Pilot Experience with ABO-Incompatible Kidney Transplantation as a Second Transplant.

BACKGROUND: Despite advances in immunosuppressant medications, improvement in long-term survival for kidney transplant recipients has been more difficult to achieve. In fact, the number of patients with failing grafts who must either return to dialysis or undergo a second transplant is increasing. Second transplantation is associated with reduced mortality rates compared to remaining on dialysis after an initial graft loss. Nowadays, excellent ABO-incompatible kidney transplant outcomes have been achieved. However, there have been no reports on ABO-incompatible kidney transplantation as a second transplant. PATIENTS AND METHODS: Three patients who received their graft from an ABO-incompatible living donor at our institution as a second transplant were enrolled in this study. We focused on immunosuppressive therapy for second ABO-incompatible kidney transplantation, donor-specific antibody status before the second transplant, patient and graft survivals, and complications. RESULTS: All 3 patients successfully underwent ABO-incompatible kidney transplantation as a second transplant with a follow-up period of 141, 39, and 24 months. Patient and graft survival rates were 100%. CONCLUSIONS: ABO-incompatible kidney transplantation may be an acceptable treatment for patients who need a second renal replacement therapy after their initial graft failure.

Clinical Outcomes of ABO-Incompatible Kidney Transplantation in Patients with End-Stage Kidney Disease due to Diabetes Nephropathy.

BACKGROUND: Diabetes nephropathy is one of the most common causes of end-stage kidney disease (ESKD) worldwide. The data are clear that kidney transplantation is superior to remaining on dialysis for patients with diabetes. However, there have been no reports on ABO-incompatible kidney transplantation in patients with ESKD due to diabetes nephropathy. PATIENTS AND METHODS: We conducted a retrospective, observational study to investigate the clinical outcomes of ABO-incompatible kidney transplantation for patients with pre-existing diabetes nephropathy at our institution from April 2011 to October 2017. A total of 14 recipients were enrolled in this study. RESULTS: All 14 patients underwent successful kidney transplantation. Both overall patient and graft survival rates were 100, 89.9, and 89.9% at 1, 3, and 5 years, respectively. One patient died 20 months after transplantation with a functioning graft due to pancreas cancer. Two of the 14 patients (14.3%) developed biopsy-proven acute cellular rejection during the follow-up period. The median observation period was 32.0 months (range 5-83 months). CONCLUSION: ABO-incompatible kidney transplantation may be an acceptable renal replacement therapy for ESKD patients with diabetes.

Isolated V-Lesion in an ABO-Incompatible Kidney Transplant Recipient Receiving Rituximab.

We report an ABO-incompatible kidney transplant performed on a 69-year-old female patient, whose donor was her 69-year-old husband. The patient received an immunosuppressive protocol using rituximab without splenectomy. Renal biopsy was done on posttransplant day 8 due to poor early graft function, and an isolated v-lesion was found, which responded to steroid pulse therapy and gusperimus hydrochloride administration. Our results indicate that isolated v-lesions can occur in ABO-incompatible kidney transplant recipients receiving rituximab and that this finding should be treated as acute rejection. To our knowledge, this is the first report of an isolated v-lesion in an ABO-incompatible kidney transplant recipient who had been administered rituximab.

Favorable Outcomes of Elderly ABO-Incompatible Kidney Transplantation-Pilot Single Center Experience.

BACKGROUND: The growth in the end-stage kidney disease (ESKD) population has been predominantly in the older adult population. In Japan, ABO-incompatible kidney transplantation has become an acceptable treatment option. However, few studies have been conducted on elderly ABO-incompatible kidney transplantation. PATIENTS AND METHODS: Seventeen patients aged 60 years and older who received their grafts from ABO-incompatible living donors at our institution between December 2006 and September 2016 were enrolled in this study, and the outcome of these recipients was evaluated. RESULTS: All 17 patients underwent successful kidney transplantation. Both overall patient and graft survival rates were 100, 100, and 83.3% at posttransplant 1, 3, and 5 years respectively. Six of the 17 patients (35.3%) had an episode of biopsy-proven acute cellular rejection. Two patients who developed steroid- and deoxyspergualin-resistant acute rejection required anti-human thymocyte immunoglobulin. CONCLUSION: ABO-incompatible kidney transplantation may be an effective radical renal replacement therapy for elderly patients with ESKD, although it could be a high-risk procedure.

