T. Shimizu

Acute antibody-mediated rejection in living ABO-incompatible kidney transplantation: long-term impact and risk factors.

The impact of acute antibody‐mediated rejection (AAMR) on the long‐term outcome on ABO‐incompatible (ABOI) kidney transplantation is not well understood. We retrospectively analyzed the long‐term impact of AAMR and risk factors for AAMR in 57 consecutive recipients performed between 1999 and 2004. Nineteen patients (33%) who developed AAMR within 3 months posttransplantation constituted of the AMR group. The graft survival rate was significantly lower in the AMR group (AMR vs. non‐AMR, respectively; 5 years: 84% vs. 95%; 8 years: 45% vs. 95%; p = 0.009). The prevalence of transplant glomerulopathy at 1 year posttransplantation was significantly higher in the AMR group (AMR 64% vs. non‐AMR 3%, p < 0.001). Multivariate analysis demonstrated that anti‐blood group IgG antibody titers of 1:32 at the time of transplantation (OR, 9.52; p = 0.041) and donor‐specific anti‐HLA antibodies (DSHA) detected by Luminex single bead method (OR, 5.68; p = 0.015) were independent risk factors for AAMR regardless of baseline anti‐blood group IgG antibody titers. Our results indicate that AAMR has a heavy impact on the long‐term outcome and preoperative DSHA appears to have a more significant association with poor graft outcomes than anti‐blood group antibodies, even in ABOI kidney transplantation.

Evaluation of immunosuppressive regimens in ABO-incompatible living kidney transplantation- : Single center analysis

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.

Analysis of Renal Transplant Protocol Biopsies in ABO-Incompatible Kidney Transplantation

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.

ABO-Incompatible Living Kidney Transplants: Evolution of Outcomes and Immunosuppressive Management.

ABO‐incompatible living kidney transplantation (ABO‐ILKT) has steadily become more widespread. However, the optimal immunosuppressive regimen for ABO‐ILKT remains uncertain. We aimed to determine the longitudinal changes in the outcomes from ABO‐ILKT compared with those from ABO‐compatible living kidney transplantation (ABO‐CLKT) over the last 25 years. Of 1195 patients who underwent living kidney transplantations (LKT) at our institute between 1989 and 2013, 1032—including 247 ABO‐ILKT and 785 ABO‐CLKT cases—were evaluated for graft survival, patient survival, infectious adverse events, and renal function. The patients were divided into four groups according to the transplantation era and ABO‐compatibility. In the past decade, ABO‐ILKT and ABO‐CLKT recipients yielded almost equivalent outcomes with respect to the 9‐year graft survival rates, which were 86.9% and 92.0%, respectively (hazard ratio [HR] 1.38, 95% confidence interval [CI] 0.59–3.22, pu2009=u20090.455). The graft survival rate for ABO‐ILKT conducted between 2005 and 2013 was better than that for ABO‐ILKT conducted between 1998 and 2004 (HR 0.30, 95% CI 0.13–0.72, pu2009=u20090.007). ABO‐ILKT recipients showed substantial improvements in the graft survival rate over time. Graft survival was almost identical over the past decade, regardless of ABO‐incompatibility. Currently, ABO‐ILKT is an acceptable treatment for patients with end‐stage renal disease.

Histopathological evaluation of 0‐h biopsy specimens of donor kidney procured by laparoscopic donor nephrectomy

Abstract:u2002 We evaluated the histopathology of donor kidneys procured by laparoscopic donor nephrectomy (LDN), by examining allograft biopsy specimens obtained immediately after donor nephrectomy (0‐h biopsies).

Histological analysis of late renal allografts of antidonor antibody positive patients with C4d deposits in peritubular capillaries

Abstract:u2002 The association of humoral immunity with late renal allograft dysfunction has recently been recognized, and many reports have revealed C4d deposits in peritubular capillaries (C4d in PTC), and the presence of serum antidonor HLA antibody in patients suffering from graft dysfunction, long time after transplantation. In this study, morphological changes in renal allograft biopsies more than 1 year after transplantation in 14 patients with C4d in PTC and serum antidonor antibody were investigated for the presence of chronic rejection (CR). In addition to the light microscope study, an electron microscope study was done to evaluate the multilayering of the peritubular capillary basement membrane (MLPTC). Histologically, only seven of 14 patients met the criteria of CR, and 71.4% (5/7) of CR patients had episodes of acute humoral rejection (AHR), coexisting with acute tubulointerstitial rejection. Peritubular capillaritis was observed in all patients, although it differed in severity. Transplant glomerulitis and interstitial inflammation were also observed in many patients: 71.4% (10/14) and 92.9% (13/14) respectively. MLPTC was observed in 12 patients (85.7%), but the severity of the MLPTC did not reflect the severity of peritubular capillaritis or any other histological features. The long‐term outcomes of the patients CR, especially those with episodes of AHR, were poor, and two of them lost their graft functions. On the other hand, patients without CR had relatively favourable outcomes. In conclusion, we confirmed the diverse morphological changes of late renal allografts, which cannot be categorized as chronic humoral rejection (CHR), and such patients who do not have typical morphological changes such as CHR, should be followed‐up on a long‐term basis in order to clarify the significance of C4d on PTC in late renal allografts.

