Takehiro Ohara

Angiotensin-Converting Enzyme Polymorphism and Development of Diabetic Nephropathy in Non-Insulin-Dependent Diabetes mellitus

We determined the distribution frequency of angiotensin-converting enzyme insertion/deletion (I/D) polymorphism in 111 Japanese patients with non-insulin-dependent diabetes mellitus (NIDDM) of at least 10 years duration (80 patients with diabetic nephropathy and 31 patients without nephropathy) and 76 healthy Japanese controls. Patients with diabetic nephropathy showed an excess of the ID genotype compared with patients without nephropathy (p < 0.02) and less of the II genotype compared with healthy controls (p < 0.01) and patients without nephropathy (p < 0.01). NIDDM patients with the II genotype have a decreased risk for the development of diabetic nephropathy.

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.

Renal Involvement in POEMS Syndrome

We describe a patient with POEMS syndrome whose renal biopsy specimen also showed nephropathy. Immunoelectron microscopy of the renal biopsy revealed the localization of immunoglobulin (IgA and lambda light chain) in the subendothelial space of the glomerular capillaries, a previously unrecognized finding. We conclude that the renal pathology in POEMS syndrome is unusual and distinct from microangiopathic glomerular involvement or idiopathic mesangiocapillary glomerulonephritis.

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.

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).

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.

Effect of Prostaglandins on Renal Function in Uninephrectomized Humans

We examined the effects of unilateral nephrectomy (UN) and administration of indomethacin in 15 healthy humans. Glomerular filtration rate (GFR), effective renal plasma flow (ERPF), urine flow, sodium and potassium excretions, urinary excretion rate of prostaglandin E2 (PGE2) and 6-keto prostaglandin F1 alpha (6-keto PGF1 alpha) in the remaining kidney were all significantly (p < 0.01) increased 10 days after UN. Indomethacin administered at 75 mg/day for 3 days abolished the increase in GFR, ERPF and sodium excretion with reduced urinary excretion rate of PGE2 and 6-keto PGF1 alpha but not the increase in urine flow and potassium excretion. These findings suggest that renal prostaglandins may play a role in renal functional adaptation following UN.

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.