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Objectives To evaluate whether the long-term usage of mirabegron, which was reported to have potential side effects on male reproductive organs in animal studies, was harmful to spermatogenesis in human testis. Methods Thirty consecutive patients with spinal cord injury (20-48 years old) who performed clean intermittent catheterization were involved in this study. Ten patients were treated with mirabegron (50 mg/d) for more than 2 years and refrained from using an antimuscarinic agent due to the side effects of constipation and dry mouth. Twenty patients were treated with neither anticholinergic agents nor mirabegron. All underwent conventional testicular sperm extraction. The sperm recovery rate and histopathologic findings of the retrieved testicular tissue were compared between both groups. Results We found no difference in the sperm recovery rate (P = .083) between both groups. Spinal cord injury patients treated with mirabegron had better spermatogenesis than those not treated with mirabegron (P Conclusions From these data, we conclude that the therapeutic dose of mirabegron had no harmful effect on spermatogenesis in spinal cord injury patients of reproductive age.

INTRODUCTION AND OBJECTIVE:Testosterone is the major sex hormone in males and plays an important role in the development of the penis and testes, muscle size, bone growth, sex drive, and sperm prod...

Background Sarcoidosis is a chronic systemic disease that is characterized by the formation of noncaseating granuloma and whose etiology is unclear. It is unclear whether patients with sarcoidosis are suitable organ donors. Case We treated a 56-year-old woman with pulmonary sarcoidosis who donated her kidney. She was previously in good health and was diagnosed with pulmonary sarcoidosis during her preoperative examination. Because she presented with no symptoms and was otherwise in good condition, donor nephrectomy was performed. Results Baseline biopsy examination showed no evidence of sarcoidosis. One year after transplantation, both the donor and the recipient had not developed kidney dysfunction or recurrence of sarcoidosis. Conclusion This is a rare case in which a patient with pulmonary sarcoidosis donated a kidney for transplantation, and both the recipient and the donor were clinically healthy. A patient with sarcoidosis and no kidney lesion can donate a living kidney, because transplantation appears to be safe for both the recipient and the donor.

Pyoderma gangrenosum (PG) is a skin disease characterized by an unknown neutrophilic infiltration in dermis and a nonbacterial destructive ulcer. Post-operative PG is an extremely rare type that occurs around surgical sites during the immediate post-operative period. It is usually diagnosed as surgical site infection at the time of presentation. The condition rapidly worsens despite antibiotic treatment and debridement. We report on a case of post-operative PG in a 64-year-old man after radical prostatectomy. Following the operation, redness and pus from surgical site rapidly progress although repeated antibiotic therapy and debridement were performed. Although the patient received appropriate debridement and broad-spectrum antibiotic treatment, the ulcerative lesion spread surrounding drain region and the condition of the skin region deteriorated. The diagnosis of PG was made by a skin biopsy that presented only neutrophilic invasion in the dermis without vasculitis, tumor, or malignancy. Finally, the patient died of lesion progression in whole body and multiple organ dysfunction. Considering PG along with ulcers, wounds, and post-operative complications is critical for prompt diagnosis and proper treatment.

We herein describe the unique case of a 59-year-old man who underwent living kidney transplantation for IgA nephropathy (IgAN) and developed progressive kidney failure associated with the appearance of proliferative glomerulonephritis. An early protocol biopsy revealed recurrent IgAN with mesangial IgA2 deposits restricted to a single immunoglobulin λ light-chain isotype. Despite treatment with tonsillectomy and rituximab, the patient eventually lost his allograft 31 months after transplantation. Serum electrophoresis showed a monoclonal IgA pattern. This case might share common pathological characteristics with the newly described entity referred to as proliferative glomerulonephritis with monoclonal IgG deposits.

Shimizu T, Ishida H, Shirakawa H, Omoto K, Tsunoyama K, Tokumoto T, Tanabe K. Clinicopathological analysis of acute vascular rejection cases after renal transplantation. Clin Transplant 2010: 24 (Suppl. 22): 22–26. © 2010 John Wiley & Sons A/S. Abstract: Histopathological change of acute vascular rejection (AVR) is characterized by intimal arteritis and transmural arteritis. In this report, we discuss the clinicopathological analysis of AVR cases after renal transplantation (RTX). Patients: AVR was diagnosed in 17 patients from 17 renal transplant patients followed in our institute between January 2003 and September 2008. We retrospectively reviewed these 17 patients. Results: Among 17 cases of AVR, 10 cases were mild (v1 in Banff 07 classification), five were moderate (v2), and two were severe (v3). Interstitial inflammation (i1–i3) was present in all 17 biopsies. Moderate to severe tubulitis (t2–t3) was present in seven biopsies, and transplant glomerulitis (g1–g3) was present in 11, peritubular capillaritis (ptc1–ptc3) was in 15 of 17 biopsies. C4d deposition in peritubular capillary (PTC) was observed in 6 of 17 cases. By assaying with plastic beads coated with anti-human leukocyte antigen (HLA) antigen performed in 17 cases, the circulating ant-HLA alloantibody was detected in 10 patients, of which 5/10 were donor-specific antibodies (DSA). Acute antibody-mediated rejection (AAMR) was diagnosed in three cases. Many of v1 cases, steroid pulse therapy (SP) were effective. In v2 and v3 cases, six of seven were steroid-resistant rejection and were need more anti-rejection therapy (ART), such as muromonab CD3 (OKT3) injection, gusperimus (DSG) injection, plasmapheresis, intravenous immune globulin, and injection of rituximab. Ten of 17 patients recovered their renal allograft functions by ART, and 16 of 17 patients’ grafts are functioning. Deterioration of renal allografts’ function after biopsies was seen in seven patients with one of them lost their graft. Conclusions: In some cases, AVR might be provoked by anti-donor antibodies. The prognosis of the graft exhibiting AVR was relatively good in present immunosuppression and ART.