ABO-incompatible kidney transplantation as a renal replacement therapy-A single low-volume center experience in Japan.

INTRODUCTION: Living donor kidney transplantation is preferable to deceased donor transplantation due to its superior long-term patient and graft survivals. However, ABO blood group incompatibility is a major barrier to living donor kidney transplantation. ABO-incompatible kidney transplantation has been performed in Japan since the late 1980's, but it is still globally uncommon. The objective of this study is to compare the clinical outcomes of ABO-incompatible kidney transplantation (ABO-IKT) with that of ABO-compatible kidney transplantation (ABO-CKT) at an institution where only about two kidney transplants are performed a month on average. DESIGN: A single center propensity score-matched cohort study. PATIENTS AND METHODS: We retrospectively collected and analyzed the data of 240 patients with end-stage kidney disease (ESKD) who underwent living donor kidney transplantation at Osaka City University Hospital from January 1999 to December 2016, of which 66 patients were ABO-IKT. The remaining 174 patients who underwent ABO-CKT were studied as the control group, and the clinical outcomes of ABO-IKT and ABO-CKT recipients were compared based on propensity score matching. RESULTS: After propensity score matching, there were no significant differences in both patient survival and death-censored graft survival rates between the ABO-IKT and ABO-CKT groups. Moreover, there were no significant differences in estimated glomerular filtration rate as well as frequency of acute cellular rejection, antibody-mediated rejection, infectious adverse events, malignancies, and post-operative bleeding between the two groups. CONCLUSION: Currently, ABO-IKT may be an acceptable treatment for patients with ESKD even at a low-volume transplant center.

Clinical Outcome of Elderly Kidney Transplant Recipients from Spousal Donors.

INTRODUCTION: Patients aged 60 years and older stand for the fastest growing group of patients with end-stage renal disease worldwide, and the need for kidney transplants among this population is rising. In Japan, living donor kidney transplantation is mainly performed to deal with the severe shortage of deceased donors, and the number of spousal transplants is currently increasing. PATIENTS AND METHODS: A total of 164 patients with ESRD underwent living donor kidney transplantation at our institution, of whom 21 patients aged 60 years and older had spousal kidney transplantation. ABO-incompatible kidney transplantation was performed in 5 of the 21 cases. We analyzed these recipients. RESULTS: Patient and graft survival rates were 100%. The incidence of acute rejection was 23.8%. Eight patients experienced cytomegalovirus viremia, two patients experienced Pneumocystis jiroveci infection, and one experienced bacterial pneumonia. Two patients developed cancers and underwent curative operation after transplantation. CONCLUSIONS: Elderly kidney transplantation from spousal donors is associated with age-related immune dysfunction, which may develop infections and malignancies and could be immunologically high risk due to the high rate of ABO-incompatibility and poor histocompatibility. An effort to minimize the adverse effect of immunosuppression and to reduce the risk of acute rejection may be needed for an excellent long-term outcome.

Late-onset neutropenia and acute rejection in ABO-incompatible kidney transplant recipients receiving rituximab and mycophenolate mofetil.

INTRODUCTION: Using rituximab, we have performed successful ABO-incompatible kidney transplantations in recipients without splenectomy as well as in those with high pretransplant anti-A/B antibody titers. A common and increasingly recognized toxicity of rituximab is late-onset neutropenia (LON), defined as unexplained grades III to IV neutropenia occurring at least 4weeks after the last dose of rituximab in the absence of an alternative explanation. PATIENTS AND METHODS: Between May 2006 and December 2011, 25 patients who received rituximab underwent successful ABO-incompatible kidney transplantation and were enrolled as the subjects in this study. The incidence rate and clinical features of LON as well as the relationship between LON and acute rejection in these patients were studied. RESULTS: Twelve recipients (48%) experienced LON 2 to 12months after transplantation. Five of the 12 patients (41.6%) who developed LON had an episode of biopsy-confirmed acute cellular rejection, as compared with one of the 13 patients (7.7%) who did not develop LON. Moreover, 3 patients who experienced LON developed steroid and deoxyspergualin-resistant acute cellular rejection requiring OKT-3 administration. CONCLUSIONS: The frequency of acute cellular rejection was higher in ABO-incompatible kidney transplant recipients with LON than in those without LON. Our findings suggested that these recipients who developed LON after rituximab administration may be at an increased risk for acute cellular rejection.

