S. Teraoka

Postoperative production of anti-donor antibody and chronic rejection in renal transplantation.

To study the relevance of anti-donor antibody (ADA) to chronic rejection in kidney transplantation, we retrospectively examined the long-term kinetics of ADA by flow cytometric analysis. Among 537 recipients who underwent living-donor kidney transplantation between 1986 and 1994, 29 patients with chronic rejection (CR group) and 33 patients with stable graft function (ST group) were randomly selected for analysis. Patient serum taken 1 or 2 days before transplantation, serum taken 1 month after transplantation, and the most current serum were analyzed for the presence of ADA to donor T and B cells. In the CR group, IgG antibody to donor B cells of the most current serum was positive in 25 of 29 patients, whereas it was positive in only 5 patients in the ST group P<0.001. The mean fluorescent intensity of the antibody was also significantly higher in the CR group than that in ST group P<0.01. In contrast, IgG antibody to donor T cells of the most current serum was positive in only five patients in the CR group. No significant difference was observed in the pretransplant and 1-month posttransplant sera between the CR and ST groups. We conclude that the posttransplant production of IgG antibody to donor B cells seemed to be highly relevant to chronic rejection.

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.

Therapeutic Effects of Oral Sorbent in Undialyzed Uremia

The present study was carried out to clarify whether an oral sorbent, AST-120 (Kureha Chemical Ind Co, Tokyo), may postpone the initiation of dialysis therapy. The subjects were randomly divided into two groups, control and AST. The AST group consisted of 27 undialyzed uremic patients. Serum creatine concentrations (SCr) were 4.3 to 8.1 mg/dL (5.8 +/- 1.1 mg/dL, mean +/- SD). The control group consisted of 24 uremic patients who were not given AST-120 during the conservative therapy period before the initiation of hemodialysis. AST-120 (3.2 to 7.2 g/d) was administered to the patients in the AST group for 2.4 to 30.1 months (13.2 +/- 7.4) before the initiation of hemodialysis. The slopes of reciprocal creatinine v time in the control group were -1,251 +/- 856 x 10(-5) dL/mg/month during the 6 to 12 months before the initiation of dialysis therapy, and in the AST group, they were -1,004 +/- 1,012 x 10(-5) dL/mg/month before administration, and -347 +/- 509 x 10(-5) dL/mg/month after administration of AST-120 (P less than 0.01). All 24 patients in the control group and 21 of 27 in the AST group were introduced to hemodialysis. SCr and serum urea nitrogen (SUN) at the initiation of hemodialysis did not differ between the control and AST group: 10.8 +/- 2.6 and 11.0 +/- 2.2 mg/dL and 92.7 +/- 22.2 and 94.1 +/- 21.6 mg/dL, respectively. The times to the 50% undialyzed level were 5.0 months in the control group, and 14.3 months in the AST group.(ABSTRACT TRUNCATED AT 250 WORDS)

Improved Outcomes of Renal Transplantation from Cardiac Death Donors: A 30‐Year Single Center Experience

Outcomes of renal transplantation from donation after cardiac death (DCD) donors over 30 years were analyzed. Between 1975 and 2004, 256 renal transplantations from DCD donors were performed. The recipients were divided into four groups according to a time period as follows: 1975–1979 (Group 1; n = 18), 1980–1989 (Group 2; n = 81), 1990–1999 (Group 3; n = 84) and 2000–2004 (Group 4; n = 73). Of the 256 transplanted kidneys from DCD donors, 38 (15%) functioned immediately after transplantation. The incidence of delayed graft function (DGF) was 72%. Warm ischemic time and total ischemic time were 7.4 ± 9.4 min and 11.9 ± 5.6 h, respectively. The overall graft survival rates at 1, 5 and 10 years were 80%, 72% and 53%, respectively. Graft survival rates in each group have continually improved over time (5‐year graft survival; 23% vs. 64% vs. 74% vs. 91%, respectively). However, there was no significant difference in graft survival rates between the groups of patients who survived with a functioning graft for more than 1 year. A multivariate Cox regression analysis showed acute rejection and donor age to be independently associated with graft outcome. DCD donors are a valuable source of kidneys for transplantation with promising long‐term outcomes.

Islet transplantation using donors after cardiac death: report of the Japan Islet Transplantation Registry.

Background. This report summarizes outcomes of islet transplantation employing donors after cardiac death (DCD) between 2004 and 2007 as reported to the Japan Islet Transplantation Registry. Method. Sixty-five islet isolations were performed for 34 transplantations in 18 patients with insulin-dependent diabetes mellitus, including two patients who had prior kidney transplantation. All but one donor (64/65) was DCD at the time of harvesting. Results. Factors influencing criteria for islet release included duration of low blood pressure of the donor, cold ischemic time, and usage of Kyoto solution for preservation. Multivariate analysis selected usage of Kyoto solution as most important. Of the 18 recipients, 8, 4, and 6 recipients received 1, 2, and 3 islet infusions, respectively. Overall graft survival defined as C-peptide level more than or equal to 0.3 ng/mL was 76.5%, 47.1%, and 33.6% at 1, 2, and 3 years, respectively, whereas corresponding graft survival after multiple transplantations was 100%, 80.0%, and 57.1%, respectively. All recipients remained free of severe hypoglycemia while three achieved insulin independence for 14, 79, and 215 days. HbA1c levels and requirement of exogenous insulin were significantly improved in all patients. Conclusion. Islet transplantation employing DCD can ameliorate severe hypoglycemic episodes, significantly improve HbA1c levels, sustain significant levels of C-peptide, and achieve insulin independence after multiple transplantations. Thus, DCD can be an important resource for islet transplantation if used under strict releasing criteria and in multiple transplantations, particularly in countries where heart-beating donors are not readily available.

