Lupus Nephritis

Objective. To determine the cumulative rate of relapse of lupus nephritis that has been treated successfully with cyclophosphamide (CYC), and to estimate the association between time to relapse and demographic, clinical, laboratory, and treatment variables.Methods. This was an observational study of 48 systemic lupus erythematosus (SLE) patients who were treated successfully with CYC between 1979 and 1993 and followed up thereafter at 3 university hospitals. Demographic and clinical variables, laboratory data during the first month of nephritis, and therapy-related variables were recorded from charts. Renal biopsy specimens were retrieved and analyzed by a pathologist. Relapse of nephritis was the outcome of interest. Descriptive analysis of patients who did and those who did not have a relapse was performed by chi-square test, Fisher's exact test, and Wilcoxon 2-sample test. The cumulative rate of relapse was computed using the actuarial method. Univariate comparisons of time to relapse were computed by log-rank test. Proportional hazards modeling was used to assess the combined effect of patient characteristics that have been hypothesized to be prognostic factors.Results. Nephritis relapsed in 11 patients. Previous hematologic disorder, arthritis or arthralgia, and the use of CYC in oral form were more frequent in patients who had a relapse. The cumulative rate of relapse was 25% and 46% at 5 years and 10 years, respectively. A significant univariate difference in time to relapse was found when patients were stratified by time from diagnosis to initiation of CYC treatment (⩽ 5 months versus >5 months; P = 0.02). By multivariate analysis, age <29 years at nephritis onset (relative risk [RR] 6.29, 95% confidence interval [95% CI] 1.13–34.94, P = 0.03) and delay of >5 months from onset of nephritis to initiation of CYC therapy (RR 3.66, 95% CI 1.06–12.63, P = 0.04) were independently associated with time to relapse.Conclusion. A selected population of SLE patients may have long-term remission of renal disease following successful CYC therapy. Patients in whom CYC treatment is delayed or who are young at the time of nephritis onset are at increased risk of relapse.

Many immunedeficiency syndromes are associated with autoimmune disorders. We here report on a girl with a systemic lupus erythematosus-like disease who suffered from both hyperimmunoglobulin M syndrome (HIGMS) and C1q deficiency. Despite severe central nervous system-lupus like disease, probably due to C1q deficiency, kidney function was relatively spared. IgM autoantibody might play a protective role against lupus-glomerulonephritis.

Background. FcgRIIa is a low affinity receptor that has two co-dominantly expressed alleles, R131 and H131, which differ in their ability to bind immunoglo- bulin G (IgG) subclasses. Cells expressing H131 bind more efficiently complexed IgG2 and IgG3 than those expressing the R131 variant. The FcgRIIa polymorph- ism has been shown to be associated with lupus nephritis. Here we evaluated

ObjectiveThe autoantibody specificities that dominate the deposits in lupus kidneys remain unclear. Reasoning that previously utilized elution buffers such as acidic glycine and ammonium thiocyanate may not have been maximally effective in eluting all Ig deposits from the kidneys, this study was conducted to experiment with a stronger dissociating agent, urea-glycine.The autoantibody specificities that dominate the deposits in lupus kidneys remain unclear. Reasoning that previously utilized elution buffers such as acidic glycine and ammonium thiocyanate may not have been maximally effective in eluting all Ig deposits from the kidneys, this study was conducted to experiment with a stronger dissociating agent, urea-glycine.MethodsSeven antinuclear antibody–positive, nephritic female (SWR × NZB)F1 (SNF1) lupus mice were selected for the elution study. Deposited Ig was eluted from their kidneys using 3 different elution buffers: 0.15M glycine-HCl buffer, 1.3M ammonia thiocyanate/0.15M glycine-HCl buffer, and 5M urea/0.15M glycine-HCl buffer. All eluates were tested for specificity against a variety of nuclear and glomerular antigens.Seven antinuclear antibody–positive, nephritic female (SWR × NZB)F1 (SNF1) lupus mice were selected for the elution study. Deposited Ig was eluted from their kidneys using 3 different elution buffers: 0.15M glycine-HCl buffer, 1.3M ammonia thiocyanate/0.15M glycine-HCl buffer, and 5M urea/0.15M glycine-HCl buffer. All eluates were tested for specificity against a variety of nuclear and glomerular antigens.ResultsCompared with conventional elution buffers, the urea-based regimen eluted severalfold more IgG and IgM antinuclear antibodies from the kidneys of nephritic SNF1 lupus mice. IgG anti–double-stranded DNA (anti-dsDNA) antibodies were not only the most prevalent species in these renal deposits, they were also heavily enriched in the kidneys, relative to the corresponding serum levels. A substantial fraction of the anti–single-stranded DNA and antihistone/DNA (but not antihistone) reactivity in these eluates was due to cross-reactive anti-dsDNA antibodies. No reactivity with SSA, SSB, Sm, RNP, Jo-1, Scl-70, or ribosomal P antigens could be demonstrated in these eluates. Importantly, the urea-glycine eluates differed from the conventional eluates in having significantly greater reactivity to glomerular substrate and laminin.Compared with conventional elution buffers, the urea-based regimen eluted severalfold more IgG and IgM antinuclear antibodies from the kidneys of nephritic SNF1 lupus mice. IgG anti–double-stranded DNA (anti-dsDNA) antibodies were not only the most prevalent species in these renal deposits, they were also heavily enriched in the kidneys, relative to the corresponding serum levels. A substantial fraction of the anti–single-stranded DNA and antihistone/DNA (but not antihistone) reactivity in these eluates was due to cross-reactive anti-dsDNA antibodies. No reactivity with SSA, SSB, Sm, RNP, Jo-1, Scl-70, or ribosomal P antigens could be demonstrated in these eluates. Importantly, the urea-glycine eluates differed from the conventional eluates in having significantly greater reactivity to glomerular substrate and laminin.ConclusionThis novel urea-based elution provides further support for the dominance of antibodies in lupus kidneys, with strong polyreactivity to DNA and glomerular substrate.This novel urea-based elution provides further support for the dominance of antibodies in lupus kidneys, with strong polyreactivity to DNA and glomerular substrate.

To evaluate the efficacy of pentoxifylline in the treatment of refractory nephrotic syndrome secondary to lupus nephritis. We studied 11 patients who met the following inclusion criteria: (1) systemic lupus erythematosus (SLE) according to the American College of Rheumatology criteria; (2) lupus nephritis class III, IV, or V according to the World Health Organization; (3) proteinuria in the nephrotic range (&gt; or = 3 g/24 h) for at least 6 months despite treatment. All patients received pentoxifylline 800-1600 mg/day. Clinical and laboratory data, including creatinine, urine test, creatinine clearance, and 24-h urinary protein, were collected monthly for 6 months. No changes in treatment were allowed, except for alterations in the dose of prednisone. All patients had received corticosteroids and immunosuppressants for at least 6 months. All patients showed a decrease in proteinuria concentrations after use of pentoxifylline from a median of 5.5 to 2.0 (p = 0.003). No patient disco...