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A 21-yr-old man of blood type O receiving hemodialysis for IgA nephropathy underwent living-related ABO-incompatible (ABOI) renal transplantation from his mother, whose blood type is A. He was negative for flow cross-match, anti-human leukocyte antigen (HLA) antibody, and anti-MICA antibody. Pre-treatment anti-A IgG titer was 1:256. Desensitization consisted of tacrolimus, mycophenolate mofetil, methylprednisolone, rituximab, and plasmapheresis. He developed acute antibody rejection at day 2 post-transplant, which was successfully treated. After renal artery reconstruction surgery at day 91 for renovascular hypertension caused by renal artery stricture, the patient suffered from acute prostatitis, which subsequently induced type III acute antibody-mediated rejection. Even after recovery from the rejection after temporary hemodialysis, graft function progressively deteriorated and consecutive allograft biopsy showed progressive thrombotic microangiopathy (TMA) without any evidence of donor-specific antibody other than anti-A antibody. The tacrolimus dose was kept low for fear of tacrolimus-induced TMA. Despite these efforts, the patient resumed hemodialysis six months' post-transplant., (© 2011 John Wiley & Sons A/S.)

Objectives: Steroids have been a gold-standard drug of immunosuppressive regimens in kidney transplantation. Steroid minimization protocols have been applied to minimize the adverse effects of steroids. We have evaluated the short-term outcomes of our early steroid discontinuation regimen., Methods: A total of 128 recipients who received kidney from ABO-compatible, flow crossmatch-negative living-related donors were included in this study. Immunosuppressive regimens consisted of tacrolimus (TAC), mycophenolate mofetil (MMF), and basiliximab. In a cohort of recipients, designated as a steroid early discontinuation (ESD) group, only three doses of methylprednisolone (MP) were given (500, 250, 125 mg). In the other cohort of recipients, designated as a chronic steroid (CS) group, MP was given chronically, being tapered to 4 mg at one month post-transplant. TAC and mycophenolic acid (MPA) blood levels were monitored. The following data were retrospectively compared between the two groups at 1, 3, 6, 9, 12 months post-transplant: serum creatinine (sCr), urine protein per gCr (uP/Cr), the incidence of biopsy-proven acute rejection (BPAR), graft survival (GS), area-under-the-curve of blood levels of tacrolimus (TAC-AUC(0-12), ng h/mL) and mycophenolic acid (MPA-AUC(0-12), mug h/mL), MMF dose (mg), the incidence of opportunistic infection, post-transplant diabetes mellitus (PTDM), and histopathologic findings of protocol biopsy according to the Banff '07 classification., Results: sCr and uP/Cr were comparable between the two groups up to 12 months except for sCr at one month (ESD group > CS group). TAC-AUC(0-12) was significantly higher in ESD group at one month but was equivalent thereafter, while the prevalence of biopsy-proven tubulotoxicity was not different. MMF dose was comparable throughout the period between two groups. The incidence of BPAR until 12 months was equivalent. Of note, 60% of BPAR cases in ESD group occurred within one month. Prevalence of opportunistic infection or PTDM was equivalent. Graft survival was 100% in both groups. The following histopathologic scores up to 12 months were also equivalent: t, i, g, v, ci, ct, cg, cv, mm, ah, and ptc., Conclusions: Favorable short-term outcomes were achieved both clinically and histologically using our early steroid discontinuation protocol compared with the conventional protocol with chronic steroid treatment.

Objective: To investigate lower urinary tract symptoms (LUTS) and their impact on quality of life (QOL) in patients having undergone renal transplantation (RTX)., Methods: Forty-three patients (25 males and 18 females; age 20-68 years) undergoing RTX at Hokkaido University Hospital were included in this study. Median follow-up after RTX was 41 months (range 6-184). Pre-transplant dialysis had been carried out in 38 patients (median: 4.3 years, range: 1 month-31 years). All patients were assessed by uroflowmetry (UFM), postvoid residual urine volume (PVR), 24 h bladder diary, and International Prostate Symptom Score (IPSS). QOL score and King's Health Questionnaire (KHQ) were used for the assessment of LUTS-related QOL., Results: Mean fluid intake volume and urine output volume for 24 h were 2136 mL (1150-3430 mL) and 2446 mL (1336-4733 mL), respectively. Voiding dysfunction assessed by UFM and PVR was observed in 12 patients (28%) showing higher IPSS. QOL score and overall QOL in KHQ were not different between patients with and without voiding dysfunction. Although 19 (49%) had polyuria, 20 (51%) had nocturnal polyuria, which affected nocturia in IPSS as well as sleep/energy disturbances in KHQ compared with patients without nocturnal polyuria., Conclusions: Patients having RTX frequently present voiding dysfunction and nocturia basically caused by nocturnal polyuria. We should focus on LUTS in these patients to provide an appropriate management.