Conversion of stable ABO-incompatible kidney transplant recipients from mycophenolate mofetil with standard exposure calcineurin inhibitors (CNIs) to everolimus with very low exposure CNIs-a short-term pilot study.

BACKGROUND: A recent report has demonstrated that as with mycophenolate mofetil (MMF), everolimus is capable of inhibiting human B-lymphocyte function and activation including B-lymphocyte proliferation, apoptosis, and immunoglobulin production in vitro. Everolimus may therefore be used as an immunosuppressant in ABO-incompatible kidney transplantation. METHODS: A three-month pilot study was performed to examine the efficacy and safety of conversion of stable ABO-incompatible kidney transplant recipients from MMF with standard exposure calcineurin inhibitors (CNIs) to everolimus with very low exposure CNIs. Sixteen recipients were enrolled in the study. The patients without acute rejection by graft biopsy were switched from MMF to everolimus with CNI minimization. At three months after conversion, graft biopsies were performed to check for acute rejection and C4d deposition. RESULTS: Conversion to everolimus with CNI minimization for three months did not induce acute rejection and C4d deposition in all of the ABO-incompatible kidney transplant recipients. A slight elevation of anti-A/B antibody titer occurred in our present study. Everolimus was associated with hyperlipidemia and edema. CONCLUSIONS: These results demonstrated that short-term conversion from MMF to everolimus after one yr post-transplant may be a safe and effective alternate for ABO-incompatible kidney transplant recipients requiring temporary discontinuation of MMF.

Chronic kidney disease in patients with ileal conduit urinary diversion.

While renal dysfunction is often observed in patients following urinary diversion due to bladder cancer, there have been few studies on this subject. A cross-sectional study was performed on the renal function of ileal conduit urinary diversion patients and the prevalence and risk factors for chronic kidney disease (CKD) were examined. Patients with ileal conduit urinary diversion (n=102), who were being followed-up as outpatients and who were in stable condition, as well as age- and gender-matched healthy control subjects (n=63) were selected for this study. The prevalence of CKD was compared between the patients and healthy subjects. Next, the clinical factors associated with the presence of CKD were investigated in the patients with ileal conduit diversion using logistic regression analysis. The prevalence of CKD was significantly higher in the patients with ileal conduit diversion compared with the healthy subjects [60 patients (58.8%) vs. 11 healthy subjects (17.5%), P<0.0001]. The mean decrease in the estimated glomerular filtration rate per year of the patients with urinary diversion was 0.95±2.0 ml/min/1.73 m(2). Multiple logistic regression analysis revealed that the independent and significant factors associated with the presence of CKD were older age and the presence of hypertension, urolithiasis and a past history of hydronephrosis. In conclusion, an increased prevalence of CKD was revealed in the patients with ileal conduit urinary diversion, suggesting the need for better management of hypertension, urolithiasis and hydronephrosis following surgery.

Conditioned taste aversion dependent regulation of amygdala gene expression.

The present experiments investigated gene expression in the amygdala following contingent taste/LiCl treatment that supports development of conditioned taste aversion (CTA). The use of whole genome chips and stringent data set filtering led to the identification of 168 genes regulated by CTA compared to non-contingent LiCl treatment that does not support CTA learning. Seventy-six of these genes were eligible for network analysis. Such analysis identified "behavior" as the top biological function, which was represented by 15 of the 76 genes. These genes included several neuropeptides, G protein-coupled receptors, ion channels, kinases, and phosphatases. Subsequent qRT-PCR analyses confirmed changes in mRNA expression for 5 of 7 selected genes. We were able to demonstrate directionally consistent changes in protein level for 3 of these genes; insulin 1, oxytocin, and major histocompatibility complex class I-C. Behavioral analyses demonstrated that blockade of central insulin receptors produced a weaker CTA that was less resistant to extinction. Together, these results support the notion that we have identified downstream genes in the amygdala that contribute to CTA learning.

Clinical outcome of ABO-incompatible living unrelated donor kidney transplantation.

