S R MEADOW, FRCP, DCH, senior lecturer and consultant paediatrician a nephrotic syndrome and a high proportion of crescents in renal biopsy specimens was associated with a poor outcome. Neither the clinical presentation nor the renal morphology were, however, precise determinants of outcome. Outcome was not related to age, associated streptococcal infection, or recurrences of the rash. The clinical state two years after presentation was compared with the state six and a half years or more after presentation in 76 patients. The clinical state had changed in 32 patients, in 17 of whom it had deteriorated. It was not possible to identify with any certainty the patients who would deteriorate (or improve). Patients who have had Henoch-Schonlein nephritis should be followed up for at least five years.

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Although the short- and medium-term (5-10 years) outcome of patients with lupus nephritis has been studied extensively, there are very few data on the second and subsequent decades. We studied outcome in 110 local patients investigated at a single centre before 1986, who all had potential follow-up of more than 10 years (actual 2-31 years, median 15.5 years). At last follow-up, 40 patients were dead and 70 alive, nine of whom were on maintenance dialysis or transplanted, actuarial survivals being 84%, 72%, 62%, 61% and 54% at 5, 10, 15, 20 and 25 years for the group as a whole. Survival was better in the cohort 1976-86 (n = 60) than in that from 1963-75 (n = 50) (90, 81 and 76% vs. 78, 56 and 43% at 5, 10 and 15 years, p < 0.001). Sepsis (12) and myocardial infarction (8) were the principal causes of death. Of living patients with renal function, 38% had normal urine and renal function, 11 were off all treatment (19%), 62% had persistent proteinuria and 18% had reduced but generally stable renal function. Renal failure, in those patients who developed it, occurred during the first decade and none of 67 patients actually followed more than 10 years subsequently went into renal failure. Induction treatment was with prednisolone, combined with azathioprine in more severe forms of nephritis, and from the middle 1970s to 1986, 30 with methylprednisolone and in 12 cases plasma exchange. Seventeen other patients were treated using oral cyclophosphamide during the 1960s. No patient received i.v. cyclophosphamide as induction therapy, although nine patients had this form of treatment later, largely because of non-compliance. Serious complications of lupus and/or its treatment occurred in 49%: sepsis in 32, ischaemic heart disease in 20, thrombosis in one and avascular necrosis of bone in eight. In contrast, fracturing osteoporosis occurred in only three, and cataracts requiring surgery and diabetes mellitus in none. The very long-term outlook of lupus nephritis, especially its more severe forms, has improved, but that with current management strategies only a minority of patients are able to stop treatment altogether, and the incidence of serious complications is high.

Mononuclear inflammatory cells were studied using monoclonal antibodies in the interstitium and glomeruli of 35 renal biopsy specimens from patients with lupus nephritis already taking immunosuppressants. The aims of this study were to assess the composition and significance of the infiltrate, and to assess correlations with immediate glomerular function and ability to predict the future course of the disease. The majority of interstitial cells were T lymphocytes and monocytes/macrophages. The number of interstitial CD4 + ve T helper/inducer lymphocytes was greater than that of CD8 + ve T cytotoxic/suppressor cells in only 19 out of 35 biopsies, the mean CD4:CD8 ratio being only 1.5 +/- 1.2. NK cells and B lymphocytes were a minor component only. Some expression of IL-2, transferrin and C3b receptors was seen on interstitial cells, but HLA-DR expressing cells were much in excess of controls and the numbers of tubular cells expressing HLA-DR was also increased. The number of interstitial T cells, CD4 + ve cells and monocytes/macrophages was highly correlated with the extent of chronic damage judged by optical microscopy. There was also an association between glomerular function at biopsy and numbers of interstitial T cells, CD8 + ve cells, monocytes/macrophages and DR expressing cells. Subsequent decline in renal function, however, was associated only with numbers of monocytes/macrophages and the rather small number of C3b receptor-positive cells. The presence of tubulointerstitial immune aggregates of Ig and/or C in 63% of patients was associated with greater numbers of NK cells. As previously described, the degree of renal function at biopsy correlated with a chronicity index based on optical microscopy. No correlations were found between numbers or types (mostly monocyte/macrophages) of intraglomerular leukocytes and clinical or biopsy features, except that more proliferative types showed greater leukocyte numbers. One hypothesis consistent with our findings is that interstitial T cells and monocytes may be important determinants of pathogenesis and progression of lupus nephritis. While several mechanisms may play an initial role, interstitial monocytes may be the major factor in chronic injury.

The literature on the treatment of lupus nephritis is scattered, much of it in rheumatological rather than nephrological journals. Whatever our ignorance of the nature and genesis of lupus nephritis, under empirical treatment the prognosis, especially for severe forms, has improved dramatically during the past 20 years. For severe lupus nephritis, the evidence that the addition of cytotoxic agents to corticosteroids improves outcome is now secure, and discussion centres mainly on which drug to use and by what route. Intravenous methylprednisolone is at least as effective as high-dose tapering oral therapy for initial treatment, and carries fewer side-effects. The role of plasma exchange in lupus remains undefined: it may have a role in the treatment of cerebral manifestations or otherwise resistant patients, but controlled trials have failed to show benefit. Future developments will probably centre around the use of specific monoclonal antibodies which target specific groups and subgroups of cells, "humanised" by the splicing of human Fc piece to rodent (fab)2, perhaps bearing toxins. To use these agents to best advantage, however, we will have to understand better than we do today the nature of the cellular defects in the immune response which underlie the lupus syndrome.

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