The aim of the current study was to evaluate long-term outcomes of pediatric live kidney transplantation in patients with genitourinary anomalies relative to those with primary kidney diseases. The study included 35 pediatric patients who received a live kidney transplantation during the last 25 yr (28 males, six females). Median age at the time of transplantation was nine yr (range 1-15 yr), and the median follow-up period was 151 months (range 6-239 month). The patients were divided into two groups. The urological group (n = 14) included patients with primary obstructive/reflux nephropathy. The renal group (n = 20) included patients with primary renal disorders. Differences between groups in graft survival, clinical course, and final graft function were evaluated. Original diseases represented in the urological group included five cases with primary VUR and eight cases with secondary VUR. Diseases in the renal group included eight cases with bilateral hypo-dysplastic kidney, three cases with focal/segmental glomerular sclerosis, two cases with membranous proliferative glomerulonephritis, two cases with congenital nephrotic syndrome and five cases with other forms of chronic nephritis. Ten of 14 cases in the urological group, relative to six of 20 in the renal group, were preemptive. Median age at transplantation was 7.5 or 10 yr old, respectively, in the urological or renal group. Twelve kidney recipients in the urological group had also undergone other urinary surgeries, including upper urinary tract drainage, ureteroneocystostomy, augmentation cystoplasty, endoscopic incision of posterior-urethral valve, urethroplasty, etc. Cumulative post-operative complications occurred in nine or 16, respectively, in the urological or renal group. The acute rejection free and overall graft survival were similar in both groups. One patient in the urological group lost his graft while six patients in the renal group lost their grafts. Thus, the post-transplant clinical outcome of pediatric transplantation in patients with urological anomalies is comparable to that of recipients with primary renal disease. Appropriate urinary tract reconstruction and management is essential to reduce the risk of graft dysfunction because of urinary problems.

Deep venous thrombosis (DVT) possibly occurs in the perioperative period, and induces serious complications such as a pulmonary embolism. On the other hand, allograft renal vein thrombosis leads to a high incidence of graft loss. We experienced a case in which a serious DVT occurred prior to renal transplantation; however, a successful renal transplantation in the right iliac fossa was performed after 2 years of anticoagulant therapy. It is suggested that the external iliac vein even after suffering from DVT can be anastomosed to an allograft vein successfully, when enough blood fl ow or a lower venous pressure is confirmed. However, one should be aware of the risk factors and the adequate management of thrombosis in renal transplantation because of the serious complications of DVT and the poor prognosis of allograft vein thrombosis.

To establish guidelines for avoiding the side effects of mycophenolate mofetil (MMF) in renal transplant recipients with tacrolimus (TAC)-based immunosuppression, the relationship between the daily dose of MMF and the occurrence of side effects was analyzed in this study. The frequency of side effects was investigated retrospectively in 28 renal transplant recipients treated with immunosuppression (men 14 : women 14, age: 33.0+/-12.4 years, weight: 50.9+/-10.7 kg). Cytomegalovirus (CMV) infection and diarrhea were the most frequent side effects in the early transplant phase (from transplantation to 3-month biopsy) in the recipients. In 18 recipients, excluding the recipients with risk factors for CMV infection (ABO-incompatible transplantation, donor (+)/recipient (-) CMV serostatus, etc.), no significant correlation was shown between the daily dose of MMF and the occurrence of CMV infection in the two-sample t-test. On the other hand, the daily dose in the diarrhea group (33.2+/-4.3 mg/kg/day, n = 5) was significantly higher than that in the no-diarrhea group at 30 days (28.4+/-3.7 mg/kg/day, n = 23, p < 0.05) and 90 days (25.7+/-4.4 mg/kg/day, n = 21, p < 0.005) after transplantation, respectively. The receiver-operating characteristic (ROC) curve also revealed that the risk of diarrhea increased with a daily MMF dose higher than 30 mg/kg/day. In conclusion, to decrease the risk of diarrhea in the early transplant phase in renal transplant recipients with TAC-based immunosuppression, the daily dose of MMF should not be more than 30 mg/kg/day.

