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Biomedical subjects

M Kyo

Publications and source records attributed to M Kyo.

At least 19 recordsLinked to original sources

Retrospective study of the effects of cyclosporine in comparison with azathioprine on renal transplant recipients infected with hepatitis C virus.

A recent report noted that cyclosporine (CsA) inhibits replication of the hepatitis C virus (HCV) in vitro. Thus, CsA may be a superior immunosuppressant for renal transplant recipients infected with HCV. In the present retrospective study, we assessed whether CsA reduced the clinical impact of HCV infection among those patients. A total of 405 renal transplants were performed between 1973 and 2005, of whom we studied 189 who received CsA-based immunosuppression (CsA group) vs 108 who received an azathioprine-based regimen (AZA group). There were 44 HCVAb carriers and 145 noncarriers in the CsA group, and 41 carriers and 67 noncarriers in the AZA group. Our results showed that patient survival rate was significantly worse among HCVAb carriers than among noncarriers, as the overall survival rates were 82.9% and 90.9%, respectively, after 10 years and 71.5% and 85.7%, respectively, after 20 years (P = .0003). Patient survival rates were also significantly worse in HCVAb carriers than in noncarriers in both groups, which were 83.2% and 95.0%, respectively, after 10 years, and 74.7% and 88.8%, respectively, after 20 years (P = .0147) in the CsA group, and 82.9% and 83.6%, respectively, after 10 years and 70.7% and 80.6%, respectively, after 20 years (P = .0171) in the AZA group. Conversely, no significant difference was seen in patient survival rate for HCVAb carriers between the two groups (83.2% vs 82.9% at 10 years, and 74.7% vs 70.7% at 20 years, P = .8195). Our results confirmed that HCV infection has a negative impact on the long-term survival of renal transplant patients who receive either a CsA-based or an AZA-based regimen, suggesting that CsA does not have a positive impact on HCV carriers.

Adult↗

Combined therapy of deoxyspergualin and plasmapheresis: a useful treatment for antibody-mediated acute rejection after kidney transplantation.

Antibody-mediated acute rejection (AbAR) is one of the primary causes of graft impairment in kidney transplant recipients. Deoxyspergualin (DSG), which displays an antiproliferative action against antigen-stimulated B cells inhibiting antibody production, may be effective to rescue AbAR in combination with plasmapheresis by suppressing antibody production and elimination. In the present study, we report our experience with DSG/plasmapheresis therapy for the treatment of AbAR. Five kidney transplant patients experienced a steroid-resistant acute rejection requiring dialysis followed by an AbAR that was confirmed by biopsy and flow cytometry crossmatch (FCXM) results. DSG was administration at 3 mg/kg per day for 10 days with plasmapheresis reduce antidonor antibody. Treatment outcome, effectiveness, and adverse events were examined; in two cases sequential FCXM examinations were performed to evaluate antibody status. All five patients received DSG/plasmapheresis therapy. The number of plasmapheresis treatments ranged from 1 to 9 according to treatment outcomes. Four patients recovered graft function following treatment; whereas one showed no response to the treatment, and the graft was lost. No serious side effects or infections were observed during or after treatment. Monitoring of sequential FCXM correlated with the clinical course. AbAR shows a worse prognosis than cellular rejection. It is refractory to conventional antirejection therapy. In the present study, DSG/plasmapheresis therapy was effective in four of five patients (80%) with AbAR. It may be considered the first choice of treatment for cases of acute humoral rejection.

Acute Disease↗

Sequential blood level monitoring of basiliximab during multisession plasmapheresis in a kidney transplant recipient.

Basiliximab, a chimeric monoclonal antibody against the alpha chain of the interleukin-2 receptor (IL-2R) has been used in renal transplant patients. We monitored sequential blood concentrations of basiliximab in a patient who received a kidney transplant with basiliximab-based immunosuppression together with multiple sessions of plasmapheresis. A 34-year-old man received a living-related kidney transplant with induction immunosuppression including tacrolimus, mycophenolate, methylprednisolone, and basiliximab. Severe antibody-mediated acute rejection lead to a requirement for hemodialysis. Deoxyspergualin was administered for 10 days at a daily dose of 5 mg/kg combined with eight sessions of double filtration plasmapheresis (DFPP). After treatment, the serum creatinine returned to 0.95 mg/dL, and there were no major complications or infections. Sequential basiliximab blood levels of the patient were monitored following transplantation. The serum basiliximab concentration decreased by 72.4% after five consecutive DFPPs, and by 87.6% after eight DFPP sessions. The elimination rate of basiliximab (DeltaBLX) was 6.1% before DFPP, but increased over eight DFPPs to 20.5%. Serum basiliximab concentrations declined to 0.16 microg/mL on day 33, which is below the IL-2R saturation concentration (0.2 microg/mL). Multiple sessions of plasmapheresis using DFPP enhanced the elimination of serum basiliximab at an average elimination rate of 19.1%. In the patient reported on here, the serum basiliximab concentration fell to below the IL-2R saturation level (0.2 microg/mL) within 1 month of living-related kidney transplantation. We recommend that additional basiliximab infusions be considered for cases undergoing more than three plasmapheresis sessions.