How Do Living Kidney Donors Develop End-Stage Renal Disease?

The clinical course and risk factors for developing end‐stage renal disease (ESRD) after heminephrectomy in living kidney donors have scarcely been investigated. We reviewed medical records and identified eight case donors who developed chronic kidney disease (CKD) stage 5 or ESRD, and subsequently investigated the association between postoperative clinical courses and changes in renal function. To conduct a case‐control study, we also selected a control group comprising 24 donors who had maintained stable renal function and were matched for age, sex and follow‐up time since donation. Except for one donor who developed ESRD caused by a traffic accident, none of the donors developed progressive renal dysfunction immediately after donation. Their renal functions remained stable for a long period of time, but started to decline after developing new comorbidities, especially risk factors known as progression factors (proteinuria or hypertension) or accelerating factors (cardiovascular [CV] event or infection) of CKD. As compared with the control donors, incidence of postoperative persistent proteinuria, acute CV event, severe infection and hospitalization due to accelerating factors of CKD were significantly higher in the case donors. These results suggest the importance of long‐term (more than 10 years) follow‐up of donors with special attention on the risk factors of CKD.

Thickening of the peritubular capillary basement membrane is a useful diagnostic marker of chronic rejection in renal allografts.

In kidney transplantation, the multilayering of the peritubular capillary basement membrane (MLPTC) in electron microscopy (EM) has been recognized as a feature of chronic rejection (CR). In this study, thickening of the peritubular capillary (PTC) basement membrane was evaluated by light microscopy (LM) to determine whether it corresponds to the MLPTC in EM and whether it can be used as a diagnostic marker of CR. Forty‐eight patients with late renal allograft were divided into chronic allograft nephropathy (CAN) with CR (Group 1, n = 23), CAN without CR (Group 2, n = 19) and CAN‐free (Group 3, n = 6). The thickening of the PTC basement membrane (ptcbm) was scored from grades 0 to 2 (ptcbm score), and the MLPTC thickness was measured in EM. Interobserver agreement on ptcbm scores was statistically significant (Kappa coefficient = 0.63). LM and EM lesions corresponded very well. The ptcbm score was highest in Group 1, and ptcbm2 corresponded closely with CR. Group 1 showed significantly thicker MLPTC than Groups 2 and 3. The results validated the usefulness of the ptcbm score and suggested that the thickening of the PTC basement membrane can be a novel diagnostic marker of CR.

Glomerular Expression of Plasmalemmal Vesicle-Associated Protein-1 in Patients with Transplant Glomerulopathy

Transplant glomerulopathy (TG) is a prominent feature of chronic rejection that is characterized by double contours of the glomerular capillaries (GC). In this report, we demonstrate that one of the histopathological features of TG is a phenotypic change of glomerular endothelial cells which is illustrated by increased caveolae formation. To verify the endothelial changes in this disease, we examined the expression of plasmalemmal vesicle‐associated protein‐1 (PV‐1), a glycoprotein associated with plasmalemmal vesicles (caveolae), in the glomeruli of TG patients using pathologische anatomie Leiden‐endothelium (PAL‐E) antibody. Twenty‐six cases of chronic allograft nephropathy (CAN) with TG were examined, compared with 16 cases of CAN without TG, type I MPGN (4 cases), and transplant glomerulitis (8 cases). Overall, 24 of 26 (92.3%), 4 of 16 (25%), 0 of 4, 0 of 8 cases were PAL‐E‐positive for GC, respectively. Further, the extent of glomerular PAL‐E expression was positively correlated with both the grade of TG (rs= 0.72, p = 0.0003) and proteinuria (g/day) (rs= 0.51, p = 0.02). A correlation was not observed between glomerular PAL‐E positivity and peritubular capillary C4d deposits (Yetes chi = 0.23, p = 0.89). In summary, the present study demonstrates expression of PV‐1 in the GC of TG which is correlated with the grade of TG and proteinuria.

De novo membranous nephropathy and antibody-mediated rejection in transplanted kidney

Honda K, Horita S, Toki D, Taneda S, Nitta K, Hattori M, Tanabe K, Teraoka S, Oda H, Yamaguchi Y. De novo membranous nephropathy and antibody‐mediated rejection in transplanted kidney.
Clin Transplant 2011: 25: 191–200.

Persistent Glomerular Hematuria in Living Kidney Donors Confers a Risk of Progressive Kidney Disease in Donors After Heminephrectomy

Although glomerular hematuria is likely a sign of chronic kidney disease that will develop into overt nephropathy after donation, it remains unclear whether prospective donors with hematuria should be excluded. We reviewed the medical records of 242 donors who donated at our institution from 2001 to 2007 and surveyed the prevalence of hematuria pre‐ and postdonation. We then investigated the association of hematuria with proteinuria postdonation and trends in glomerular filtration rate. Before donation, 8.3% of 242 donors presented with persistent hematuria, a finding that was significantly associated with dysmorphic hematuria before donation. Most cases of predonation persistent hematuria persisted after donation, and the overall prevalence increased to 15.3%. During a median follow‐up period of 2.3 years after donation, 8.3% developed persistent proteinuria, with incidence being significantly higher in donors having persistent hematuria with dysmorphic red blood cells (d‐RBC) both before and after donation. Postdonation persistent hematuria with d‐RBC was also associated with a progressive decline in renal function. These results indicate that persistent glomerular hematuria is strongly associated with a higher incidence of postdonation progressive kidney disease. Potential donors with persistent glomerular hematuria should be excluded, while those with isolated hematuria need to be evaluated with heightened caution.