Objectives: Cyclosporine (CSA) and tacrolimus (TAC) frequently induce nephrotoxicity and similar pathologic changes. Acute CSA-induced nephrotoxicity has been reported to be mediated by activation of vasoconstrictors such as endothelin. The purpose of the present study was to investigate the acute effects of TAC and CSA on the renal microcirculation and upon a vasodilator such as nitric oxide (NO) production., Methods: Renal blood flow (RBF) in the microcirculation was measured by a Laser Doppler flow meter in uninephrectomised rats. RBF, mean arterial pressure (MAP), and renal vascular resistance (RVR) were measured in the following groups: (a) TAC (0.1 to 2.0 mg/kg/h, n = 3 approximately 6); CSA (20 and 50 mg/kg/h, n = 5); (b) L-NAME (10 mg/kg), an NO synthase inhibitor, 8 minutes prior to TAC (0.5 and 1.5 mg/kg/h, n = 5), or CSA (20 and 50 mg/kg/h, n = 5). Stable NO end-products, serum NO(2) and NO(3), were measured by the Griess method (n = 5)., Results: None of the parameters were changed by TAC alone, whereas TAC with L-NAME significantly reduced RBF (-28 +/- 7%) and increased RVR (46 +/- 17%) in a dose-dependent manner. CSA alone significantly reduced RBF (-37 +/- 6%) and increased RVR (69 +/- 22%) without any changes in MAP. The effects of CSA were enhanced by L-NAME. Serum concentration of NO(2) + NO(3) was significantly reduced by both L-NAME alone and CSA (50 mg/kg) (P < .05), while there were no changes with TAC (1.5 mg/kg)., Conclusions: Blockade of NO production enhance the vasoconstrictive effect of CSA, and unmasked such an effect of TAC. These results suggest that the nephrotoxicity of CSA and TAC may involve the NO system.

A 58-year-old woman, who had been suffering from chronic renal failure on hemodialysis since 1999, underwent living renal transplantation on January 14, 2003. The donor was her husband, and his left kidney was resected by a hand-assisted retroperitoneoscopic technique. Vascular clamps were removed after vascular anastomoses, but the color of two-thirds of the graft back side was dark, and urine excretion was not observed for 1 hour. The intimal dissection of the graft artery developed false lumen that occluded the blood flow to the transplanted kidney. The graft was resected from the recipient, and an angioplasty was performed for the false lumen of the graft artery after the second cold preservation. The graft with repaired artery was re-transplanted, and urine excretion was observed immediately after operation. Total ischemia time was 5 hours. Clinicopathological acute rejection episode and stenosis of graft artery did not occur for 6 months after operation. The intimal dissection of graft artery might occur at the time of catheterization on the perfusion for cold preservation and/or vascular anastomosis.

Post-transplant lymphoproliferative disorder (PTLD) is a well-known complication of organ transplantation. Plasmacytic hyperplasia (PH) is thought of as the mildest form of PTLD; however, a graftectomy is necessary in most situations. We experienced an interesting case of PH arising in a kidney allograft, which could be relieved with a reduction in immunosuppression. A 27-year-old female underwent a living-related kidney transplantation. A 3-month non-episode protocol biopsy unexpectedly showed the devastating appearance of polymorphic plasma cell infiltration into the graft intersitium, compatible with PH. The PH was located in the graft by radiographic examinations. The infiltration of plasma cell disappeared completely on the 6-month graft biopsy specimen following immunosuppression reduction and the graft is functioning, although it was damaged by a subsequent acute rejection. Our present case indicates that some PTLD can be completely cured with a reduction in immunosuppression alone. The diagnostic modality for the evaluation of PTLD cell extinction is necessary to maintain graft function with adequate immunosuppression thereafter.