Acute Disease↗

Increased expression of renin in chronic allograft nephropathy.

BACKGROUND: Chronic allograft nephropathy (CAN) is the main cause of renal transplant failure in the first decade posttransplant. The precise pathogenetic mechanism for CAN is not completely understood. A possible role of renin-angiotensin system for CAN has been suggested through clinical observations that angiotensin-converting enzyme inhibition and angiotensin II receptor blockers prevent CAN. METHODS: Distribution of renin-positive cells in allograft biopsy specimens was examined immunohistochemically in 23 renal transplant recipients diagnosed with CAN Biopsy specimens obtained from seven recipients with stable renal function were examined as controls. Histologic evaluation was performed based on the Banff 97 classification. RESULTS: Renin-positive cells were found in the juxtaglomerular apparatus (JGA) adjoining the afferent arterioles in both groups. When the number of renin-positive cells in JGA was defined as a renin index, it was significantly higher in the CAN than the control group (P = .007). There was no significant difference in age, interval between transplantation and biopsy, and blood pressure between groups. Only a significantly higher serum creatinine was found in the CAN group. CONCLUSIONS: The increased renin-positive cells in JGA suggest a significant role of the intrarenal renin-angiotensin system activation in the development of CAN.

Adult↗

Risk factors for graft loss in patients with recurrent IGA nephropathy after renal transplantation.

BACKGROUND: The recurrence rate of IgA nephropathy (IgAN) in transplanted kidneys has been reported to be >50%. Although recurrent IgAN has a benign clinical course, recent data suggest that it leads to graft loss in a substantial number of patients. METHODS: We performed a retrospective single-center analysis of 34 renal transplant recipients, with biopsy-proven IgAN as the cause of end-stage renal failure. RESULTS: Renal allograft biopsies were performed in 30 patients, of whom 24 did and 6 did not have biopsy-confirmed recurrent transplant IgAN. Recurrent transplant IgAN was more often detected in men and at later timepoints after post-transplantation. Four patients with recurrent transplant IgAN progressed to graft failure. Progression to graft failure was associated with worsened renal function, higher systolic blood pressure, and the lack of presenation of angiotensin-converting enzyme inhibitors (ACEs) at the time of allograft biopsy. Immunologic factors such as frequency of acute rejection, HLA typing, and immunosuppression did not show a relation to recurrence or graft loss. CONCLUSIONS: Recurrent transplant IgAN increased with long-term graft survival and risk factors for graft loss due to recurrent IgAN were similar to those among IgAN in native kidneys.

Adult↗

Comparison of histopathological characteristics of allograft biopsy between responder and non-responder to antiproteinuric effect of angiotensin-converting enzyme inhibitor (ACEI).

Angiotensin-converting enzyme inhibitor (ACEI) has become recognized as agents that have renoprotective effects in the treatment of progressive renal diseases including post-transplant kidneys. Previously we demonstrated the safety and effectiveness of ACEI treatment on the hypertensive proteinuric post-transplant patients (N = 10) who had been followed up for 12 months. However, not all patients show good response in urinary protein reduction. We aimed to analyse the histopathological factor(s) affecting the responsiveness of proteinuria to ACEI treatment. Fourteen post-transplant patients with proteinuria who were treated with ACEI and underwent allograft biopsy were analysed. Eight patients showed 50% or more reduction in proteinuria (responder). The other 6 patients showed less (< 50%) reduction in proteinuria (non-responder). There was no difference in clinical characteristics (BP, renal function, donor age, recipient body mass index), dietary sodium or protein intake, and diuretic use between the two groups. As a histopathological characteristic, glomerular size in responder group was significantly larger than that in non-responder group. This suggests that the large glomerular size at least partly contributes to the responsiveness in urinary protein reduction to ACEI treatment in kidney allograft recipients with proteinuria.

Adult↗

The differences between late graft loss group and long-term graft survival group in renal transplantation.

