Atsushi Aikawa

Expression of ACE and ACE2 in Individuals With Diabetic Kidney Disease and Healthy Controls

BACKGROUND Angiotensin-converting enzyme (ACE) 2 (ACE2) is expressed mainly in the heart and kidney and forms angiotensin-1-7 from angiotensin II. ACE2 might act in a counterregulatory manner to ACE. There is little information about renal ACE and ACE2 expression in human diabetic nephropathy. STUDY DESIGN Cross-sectional study. SETTING & PARTICIPANTS Kidney tissue from 20 patients with type 2 diabetes and overt nephropathy and 20 healthy kidney donors. PREDICTOR Diabetes status. OUTCOMES & MEASUREMENTS Renal expression of ACE and ACE2 assessed by means of immunohistochemistry and in situ hybridization. Correlation between ACE and ACE2 expression and levels of various biochemical parameters. RESULTS Decreased ACE2 and increased ACE expression in both the tubulointerstitium and glomeruli resulted in a significant (P < 0.001) increase in ACE/ACE2 ratio in patients with diabetes with overt nephropathy compared with controls, although ACE messenger RNA in the tubulointerstitium did not significantly increase. ACE/ACE2 ratio correlated positively with values for mean blood pressure, fasting blood glucose, serum creatinine, proteinuria, and hemoglobin A(1c) and inversely with estimated glomerular filtration rate (P < 0.001). LIMITATIONS Inclusion of small number of human renal biopsy specimens with structural distortion of cortical tissue. CONCLUSIONS The high ACE/ACE2 ratio in kidneys of patients with type 2 diabetes with overt nephropathy may contribute to renal injury.

Significance of subclinical rejection in early renal allograft biopsies for chronic allograft dysfunction.

Abstract:  To determine the significance of early subclinical rejection of renal allografts, we reviewed 127 biopsy specimens obtained soon after transplantation. Histological finding was categorized according to a modification of the Banff scheme as: acute rejection (AR), borderline changes (BL); non‐specific inflammatory changes, (NI) and no rejection (NR). Subclinical rejection was defined as AR, BL or NI. Patients with BL or NI were divided into two groups; one was treated with high‐dose methylprednisolone (MP), the other remained untreated. Freedom from chronic allograft dysfunction (defined as non‐doubling of serum creatinine 5 yr after transplantation) was significantly more frequent in the NR group (89%) than in the BL (70%) and AR (64%) groups. At 1 yr after transplantation, mean serum creatinine had increased significantly only in the untreated group (p < 0.05), and re‐biopsy showed that interstitial fibrosis had developed to a significantly greater extent in the untreated group than in the treated group (p < 0.01). Subclinical rejection in the early protocol biopsies correlated closely with subsequent allograft dysfunction. High‐dose MP treatment for early subclinical rejection may be effective in suppressing the development of interstitial fibrosis at 1 yr after transplantation.

Estimation of damaged tubular epithelium in renal allografts by determination of vimentin expression

Background: Various invasive and non‐invasive methods have been investigated for their prognostic value in predicting the outcome of renal allografts. In the present study, vimentin expression in tubular epithelial cells (TEC) was determined by the immunohistochemical examination of biopsy specimens and the prognostic value of this method was assessed.

ABO incompatible renal transplants: Good or bad?

ABO incompatible kidney transplantation (ABOi-KT) was previously considered to be an absolute contraindication for patients with end-stage kidney disease (ESKD) due to hyperacute rejection related to blood type barrier. Since the first successful series of ABOi-KT was reported, ABOi-KT is performed increasingly all over the world. ABOi-KT has led to an expanded donor pool and reduced the number of patients with ESKD awaiting deceased kidney transplantation (KT). Intensified immunosuppression and immunological understanding has helped to shape current desensitization protocols. Consequently, in recent years, ABOi-KT outcome is comparable to ABO compatible KT (ABOc-KT). However, many questions still remain unanswered. In ABOi-KT, there is an additional residual immunological risk that may lead to allograft damage, despite using current diverse but usually intensified immunosuppressive protocols at the expense of increasing risk of infection and possibly malignancy. Notably, in ABOi-KT, desensitization and antibody reduction therapies have increased the cost of KT. Reassuringly, there has been an evolution in ABOi-KT leading to a simplification of protocols over the last decade. This review provides an overview of the history, outcome, protocol, advantages and disadvantages in ABOi-KT, and focuses on whether ABOi-KT should be recommended as a therapeutic option of KT in the future.