Background To evaluate the role of the oral glucose tolerance test (OGTT) before transplantation and to examine the risk factors for new-onset diabetes after transplantation (NODAT) during long-term follow-up of renal transplant recipients receiving FK-based therapy. Methods The study evaluated 378 patients pre-transplantation using the OGTT and assigned them to one of three groups: Group 1, normal pattern; Group 2, impaired fasting glucose (IFG)/impaired glucose tolerance (IGT) pattern (IFG/IGT); and Group 3, DM pattern. Results Although the incidence of NODAT was higher in Group 3 than in groups 1 and 2, no significant difference was found between the three groups with regard to graft survival during long-term follow-up. Multivariate analysis showed that only a family history of diabetes was a significant factor determining NODAT progression. Conclusions Impaired glucose tolerance appears to be a threshold influencing NODAT; however, it was not a significant factor in graft survival. Careful monitoring and management based on the result of the pre-transplantation OGTT appear to prevent the deterioration of impaired glucose tolerance in renal transplant recipients receiving FK-based therapy, even when a pre-operative OGTT shows impaired glycemic control.

Recently, B-cell infiltrates in acute rejection grafts have attracted interest as an indicator of refractory rejection. Here, we report a case of deceased donor renal transplantation in a Japanese recipient operated overseas in which the recipient suffered from persistent tubulointerstitial rejection episodes associated with B-cell infiltrates. A 59-yr-old man with end-stage renal disease caused by immunoglobulin A nephropathy underwent deceased donor renal transplantation overseas in December 2005. The initial post-operative course was uneventful. The patient was referred to our hospital one month after transplantation. He maintained stable renal function throughout the follow-up period. The maintenance immunosuppressive regimen consisted of tacrolimus, mycophenolate mofetil and methylprednisolone. His serum creatinine concentration remained around 1.0 mg/dL, with no evidence of proteinuria. However, a discrepancy was detected between the renal function and the pathological findings. The pathology showed subclinical tubulointerstitial rejection with nodular B-cell infiltrates refractory to aggressive antirejection therapy. A steroid pulse and 15-deoxyspergualin were ineffective and the patient developed interstitial fibrosis and tubular atrophy by one yr after the transplantation, with persistent tubulitis and B-cell infiltrates. We treated the refractory rejection with B-cell infiltrates with a single 200 mg/body dose of rituximab and obtained an improvement. The pathological findings after administering rituximab consisted of mild tubulitis classified as Banff borderline, and elimination of the nodular B-cell infiltrates. At present, 20 months after renal transplantation, the patient continues to maintain stable renal function, with a good serum creatinine concentration (0.87 mg/dL).

A 54-yr-old Japanese male received overseas deceased kidney transplantation in January 2006. His allograft functioned immediately and he received immunosuppression with cyclosporine A (CyA), mycophenolate mofetil (MMF), and prednisone (PR). On day 24 after transplantation, he came back to Japan. His serum creatinine level (s-Cr) was 1.39 mg/dL at two months after transplantation when he was admitted into Toda Central General Hospital on March 2006, for follow-up his renal allograft. He had taken only two immunosuppressive drugs, MMF and PR, and had not taken CyA at that time. His serum creatinine gradually rose after hospitalization. Allograft biopsy performed on April 6, 2006, showed acute vascular rejection (Banff 97 acute/active cellular rejection Grade III), together with suspicious for acute humoral rejection (Banff 97 antibody-mediated rejection Grade II). After treatment of two courses of steroid pulses and five d of gusperimus, acute vascular rejection and acute humoral rejection were relieved, which had been proven by the third allograft biopsy. In conclusion, this was a case of acute vascular rejection after overseas deceased kidney transplantation, resulted from non-compliance with immunosuppressive therapy.

A 41-year-old Japanese male patient with end-stage renal disease received ABO compatible living related kidney transplantation from his sister on April 2003. The kidney functioned immediately after kidney transplantation. Protocol allograft biopsy at 1 yr after kidney transplantation was performed on April 2004. His serological data was not particular and he did not suffer with chronic inflammation. The allograft biopsy specimen revealed moderate accumulations of polymorphonuclear leukocytes in peritubular capillaries (PTCs), dilatation of PTCs and moderate infiltrations of polymorphonuclear and/or mononuclear cell in glomeruli (Transplant glomerulitis, moderate). Immunofluorescent study (IF) of a frozen section of the allograft biopsy specimen showed a strong, diffusely distributed endothelial-staining pattern in PTCs for C4d. The C4d was also strongly detected in a linear glomerular basement membrane (GBM) pattern. And widespread moderate C3c deposits, weak IgM, and IgG deposits were also seen in PTCs. Immunofluorescent study also showed granularly peripheral and mesangial deposits of strong IgM, C1q, and moderate IgG in glomeruli, IgA and C3c were faintly positive. The panel reactive antibody, which had been negative before transplantation, was positive for both HLA classes I and II at that time. We diagnosed as acute humoral rejection (AHR) and he was treated with course of steroid pulses and 5 d of gusperimus (DSG); and a total of three times Plasma exchange (PE) treatment was added. The level of serum creatinine, once increased to 1.7 mg/dL, decreased gradually to 1.4 mg/dL. He has a stable graft function. This is the only case of various depositions of immunoglobulins and complements in PTC and/or glomerular capillaries during AHR.

In Japan, the complement-dependent cytotoxicity (CDC-crossmatch) test and the anti-donor antibody flow cytometric assay (FCXM) are used to evaluate presensitization among transplantation candidates. We introduced the flow cytometric panel reactive antibody method (FlowPRA) at our institution, and in this paper, we compared the results of FCXM and FlowPRA. Sera of a total of 238 patients receiving the first graft were analyzed by FlowPRA retrospectively. Specimens from 125 of these patients were also analyzed by FCXM, and the results obtained using the two methods were compared. In addition, postoperative pathological findings by graft biopsy were examined in patients with PRA class 1(+) or PRA class 2(+). (i) Class 1 antibodies were detected in 36 of the 238 patients (15%), class 2 antibodies in six patients (3%), and both class 1 and class 2 antibodies in five patients (2%). (ii) Totally 125 patients analyzed by both FCXM and FlowPRA, 28 patients (22%) who tested negative by FCXM were, however, found to be positive by FlowPRA, and 16 of these 28 patients (57%) had shown evidence of humoral rejection suspected of antibody-mediated in the early postoperative stage. A large proportion of patients who tested negative by FCXM but positive by FlowPRA experienced rejection. Thus, for detecting 'high responders' in patients receiving the first graft, use of FlowPRA to detect antibodies may be superior to that of FCXM.

