K Arai

Relation between ABO blood type antigen and antibody and acute vascular rejection in ABO incompatible kidney transplantation

THE CLINICAL course and pathology of acute vascular rejection (AVR) in ABO-incompatible kidney transplantation (ABOIncKTx) seems to be different from acute rejection (AR) in ABO-compatible KTx. The anti-A or B blood type antibody (Ab) may react on the blood type A or B antigen (Ag) of the renal allografts as an Ab-mediated immunologic reaction. However, the mechanism of AVR in ABOIncKTx is still unknown and there were many ABOIncKTx patients without AVR under the existence of antidonor blood type antibody. Therefore we investigated the localization of the blood type Ag in renal allografts and the sequential change of blood type Ab following pretreatment and Tx and characteristic pathologic findings of AVR in ABOIncKTx.

Living related kidney transplantation in a patient with autosomal-recessive Alport syndrome.

Abstract:  We discuss a patient with Alport syndrome who received a renal transplant from a donor with thin basement membrane disease. A 30‐year‐old woman, diagnosed with Alport syndrome on the basis of sensorineural hearing loss, characteristic renal biopsy findings and a family history of microhaematuria, entered chronic haemodialysis therapy. She then received a renal transplant donated from her father, who had sensorineural hearing loss and persistent microhaematuria. On the day of renal transplantation, a 1‐h graft biopsy after reperfusion showed thin basement membrane disease. We re‐tested the patients native kidney biopsy specimen by immunohistochemical staining using α‐chain‐specific collagen type IV monoclonal antibodies. There was no expression of collagen type IV α3‐, α4‐ and α5‐chain on glomerular basement membrane, but positive staining of α5‐chain on Bowmans capsular basement membrane was noted. A diagnosis of autosomal‐recessive Alport syndrome was made. We concluded that this family might display different phenotypic expressions of the same genotype: one suffered end‐stage renal disease and the other thin basement membrane disease.

Clinical course of congenital nephrotic syndrome and Denys‐Drash syndrome in Japan

Abstract Background : The prognosis of Japanese patients with congenital nephrotic syndrome (CNS) and Denys‐Drash syndrome (DDS) is not clear.

Post‐transplant early recurrent proteinuria in patients with focal glomerulosclerosis‐ Angiotensin II immunostaining and treatment outcome

Abstract:  We reviewed the transplantation data and results of histopathological studies with additional angiotensin II (AII) immunostaining of renal graft biopsies of nine cases (10 grafts) with recurrent proteinuria and three controls without recurrent proteinuria that received renal transplantation for primary focal segmental glomerulosclerosis (FSGS) between 1986 and 2002. Recurrent FSGS was confirmed in six grafts from nine cases by light microscopy. In cases with recurrent proteinuria, loss of graft function was noted in all six renal grafts received between 1986 and early 1992 but in none of four grafts received between late 1992 and 2002. Two of four patients of the late group but none of those of the early group received angiotensin converting enzyme (ACEI) or angiotensin II receptor blocker (ARB) with plasma exchange (PE). In control cases without proteinuria, AII immunostaining was detected in tubules but not in glomeruli in 1‐hour biopsies as well as later on. In cases with recurrent proteinuria, AII immunostaining was detected in both tubules and glomeruli, although glomerular AII staining was not observed in 1‐hour biopsies. Our results suggest that effective treatment of post‐transplantation recurrent FSGS requires ACEI or ARB with PE in the absence of another etiology.

Activation of nuclear factor-kappa B and macrophage invasion in cyclosporin A- and tacrolimus-treated renal transplants

