Kazumasa Oka

Japan renal biopsy registry: The first nationwide, web-based, and prospective registry system of renal biopsies in Japan

BackgroundThe Committee for the Standardization of Renal Pathological Diagnosis and the Working Group for Renal Biopsy Database of the Japanese Society of Nephrology started the first nationwide, web-based, and prospective registry system, the Japan Renal Biopsy Registry (J-RBR), to record the pathological, clinical, and laboratory data of renal biopsies in 2007.MethodsThe patient data including age, gender, laboratory data, and clinical and pathological diagnoses were recorded on the web page of the J-RBR, which utilizes the system of the Internet Data and Information Center for Medical Research in the University Hospital Medical Information Network. We analyzed the clinical and pathological diagnoses registered on the J-RBR in 2007 and 2008.ResultsData were collected from 818 patients from 18 centers in 2007 and 1582 patients from 23 centers in 2008, including the affiliated hospitals. Renal biopsies were obtained from 726 native kidneys (88.8%) and 92 renal grafts (11.2%) in 2007, and 1400 native kidneys (88.5%) and 182 renal grafts (11.5%) in 2008. The most common clinical diagnosis was chronic nephritic syndrome (47.4%), followed by nephrotic syndrome (16.8%) and renal transplantation (11.2%) in 2007. A similar frequency of the clinical diagnoses was recognized in 2008. Of the native kidneys, the most frequent pathological diagnosis as classified by pathogenesis was immunoglobulin (Ig) A nephropathy (IgAN) both in 2007 (32.9%) and 2008 (30.2%). Among the primary glomerular diseases (except IgAN), membranous nephropathy (MN) was the most common disease both in 2007 (31.4%) and 2008 (25.7%).ConclusionsIn a cross-sectional study, the J-RBR has shown IgAN to be the most common disease in renal biopsies in 2007 and 2008, consistent with previous Japanese studies. MN predominated in the primary glomerular diseases (except for IgAN). The frequency of the disease and the clinical and demographic correlations should be investigated in further analyses by the J-RBR.

Prevalence, characteristics, and outcome of BK virus nephropathy in Japanese renal transplant patients: analysis in protocol and episode biopsies

Abstract:  Background:  BK virus nephropathy (BKN) is recognized as a cause of graft loss in renal transplant patients. This may be related to the introduction of new and potent immunosuppressive regimens. In Japan, our experience regarding its prevalence, clinical significance, and outcome is still limited. In this study, our primary purpose is to outline the prevalence, outcome, and clinical characteristics of BKN as observed at Osaka University Hospital.

Histological reaction of sintered nanohydroxyapatite-coated cuff and its fibroblast-like cell hybrid for an indwelling catheter.

Rapid tissue-ingrowth of a sintered hydroxyapatite(HAp)-coated and cell-hybrid subcutaneous cuff equipped with an indwelling catheter was developed. The rod-like HAp nanoparticles were coated by covalent bonding on the surface of the silk fibroin (SF) fibers for about 100 microm of the length. The fibers were transplanted three-dimensionally on a cuff substrate made of silicone elastomer with an adhesive. The fibroblast-like cells, explanted and proliferated from skin tissue containing the epidermis, dermis, and subcutaneous tissue of Japanese white rabbits, were incubated on the three-dimensional cuff for three days. Three types of cuff--polyester, HAp-coated, and cell-hybrid cuffs--were percutaneously implanted into the backs of the same animals for 3 and 7 days. The subcutaneous tissues around the cuffs were stained with hematoxylin-eosin. Immunohistochemical staining to identify macrophages and alpha-smooth muscle actin (alpha-SMA) was also done and examined by light microscopy. The alpha-SMA-positive area was very limited in the polyester cuff group even after 7 days, although many macrophages infiltrated into the fibers. In the cell-hybrid cuff group, on the other hand, an alpha-SMA-positive area was formed extensively after 3 and 7 days, causing severe inflammation. In the HAp-coated cuff group, an alpha-SMA-positive area was formed among the fibers with little inflammation. The extent order of the alpha-SMA-positive area was cell-hybrid cuff >> HAp-coated cuff >> polyester cuff, while the degree of inflammatory cells order was cell-hybrid cuff >> polyester cuff >> HAp-coated cuff.

Nilvadipine attenuates mesangial expansion and glomerular hypertrophy in diabetic db/db mice, a model for type 2 diabetes.