Transplant glomerulopathy (TGP) is a unique disease entity with characteristic pathological findings. Although ultrastructural studies for TGP have been performed, histogenesis of TGP is not fully understood. The present study was designed to investigate the relation of complement fragment C4d to the histogenesis of TGP. Nine cases of isolated TGP were randomly selected. A commercially available monoclonal antibody against complement fragment C4d was used in allograft biopsies. To evaluate the extent and severity of deposition of the C4d complement in the glomerular and peritubular capillaries, indirect immunofluoresce method was performed on frozen sections. Intense deposition of C4d in the glomerular basement membrane and peritubular capillaries was found in association with morphological appearance of TGP. Peritubular capillaries were affected in all the patients, showing splitting and multilayering of peritubular capillary basement membrane. These changes, which diffusely affect most capillaries, and their severity pattern were quite similar in each patient. In early stages of all patients with cellular rejection, C4d was not detected in the glomerular and peritubular capillaries. In addition, no C4d deposition was detected in all zero-hour biopsies without diagnostic abnormality. These findings suggest that C4d deposition in the glomerular and peritubular capillaries might be associated with the pathogenesis of TGP in renal transplantation.

We examined histological features of allograft biopsies in ABO minor-mismatched kidney transplantation. Forty-five patients who underwent ABO minor-mismatched kidney transplantation between September 1999 and December 2001 at our institute. The mean age was 32.6 years, with 28 males and 17 females. We divided them into five groups based on the donor and recipient ABO blood groups. Group 1, O renal allografts given to A patients (13 patients); Group 2, O to B (9). Group 3, O to AB (2); Group 4, A to AB (9); and Group 5, B to AB (12). From September 1999 to April 2002, we performed 127 allograft biopsies in these 45 ABO minor-mismatched kidney transplant recipients. Among a total of 127 biopsy specimens, 47 specimens were taken as 0- or 1-h biopsies and 6 were protocol biopsies. Pathological analysis of 74 episode biopsy specimens showed: acute humoral rejection (AHR) in 13 (18%); acute cellular rejection (ACR) in 17 (23%); combined AHR and ACR in eight (11%); borderline change in six (8%); chronic rejection in 10 (12%); cyclosporin or tacrolimus nephrotoxicity in seven (10%) and chronic allograft nephropathy in three (4%). In total, some form of acute rejection (AR) was seen histologically in 38 biopsy specimens (48%) from 19 patients (42%). When we investigated AR in two separate categories, i.e. AHR and ACR, AHR was diagnosed in 21 biopsy specimens (26%) from IS patients (33%) and ACR was seen in 25 biopsy specimens (31 %) from 13 patients (29%). We compared the incidence rate of acute rejection in the cases of ABO minor-mismatched renal transplantation with ABO-incompatible and ABO-compatible cases between January 1989 and December 1999. The incidence rate of AR in ABO minor-mismatched cases (42%) was statistically lower than that in ABO-incompatible cases (63%). There was no statistical difference in the incidence rate of AR between ABO minor-mismatched cases and ABO-compatible cases (49%). There was statistical difference in the incidence of AR among the donor and recipient ABO blood groups. Group 4 (A allografts given to AB patients) had the statistically highest rate of AR (89%), followed by Group 1 (54%), Group 5 (33%) and Group 2 (11%), and there was no AR case in Group 3 (O to AB). In conclusion, the incidence rate of AR in ABO minor-mismatched kidney transplantation is statistically lower than ABO-incompatible cases and is not statistically different from that in ABO-compatible cases. The incidence cases of AHR are slightly higher than that of ACR in ABO minor-mismatched kidney transplantation and this finding is similar to findings of ABO incompatible kidney transplantation. Finally, there is a statistical difference in AR incidence among the donor and recipient ABO blood groups.

Background Kidney grafts with multiple renal arteries have been considered a relative contraindication because of the increased risk of complications. In the present study, we retrospectively reviewed multiple renal artery reconstruction in kidney transplantation to elucidate the usefulness of these grafts. Methods. From January 1997 until August 2001, 431 recipients underwent kidney transplantation at our institution; 393 patients are reviewed. The surgical techniques of vascular reconstruction and short-term outcome are reported. The living kidney transplant recipients were divided into vascular reconstructed and nonreconstructed groups, and mean serum creatine levels, warm and total ischemic times, and incidences of acute rejection and posttransplantation hypertension were compared. Results. We noted multiple renal arteries in 96 (2404%) of the 393 grafts. Arterial reconstruction was performed on 53 (13.5%) grafts, whereas 43 (109%) small polar arteries were simply ligated. Surgical management of the multiple arteries was variable. The most common reconstruction was conjoined anastomosis (17 cases) between two arteries of equal size and end-to-side anastomosis (14 cases) of smaller arteries to larger arteries. In nine cases, autogenous hypogastric or epigastric artery grafts were used to reconstruct multiple renal arteries. Multiple anastomosis was performed in six cases. In seven cases, complicated surgical vascular reconstruction was performed. The mean total ischemic times in the reconstructed and nonreconstructed groups were 102.6 and 71.0 min, respectively (P