Abstract:  This retrospective study was designed to compare the efficacy of cyclosporin A (CyA) and tacrolimus (FK506) on chronic rejection (CR) associated with nuclear factor‐kappa B (NF‐κB) activation and macrophage invasion. Non‐episodic day 50 protocol renal biopsy was performed in 63 consecutive patients with renal transplants from living donors, treated with either CyA or FK506. Southwestern histochemistry for NF‐κB, immunostaining for CD68, and Banff classification were performed, and these findings were compared with outcome over 34 ± 13 months. Compared with specimens from FK506‐treated patients (n = 20), specimens from CyA‐treated patients (n = 43) showed a significant increase in tubulointerstitial CD68‐positive cells (1.5 ± 0.9 vs. 0.9 ± 0.8, p < 0.01), although no significant differences were observed in NF‐κB activation. Specimens with Banff acute rejection (AR) grade ≥ 1A (n = 20) showed increased macrophages (p < 0.01) compared with specimens with AR < 1A (n = 43). Specimens from patients with clinical AR prior to day 50 biopsy (n = 23) also showed increased macrophage invasion (p < 0.01) compared with specimens from patients without prior clinical AR (n = 40). The cumulative well‐functioning (serum creatinine <1.5 mg/dL) graft survival rate was significantly lower in patients with increased tubulointerstitial CD68‐positive cells (n = 63, p < 0.05). Our findings suggest that tacrolimus is more effective than CyA against CR with respect to macrophage invasion and AR.

Clinical management and outcome of preemptive renal transplantation in children and adolescents

AbstractBackground. Recently, pediatric renal transplantation without prior maintenance dialysis (preemptive transplantation) has been performed. The details of perioperative management and outcomes of preemptive transplantation in Japanese pediatric recipients are unclear. Methods. Patients who received preemptive renal transplantation at the age of 18 or younger were studied retrospectively. Results. Eight patients with a mean age of 13 received preemptive transplantation from a parental donor. Their mean creatinine clearance was 8.4 ml/min per 1.73 m2 at the time of transplantation. Two patients required treatment for hyperkalemia before transplant. Initial immunosuppressive therapy was the conventional protocol in one recipient, cyclosporine in three, and tacrolimus in four. Three recipients developed clinical acute rejection between 6 days and 1 month posttransplant and were treated with high-dose methylprednisolone and deoxyspergualin. Noncompliance with immunosuppressive drug therapy was identified in one recipient and suspected in another. The follow-up period was between 6 months and 25 years after preemptive transplantation. All recipients were alive with functioning grafts at the last follow-up. The primary reason for selecting preemptive transplantation was the parents desire to avoid dialysis. Conclusion. Preemptive transplantation was safe and successful. Preemptive transplantation should be performed before dialysis is indicated to avoid hyperkalemia at the time of the operation. Patients who receive preemptive renal transplantation should be followed closely for noncompliance with immunosuppressive drug therapy.

BK virus nephropathy in a patient with ABO-incompatible renal transplantation.

Abstract:  A 43‐year‐old woman with end‐stage renal disease originating from IgA nephropathy entered chronic haemodialysis therapy. She then received an ABO‐incompatible living related renal transplantation. Initial immunosuppression consisted of azathioprine, methylprednisolone and tacrolimus. At 155 days after transplantation, the azathioprine was changed to mycophenolate mofetil for continuous graft dysfunction. Furthermore, a total of three courses of anti‐rejection therapy was given. At 665 days after transplantation, diagnosis of BK‐virus nephropathy was made by immunohistochemical analysis and viral DNA assay. Therefore the immunosuppression therapy was reduced for graft dysfunction. All five renal biopsy specimens were examined retrospectively in order to determine when the BK virus nephropathy had developed. The expressions of SV40 large T antigens were detected from the third (117 days) to the fifth (665 days) biopsies, with increasing numbers of SV40 large T antigen positive cells. In addition, many cells contained inclusion bodies which were already present in the urinary sediment for 3 months post‐transplantation. Although it is difficult to make a diagnosis of early stage of BKVN, we have to consider with caution if urinary cells with inclusion body are seen. Awareness of BKVN at the earliest opportunity is important in order to avoid over‐immunosuppression.

Sotos syndrome associated with complete ureteral duplication and bilateral vesicoureteral reflux

A 4-year-old boy with Sotos syndrome had repeated urinary tract infections. Complete right ureteral duplication and bilateral vesicoureteral reflux were, diagnosed, and anti-reflux surgery was performed. This child also had elevated serum creatine kinase levels and atypical absence seizures. The associations of ureteral duplication, continuously elevated serum creatine kinase level, and atypical absence seizure have not been reported previously in Sotos syndrome.