Urinary angiotensin-converting enzyme 2 in patients with CKD.

Aim:  Angiotensin‐converting enzyme 2 (ACE2) is a type I membrane protein that antagonizes the action of angiotensin II. Because of the need for invasive kidney biopsy, little is known about the role of renal ACE2 in human kidney diseases. The authors studied if urinary ACE2 could provide a novel clue to renal ACE2 in chronic kidney disease (CKD).

Reversible Cerebellar Lesions Induced by Metronidazole Therapy for Helicobacter Pylori

Metronidazole is widely used for chronic or refractory infection and has recently also been used for the treatment of Helicobacter pylori. The authors report the case of a Japanese patient presenting with reversible cerebellar lesions induced by prolonged administration of metronidazole for treatment of H pylori with magnetic resonance imaging findings. Although rare, prolonged and high‐dose administration of metronidazole may induce cerebellar lesions. Increased awareness of this phenomenon is important, as these lesions are reversible with discontinuation of this drug.

First report of a 7-year survey on ABO-incompatible kidney transplantation in Japan

AbstractBackground. As of December 1997, more than 170 000 patients in Japan were receiving hemodialysis, 30% to 50% of whom were waiting for a kidney transplant. However, in contrast to the situation in the United States and Europe, kidney transplantation is uncommon, because of the small number of cadaveric kidneys that are donated. As a result, living-related kidney transplantation is performed in as many patients as possible, even in ABO-incompatible cases. Methods. We statistically analyzed the data for 167 ABO-incompatible living donor kidney transplantations that were carried out between January 1989 and December 1997. Results. The overall patient survival rates at 1, 3, 5, and 7 years after transplantation were 90.2%, 90.2%, 88.0%, and 84.8%, respectively, with respective overall graft survival rates of 79.6%, 76.1%, 66.3%, and 56.5%. Conclusions. ABO-incompatible living kidney transplantation is an effective radical treatment for endstage renal disease (ESRD).

Protocol biopsies for focal segmental glomerulosclerosis treated with plasma exchange and rituximab in a renal transplant patient

Sakai K, Takasu J, Nihei H, Yonekura T, Aoki Y, Kawamura T, Mizuiri S, Aikawa A. Protocol biopsies for focal segmental glomerulosclerosis treated with plasma exchange and rituximab in a renal transplant patient.
Clin Transplant 2010: 24 (Suppl. 22): 60–65.

Increased ACE and decreased ACE2 expression in kidneys from patients with IgA nephropathy.

Background: Angiotensin-converting enzyme (ACE)2 forms angiotensin-1–7 which may protect kidney in a counterregulatory manner to angiotensin II. Recent studies revealed increased ACE and decreased ACE2 expression in kidneys of patients with diabetic nephropathy. However, these changes may not be specific for diabetic nephropathy. We studied ACE and ACE2 expression in patients with IgA nephropathy. Methods: Renal ACE and ACE2 expression was assessed by immunohistochemistry and in situ hybridization in 30 patients with IgA nephropathy and 21 healthy controls. Correlation between ACE and ACE2 expression and levels of various biochemical parameters was also assessed. Gene expression was also assessed in minimal change nephrotic syndrome (MCNS) and membranous nephropathy (MN) as disease controls. Results: Reduced ACE2 expression (p < 0.01) and increased ACE expression in glomeruli (p < 0.001), and reduced ACE2 expression in tubulointerstitium (p < 0.001) were observed in patients with IgA nephropathy compared to healthy controls, although the changes in ACE2 mRNA were not statistically significant. Reduced renal ACE2 expression was also found in MN but not in MCNS. Correlation between renal ACE and ACE2 expression and proteinuria was not observed in IgA nephropathy. Conclusion: IgA nephropathy is associated with increased ACE and decreased ACE2 expression in kidneys, as in diabetic nephropathy.

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.