A 61-year-old-woman with end-stage renal disease caused by IgA nephropathy received living unrelated kidney transplantation from her husband in February 2001. Pre-transplant donor-specific T- and B-cell cross-match was negative. Immunosuppressive treatment consisted of tacrolimus (TAC), mycophenolate mofetil (MMF), methylprednisolone (MP) and antilymphocyte globulin (ALG). The kidney functioned immediately after kidney transplantation. On post-operative day 9, the level of serum creatinine (S-Cr) rose from 1.1 to 1.5 mg/dL. The allograft biopsy specimen taken on the day revealed moderate accumulations of polymorphonuclear leucocytes in peritubular capillaries (PTCs), dilatation of PTCs and transplant glomerulitis, moderate to severe. Immunofluorescent study of a frozen section of the allograft biopsy specimen showed a strong, diffusely distributed endothelial staining pattern in PTCs for the stable complement split product C4d. Post-transplant donor-specific T- and B-cell cross-matches performed on post-operative day 13 were positive. From the allograft biopsy and the positive post-transplant donor-specific T- and B-cell cross-matching, acute humoral rejection (AHR) associated with the development of antidonor antibodies (ADA) was diagnosed. Plasma exchange (PE) treatment was initiated on day 11. After a total of 13 treatments of PE, donor-specific T- and B-cell cross-matches became negative and the biopsy performed on day 72 revealed mild transplant glomerulopathy without accumulation of polymorphonuclear leucocytes in PTCs or a C4d staining pattern in PTCs of immunofluorescence. The allograft functioned well and the creatinine level was 1.1 mg/dL 7 months post-transplant. This was a case of AHR after renal transplantation associated with the development of ADA, which was triggered by spousal-donor antigens. The presence of widespread C4d deposition in PTCs in renal allograft biopsies played a role in the diagnosis of AHR and the diagnosis was confirmed by positive donor-specific T- and B-cell cross-matches at the time of rejection, which were negative at pre-transplantation. Several treatments of PE were effective for resolving AHR in this case and the effect of PE in the treatment of AHR could be assessed by the degree of peritubular capillaritis (PTCitis) and C4d deposits in PTCs.

A 38-yr-old man with factor H dysfunction and unknown glomerular disease received first and second renal transplantations (Tx) from living-related donors. His examination showed a low percentage activity of factor H (31%). Factor H dysfunction has been known to be associated with type II or III membranoproliferative glomerulonephritis (MPGN), haemolytic uraemic syndrome and IgA GN. The first graft from his mother showed diffuse mesangial deposit of IgA. His son has had IgA GN and his data also revealed a low percentage activity of factor H (33%) He and his son both showed a low activity of C3. Moreover, his father, who was the donor of the second Tx, had a low percentage activity of factor H (25%), and presented with mild glomerular deposit of C3 at operation, while he has been healthy through his entire 67 yr of life. Each of them had a low percentage activity of factor H. These findings through three generations suggested the inheritance of factor H dysfunction. The patient presented with proteinuria 3 months after the first Tx. At the first biopsy 30 months after the first Tx, light microscopy revealed minor glomerular abnormalities with electron dense deposits in subepithelial, intramembranous and mesangial regions, while immunofluorescence showed massive glomerular deposits of C3. In the second biopsy 51 months after the first Tx, the glomerulonephritis developed mesangial proliferation and crescent formation, accompanied by more massive C3 deposit and intramembranous, mesangial and subepithelial dense deposits. He then required redialysis. At the second and third biopsies within 2 months after the second Tx, the renal graft showed similar findings to the first biopsy after the first Tx. He perhaps presented with a recurrence of complement-associated GN, showing an atypical form of MPGN after Tx. These findings suggest that factor H dysfunction may play an important role of a certain pathogenesis of GN.

A 46-yr-old Japanese male who underwent a second cadaveric kidney transplantation on 31 October 1996 after suffering Type II diabetic mellitus for 25 yr was admitted to our institute on 23 January 1999, because of colickyabdominal pain and abdominal discomfort. Elevated levels of serum creatinine, severe proteinuria and microscopic haematuria were observed. The allograft biopsy specimen disclosed crescentic glomerulonephritis. Immunofluorescence showed granular deposits of mainly IgA and C3 along glomerular capillary walls and mesangial areas. Electron microscopy showed extensive subepithelial and mesangial electron dense deposits. Rapid and irreversible worsening of graft function led to resumption of haemodialysis on 31 May 1999. We speculated that this case was an atypical form of de novo Henoch-Schonlein purpura nephritis (HSPN) in transplanted kidney because of the histopathological findings of the allograft biopsy and clinical symptoms.

Background Our previous studies showed that the incidence of humoral rejection was extremely high in ABO-incompatible living kidney transplantation. This result suggests that anti-A/B antibody titers directly influence the graft survival of ABO-incompatible kidney transplantation. In this study, we examined the impact of preoperative anti-A/B antibody titers on the results of ABO-incompatible living kidney transplantation. Methods Sixty-seven patients underwent ABO-incompatible living kidney transplantation at our institution between January 1989 and December 1995. The mean age was 34.9 years with 38 males and 29 females. Sixty-one of the 67 recipients were included in an analysis of the impact of anti-A/B antibody titer in long-term graft survival. The remaining six patients were excluded because of death with a functioning graft (three patients) and withdrawal of immunosuppression due to nonimmunological reasons (three patients) within 1 year after renal transplantation. Results The graft survival rate for the level of less than 1:16 in maximum IgG antibody before transplantation (n=21) at 1, 5, and 8 years was 81.0, 66.8, and 66.8%, respectively. The corresponding values for the level of 1:32-1:64 (n=33) and higher than 1:128 (n=7) were 93.9, 90.5, and 79.7%, and 42.9, 28.6, and 28.6%, respectively (log-rank test, P=0.0007). There was no significant association between maximum anti-A/B IgM titers, minimum anti-A/B IgM titers, minimum anti-A/B IgG titers, and graft survival. Conclusions Preoperative maximum anti-A/B IgG titers correlated with the long-term graft survival in ABO-incompatible living kidney transplantation. Thus, preoperative maximum levels of anti-A/B IgG titers are one of the good predictors of the results of ABO-incompatible living kidney transplantation.