In renal transplantation, the long-term graft survival rate has not been improved. Until now, the differences between late graft loss and long-term graft survival have still not been estimated thoroughly. We have attempted to define clinical risk factors and parameters for late graft loss by comparing the differences in these two groups. Data from the Osaka University Database were assessed on 156 renal allografts during a 7-yr period. Thirty-six patients comprised the late graft loss group (patients in this group had graft function without need for dialysis for more than 3 yr post-transplantation, afterwards lost the allograft: 'loss group'). One hundred and twenty patients comprised the long-term graft survival group (patients in this group had graft function without need for dialysis until 31 December 1999: 'survival group'). Various immunological and non-immunological parameters were included in an univariate regression analysis. This analysis showed that donor age (P < 0.01), HLA mismatch number (P < 0.01) and a repeat of acute rejection (P < 0.01) were significant factors. Serum creatinine levels at 3 months (P = 0.01), proteinuria at 1 yr (P < 0.01) and antihypertensive treatment at 2 yr (P = 0.03) after transplantation were predictive of the risk of late graft loss. CsA trough concentration at 3-6 months (P < 0.05) and body mass index increase at 1 yr (P = 0.046) were elevated in the loss group. These results from a single centre suggest that immunological as well as non-immunological factors are associated with the pathogenesis of late graft loss.

Adult↗

A case of tacrolimus nephrotoxicity appearing in a second renal transplantation patient.

We experienced a case of a second renal transplantation patient. With the use of cyclosporin, he lost his first graft because of chronic rejection; with the use of tacrolimus, his second graft suffered from drug nephrotoxicity. On his second renal transplantation, his graft function deteriorated and required haemodialysis with the use of tacrolimus. Repeated biopsies did not reveal the typical characteristics of acute tacrolimus nephrotoxicity and acute rejection. His tacrolimus trough level was not high during the clinical course; however, by reducing tacrolimus dosage, his graft function eventually recovered to mild renal dysfunction. This observation was helpful for clinical diagnosis of the functional toxicity of tacrolimus. The case is interesting in considering the functional toxicity of tacrolimus and the difference between tacrolimus and cyclosporin in terms of immunosuppressive and nephrotoxic actions.

Biopsy↗

Chronic cyclosporin-induced nephropathy.

AIMS: There is still no consensus about the prognostic influence of chronic nephropathy induced by low-dose maintenance therapy with cyclosporin. Our aim was to investigate the prognostic effect of cyclosporin nephropathy in Japanese renal transplant recipients. MATERIAL: We retrospectively investigated the clinical records of 1,323 kidney transplant recipients who received cyclosporin at 65 institutions in Japan from 1982 to 1991. METHOD: Renal biopsy was performed in 461 patients. RESULTS: At 5 years and 9 years after transplantation, the patients who had cyclosporin nephropathy associated with immunological rejection, glomerulonephritis, or both showed a significantly worse prognosis than those with cyclosporin nephropathy alone (p < 0.01). There was no significant difference in the loss of renal function at 9 years after transplantation between patients showing no abnormalities and patients with cyclosporin nephropathy alone. Even when cyclosporin nephropathy was absent, the long-term prognosis was unfavorable in recipients with immunological rejection or glomerulonephritis. CONCLUSIONS: These results suggest that cyclosporin nephropathy does not influence the prognosis of renal transplantation in patients on low-dose maintenance therapy with cyclosporin.

Chronic Disease↗

Clinicopathological evaluation in non-episode biopsies of renal transplant allograft.

Histopathological findings in renal allograft with stable function remain unclear. We therefore performed non-episode biopsy in the long-surviving renal allograft to investigate the histopathological changes. Our data show that, although arteriolopathy is characteristic of drug-induced nephropathy, it is unrelated to dosage and concentration of cyclosporine or tacrolimus in non-episode biopsy. We evaluated therefore the clinicopathological findings of arteriolopathy in this study. Non-episode biopsy was defined as follows: as serum creatinine level lower than, 2.0 mg/dl and a urinary protein level lower than 500 mg/day. A total of 65 biopsy specimens were enrolled in this study as non-episode biopsy. Twenty-nine specimens revealed arteriolopathy. There were no statistically significant differences between arteriolopathy and dosage or concentration of cyclosporine or tacrolimus. Arteriolopathy in non-episode biopsy was related to time of biopsy, kidney age, hypertension, and hyperlipidemia, suggesting that it is important for graft survival to strictly control blood pressure and blood lipid level.

Adult↗

Factors influencing vertebral bone density after renal transplantation.