Clinical and Histological Analysis of Chronic Tacrolimus Nephrotoxicity in Renal Allografts

AIMnTacrolimus (TAC) is an effective primary immunosuppressive agent in kidney transplantation. Chronic nephrotoxicity due to TAC has been reported to be similar to that of cyclosporine in kidney transplant patients. Since, the severity and influence of chronic TAC nephrotoxicity are not fully elucidated, we studied the clinicohistological characteristics of chronic TAC nephrotoxicity in kidney transplants.nnnPATIENTS AND METHODSnWe retrospectively studied the clinicohistological profiles of 15 transplant patients under TAC-based immunosuppression, who were diagnosed as chronic TAC nephrotoxicity by allograft biopsies, showing characteristic arteriolopathy--periodic acid-Schiff PAS--positive hyaline thickening in small arteries--between January 2004 and December 2005. The mean recipient age was 37.3 years and they consisted of 11 men and 4 women. The mean age of their donors was 59.4 years.nnnRESULTSnThe diagnoses of chronic TAC nephrotoxicities were established at an average of 54.7 months postoperatively. The severities of arteriolopathy were moderate in eight cases and severe in eight cases. The mean dosage of TAC at the time of diagnoses was 0.054 mg/kg with mean whole blood trough levels of 5.09 ng/mL, which is recognized to be within the so-called recommended level. Moderate to severe arteriosclerosis of medium-sized arteries were observed in 12 cases (80.0%).nnnCONCLUSIONnThe existence of moderate to severe arteriosclerosis in medium-sized arteries would have the potential of causing chronic TAC nephrotoxicities, rather than the dosage or whole blood trough level of TAC.

Risk Factors for Deterioration of Renal Function After Donor Nephrectomy

INTRODUCTIONnThere are few recent studies investigating increased risks for adverse effects leading to chronic kidney disease (CKD) among kidney donors. The aim of this study was to identify factors that protect renal function among actual live kidney donors.nnnMATERIALS AND METHODSnWe enrolled 68 individuals who had undergone donor nephrectomy in this study. We assessed donor age, body mass index (BMI), casual blood pressure, preoperative and 3-month follow-up serum creatinines, serum total cholesterol, and several other clinical parameters. The severity of arteriosclerosis in the arteriolar and interlobular arteries of the donor kidney was semiquantitatively evaluated in 4 grades using back table biopsies. Impairment of renal function after surgery was expressed by differences in serum creatinine levels.nnnRESULTSnThe ratio of glomerular sclerosis, systolic blood pressure, and diastolic blood pressure positively correlated with donor age. Deterioration of renal function after donor nephrectomy negatively correlated with BMI and positively correlated with severity of arteriosclerosis in interlobular arteries. A multiple regression analysis model with respect to the severity of arteriosclerosis in interlobular arteries showed significant influence, of serum creatinine and systolic blood pressure.nnnCONCLUSIONSnPreventing progression of arteriosclerosis and selecting the optimal BMI before donor nephrectomy will help to avoid impaired renal function among live kidney donors.

Clinical characteristics and outcomes of adenovirus infection of the urinary tract after renal transplantation

Urinary tract infection caused by human adenovirus (HAdV) after renal transplantation (RT) results in graft loss because of concomitant nephropathy and acute rejection and may result in death because of systemic dissemination.

Continent Orthotopic Ileal Neobladder After Kidney Transplantation in a Patient With Urothelial Cell Carcinoma Associated With Chinese Herb Nephropathy

A 58-year-old man underwent kidney transplantation on November 14, 2002 for end-stage kidney disease after Chinese herb nephropathy. Immunosuppressive therapy was maintained with tacrolimus, mycophenolate mofetil, and methylpredonisolone. He was diagnosed with right ureteral cancer and underwent right nephroureterectomy on December 13, 2003. Then, he underwent left nephroureterectomy for left ureteral cancer on March 5, 2004. Subsequently, he was diagnosed with multiple bladder cancers and carcinoma in situ. On August 31, he underwent radical cystectomy with an orthotopic ileal neobladder (Studers method). The postoperative course was uneventful. After 3 years follow-up, this patient shows no evidence of recurrence and his serum creatinine level is stable (1.7 mg/dL). The continence is maintained during both day and night; he voids without intermittent self-catheterization. We suggest that an orthotopic ileal neobladder is a safe method of urinary diversion after cystectomy in kidney transplant recipients.