Takero Naito

Risk Factors for Infection and Immunoglobulin Replacement Therapy in Adult Nephrotic Syndrome

Infection has been recognized as an important cause of morbidity and mortality in children with nephrotic syndrome. However, the incidence and severity of infection and the mechanisms responsible for the increased susceptibility to infection are still unclear in adults. We studied 86 consecutive adult patients with nephrotic syndrome but no diabetic nephropathy. Risk factors for infection were evaluated by logistic regression analysis. Infections were found in 16 patients (19%), of whom six died of infection and two developed end-stage renal failure associated with infection. The relative risk for bacterial infection among patients with serum immunoglobulin G (IgG) levels below 600 mg/dL was 6.74 compared with that for patients with serum IgG levels over 600 mg/dL (95% confidence interval, 1.22 to 36.32; P = 0.029). In patients with serum creatinine levels over 2.0 mg/dL, the relative risk of bacterial infection was 5.31 compared with patients with serum creatinine levels below 2.0 mg/dL (95% confidence interval, 1.08 to 26.09; P = 0.040). Intravenous immunoglobulin (10 to 15 g) was administered prospectively every 4 weeks to 18 patients with serum IgG levels below 600 mg/dL until serum IgG levels increased to over 600 mg/dL. Administration of immunoglobulin resulted in a decreased rate of bacterial infections to a level equal to that in patients with endogenous levels over 600 mg/dL. These data indicate that hypogammaglobulinemia and renal insufficiency are independent risk factors for bacterial infection in adult patients with nephrotic syndrome. The effects of intravenous immunoglobulin suggest that maintenance of serum IgG levels over 600 mg/dL may reduce the risk of infection.

Effect of cyclosporine therapy on idiopathic membranous nephropathy presented with refractory nephrotic syndrome

AbstractBackground. Recent studies suggested the possible benefits of cyclosporine (CsA) therapy in patients with membranous nephropathy, although most of these studies were short-term. An uncontrolled retrospective study was undertaken to evaluate the long-term effect of CsA therapy on idiopathic membranous nephropathy presented with refractory nephrotic syndrome. Methods. The subjects were eight patients with idiopathic membranous nephropathy presenting with refractory nephrotic syndrome. All patients had received a course of corticosteroid therapy before CsA therapy, and had not responded to the corticosteroid, including one or two administrations of intravenous methylprednisolone pulse therapy. The CsA doses were adjusted to maintain trough blood level at 100 ng/ml during the first 3 months and then reduced to maintain the level at 50 ng/ml in patients who had responded to partial remission. Results. CsA therapy induced a marked decrease in proteinuria from the first month, and a significant decrease from month 3 and thereafter. The mean serum total protein and albumin levels rose, and total cholesterol fell significantly with CsA therapy. The serum creatinine level was unchanged during CsA therapy. Three patients showed complete remission and two were in partial remission, while three were nephrotic at 12 months of CsA therapy. From 18 to 24 months of CsA therapy, three patients were in complete remission, four were in partial remission, and one patient was nephrotic. There were no side effects of CsA, except for gum hyperplasia and hypertrichosis in one patient. Conclusion. These results suggest that long-term CsA therapy at a low or moderate dose is potentially effective and safe in most nephrotic patients with idiopathic membranous nephropathy refractory to corticosteroid therapy.

Nature of renal involvement in the acro-renal-ocular syndrome.

A 16-year-old female with acro-renal-ocular syndrome complicated by ventricular septal defect is described. Renal biopsy was performed for the first time in this syndrome, and the results suggested that proteinuria and renal dysfunction were caused by chronic pyelonephritis secondary to malrotation of the kidney and anomalous pelves. Chronic renal failure and hypoplasia of the optic papillae were also observed in the patients mother, suggesting a participation of heredity in the pathogenesis of the syndrome.

Role of Plasminogen Activator Inhibitor on Nephrotoxic Nephritis and Its Modulation by Tumor Necrosis Factor

To evaluate the suggested imbalance between coagulation and fibrinolysis in the development of glomerulonephritis, plasminogen activator inhibitor (PAI) activity was studied in the plasma of rats with nephrotoxic nephritis. PAI activity rose within 1 h of the injection of nephrotoxic globulin (NTG), peaked at 2 h and returned to the normal range within 24 h. PAI activity was dependent on the dose of NTG and increased significantly during passage through the kidney. PAI activity was also detected in the culture supernatant from isolated glomeruli with nephrotoxic nephritis. Intracapillary fibrin deposits were formed within 2 h; their numbers increased gradually over 24 h. Tumor necrosis factor (TNF) also induced a progressive increase in PAI activity in normal rats. The injection of TNF to rats with NTG synergistically accelerated both the increase in PAI activity and the prevalence of fibrin deposits. These results suggest that PAI may be released from the glomeruli affected by nephrotoxic nephritis and imply that PAI may play a role in the local coagulation in the capillaries of the nephritic kidneys, although this is probably not the only mechanism which explains the continued formation of the glomerular fibrin deposits.

Application of Genetically Engineered Tubular Epithelial Cells in Kidney Disease

We constructed an ex vivo gene transfer system to deliver cytokines into the kidney and circulation using genetically modified renal tubular epithelial cells (TEC). TEC were infected with recombinant retroviruses expressing macrophage (Mϕ) growth factors using a retroviral Moloney murine leukemia virus-based MFG vector. These infected TEC have the capacity to secrete stable and sustained amounts of cytokines for prolonged periods (>4 months) in vitro and in vivo (>28 days). Implanting genetically modified TEC secreting Mϕ growth factors under the kidney capsule initiates severe local renal injury in mice with a deficiency in Fas (Faslpr gene). This system offers a novel and powerful approach to probe for the impact of sustained cytokine expression in the progression of kidney destruction.