BACKGROUND: ABO-incompatible living unrelated donor kidney transplantation is an immunologically high-risk procedure, but few reports have been made on the outcomes of these transplants. PATIENTS AND METHODS: We analyzed 12 kidney transplants using ABO-incompatible living-unrelated donors performed at our institution between January 1999 and December 2007, focusing on the immunosuppressive protocols, complications and graft survivals. RESULTS: Patient and graft survival rates were 100%. One patient experienced antibody-mediated rejection and intractable acute cellular rejection, one had antibody-mediated rejection and one had acute cellular rejection, but their grafts survived after intensive immunosuppressive treatment. There were no severe complications among the recipients. CONCLUSIONS: In ABO-incompatible living unrelated donor kidney transplantation, severe rejections may occur due to ABO incompatibility and poor histocompatibility. Therefore, appropriate desensitization, immunosuppression and recipient care are needed for a successful transplant. Recent significant improvements in outcomes indicate that it has become a viable treatment option, given the lack of available donor organs.

Association between chronic kidney disease and small residual urine volumes in patients with benign prostatic hyperplasia.

AIM: It has been well described that large residual urine volumes (≥300 mL) affect renal function in advanced benign prostatic hyperplasia (BPH). However, it is not clear whether small residual urine volumes (<100 mL) are related to renal function. The present study was performed to examine the association between chronic kidney disease (CKD) and the post-void residual urine volume (PVR) in BPH patients. METHODS: A cross-sectional study was performed in 160 consecutive BPH patients with PVR of less than 100 mL. We first determined the stage of CKD and compared the PVR in subjects with/without CKD. Next, we divided the subjects into three groups according to the extent of PVR (PVR < 12 mL, 12 mL ≤ PVR < 50 mL, 50 mL ≤ PVR < 100 mL) and compared the estimated glomerular filtration rate (eGFR) among these groups. Moreover, risk factors associated with CKD, including the presence of post-void residual urine, were explored by multiple logistic regression analysis. RESULTS: The PVR of the patients with CKD was significantly greater than that of the patients without CKD. The group with the normal PVR (group PVR < 12 mL) had a significantly higher eGFR compared with the other two groups. Multivariate analysis demonstrated that the presence of post-void residual urine (PVR ≥ 12 mL) was a significant and independent risk factor associated with the presence of CKD. CONCLUSION: In BPH patients, the PVR of the patients with CKD was significantly greater than that of the patients without CKD and the presence of post-void residual urine (PVR ≥ 12 mL) was independently associated with CKD, indicating a close association between CKD and small residual urine volumes.

[A case of dedifferentiated liposarcoma of the spermatic cord].

A 61-year-old man was referred to our department because of painless and stony hard mass beside the left testis. Serum levels of lactate dehydrogenase, alpha-fetoprotein and human chorionic gonadotropin were within normal ranges. The ultrasonography of the mass showed almost homogenous and relatively low intensity echogram. The mass which derived from the left spermatic cord and was partially surrounded by fat-like soft and yellow tissue, was removed with the left testis by usual orchiectomy. Histopathological diagnosis was liposarcoma, whose subtype was dedifferentiated type derived from well differentiated type. Postoperatively, a para-aortic mass, which resembled lymphnode metastasis, was pointed by computed tomographic scan and was removed surgically. However, it was histopathologically diagnosed as neurogenicganglioma irrelevant to liposarcoma. He has been free of disease for about 1 year without any adjuvant therapy.

[A case of primary mucinous adenocarcinoma of the scrotal contents].

A 48-year-old man consulted our hospital complaining of painless swelling of the left scrotal contents that had gradually increased for 5 years. Serum LDH, alpha-fetoprotein and HCG were within normal ranges. The ultrasonography showed heterogeneous echogram including high-echogenic spots and relatively a low-echogenic hydrocele. Left high orchiectomy was performed and the removed tissue was 24 x 16 x 15 cm in size, which had large cystic cavity filled with cloudy and deep-green mucin. Pathological diagnosis was mucinous adenocarcinoma. Postoperatively analyzed serum CEA, CA19-9 and PSA were within normal ranges. Systemic X-ray examinations, such as lung, abdominal and pelvic CT scan, upper GI series and barium enema, did not show any abnormal SOL suggesting carcinoma. Therefore, we diagnosed this case as a primary adenocarcinoma in the scrotal contents. The patient has been observed without any adjuvant therapy since operation, but no signs of recurrence have been identified for one year and six months.

