Kazuya Takasawa

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.

Clinicopathologic features of glomerular lesions associated with hepatitis C virus infection in Japan

BackgroundWe determined the incidence of hepatitis C virus (HCV)-related glomerulonephritis in Japan and the glomerular localization of HCV-related antigens in this disorder.MethodsWe analyzed urinalysis findings in 100 consecutive Japanese patients with HCV chronic liver disease from 1993 to 1994. Immunohistochemical analysis using monoclonal or polyclonal antibodies to HCV-core antigen and polyclonal antibodies to HCV-envelope antigen was done on kidney specimens from 11 of 29 patients with antibody to HCV (anti-HCV-Ab).ResultsEight of 100 patients had proteinuria, but only 2 cases (2%) were related to HCV nephropathy. Pathohistologic analysis showed 10 patients to have hepatic glomerulosclerosis, and 9 patients had mesangial proliferative glomerulonephritis involving primary immunoglobulin A nephropathy. Membranoproliferative glomerulonephritis was seen in 4 biopsy specimens that showed subendothelial electron-dense deposits and annular structures with characteristic cryogloblin. HCV core antigen was detected along the capillary walls with the same pattern as that of immunoglobulin G deposition and electron-dense deposits in 5 of 6 specimens from patients with both anti-HCV-Ab and HCV ribonucleic acid positive in the sera, but could not be detected in any of 3 specimens, from patients with anti-HCV-Ab but no HCV ribonucleic acid. Envelope antigen was not detected in the glomeruli of any specimens.ConclusionsGlomerular lesions associated with HCV infection were characterized by deposition of immune complexes containing HCV core antigen and immunoglobulin G, and by the subendothelial deposition of cryoglobulin. These HCV-related glomerular diseases are rare in Japan (2% incidence), and these lesions should be distinguished from hepatic glomerulosclerosis related to advanced liver disease and other primary glomerular diseases.

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.