BackgroundThe renoprotection achieved by angiotensin II blockade in the treatment of diabetic nephropathy is well established in both the clinical and the experimental settings. In contrast, the therapeutic efficacy of calcium channel blockers (CCBs) in the treatment of diabetic nephropathy still remains controversial.MethodsIn the present study, we compared the effects of an angiotensin-converting enzyme inhibitor, enalapril, and a dihydropyridine CCB, nilvadipine, on nephropathy in the db/db mouse, a rodent model of type 2 diabetes. Male db/db mice were divided into the following three groups at the age of 11 weeks, when treatment was started: vehicle, enalapril (10 mg/kg per day), and nilvadipine (10 mg/kg per day). Blood pressure, urine, and blood chemistry were monitored at the age of 17 and 27 weeks, and kidney samples were obtained at 29 weeks. Morphological changes were analyzed on periodic acid-Schiff-stained sections. Lipid peroxidation in kidney homogenates was measured.ResultsBlood pressure remained normal and was similar in the three groups until 27 weeks. Blood glucose exceeded 300 mg/dl throughout the study in all groups. Reduction of microalbuminuria at 27 weeks, compared to the vehicle group, was 37% and 52% in the enalapril- and nilvadipine-treated groups, respectively. Increased lipid peroxidation was suppressed by 15% and 83% in the enalapril- and nilvadipine-treated groups, respectively. Glomerular hypertrophy, assessed by cross-sectional glomerular area, was significantly suppressed in the nilvadipine group, but not in the enalapril group, compared to the vehicle group.ConclusionsNilvadipine shows a stronger renoprotective effect than enalapril in the db/db mouse, independent of the blood-pressure-lowering effect. An antioxidative effect, indicated by the reduction in lipid peroxidation, may partly contribute to the renoprotection conferred by nilvadipine.

Randomized prospective study of effects of benazepril in renal transplantation: an analysis of safety and efficacy

AbstractBackground. Prolonging the survival of transplanted kidneys is one of major tasks of modern nephrology. Angiotensin-converting enzyme inhibitors (ACEIs) compose a class of antihypertensive agents that has established efficacy in the treatment of hypertension and in slowing the progression of diabetic nephropathy and chronic glomerulonephritis. ACEIs are not widely accepted as a standard medication in the treatment of hypertension in renal transplant recipients because of the potential risk for decreased renal blood flow and glomerular filtration rate associated with a single kidney and concomitant cyclosporin use. Methods. We undertook a prospective randomized study of ACEI (benazepril) treatment in 76 posttransplant patients to determine the safety, efficacy, and side-effect profile of benazepril. Forty-one patients were assigned to the benazepril group and 35 patients were assigned to the control group. Results. The mean arterial blood pressure at a 12-month follow-up was lower than that at the time of initiation of benazepril or control therapy, with a decrease from 101 ± 10 mmHg to 94 ± 7 mmHg (P < 0.05) in the benazepril group and from 102 ± 12 mmHg to 94 ± 10 mmHg in the control group after 12 months of treatment. The serum creatinine concentrations did not change throughout the follow-up period. Conclusions. Benazepril was demonstrated to be an effective antihypertensive without any unfavorable effects on graft function. A significant antiproteinuric effect of benazepril was observed in patients with overt proteinuria. Further follow-up of this patient population will contribute to the establishment of the long-term renoprotective effect of benazepril in renal allograft recipients.

Association of treatment with 15-deoxyspergualin and BK virus nephropathy in kidney allograft recipients

Abstract:  Objective:  BK virus nephropathy (BKVN) has been proposed as an important cause of allograft dysfunction and loss in kidney allograft recipient over the last decade. Intense immunosuppression and tubular injury have been shown to promote the replication of polyomavirus. 15‐deoxyspergualin (DSG), an effective immunosuppressive agent, is used as a rescue drug for acute rejection in clinical renal transplantation in Japan. To determine whether DSG is a risk factor for BKVN and outline the relationship among BKVN, DSG, and other risk factors, we analyzed 88 patients who received living‐related renal transplantation between January 1999 and April 2003.