Because of a shortage of cadaver donors in Japan, ABO-incompatible living kidney transplantation has been carried out. Sixty-seven ABO-incompatible living kidney transplantations (LKT) were performed between January 1989 and December 1995 at our institution. In our previous report on the long-term results of ABO-incompatible LKT, graft survival of ABO-incompatible LKT up to 3 years was significantly lower than that of ABO-compatible LKT, but no significant difference was seen from 4 to 8 years. We removed anti-A/B antibodies by immunoadsorption and/or double filtration plasmapheresis before kidney transplantation. There was a significant difference between the anti-A/B antibody titers before and after plasmapheresis. The anti-A/B antibody titers also were well suppressed over the long term after transplantation.

We evaluate the efficacy of a new technique of minimally invasive treatment for benign prostatic hyperplasia involving direct injection of dehydrated ethanol.Dehydrated ethanol was injected transurethrally with lumbar or sacral and urethral anesthesia in 10 patients with prostatic hyperplasia. Endoscopic injection was performed at 4 to 8 sites in the prostate and 3.5 to 12.0 ml. ethanol were used.There were no intraoperative complications but postoperative urinary retention occurred transiently in all patients which required catheterization for a mean of 8.8 days. Mean symptom score plus or minus standard deviation was 12.2+/-5.8 at 3 months postoperatively, which was significantly improved from 23.1+/-7.0 preoperatively (p0.01). Mean quality of life score also improved significantly from 5.1+/-0.6 preoperatively to 3.2+/-1.5 at 3 months postoperatively (p0.01), mean peak urinary flow rate increased from 8.0+/-2.2 (9 patients) to 13.1+/-3.6 ml. per second (p0.05) and mean residual urine volume decreased from 129.1+/-55.3 (9 patients) to 49.3+/-34.7 ml. (p0.05). There was no significant change in prostate volume. Acute epididymitis and chronic prostatitis occurred in 1 patient each.This technique can be performed as an outpatient procedure and appears to be safe and cost-effective. Retrograde ejaculation can be avoided.

Background Since a report on the first successful pregnancy of a woman on long-term haemodialysis in Japan in 1977, there has been a growing number of case reports on successful pregnancy in patients on dialysis. We undertook a nationwide survey on pregnancy in women on renal replacement therapy in 1996. Methods A preliminary questionaire was sent to 2504 dialysis units and 143 renal transplant units in Japan. For each reported pregnancy, a more detailed questionaire was sent to collect nephrological, obstetric and neonatal information. Results There were 172 pregnancies (0.44%) reported in 38889 women on dialysis, with 90 successful pregnancies (0.23%), and 194 pregnancies reported in 852 female renal transplant recipients. Detailed pregnancy information was collected from 74 women on dialysis and 194 renal transplant recipients. Of the 74 pregnancies in the women on dialysis, 36 (48.6%) resulted in surviving infants, nine (12.2%) in neonatal death, nine (12.2%) spontaneous abortions and 14 (18.9% elective abortions were reported. The outcome of six pregnancies (8.1%) was unknown. Of 194 pregnancies in renal transplant recipients, 159 (82.0%) resulted in surviving infants, two (1.4%) in neonatal death and 28 (14.4%) in spontaneous or elective abortion. In five cases the pregnancy outcome was not reported. No congenital anomalies were reported, except two infants with mental retardation and one with epilepsy. Conclusion The current survey revealed that the rate of successful pregnancy in women on dialysis has improved. More than half of the pregnancies resulted in infant survival. But, premature birth is a major problem for the children of women on dialysis and there is a higher rate of neonatal death. There are significant differences in gestational age, birth weight, frequency and severity of prematurity and rates of neonatal death between pregnancies of women undergoing dialysis and those who are renal transplant recipients.

Background. One of the most serious problems facing major transplant programs is the severe shortage of organs. Expansion of the donor pool to include non-traditional donors, such as non-heart-beating donors (NHBDs), would considerably expand the availability of organs. Methods. Between 1983 and 1996, we performed a total of 125 non-heart-beating cadaveric renal transplantations under cyclosporine-based or tacrolimus-based immunosuppression. Thirty-nine recipients were females and 86 were males. Total ischemic time (TIT) and warm ischemic time (WIT) were an average of 761±347 min (322-2027 min) and 7.4±13.1 min (0-45 min), respectively. Results. Of the 125 transplanted kidneys from NH-BDs, 98 (78.4%) developed delayed graft function (DGF), which lasted a mean of 16±21 days (range 3-37 days). One hundred and eight patients (86.4%) were off dialysis by the time of discharge. Of the 125 grafts, 11 (8.8%) were primary nonfunction. The average of the nadir of serum creatinine levels, which was evaluated using 108 patients who were off dialysis by the time of discharge, was 1.4±0.5 mg/dl. The lowest creatinine levels (nadir) were under 2.0 mg/dl in 98 (78.4%) of the 125 patients. Acute rejection occurred in 64 (51.2%) of the 125 recipients. Patient survival rates were 90% at 5 years and 88% at 10 years. Graft survival rates were 65% at 5 years and 46% at 10 years. We tried to find the risk factors that affected graft survival. We examined the various possible risk factors, including harvesting condition (controlled versus uncontrolled), HLA-AB mismatches, HLA-DR mismatches, graft weight, donor age and sex, recipient age and sex, posttransplant DGF, acute rejection, WIT, and TIT. However, no significant risk factor was identified except acute rejection. We tried to discover the risk factors that caused primary nonfunction. Possible risk factors, including donor age, TIT, WIT, graft weight, and harvesting condition were compared, but no significant risk factor was identified. Long-term renal function was evaluated by serum creatinine levels. Serum creatinine levels at 1, 5, and 10 years were 1.76±0.7 mg/dl, 1.7±0.96 mg/dl, and 1.53±0.6 mg/dl, respectively. e Conclusions. In conclusion, our data demonstrated that the procurement of kidneys from NHBDs leads to acceptable long-term graft survival and renal function, despite a high incidence of DGF.