The circadian variation of clinical pharmacokinetics of tacrolimus was studied using 16 adult renal transplant recipients 1 month after the operation. The recipients were administered tacrolimus twice a day (9 a.m. and 9 p.m.), and whole-blood samples were obtained just prior to and 1, 2, 3, 6, 9, and 12 hours after oral administration. Histological specimens of transplant kidney were collected by an allograft core biopsy on day 28 after the transplantation. There were no circadian changes in the area under the concentration-time curve (AUC0-12) (214 ng.h/mL during daytime vs. 223 ng.h/mL during nighttime) resulting from morning and night doses. A slight delay in mean residence time (MRT0-12) and time to the peak concentration (tmax) was found after night doses, but there was no statistical significance. Three patients (18.8%) had a clinical acute rejection (AR) episode 4 to 6 weeks after transplantation, and AUC0-12 at nighttime was significantly lower (18.4% on average) in patients with AR in comparison to those without AR. There was no statistical significance in maximum concentration (Cmax) or morning/night trough levels between patients with and without AR. In regard to the correlation between tacrolimus concentrations in each sampling time and AUC0-12, the morning trough concentrations were less predictable for daytime AUC0-12 (r2 = 0.125), but there was a weak correlation to nighttime AUC0-12 (r2 = 0.424). Tacrolimus concentrations at 2, 3, and 6 hours after the morning dose (C2, C3, and C6) had a good correlation against daytime AUC. The results of this study indicate that the variance on the clinical pharmacokinetics of tacrolimus between daytime and nighttime in renal transplant patients is not significant, while the lower nighttime AUC corresponded to the occurrence of AR.

Purpose: Laparoscopic nephrectomy is being employed in renal transplantation because of its minimal invasiveness, and several modifications in surgical procedures have been proposed. We devised a new technique of retroperitoneoscopic hand-assisted nephrectomy (RHAN) for live donor. We report the early experiences with this technique in 5 cases of live renal graft donor. TECHNIQUES AND SUBJECTS: The donors are placed in a modified decubitus position under general anesthesia, and all the laparoscopic surgical procedures were performed retroperitoneally using 3 port sites and a sealing device (LAP DISC) under a pressure of 10 mmHg. The LAP DISC is placed through a para-rectus abdominal skin incision of approximately 8 cm in length into the retroperitoneal cavity and used as a rout for instrumental as well as hand-assisted manipulations during the surgery. The hand-assistance through the LAP DISC made the surgical manipulation considerably easier and allowed the immediate removal of the graft after the interruption of the renal blood flow. This procedure was applied to 5 subjects, 4 in the left and one in the right kidney., Results: The operating data were 264-359 min for operating time, 0.9-3.9 min for warm ischemic time and 40-755 ml for intra-operative blood loss, respectively. The serum creatinine level of the recipients at day 7 was 0.9-2.7 mg/dl. These values, except for operating time, were at the same range as those of the open live donor nephrectomy in our clinic. The 5 donors discharged 7-9 days after RHAN without any surgical complications., Conclusion: Our technique of RHAN will be a minimal invasive one in terms of both for the donors and the grafts, and be widely acceptable for donor nephrectomy on either side.

Background: The circadian variation of clinical pharmacokinetics of tacrolimus in kidney transplant recipients receiving continuous intravenous administration has not been clarified. The aim of this study was to evaluate the circadian variation of this drug in continuous intravenous administration, with regard to the dosing scheme for conversion from intravenous to oral therapy., Methods: The blood concentration-time curve was studied in 10 living-related kidney transplant recipients, aged 18-51 years (mean, 36.5 years), 1 day before operation for preoperative oral administration, the third postoperative day for continuous intravenous administration and the sixth postoperative day at the conversion from intravenous to oral therapy., Results: Although the total body clearance of daytime was slightly higher than that of night-time, the intravenous tacrolimus infusion maintained an adequate therapeutic blood concentration for 24 h. There were significant differences between the preoperative and the postoperative state in the area under the curve, total body clearance and bioavailability for the oral administration. The mean absolute bioavailability was 17.7% in preoperative and 11.1% in postoperative state, respectively and a large interindividual variation was confirmed in this parameter, which was 7.0-27.2% for preoperative and 6.4-22.0% for postoperative area under the curve, respectively., Conclusion: This study proposes that intravenous administration is a safe and appropriate method to achieve the required blood concentration in patients with various tacrolimus metabolism in the early post-transplant period. As the oral tacrolimus absorption was found to be variable between preoperative and postoperative states in identical patients, the conversion dosage cannot be calculated from preoperative oral or postoperative intravenous pharmacokinetics. Frequent blood concentration monitoring is needed to ensure safe treatment.