Persistent high prevalence of thyroid antibodies after immunosuppressive therapy in subjects with glomerulonephritis. A prospective three-year follow-up study.

The prevalence of thyroid antibodies, indicating an autoimmune thyroiditis, has been shown to be significantly increased in patients with autoimmune diseases. A 3-year prospective follow-up study of 42 patients with biopsy-confirmed glomerulonephritis is presented. Although the majority of patients had been treated with immunosuppressants, the prevalence of thyroid peroxidase antibodies was unchanged in both females and males, 47 and 15% respectively, at follow-up. Likewise, the prevalence of thyroglobulin antibodies was unaffected as was that of antinuclear antibodies (ANA) when analysing males and females together. However, for males there was a trend to higher prevalence for ANA at follow-up. On the other hand, the prevalence of antineutrophil cytoplasmic antibodies declined. Furthermore, thyroid antibodies were not restricted to membranous nephropathy, and notably found in 4 out of the 8 patients with vasculitis.

Relapse rate, renal survival, and cancer morbidity in patients with Wegener's granulomatosis or microscopic polyangiitis with renal involvement.

Wegener's granulomatosis (WG) and microscopic polyangiitis (MPA) are both frequently associated with antineutrophil cytoplasmic autoantibodies (ANCA). Immunosuppressive treatment has dramatically improved outcome for these patients, but today we have to deal with the problems of relapses, cases refractory to treatment, and long-term side effects of therapy. This study comprises a consecutive series of 123 patients with WG (n=56) or MPA (n=67) with biopsy-confirmed renal involvement, followed up for a median of 55 mo (range, 0.1 to 273.2 mo). ANCA was detected by enzyme-linked immunosorbent assay in 97% of patients. Nearly half of the patients (46%) relapsed. There was no statistically significant difference in overall relapse rate according to type of ANCA. Renal survival was 78% in patients alive at the end of follow-up. Three variables seemed important for renal survival: serum creatinine, the titer of proteinase 3-ANCA measured by capture enzyme-linked immunosorbent assay, and B thrombocyte count, at time of referral. Cancer incidence data were obtained from the population-based South Swedish Regional Tumor Registry. Standardized morbidity ratio was calculated using expected values from the health care region. We found an 11-fold increase in risk for bladder cancer in patients treated with cyclophosphamide for at least 12 mo. Skin carcinoma had the strongest relationship with azathioprine use for at least 12 mo and with corticosteroid therapy for at least 48 mo. In addition, four patients developed myelodysplastic syndrome and five had carcinoma in situ of the skin. Because the therapeutic regimen used today is not efficient enough to prevent relapses and is associated with a host of side effects, of which the risk for cancer is by far the most important, improved therapy and medical care are needed for patients with WG and MPA.

Prevalence of autoantibodies associated with glomerulonephritis, unaffected after extracorporeal shock wave lithotripsy for renal calculi, in a three-year follow-up.

Extracorporeal shock wave lithotripsy (ESWL) has become a useful tool in the treatment of renal calculi, but side effects may occur. Hitherto, two case reports have been published of an anti-glomerular basement membrane disease resulting in end-stage renal failure following ESWL treatment. In this prospective study of 59 consecutive patients undergoing ESWL for renal calculi, the prevalence of autoantibodies associated with glomerulonephritis was investigated before ESWL and at 3-year follow-up. The prevalences of antinuclear, anti-glomerular basement membrane, anti-neutrophil cytoplasmic and thyroid antibodies were found to be within the respective normal ranges prior to the first ESWL treatment and to be unaffected at follow-up.

Rapid screening assay for anti-GBM antibody and ANCAs; an important tool for the differential diagnosis of pulmonary renal syndromes.

BACKGROUND: Pulmonary renal syndrome is encountered in several diseases such as Goodpasture's syndrome, antineutrophil cytoplasmic antibody (ANCA) associated systemic vasculitis, systemic lupus erythematosus (SLE) and infection-associated or drug-induced glomerulonephritis. To preserve organ function it is of vital importance to make the correct diagnosis and institute adequate therapy early, in the acute phase. METHOD: An enzyme-linked immunosorbent assay (ELISA), specially designed as a rapid screening assay for antiglomerular basement membrane (anti-GBM) antibody, proteinase-3 (PR3-) ANCA and myeloperoxidase-(MPO-) ANCA were evaluated from 1060 serum samples drawn from patients with clinically suspected pulmonary renal syndrome or rapidly progressive glomerulonephritis (RPGN). RESULTS: Of the 1060 serum samples, 142 were positive for anti-GBM antibody (n = 19), PR3-ANCA (n = 60), or MPO-ANCA (n = 73). Of the 142 samples, 10 were double positive. Reanalysis of positive sera with a quantitative ELISA yielded results manifesting good correlation with those of the the rapid screening assay. Of 918 sera found to be negative in the rapid screening assay, 105 were also tested with IIF, 11 being found to be positive. However, these 11 sera manifested no specificity for PR3 or MPO, but some were specific for bactericidal/permeability-increasing proteins, lactoferrin or elastase ANCAs. Two of the patients whose sera yielded negative results in the rapid assay had systemic vasculitis. CONCLUSION: The ELISA thus detects the true antibodies to PR3, MPO, and GBM, whereas IIF detects additional specificities. The findings suggest the rapid assay results to be of high positive predictive value, and the assay to be of high diagnostic specificity and sensitivity and thus useful in the diagnostic workup in suspected cases of RPGN or pulmonary renal syndrome.

Increased prevalence of thyroid peroxidase antibodies (TPO-Ab) in women with glomerulonephritis.

In a cross-sectional study adjusting for age, gender, and catchment area, the prevalence of thyroid antibodies was assessed in 51 consecutive subjects with biopsy-proven glomerulonephritis and in 112 control subjects admitted for extracorporeal shock-wave lithotripsy treatment for renal stones. Women with glomerulonephritis had both a significantly greater prevalence of thyroid peroxidase antibodies (odds ratio 3.85, 95% confidence interval 1.04-14.3) and an increased prevalence of elevated serum TSH values (P = 0.007). No such difference was found in men. The prevalence of thyroglobulin antibodies did not differ between the groups. It is suggested that the possibility of an autoimmune thyroid disease should be taken into consideration in patients with glomerulonephritis, particularly in women.