Background. Despite great efforts to promote the donation of cadaveric organs, the number of organ transplantations in Japan is not increasing and a serious shortage of cadaveric organs exists. These circumstances have forced a widening of indications for kidney transplantation. For this purpose, ABO-incompatible living kidney transplantations (LKTs) have been performed. Although we have already reported the short-term results of ABO-incompatible LKT, there is no report of long-term results in such cases; anti-A and anti-B antibodies could cause antibody-induced chronic rejection and result in poor long-term graft survival. In this study, we have reviewed the long-term results of ABO-incompatible LKT and tried to identify the most important factors for long-term renal function in ABO-incompatible LKT. Methods. Sixty-seven patients with end-stage renal failure underwent ABO-incompatible living kidney transplantation at our institute between January, 1989, and December, 1995. The mean age was 34.9 years (range, 8-58 years), with 38 males and 29 females. Incompatibility in ABO blood group antigens was as follows: A1

Low incidence rates of hepatocellular carcinoma and cirrhosis in HCV-antibody-positive patients on chronic hemodialysis are reported. Among the patients, two cases undergoing negative conversion of the anti-HCV-antibody were found. Considering the size of the virus particles and the pore size of the dialysis membrane, it seems the virus does not escape from the membrane pore. Indeed, virus particles may be trapped and destroyed at the membrane surface. The size of HCV-RNA titers in HCV-antibody-positive patients receiving various kinds of chronic blood purification procedures are of interest. The subjects included 15 hemodialysis patients, 10 hemofiltration patients, 9 continuous ambulatory peritoneal dialysis patients, 7 chronic renal failure predialysis patients, and 14 patients with excellent renal function. The concentration of HCV-RNA particles in patients receiving chronic hemofiltration was significantly lower than that in patients of other groups. Hemofiltration, which is routinely performed at over 150 mm Hg TMP, may be an important key to decreasing HCV-RNA particles by a mechanism such as destruction.

Background. The introduction of novel immunosuppressive drugs has made it possible to achieve dramatic improvement in graft survival rates. In particular, the current immunosuppressive regimen including mycophenolate mofetil (MMF) has yielded excellent results including a nearly 100% 1-year graft survival rate at our institution in 2001. We used enzyme-linked immunosorbent assay (ELISA) to analyze humoral activity after ABO-mismatched renal transplantation using the MMF regimen. Methods. The patient received an ABO-mismatched graft from a living related sibling. Preoperatively, he underwent plasma exchange (PEX) and double-filtration plasmapheresis (DFPP) several times to remove anti-blood type antibodies. Mycophenolate mofetil was used as one of the induction regimens, but a switch was made to other drugs because of persistent gastrointestinal tract discomfort. Mycophenolate mofetil was restarted, however, because of graft dysfunction caused by severe humoral rejection. Humoral activity in this patient was investigated by ELISA during the postoperative follow-up. Results. Anti-blood type antibody immunoglobulin (Ig) M and IgG decreased immediately before the operation because of repeated PEX and DFPP. Both IgM and IgG were postoperatively stable and graft function was excellent. However, after switching from MMF to mizoribine (MZ), renal graft function gradually deteriorated, and the deterioration was associated with elevation of anti-blood type antibody, predominantly IgG. IgM antibody production was parallel to that of IgG, but was weaker. The elevated activity of anti-blood type antibody IgG decreased to the normal level as renal function recovered after MMF was restarted. Conclusions. Anti-blood type antibody IgG decreased after the administration of MMF after ABO-mismatched renal transplantation, and it increased after withdrawal of MMF. MMF seems to affect B-cell populations that produce anti-blood type antibodies after renal transplantation across the blood barrier.

Tacrolimus (TAC) is a useful immunosuppressive agent in the prevention of rejection. However, the blood level between its therapeutic and toxic levels is narrow such that its nephrotoxicity is a problem. Moreover, its bioavailability and pharmakokinetics are highly variable. We experienced a case of acute nephrotoxicity, in which the blood level rose about 10 times above the expected level. We found a peculiar vacuolization in the transplant biopsy specimen. This change showed a marked vacuolization of the tubular cells, suggestive of acute nephrotoxicity by TAC.

Numerous studies have shown that protocol biopsies have predictive power. We retrospectively examined the histologic findings and C4d staining in 89 protocol biopsies from 48 ABO-incompatible (ABO-I) transplant recipients, and compared the results with those of 250 controls from 133 ABO-compatible (ABO-C) transplant recipients given equivalent maintenance immunosuppression. Others have shown that subclinical rejection (borderline and grade I) in ABO-C grafts decreased gradually after transplantation. In our study, however, subclinical rejection in the ABO-I grafts was detected in 10%, 14% and 28% at 1, 3 and 6-12 months, respectively. At 6-12 months, mild tubular atrophy was more common in the ABO-C grafts whereas the incidence of transplant glomerulopathy did not differ between the two groups (ABO-C: 7%; ABO-I: 15%; p = 0.57). In the ABO-I transplants, risk factors for transplant glomerulopathy in univariate analysis were positive panel reactivity (relative risk, 45.0; p < 0.01) and a prior history of antibody-mediated rejection (relative risk, 17.9; p = 0.01). Furthermore, C4d deposition in the peritubular capillaries was detected in 94%, with diffuse staining in 66%. This deposition, however, was not linked to antibody-mediated rejection. We conclude that, in the ABO-I kidney transplantation setting, detection of C4d alone in protocol biopsies might not have any diagnostic or therapeutic relevance.

Several protocols allow the successful ABO incompatible living-related kidney transplantation (ABO-ILKT), yet no single method has emerged as the best. We have made several substantial changes to our ABO-ILKT protocol over the past decade and a half and have attempted to determine whether the changes in immunosuppressive agents have resulted in a better outcome. We used methylprednisolone (MP), cyclosporine (CsA), azathioprine (AZ), antilymphocyte globulin (ALG) and deoxyspergualine (DSG) in the 105 cases of ABO-ILKT (group 1) between 1989 and 1999, and MP, tacrolimus (FK506), mycophenolate mofetil (MMF) in the 117 cases of ABO-ILKT (group 2) between 2000 and 2004. We compared the patient and graft survival rates as well as the incidence rate of acute rejection in these two eras, when different regimens were used. There were significant differences in the 1- and 5-year graft survival rates between groups 1 and 2 (1-year: 78% in group 1 vs. 94% in group 2; 5-year: 73% in group 1 vs. 90% in group 2, p = 0.008). Also, a higher incidence rate of acute rejection was significantly observed in group 1 (50/105, 48%) than in group 2 (18/117, 15%) (p < 0.001). We conclude that the FK/MMF combination regimen provides excellent graft survival results in ABO-ILKT.