To improve our understanding of the mechanisms underlying osteoporosis following renal transplantation, we compared bone mineral density (BMD) in 158 transplant recipients and in 293 patients undergoing maintenance hemodialysis with age- and sex-matched normal controls. Observations in graft recipients were made up to several years following transplantation. Dual-energy X-ray absorptiometry was used to measure BMD. Correlations with clinical variables including serum concentration of parathyroid hormone (PTH) and steroid therapy were evaluated. Lumbar BMD was lower in transplant patients than in dialysis patients at all ages, and continued to decrease with increasing interval posttransplant until the second year after transplantation. Persistent hyperparathyroidism and daily prednisolone dosage were both associated with decreased BMD. Age and creatinine clearance were independent long-term predictors of BMD by multiple regression analysis. Treatment of renal graft recipients with calcium and vitamin D supplements or calcitonin may be indicated in the early months after transplantation.

Absorptiometry, Photon↗

Arteriolopathy in non-episode biopsies of renal transplant allograft.

PURPOSE: We have been performing protocol biopsies since 1995 to predict the outcome of renal allograft. However, histopathological findings in renal allograft with stable function remain unclear. For this reason, we performed non-episode biopsy on long-surviving renal allograft and investigated the histopathological changes. Among the several diseases seen in non-episode biopsies, arteriolopathy, such as drug-induced nephropathy, is one of the most frequent diseases. However, it is unrelated to the dosage and the concentration of cyclosporine or tacrolimus. Consequently, we evaluated the clinicopathological findings of arteriolopathy in this study in order to clarify whether cyclosporine (CsA) or tacrolimus (FK506) is responsible for these findings. MATERIALS AND METHODS: We defined non-episode biopsy as a case with a serum creatinine level less than 2.0 mg/dL and containing less than 500 mg/dL of urinary protein. Final results showed that 71 cases were identified as non-episode biopsy. We then evaluated the histopathological findings and the clinical characteristics of these cases. RESULTS: Thirty-two of the 71 non-episode biopsy specimens showed findings of arteriolopathy. The frequency and the severity of arteriolopathy are not concerned with dosage and concentration of CsA or FK506. The arteriolopathy seen in non-episode biopsy was related to the time of the biopsy and the kidney age. Arteriolopathy in nonepisode biopsy also had a relationship with hypertension, suggesting that it is important to strictly control blood pressure for graft survival.

Adult↗

A case of relapse of C-ANCA-associated glomerulonephritis in post-transplant patients.

We experienced a case of relapse of proteinase 3-specific antineutrophil cytoplasmic autoantibody (C-ANCA)-associated rapid progressive glomerulonephritis (RPGN) in a patient after renal transplantation. A 19-yr-old man, who underwent a living donor kidney transplantation, presented a rapid renal function deterioration along with a sign of infection. Initially he was treated as acute rejection, but renal function did not improve. Renal biopsy revealed crescentic glomerulonephritis, and C-ANCA titer was 12 EU/mL, resulting in the diagnosis of C-ANCA-associated RPGN. He was treated with three consecutive methylprednisolone pulses twice in addition to the basal immunosuppressive medications (cyclosporine A and mizoribine), then his renal function improved to normal. Bearing the possibility of recurrence of glomerulonephritis in mind, we re-evaluated the nature and disease course of renal failure of original kidney. He experienced a rapid deterioration of renal function in 1992, and eventually CAPD was started in 1992. His serum in 1992 revealed high titer of C-ANCA (24 EU/mL), and renal biopsy performed in 1992 showed a crescentic glomerulonephritis. Taken together, we diagnosed this event as a relapse of C-ANCA-associated GN. Lessons from our experience are: 1) steroid pulse and high-dose corticosteroid therapy may be useful for the treatment of relapse of C-ANCA-associated GN patients after renal transplantation; 2) the possibility of a relapse of C-ANCA-associated GN following renal transplantation has to be kept in mind, especially when infection precedes the deterioration of allograft kidney function.

Adult↗

Comparative study of transurethral laser prostatectomy versus transurethral electroresection for benign prostatic hyperplasia.

