Hiroko Kushimoto

Usefulness of a Highly Sensitive Urinary and Serum IL-6 Assay in Patients with Diabetic Nephropathy

Background/Aim: Interleukin-6 (IL-6) promotes the growth of renal mesangial cells. IL-6 may play a major role in such mesangial proliferation, but there has been little research on IL-6 in relation to diabetic nephropathy because of the difficulty in measuring urinary and serum IL-6 levels. Using a newly developed, highly sensitive IL-6 assay, we studied the relationship between serum and urinary IL-6 and diabetic nephropathy. Methods: We investigated 72 patients with type 2 diabetes. Urinary and serum IL-6 concentrations were measured using a chemiluminescent enzyme immunoassay with a detection limit of 0.11 pg/ml. Results: There was a significant increase of the serum IL-6 level as diabetic nephropathy progressed, with the level being 1.4 ± 0.3 pg/ml in patients with normal albuminuria, rising to 2.4 ± 0.6 pg/ml in patients with microalbuminuria and then to 4.4 ± 0.8 pg/ml in those having proteinuria. The serum IL-6 level was also significantly correlated with fibrinogen and aortic pulse wave velocity. The urinary IL-6 level was also significantly increased in diabetic patients as nephropathy progressed. Both serum and urinary IL-6 levels were high in the group with nephropathy, but there was no correlation between the two. Conclusion: The urinary IL-6 level seems to be a good indicator of diabetic nephropathy, and atherosclerotic changes were related to the serum IL-6 level. The serum IL-6 may, therefore, be useful in the evaluation of atherosclerosis including nephropathy.

The Evaluation of Corticosteroid Therapy in Conjunction with Plasma Exchange in the Treatment of Renal Cholesterol Embolic Disease

In this report, we describe 5 patients with cholesterol atheroembolic renal failure. In 3 of the 5 patients, combined therapy with corticosteroids and plasma exchange was performed. These 3 patients survived, with 2 showing an improvement in renal function. The 2 remaining patients died of multifactorial causes. The literature on therapy for cholesterol atheroembolic renal failure is reviewed and the efficacy of combined therapy by use of corticosteroids and plasma exchange is evaluated.

Complement C4d deposition in transplanted kidneys : preliminary report on long-term graft survival

Abstract:  The effects of antibody‐mediated rejection on long‐term graft survival have not been fully investigated. The aim of this study is to clarify the influence on long‐term survival of deposition of the complement split product C4d in allografts using polyclonal anti‐C4d antibody. Inclusion criteria were recipients who underwent graft biopsy during acute deterioration of graft function within the first 2 yr after transplantation. Patients whose graft did not survive more than 1 yr and who received graft from an human leucocyte antigen (HLA)‐identical sibling or an ABO‐incompatible donor were excluded. Among the 92 recipients investigated, 22 (23.9%) had peritubular capillary C4d deposition, 15 (16.3%) had glomerular capillary C4d deposition and seven (7.6%) had both peritubular and glomerular capillary C4d deposition. Twenty of these 22 patients revealed acute cellular rejection, including borderline changes. There was no significant relationship between pathological severity of acute rejection and presence or absence of peritubular capillary C4d deposition. Graft survival was inferior in patients with peritubular capillary C4d deposition to that in patients without C4d deposition (p = 0.0419). Graft survival in patients with glomerular C4d deposition did not differ from that in patients without C4d deposition. In conclusion, C4d deposition in peritubular capillaries has a substantial impact on long‐term graft survival.

Treatment With Cytapheresis for Antineutrophil Cytoplasmic Antibody‐associated Renal Vasculitis and Its Effect on Anti‐inflammatory Factors

Abstract:  To evaluate the efficacy of cytapheresis for the treatment of rapidly progressive glomerulonephritis (RPGN) caused by myeloperoxidase antineutrophil cytoplasmic antibody (MPO‐ANCA)‐associated vasculitis, the renal prognosis and the mortality rate at 1 year after treatment were compared between a Cytapheresis Group and a Steroid Pulse Group. The Cytapheresis Group included 10 patients who were treated with cytapheresis and oral corticosteroids. Five had granulocytapheresis with the Adacolumn (Japan Immuno Research Laboratories Co. Ltd, Takasaki, Japan) and the remaining five had leukocytapheresis with the leukocyte removal filter, Cellsorba (Asahi Medical Co. Ltd, Tokyo, Japan). The Steroid Pulse Group was comprised of 12 patients who were treated with methylprednisolone pulse therapy and oral corticosteroids. In the Cytapheresis Group, renal function recovered in 70% of the patients and the mortality rate was 10%. In the Steroid Pulse Group, renal function recovered in 66.7% and the mortality rate was 33.3%, with infection as the cause of death. Total doses of corticosteroids converted to prednisolone dose during a 1 month period, ranged from 280 mg to 1226 mg in the Cytapheresis Group. On the other hand, these dosages ranged from 2375 mg to 8380 mg in the Steroid Pulse Group. These results indicated that the mortality rate by infection could be reduced by adding cytapheresis therapy. Concerning the mechanism of cytapheresis, anti‐inflammatory factors such as soluble tumor necrosis factor receptor, and interleukin‐10 reduced after cytapheresis. These changes might be responsible for the efficacy of cytapheresis. In conclusion, cytapheresis is thought to be one of the effective treatments for RPGN caused by MPO‐ANCA‐associated vasculitis, reducing the levels of anti‐inflammatory factors.