Introduction: Subcapsular cortical damage (SCCD) is a characteristic pathological change, which is seen in renal allograft biopsy specimen obtained immediately after laparoscopic donor nephrectomy (LDN). In this study we evaluated the early and late histopathological effect of SCCD examining renal allograft biopsy specimens obtained after kidney transplantation. Materials and methods: Laparoscopic donor nephrectomy was performed on 250 donors between July 2000 and September 2004 in our institution. Allograft biopsy of all 250 kidneys was performed immediately after LDN (zero hour biopsy). Of 250 biopsy specimens, 105 were diagnosed as SCCD and the allograft biopsy specimens obtained from 105 recipients after transplantation were enrolled in this study. All specimens were routinely examined by using light microscopy and immunofluorescence. Results: In 87 patients 256 allograft biopsy specimens did not show post-pathological changes of SCCD. Twenty biopsy specimens obtained from 18 recipients showed tubular necrosis and a partly tubular regeneration and patchy interstitial hemorrhage, which seemed to be caused by SCCD. Ten allograft biopsy specimens from nine recipients demonstrated residual pathologic changes in SCCD early after transplantation. The other 10 specimens from nine recipients had abnormal histopathologic changes including interstitial edema and fibrosis, tubular atrophy and glomerular sclerosis in the subcapsular cortex late after transplantation. Conclusion: The early change of SCCD after transplantation remained intact and partial regeneration and the late showed subcapsular fibrosis with glomerular sclerosis. The incidence of the subcapsular lesions due to SCCD after transplantation was 17% in 105 allografts.

Background: Recently, it has been revealed that alloantigen-independent causes are important factors for late graft loss in kidney transplantation. We compared the results of living kidney transplantation from HLA-identical siblings with those from HLA-non-identical siblings to analyse the impact of alloantigen-independent factors on long-term graft survival. Methods: Two hundred and sixty-six recipients who were grafted from their siblings between 1983 and 2002 were subdivided into those transplanted from HLA-identical donors (n = 86) and those from HLA-non-identical donors (n = 180). Results: The incidence of acute rejection was significantly lower in the HLA-identical group than in the HLA-non-identical group (9.3% vs 53.9%, respectively; P

In this study, we examined the impact of preoperative anti-A/B antibody titers on the results of ABO-incompatible living kidney transplantation (LKT). In all, 167 recipients underwent ABO-incompatible LKT at our institution between 1989 and 2002. These patients were subdivided into those transplanted under cyclosporine with azathioprine or mizoribine (Group 1, n=78) and those transplanted under tacrolimus or mycophenolate mofetil (Group 2, n=89). Overall patient survival at 5 and 10 years was 93.8% and 88.0%, respectively. Overall graft survival at 5 and 10 years was 76.9% and 55.9%, respectively. Graft survival in the patients with anti-A/B IgG titers over 1:128 was significantly lower in group 1, whereas no significant correlation between the anti-A/B IgG titers and graft survival was found in group 2. In conclusion, no correlation between anti-A/B antibody titers and the results of ABO-incompatible LKT was seen after tacrolimus or mycophenolate mofetil application.

We tried to establish the technique of retroperitoneoscopic live donor nephrectomy (RPLDN). Between July 2001 and March 2004, 135 renal transplant donors underwent RPLDN. Low (average: 7 mmHg) CO2 gas pressure was employed during the procedure. All procedures were performed through a three-port retroperitoneal approach without opening the peritoneal cavity. The hand-assisted technique was not used. One hundred and twenty-seven cases were of left and eight cases were of right nephrectomy. Donor nephrectomy was carried out successfully in all patients. In one donor, the procedure was changed to open donor nephrectomy because of severe adhesion around the renal vein due to previous surgery. No serious complications, such as massive bleeding or bowel injury were encountered. Return of bowel function took 0.7 days on average. Post-operative hospital stay was 4.9 days on average, and return to work was 12 days on average. Ureteral complications occurred in 2 patients and were treated with temporally retrograde ureteral stenting. Average serum creatinine levels were 1.5 mg/dL, 1.3 mg/dL and 1.3 mg/dL at 3, 7 and 14 days after transplantation, respectively. No patients required hemodialysis after transplantation due to acute tubular necrosis. RPLDN could be an option for laparoscopic live donor nephrectomy.

Introduction After the introduction of new immunosuppressants, such as tacrolimus and mycophenolate mofetil, we have achieved excellent results for kidney transplantation with a low acute rejection rate. Currently, nonimmunological factors are considered to be the main cause of graft loss for long-term transplant patients. In this study, we analyzed the cause of death with a functioning graft. Patients and methods We performed 1375 cases of living kidney transplantation (LKT) and 219 cases of cadaveric kidney transplantation (CKT) between January 1983 and December 2002. Of these patients, 86 LKT patients and 19 CKT patients died with a functioning graft. Results The mean duration of graft function was 4.8 ± 4.5 years. The incidence of the causes of death were: infection, 24%; stroke, 17%; cardiovascular disease, 16%; malignant disease, 15%; hepatic failure, 11%; gastric ulcer, 4%; and accident/suicide 2%. Five- and 10-year graft survivals for LKT were 80.2 and 62.0%, respectively. The corresponding values for patients (with the exception of the patients who died with a functioning graft) was 83.0% and 66.1%, respectively. The 5- and 10-year graft survival rates for cadaveric kidney transplants were 70.8% and 48.9%, respectively. The corresponding values for patients (with the exception of the patients who died with a functioning graft) were 75.3% and 52.6%, respectively. Conclusion To prevent death with a functioning graft, management of vascular disorders such as stroke and cardiovascular disease, malignant disease, and infectious disease is crucial for kidney transplant patients.

