Kiyohide Toki

Early induction of apoptosis in androgen‐independent prostate cancer cell line by FTY720 requires caspase‐3 activation

We previously reported that FTY720, a metabolite from Isaria sinclairii, induced some cancer cells to undergo apoptosis, and that FTY720‐induced apoptosis was not related to Fas‐antigens. In this study we investigated whether FTY720 was able to induce apoptosis in an androgen‐independent prostate cancer cell line, DU145, which is not only resistant to androgen‐withdrawal‐induced apoptosis but also Fas‐ and TNF‐α‐mediated apoptosis.

Factors influencing vertebral bone density after renal transplantation

Abstract 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.

Long term efficacy of simvastatin in renal transplant recipients treated with cyclosporine or tacrolimus

Abstract:  Background:  Hyperlipidemia is frequently developed following renal transplantation and results in worsening of the patients prognosis.

Perineal epidermal cyst

This paper presents a case of perineal epidermal cyst. Diagnostic imagings by ultrasonography, CT scanning and MR imaging described the mass as a cystic tumor on the perineal median raphe. It was excised for the histological diagnosis. The removed mass was shown microscopically to be filled with laminated keratin and to be lined with differentiated cornified squamous epithelium. The pathological diagnosis was benign perineal epidermal cyst.

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.

Acute renal allograft rejection in the canine: evaluation with serial duplex Doppler ultrasonography

MANY STUDIES have documented the utility of duplex Doppler ultrasonography (US) in evaluating vascular flow in human renal allografts. The increase in the resistive index (RI) and the pulsatility index (PI) can measure the increased arterial blood flow resistance as a result of rejection. A recent clinical study reported that the serial investigation technique of PI allows better recognition of rejection episodes than the single measurement of RI or PI. However, the cause of arterial blood flow resistance is still unclear, as serial biopsies of renal allograft are impossible in clinical cases. Recent advance of Doppler US, especially the new technique called “power Doppler imaging”, has made it possible to detect the slow blood flow. As the power Doppler imaging displays the total integrated Doppler power, the subtle change of renal perfusion can be detected by the imaging. In this study, we used a commercially available power Doppler unit. This high performance US unit allows us to assess the interlobular vasculature of renal allografts in the canine. This study was undertaken to correlate the duplex Doppler US and the histopathology with serial duplex Doppler examination using power Doppler US unit and biopsies in a canine acute renal rejection model.

Morphological findings in non‐episode biopsies of kidney transplant allografts treated with FK506 or cyclosporine

Abstract We conducted an analysis of biopsy specimens of non‐episode renal allografts from patients treated with tacrolimus (FK506) or cyclosporine (CsA) to evaluate chronic drug‐induced nephropathy in stable allografts. A total of 38 biopsy specimens from stable functioning renal allografts were examined. The patients had been treated with FK506 (n= 16) or CsA (n= 18) as main immunosuppressant for 0.3 to 7.4 years. Of the 38 biopsy specimens, 15 showed mild drug‐induced arteriolopathy (hyalinosis or insudative change of arterioles and small arteries) with stripeD‐form interstitial fibrosis, 10 showed minimum interstitial cellular infiltration (borderline rejection), 2 showed IgA nephropathy, 4 showed evidence of chronic rejection (transplant nephropathy) and 12 showed no abnormal findings. Of 34 renal allograft biopsy specimens with stable function, 22 (65 %) showed pathological evidence of drug‐induced nephropathy. There were no significant qualitative or quantitative differences between FK506‐ and CsA‐associated nephropathy.

Differential diagnosis of kidney transplant rejection and cyclosporin/tacrolimus nephropathy using urine cytology

Abstract: A total of 9000 urine samples from 69 kidney transplant recipients were studied for differential diagnoses of transplant rejection and cyclosporin/tacrolimus toxicity. New–Sternheimer and Papanicolaou staining were used to differentiate cells in urine. We also employed an immunocytochemical technique for further identification of exfoliated cells. With New–Sternheimer and Papanicolaou staining, the predominance of proximal tubular cells was useful to differentiate cyclosporin/tacrolimus toxicity from acute rejection in cases of increased serum creatinine level. During rejection episodes, an increased number of mononuclear cells and renal epithelial cells were found. Immunocytochemical analysis showed a significant increase of CD2‐, CD4‐ CD8‐, CD25‐ and HLA‐DR‐positive cells with rejection. However, there was no relationship between Banff criteria rejection grade and the increase of mononuclear cells.

Clinocopathological evaluation in non-episode biopsies of renal transplant allograft

Abstract 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.

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

Tanaka T, Takahara S, Hatori M, Toki K, Wang J‐D, Permpongkosol S, Yazawa K, Kokado Y, Oka K, Kyo M, Okuyama A, Yamanaka H. The differences between late graft loss group and long‐term graft survival group in renal transplantation. Clin Transplantation 2001: 15 (Supplement 5): 16–21. ©Munksgaard, 2001