Effect of a Novel Immunosuppressant, FK 506, on Autoimmune Glomerulonephritis in Brown Norway Rats

Mercuric-chloride (HgCl2) induces a lymphoproliferative disorder and autoimmune glomerulonephritis in Brown Norway rats. The effects of a new immunosuppressant FK 506 on this model of glomerulonephritis were studied. Brown Norway rats were treated with HgCl2 according to a standard protocol (HgCl2 1 mg/kg s.c. 3 times/ week). Rats developed proteinuria at day 7, which reached a plateau level at day 14. On day 14, renal histology showed prominent mesangial cellular proliferation and the expansion of mesangial matrix. Electron microscopic study showed the effacement of visceral epithelial foot processes and the microvillous transformation of the visceral epithelium. Immunofluorescence study showed a strong linear staining for IgG and the adhesion molecule ICAM-1 in all glomeruli. Coadministration of FK 506 (1 mg/kg s.c. daily) prevented the appearance of proteinuria at day 14 (621.4 ± 30.5 vs. 2.2 ± 2.7 mg/day) and the morphological lesions. These findings suggest that FK 506 could be useful for the therapy of certain types of human glomerulonephritis.

Effect of FK 506 in the treatment of autoimmune glomerulonephritis in brown Norway rats

Mercuric chloride (HgCl2) induces a lymphoproliferative disorder and autoimmune glomerulonephritis in Brown Norway (BN) rats. The effects of a new immunosuppressant, FK 506, on this model of glomerulonephritis were studied. BN rats were treated with HgCl2 according to a standard protocol (HgCl2 1 mg/kg s.c. 3 times/week). FK 506 was inoculated subcutaneously daily from day 15 to day 28. Animals were divided into 4 groups: group 1, rats were treated with normal saline alone and sacrificed on day 28; group 2, rats were treated with HgCl2 alone and sacrificed on day 14; group 3, rats were treated with HgCl2 alone and sacrificed on day 28, and group 4, rats were treated with HgCl2 and FK 506 (from day 15 to day 28) and sacrificed on day 28. Rats developed proteinuria by day 7, which reached a plateau level by day 14. On day 14, renal histology showed prominent mesangial cellular proliferation and the expansion of mesangial matrix. Electron microscopic study showed the effacement of visceral epithelial foot processes and the microvillous transformation of the visceral epithelium. Immunofluorescence study showed strong linear staining for IgG and the adhesion molecule ICAM-1 in all glomeruli. Treatment with FK 506 (1 mg/kg s.c. daily) resulted in a remarkable reduction in proteinuria on day 28 (493.5 ± 48.3 vs. 24.4 ± 13.5 mg/day) and an improvement in the morphological lesions. These findings suggest that FK 506 could be useful in the treatment of some human glomerulonephritides.

A case of relapse of C-ANCA-associated glomerulonephritis in post-transplant patients

We experienced a case of relapse of proteinase 3‐specific antineutrophil cytoplasmic autoantibody (C‐ANCA)‐associated rapid progressive glomerulonephritis (RPGN) in a patient after renal transplantation. A 19‐yr‐old man, who underwent a living donor kidney transplantation, presented a rapid renal function deterioration along with a sign of infection. Initially he was treated as acute rejection, but renal function did not improve. Renal biopsy revealed crescentic glomerulonephritis, and C‐ANCA titer was 12 EU/mL, resulting in the diagnosis of C‐ANCA‐associated RPGN. He was treated with three consecutive methylprednisolone pulses twice in addition to the basal immunosuppressive medications (cyclosporine A and mizoribine), then his renal function improved to normal. Bearing the possibility of recurrence of glomerulonephritis in mind, we re‐evaluated the nature and disease course of renal failure of original kidney. He experienced a rapid deterioration of renal function in 1992, and eventually CAPD was started in 1992. His serum in 1992 revealed high titer of C‐ANCA (24 EU/mL), and renal biopsy performed in 1992 showed a crescentic glomerulonephritis. Taken together, we diagnosed this event as a relapse of C‐ANCA‐associated GN. 
Lessons from our experience are: 1) steroid pulse and high‐dose corticosteroid therapy may be useful for the treatment of relapse of C‐ANCA‐associated GN patients after renal transplantation; 2) the possibility of a relapse of C‐ANCA‐associated GN following renal transplantation has to be kept in mind, especially when infection precedes the deterioration of allograft kidney function.

Incidence of positive C4d deposition in long-term survival cases over 10 yr after renal transplantation

Abstract:  Background:  The incidence of positive C4d deposition in peritubular capillaries (PTC) in long‐term survival cases remains controversial. Some incidences of positive C4d deposition in PTC in cases of long‐term survival less than 10 yr have been reported. We retrospectively examined the incidence of positive C4d deposition in long‐term survival cases over 10 yr after renal transplantation and the histological and clinical characteristics of the positive C4d staining cases.