In the present study, we reviewed the effect of post-transplant double filtration plasmapheresis (DFPP) on recurrent focal segmental glomerulosclerosis (FSGS) in the transplanted kidney allograft. Sixteen patients with post-transplant recurrent FSGS were enrolled in this study. Out of 16 patients with recurrent FSGS after transplantation, five did not receive DFPP and lost their grafts, while 11 did receive DFPP and four of these patients lost their grafts. Seven patients were able to maintain normal renal function for an average observation period of 57.1 +/- 40.7 months (range 7-125 months). In five patients who had a significant reduction in urinary protein after DFPP, the urinary protein level decreased from 26.60 +/- 23.05 g/day (range 3.34-62.6 g/day) to 2.95 +/- 3.42 g/day (range 0.02-8.64 g/day) and renal function was maintained. The beneficial effects of DFPP on graft outcome were more likely to occur if the patients experienced a marked drop in urinary excretion. Thus, post-transplant DFPP appears to be effective for reducing urinary protein levels and improving long-term graft survival. With the small numbers in this trial, however, none of the findings were statistically significant. We recommend the use of post-transplant DFPP to prevent the progression of recurrent FSGS.

Background Posttransplant proteinuria and hypertension are difficult to treat after renal transplantation. Therefore, we examined whether candesartan cilexetil is effective in reducing urinary protein excretion or in controlling hypertension in patients with renal allograft dysfunction. Methods Sixty-two renal transplant recipients with proteinuria were enrolled in this study. They underwent kidney transplantation under cyclosporine or tacrolimus immunosuppression between February 1983 and December 1998. Causes of proteinuria were chronic rejection in 28, glomerulonephritis in 16, cyclosporine or tacrolimus nephrotoxicity in 9, and unknown in 9 recipients. The dose of candesartan cilexetil ranged from 4 to 12 mg/day. Eleven patients with proteinuria who had not been treated with candesartan cilexetil constituted a matched control population. Results Hypertension was well controlled by administration of candesartan cilexetil. Both systolic blood pressure and diastolic blood pressure significantly decreased from 141.7+/-14.8 mm Hg to 118.7+/-11.9 mm Hg and 121.2+/-11.6 mm Hg, and from 89.0+/-13.0 mm Hg to 72.0+/-10.4 mm Hg and 74.9+/-9.4 mm Hg, at 2 months and 1 year after administration, respectively. Urinary protein excretion was reduced from 0.93+/-1.2 g/day to 0.34+/-0.7 g/day and 0.43+/-1.2 g/day at 2 months and 1 year after administration, respectively. The levels of creatinine clearance were 55.7+/-28.9 mL/min before treatment, 50.9+/-24.8 mL/min at 2 months, and 52.6+/-24.8 mL/min at 1 year after treatment, respectively. There was no clinically significant difference between them. Regarding the calcineurin inhibitor levels, there was no significant difference between the levels before and 1 year after treatment. There was a significant difference in all examinations (systolic blood pressure, diastolic blood pressure, proteinuria, and renal function) between the patients with and without candesartan at 1 year after treatment. No significant adverse effects occurred. Conclusions Candesartan cilexetil can effectively control hypertension and proteinuria without deterioration in renal allograft function. These data suggest that treatment with candesartan cilexetil may be useful for maintaining long-term renal allograft function.

Based on the long-term experience with ABO-incompatible kidney transplantation, the following can be concluded: 1. Renal transplantation across ABO incompatibility is an acceptable treatment for patients with end-stage renal failure. [table: see text] 2. Long-term patient and graft survival in ABO-incompatible kidney transplantation is influenced primarily by acute rejection episodes occurring within 1 year. 3. Despite the removal of anti-ABO natural antibodies before transplantation, hyperacute rejection crises may occur in some cases. 4. Humoral rejection is the most prominent type of rejection in ABO-incompatible renal transplantation. Even though most of this rejection is controllable with anti-rejection therapy, the prognosis for a graft that undergoes humoral rejection is significantly poor. 5. The maximum IgG titers of anti-A/B antibody before transplantation may have a harmful effect on graft acceptance in ABO-incompatible kidney transplantation. 6. Renal transplantation across ABO incompatibility is principally the most significant risk factor to affect long-term allograft function in ABO-incompatible living kidney transplantation.

Background Most investigations have revealed that the improvement in early graft survival has not resulted in a corresponding improvement in long-term graft survival. The risk factors for long-term graft survival should be clarified. Methods A single-center experience of 1100 consecutive renal transplant recipients who received kidneys from living donors from 1983 to 1998 was reviewed to clarify the time dependency of risk factors for long-term graft survival. We examined various possible risk factors, including HLA-AB and -DR mismatches, ABO-blood group incompatibility, graft weight, donor age and sex, recipient age and sex, and the presence or absence of acute rejection by using the time-dependent, nonproportional Cox's hazards model. Results Acute rejection episode, donor age, HLA-AB 4-antigen mismatches, ABO-incompatible transplantation, smaller kidney weight compared with the patient's body weight (Kw/Bw ratio less than 2.67), and transplantation from an unrelated living donor were risk factors for long-term graft outcome. Multivariate analysis for time-dependent risk factors showed that donor age of more than 60 years was the most important risk factor for long-term graft failure after 5 years posttransplantation (hazard ratio: 2.57). In contrast, acute rejection, ABO incompatibility, and nonrelated donors were significant risk factors for short-term graft failure within 5 years after kidney transplantation (hazard ratios: 2.68, 1.57, and 1.69, respectively). Conclusions Donor age of more than 60 years was a crucial risk factor affecting long-term graft survival. In contrast, acute rejection, ABO incompatibility, and nonrelated donors were significant risk factors for short-term graft failure.