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A R Clarkson

Publications and source records attributed to A R Clarkson.

At least 37 records · Page 2Linked to original sources
PubMed1994

Recurrent mesangial IgA nephritis following renal transplantation.

Recurrence of mesangial IgA deposits in renal allografts of patients whose original disease was primary IgA nephropathy (IgAN) has been studied. Forty-six patients with primary IgAN received 51 renal allografts and have been followed for 3-183 months. A prospective study of 11 patients (11 biopsies) and a retrospective analysis of 17 patients (16 biopsies; 2 nephrectomy specimens) have been combined. Seventeen of the 29 allografts had recurrent mesangial IgA deposits and of these three patients have negative urinalysis, normal glomeruli by light microscopy, and stable renal function; six patients have microhaematuria, mesangial proliferative nephritis, but at present stable renal function; and five have mesangial proliferative glomerulonephritis with microhaematuria, heavy proteinuria, hypertension, and progressive allograft failure secondary to IgA disease alone, and one of these is now back on dialysis. Three other grafts with recurrent deposits are failing because of transplant glomerulopathy or rejection. The only predictor identified for recurrence of mesangial IgA deposits was length of time post-transplantation, with allograft tissue being studied at 45.9 +/- 10.0 versus 15.3 +/- 4.8 months (P = 0.008) post-transplantation in patients with and without recurrent deposits respectively. Cyclosporin A did not prevent recurrence. By virtue of a longer follow-up of patients post-transplantation than all other reported series, these results suggest that with increasing time post-transplantation recurrence of mesangial IgA disease will become increasingly important as a cause of progressive allograft dysfunction and failure unless effective treatment is found for the primary disease.

Complement C3↗
PubMed1991

IgA antibodies to dietary antigens and lectin-binding IgA in sera from Italian, Australian, and Japanese IgA nephropathy patients.

We studied serum IgA as antibodies to dietary antigens (Ag), as lectin-binding molecules, and as conglutinin-binding immune complexes (IgAIC) in people from geographical areas in which IgA nephropathy (IgAGN) is particularly frequent. Sera from 63 Italian, 21 Australian, and 25 Japanese patients affected by IgAGN and 24 Italian, 20 Australian, and 40 Japanese healthy controls were studied. Increased values of IgAIC were detected in 42.8% of Italian patients, while only in 23.8% and 8% of Australian and Japanese patients, respectively. Mean values were significantly increased only in Italian patients (P less than 0.0001). Positive values of IgA antibodies against dietary Ag had variable prevalences, but again Italian patients showed the highest frequency, from 19% to 28.5% versus 0 to 38% in Australians and 0 to 16% in Japanese. Mean values of these antibodies were not significantly increased in any patient groups in comparison to the corresponding healthy populations. However, patients with elevated values of IgAIC had significantly higher serum concentrations of antibodies to alimentary components and a linear correlation was found between IgAIC and some IgA antibodies to food components. The relationship between these two series of data was particularly evident for Italian and Australian IgAGN patients. Moreover, the patients with positive data tended to have a cluster of increased levels of IgA antibodies against several alimentary Ag at the same time. A linear correlation was evident between values of IgA antibodies to gluten fractions and to heterologous albumins. None of these correlations was evident among healthy controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

The effect of IgA immune complexes on the proliferation of cultured human mesangial cells.

To investigate the role of IgA-containing circulating immune complexes (IgA-CIC) in mesangial cell proliferation, human mesangial cells were cultured with sera or IgA isolates from IgA-CIC-positive IgA nephropathy patients and negative controls. A solid phase anti-C3d enzyme-linked immunosorbent assay (ELISA) was used for the detection of IgA-CIC. Sera stimulated the proliferation of the mesangial cells at both 24 and 72 hours' incubation. However, there was no difference in the proliferation of cells incubated with sera from IgA-CIC-positive patients and negative controls. IgA-CIC-positive and negative IgA isolates both stimulated proliferation of mesangial cells at 24 hours' incubation. Our data do not support the hypothesis that IgA-CIC are directly responsible for mesangial cell proliferation.

Antigen-Antibody Complex↗
PubMed1989

Quantitation of glomerular angiotensin II receptors in IgA nephropathy.

Mesangial cells have receptors for angiotensin II (AII) and contract in its presence. All is known also to increase the uptake of macromolecules by the mesangium. As a first step towards the investigation of a possible role for local disturbances of the renin-angiotensin system (RAS) in immune mediated mesangial proliferative glomerulonephritis, glomerular All receptors have been quantitated retrospectively in biopsy tissue from 20 patients with IgA nephropathy for comparison with 16 biopsies that showed only minor abnormalities by light microscopy and negative immunofluorescence. An autoradiographic technique using 125I labelled [Sar1, Ile8] All facilitated the quantitation of All receptors in frozen tissue sections. Following exposure to the treated sections, x-ray film was analyzed by computerized micro-densitometry. The data obtained were optical densities of areas corresponding to the presence of glomeruli verified by reference to adjacent sections stained with periodic acid-Schiff (PAS). There was no significant difference between patients 0.67 +/- 0.16 (mean +/- SD) and controls 0.61 +/- 0.15. Among patients there was no statistically significant correlation of glomerular All receptor density with either the degree of mesangial proliferation or the extent of hyperplasia of the juxtaglomerular apparatus (JGA). There was no apparent relationship with hypertension. The absence of an increase in glomerular All receptors despite proliferation of the glomerular mesangium may represent a local down regulation in patients with IgA nephropathy.

