock protein 90 (HSP90), a molecular chaperone associated with the activation of client proteins, was recently reported to play an important role in immunologic reactions. To date, the role of HSP90 in solid organ transplantations has remained unknown. The aim of this study was to evaluate the relationship between serum HSP90α levels and acute allograft rejection after organ and tissue transplantation using serum samples from kidney allograft recipients, an in vitro antibody-mediated rejection model, and a murine skin transplantation. Results Serum HSP90α levels were significantly higher in kidney recipients at the time of acute rejection (AR) than in those with no evidence of rejection. In most cases with AR, serum HSP90 decreased to baseline after the treatment. On the other hand, serum HSP90α was not elevated as much in patients with chronic rejection, calcineurin inhibitor nephrotoxicity, or BK virus nephropathy as in AR patients. In vitro study showed that HSP90α concentration in the supernatant was significantly higher in the supernatant of human aortic endothelial cells cocultured with specific anti-HLA IgG under complement attack than in that of cells cocultured with nonspecific IgG. In mice receiving skin transplantation, serum HSP90α was elevated when the first graft was rejected and the level further increased during more severe rejection of the second graft. Conclusions The results suggest that HSP90α is released into the serum by cell damage due to AR in organ and tissue transplantation, and it is potentially a new biomarker to help detect AR in kidney recipients.

Microvascular inflammation in early protocol biopsies of renal allografts in cases of chronic active antibody-mediated rejection.

Chronic active antibody‐mediated rejection (chronic ABMR) is one important cause of late‐stage renal allograft loss. However, few reports have used protocol biopsy to observe changes over time in cases that develop chronic ABMR. The aim of this study was to use protocol biopsy to clarify the histological features of cases that develop chronic ABMR.

Preservation of deep inferior epigastric artery at kidney transplantation prevents atrophy of lower rectus abdominis muscle.

Backgrounds The deep inferior epigastric artery (DIEA), which feeds the lower rectus abdominis muscle (lower RAM), is usually transected in kidney transplantation. In this study, we investigated whether preservation of DIEA can prevent lower RAM atrophy. Methods Two hundred and forty-five kidney transplant recipients (150 men and 95 women) were enrolled in the study (mean age 39.9 years) and were divided into two groups according to whether DIEA was transected (group A, n = 175) or preserved (group B, n = 70). The extent of lower RAM atrophy calculated in computed tomography (performed 1 year after transplantation) and incidence of lower RAM atrophy were compared between the two groups. The most predictive factors for lower RAM atrophy were assessed using a multivariate logistic regression model. Results The extent of lower RAM atrophy was significantly lower in group B (15.0 ± 18.5%) than that in group A (38.9 ± 25.4%, P = 0.003). The incidence of lower RAM atrophy was less prevalent in group B (20.0%) compared with that in group A (62.9%, P < 0.001). The sacrifice of DIEA was the only independent predictive factor for lower RAM atrophy (P < 0.001). Conclusions Preservation of DIEA during kidney transplant can prevent lower RAM atrophy.

Acute kidney injury caused by systemic Neisseria gonorrhoeae infection after successful kidney transplantation

Neisseria gonorrhoeae is one of the microbes that can causes male urethritis. This microbe is most likely to be transmitted via sexual intercourse. In men, the representative infection sites are the urethra, and oral mucosa but gonococcemia is rere. We present a case of gonococcemia in a 47‐year‐old male successful kidney recipient. He temporarily lost his graft function due to acute kidney injury followed by sepsis; however, short‐course intermittent hemodialysis and long‐term intensive ceftriaxone inoculation saved his life and his graft function.