Efficacy of Granulocytapheresis and Leukocytapheresis for the Treatment of Microscopic Polyangiitis

Abstract:  We evaluated the efficacy of granulocytaperesis and leukocytapheresis for the treatment of rapidly progressive glomerulonephritis (RPGN) and lung hemorrhage caused by microscopic polyangiitis. Three patients with RPGN were treated by granulocytapheresis (GCAP) and five patients with RPGN were treated by leukocytapheresis (LCAP). The prednisolone dose was 0.4 ± 0.2 g/kg/day (mean ± SD; range 0.2–0.8 g/kg/day). Pre‐treatment serum creatinine was 3.2 ± 1.4 mg/dL (1.4–5.1 mg/dL). The patients were followed for a mean period of 15 ± 6 months (6–23 months). Renal function improved in five of the eight RPGN patients. Three lung hemorrhage episodes in two different patients were treated with GCAP and one lung hemorrhage episode was treated with LCAP combined with various doses of corticosteroids. All four lung hemorrhage episodes were ameliorated. We concluded that combined therapy of GCAP or LCAP and corticosteroids is effective for the treatment of RPGN and lung hemorrhage due to microscopic polyangiitis.

Suppression of parathyroid hormone secretion in CAPD patients by intraperitoneal administration of Maxacalcitol.

BackgroundMaxacalcitol (22-oxacalcitriol; OCT) is a novel vitamin D analogue. In previous clinical studies, OCT was administered three times a week to hemodialysis patients with refractory secondary hyperparathyroidism (2HPT), in whom it acted by inhibiting parathyroid hormone secretion, as well as causing mildly elevated serum calcium. However, intravenous injection of OCT, which requires frequent visits to the outpatient clinic, degrades the quality of life of patients with continuous ambulatory peritoneal dialysis (CAPD) who otherwise visit the clinic only once or twice per month. In the present study, we investigated whether transperitoneal absorption of OCT inhibited intact parathyroid hormone (i-PTH) in CAPD patients when the OCT was added to the peritoneal dialysis fluid.MethodsPeritoneal dialysis fluid containing 20 µg of OCT was injected into the peritoneal cavity of five CAPD patients. The serum and peritoneal fluid levels of OCT, i-PTH, calcium, and phosphate were measured before and after treatment.ResultsThe mean concentration of OCT in peritoneal dialysis fluid rapidly decreased, from 25268.0 pg/ml at 0 h to 1694.0 pg/ml at 2 h and 44.9 pg/ml at 4 h. In contrast, the mean serum OCT level increased from the pretreatment level, which was below the detection limit of the assay, to 656.0 pg/ml at 0.5 h and a peak of 759.0 pg/ml at 1 h, and thereafter gradually decreased, to 713.8 pg/ml at 2 h and 555.8 pg/ml at 4 h. Mean i-PTH significantly decreased, to 83.9% of the baseline level, at 1 h (P < 0.05) and thereafter stayed at around 90%. No consistent trends in calcium and phosphate levels were observed in the five patients.ConclusionsBy injecting OCT into the peritoneal cavity, i-PTH levels could be significantly decreased. These findings indicate the therapeutic efficacy of intraperitoneal administration of OCT for CAPD patients.

Focal segmental sclerotic lesions of the glomerulus in transplanted kidneys assessed using computerized image analysis

Abstract:  Mechanisms responsible for the development of focal segmental sclerotic lesions of the glomerulus (FSGS lesions) in transplanted kidneys were investigated by morphometric analysis. The mean glomerular area and the interstitial area were measured using computerized image analysis to compare implantation biopsies (so‐called 1‐h biopsies; 1Bx) with later biopsies (episode Bx; EBx) that had been taken for diagnostic purposes to identify the cause of deteriorating renal function. Groups of patients with (group A, n = 15) or without (group B, n = 10) FSGS lesions were compared. Twelve of 15 in group A and all in group B had lost graft function due to chronic allograft nephropathy. It was found that neither the mean glomerular area nor the interstitial area differed significantly between the two groups in either 1Bx or EBx. The interstitial area was significantly increased (P = 0.007) and the mean glomerular area tended to be increased (P = 0.085) in EBx compared with 1Bx in group A but not in group B. The serum creatinine level at the time of EBx in group A correlated with the interstitial area (P = 0.031) but not the mean glomerular area. However, there was no similar correlation in group B. In conclusion, factors for the development of FSGS lesions in transplanted kidneys may be the increase in interstitial area and possible glomerular hypertrophy following transplantation, rather than pre‐existing reduced renal mass of the donor kidneys.