Adult↗
PubMed1989

Thin membrane nephropathy: a clinico-pathological study.

Thin membrane nephropathy is common, representing approximately 11% of non-transplant renal biopsies. A family history of renal disease is present in at least 40% of patients. Electron microscopy is essential for its diagnosis. There are no immunofluorescence markers but light microscopic changes, usually mild, are invariably present and predict the ultrastructural findings although there is no correlation with their degree. The extent of the morphological changes bears no obvious relationship either to clinical or familial features. Immunogold studies indicate that there is reduction or loss of the subepithelial portion of the basement membrane, which apparently contains normal amounts of type IV collagen. Unnecessary urological investigations may be avoided by awareness of the condition and microscopic examination of urine for dysmorphic red blood cells. Prospective long-term studies are necessary to determine the nature and consequences of the condition.

Adolescent↗
PubMed1988

Therapeutic options in IgA nephropathy.

IgA nephropathy (IgAN) is a common form of glomerulonephritis that leads to end-stage renal disease at variable rates in 20% to 30% of cases. A rational approach to therapy requires an understanding of pathogenetic mechanisms that are largely unknown. Several therapeutic approaches have been used, generally in uncontrolled trials, aimed at lowering levels of circulating immune complexes, affecting cellular immunity, or removing antigens through dietary restriction. Thus far, no clear-cut beneficial effects are evident. Alternative means of changing glomerular hemodynamics through prevention of harmful mediators await exploration.

Antigen-Antibody Complex↗
PubMed1988

The effect of treatment with prednisolone or cyclophosphamide-warfarin-dipyridamole combination on the outcome of patients with membranous nephropathy.

Between 1973 and 1986, 109 patients with membranous nephropathy have been evaluated with respect to clinical presentation, pathological features and factors determining prognosis. Secondary disease was present in 21, and a further 21 were lost or followed for less than 12 months. The remaining 67 with idiopathic membranous nephropathy were allotted to one of three groups. Group 0 (26 patients) received no active treatment, Group 1 (12 patients) a combination of cyclophosphamide, dipyridamole and warfarin, and Group 2 (21 patients) high dose alternate day prednisolone therapy. Eight patients received other treatment or presented with end stage renal disease. No significant difference in outcome could be detected between the groups. Remission rates were equivalent as were numbers of patients judged as having progressive disease. There was no statistical difference with respect to duration of nephrotic syndrome, plasma creatinine at the end of study and change in plasma creatinine. No demonstrable benefit was obtained in predicting the outcome of disease or response to treatment from conventional pathological grading of stages I to IV as approximately equal numbers of each stage fell into good and bad categories of outcome. Similarly unusual histological features such as mesangial proliferation and immunofluorescence for deposits other than IgG and C3 were not helpful. A different approach to treatment of idiopathic membranous nephropathy is strongly recommended.

Adolescent↗
PubMed1988

Circulating immune complexes in systemic lupus erythematosus: a reappraisal of the solid phase C1q radioimmunoassay.

Data from a pool of 150 patients with systemic lupus erythematosus (SLE) were used to evaluate the clinical usefulness and specificity of the solid phase C1q radioimmunoassay (SPC1q RIA) for circulating immune complexes (CIC). We found that the assay results correlated with the severity of lupus nephritis but that they did not adequately reflect or predict disease activity so as to directly influence decisions regarding treatment. In addition, the contribution of non-IC reactants to the assay results was found to be of some concern. Finally, we could not demonstrate the presence of anti-DNA antibodies in CIC from patients with SLE.

Antigen-Antibody Complex↗
PubMed1987

Studies on glomerular immune solubilization by complement in patients with IgA nephropathy.

A study of the solubilization of glomerular immune deposits by serum or complement in patients with IgA nephropathy is described. Renal biopsy specimens were obtained from 15 patients with IgA nephropathy. These specimens were incubated with fresh and heated sera from healthy adults or with lyophilized complement components, i.e., C3 and C4, at 37 degrees C for one hour in plastic tubes. The sections were then stained with fluorescein isothiocyanate (FITC)-labelled anti-human IgA antisera and examined by fluorescence microscopy. Normal sera showed a marked capacity to solubilize the glomerular immune deposits characteristic of IgA nephropathy. The solubilization capacity was reduced after inactivation and absorption of sera with anti-human C3 antiserum. Lyophilized C3 or C4 did not show any ability to solubilize such deposits. It was concluded that the solubilization of glomerular immune deposits may require whole active (fresh) components of complement related to the alternative pathway.

Complement C3↗
PubMed1987

Adult Henoch-Schönlein nephritis.

A retrospective study was performed of all patients at the Royal Adelaide Hospital over a ten-year period with biopsy proven Henoch-Schönlein nephritis. The records of 27 patients were examined, with emphasis on clinical and histopathological presentation, treatment and outcome. A scheme for assessing glomerular histology is presented, and severity correlated with prognosis of the disease. At presentation unfavourable prognostic indicators were acute renal impairment, crescents in greater than 20% of glomeruli, and severe glomerular histological lesions. Four patients died as a result of the disease, and 20 of the patients had evidence of continued renal abnormality at follow-up. Adult Henoch-Schönlein nephritis is a potentially catastrophic disease, and requires careful assessment at presentation.

Biopsy↗
PubMed1987

IgA nephropathy.

IgA nephropathy is a syndrome and probably the most important glomerular disease in terms of incidence and mortality. This review documents the clinical and pathological features and concentrates on the evolving thoughts regarding pathogenesis and treatment.

Adult↗