BACKGROUND: Transurethral resection of the prostate (TURP) is the gold standard treatment for benign prostatic hyperplasia (BPH). Recently, less invasive transurethral laser prostatectomy, such as visual laser ablation (VLAP) or interstitial laser coagulation (ILCP), have been developed. Herein, we investigated the efficacy of VLAP and ILCP compared to TURP. METHODS: A total of 80 patients with BPH were treated: 20 patients by VLAP, 30 patients by ILCP and 30 patients by TURP. All patients were followed up for 12 months after their operations. Treatment outcomes were evaluated by four different criteria: (i) the International Prostatic Symptom Score (I-PSS), (ii) the maximum flow rate (Qmax), (iii) postvoided residual urine volume before treatment and one, three, six and 12 months after treatment, and (iv) prostatic volume before operation and three and six months postoperatively. RESULTS: The I-PSS, Qmax and residual urine volume were significantly improved compared to baseline levels and the improvement continued for 12 months in the three groups: for I-PSS (P<0.001 in the VLAP group and P<0.0001 in the ILCP and TURP groups), Qmax (P<0.001 in the VLAP and ILCP groups, and P<0.0001 in the TURP group), residual urine volume (P<0.01 in the VLAP group and P<0.0001 in the ILCP and TURP groups). Significant reduction of the prostatic volume was recorded only in the ILCP and TURP groups (P<0.001). CONCLUSION: Visual laser ablation and ILCP can be good alternative treatments for BPH. Visual laser ablation provides good outcomes in patients with small-sized BPH and with risk factors such as heart disease or anticoagulation therapy.

Aged↗

A clinicopathological study of IgA nephropathy in renal transplant recipients: beneficial effect of angiotensin-converting enzyme inhibitor.

BACKGROUND: Prolonging the survival of transplant kidneys is a major task of modern nephrology. It has recently been shown that deteriorating renal function and substantial graft loss were observed in 55% of renal allograft recipients with recurrent IgA nephropathy (IgAN) at long-term follow-up. To gain a useful insight into the therapeutic approach towards protecting allograft kidneys from deteriorating graft function, we compared the histological characteristics of post-transplant IgAN to primary IgAN and investigated the effects of an ACE inhibitor. METHODS: Twenty-one patients with post-transplant IgAN and 63 patients with primary IgAN were included in the histopathological study. The effectiveness of angiotensin-converting enzyme (ACE) inhibitor treatment in post-transplant IgAN was also studied in 10 patients. RESULTS: The prevalence of glomeruli with adhesions and/or cellular crescents in primary IgAN was significantly greater than in post-transplant IgAN (P<0.05), but the proportion of glomeruli with segmental sclerosis was similar in both groups. The rate of global obsolescence, and the degree of interstitial fibrosis in post-transplant IgAN were significantly greater than in primary IgAN (P<0.05). The degree of glomerular obsolescence and the severity of interstitial fibrosis correlated with the severity of glomerular lesion in primary IgAN, but not in post-transplant IgAN. In primary IgAN, glomerular diameter significantly correlated with the proportions of glomerular obsolescence, but not in post-transplant IgAN, suggesting that allograft kidneys may be in a hyperfiltration state. Both the blood pressure and the urinary protein excretion significantly improved after ACE-inhibitor treatment (P<0.001). CONCLUSION: In post-transplant IgAN, histopathological lesions indicative of acute inflammatory insults were suppressed, and glomerular hypertrophy, which may relate to haemodynamic burden such as hyperfiltration, was prominent. Preliminary study of ACE-inhibitor treatment in 10 patients showed favourable effects. A future long-term follow-up study is required to establish the effectiveness of ACE inhibitors in treatment of post-transplant IgAN.

Adult↗

Cloning of cDNA encoding NtEPc, a marker protein for the embryogenic dedifferentiation of immature tobacco pollen grains cultured in vitro.

We partially purified three Nicotiana tabacum L. embryogenic pollen-abundant phosphoproteins (NtEPa to c) which appeared in the cells undergoing a dedifferentiation process from immature pollen grains to embryogenic cells, caused by glutamine-deficiency in vitro. All the NtEPs had a highly conserved N-terminal amino acid sequence. Using degenerate oligonucleotide probes designed from the amino acid sequences, the cDNA for NtEPc was isolated from a cDNA library of pollen cultured in glutamine-free medium The cDNA sequence showed moderate homology with several type-1 copper-binding glycoproteins and with a kind of early nodulin though its function could not be predicted. Expression analysis revealed that the level of mRNA for NtEPc was high during the dedifferentiation and also in the very early period of pollen embryogenesis but it was low in the developmental process of microspores/pollen in anthers, in the in vitro maturation process and both in the stational and logarithmic growth phases of tobacco BY-2 cells. Furthermore, an acidic medium pH, which promoted the induction of dedifferentiation increased the level of mRNA for NtEPc, whereas the presence of 6-benzylaminopurine, which inhibited it, decreased the level. These results suggest that the expression of NtEPc gene is correlated with the dedifferentiation but not with pollen development or cell division.

Amino Acid Sequence↗