Possible involvement of nuclear factor-kappaB inhibition in the renal protective effect of oral adsorbent AST-120 in a rat model of chronic renal failure.

Oral adsorbent, AST-120 removes uremic toxins (such as indoxyl sulfate) and retards the progression of chronic renal failure (CRF). However, its mechanism of action has not been precisely clarified. Since indoxyl sulfate elicits renal tubular nuclear factor-kappaB (NF-kappaB) activation in vitro, the present experiments were conducted to elucidate the involvement of NF-kappaB in the beneficial effects of AST-120 using rats with 3/4 nephrectomy, a model of early-stage CRF. Daily administration of AST-120 was started at 6 weeks after 3/4 nephrectomy and continued for 18 weeks. Sham-operated rats, untreated CRF rats and AST-120-treated CRF rats were compared for NF-kappaB DNA-binding activity, gene expression and renal histology. Systolic blood pressure was increased in CRF rats, and this increase was not affected by AST-120. Blood urea nitrogen, serum creatinine and urinary protein were increased in CRF rats. Although AST-120 attenuated these increases, it did not do so to a statistically significant extent. Indoxyl sulfate, which was accumulated in serum of CRF rats, was significantly eliminated by AST-120. Renal cortical NF-kappaB DNA-binding activity was increased in CRF rats. AST-120 significantly inhibited this increase. Monocyte/macrophage infiltration and increased monocyte chemoattractant protein-1 (MCP-1) mRNA observed in CRF rats were attenuated by AST-120. Furthermore, AST-120 significantly blocked renal fibrosis with concomitant inhibition of transforming growth factor beta1 (TGF-beta1) gene expression. It appeared that AST-120 reduced NF-kappaB activation and possibly the activity of NF-kappaB-dependent pathways of interstitial inflammation including MCP-1 expression and macrophage infiltration. The anti-inflammatory effect of AST-120 mediated via inhibition of NF-kappaB is a possible mechanism by which AST-120 retards the progression of renal fibrosis in CRF.

Attenuation of renal fibrosis by proteasome inhibition in rat obstructive nephropathy: possible role of nuclear factor kappaB.

We previously reported that pyrrolidine dithiocarbamate blocked nuclear factor-kappaB (NF-kappaB) activation and attenuated interstitial inflammation and tubulointerstitial fibrosis in the rat obstructive nephropathy. Since pyrrolidine dithiocarbamate is an anti-oxidant and possesses additional biological properties, present experiment was conducted to clarify further the role of NF-kappaB in the development of tubulointerstitial fibrosis in obstructed kidney using a proteasome inhibitor that blocks NF-kappaB through stabilizing IkappaB, an endogenous inhibitor of NF-kappaB. At 5 days following unilateral ureteral obstruction (UUO) in rats, obstructed kidney exhibited tubulointerstitial fibrosis that was associated with macrophage infiltration. UUO decreased renal cortical IkappaB protein contents with concomitant increases in NF-kappaB DNA-binding activity and gene expression of monocyte chemoattractant protein-1. Administration of PSI, N-benzyloxy-carbonyl-Ile-Glu (O-t-Bu)-Ala-leucinal, a proteasome inhibitor, (3 mg/kg/day, s.c., b.i.d) to UUO rats inhibited proteasome activity and attenuated the changes in IkappaB content, NF-kappaB activity and MCP-1 mRNA expression observed in UUO rats. PSI also decreased macrophage influx and attenuated the development of fibrosis. Furthermore, up-regulated gene expression of pro-fibrogenic molecules observed in the obstructed kidney was attenuated by PSI. These results further support the notion that NF-kappaB plays an important role in the development of renal fibrosis in the obstructive nephropathy.

A case of bilateral ectopic superior cervical ganglia in man.

Bilateral ganglionic masses, likely representing fused superior and middle cervical sympathetic ganglia, were found in the mid-neck region of a cadaver during routine dissection. The displacement of the superior cervical ganglion from its normal location is a striking anomaly that does not appear to have been reported earlier. This observation may be clinically relevant for avoiding misdiagnosis of such masses as Schwannomas or other tumors. In addition, in cases where the superior cervical ganglion is absent from its usual location, it should be sought in the mid-neck region.