Kon, Sui Phin; (1994) Urinary C5b-9 and cytokines in idiopathic human membranous nephropathy. Doctoral thesis (M.D), UCL (University College London).

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Abstract

The immunopathogenic mechanisms in idiopathic membranous nephropathy (IMN) are unknown. Disease mechanisms may be similar in IMN and in passive Heymann nephritis (PHN) where proteinuria is mediated by C5b-9. Urinary C5b-9 (uC5b-9) is specific to PHN when compared to other experimental models and accompanies ongoing glomerular deposition of immune reactants. The primary aim of this study was to determine whether uC5b-9 can be used as a marker of active immunological injury in IMN. An ELISA was developed for the detection of uC5b-9. Discrepancies in the measurement of uC5b-9 reported in proteinuric patients when using different capture antibodies were addressed. Urinary C5b-9 was measured serially in seventy-six IMN patients who did not receive immunosuppression : fifty-seven patients with stable renal function (SRF) and nineteen patients with declining renal function (DRF). Patients with DRF excreted significantly more C5b-9 than those with SRF (p<0.001). Patients with DRF were less likely to decline further if C5b-9 excretion stopped (p<0.05). Three commonly used immunosuppressive regimens were employed and given to eighteen patients who developed renal impairment. Patients with uC5b-9 had a better clinical outcome if treatment abolished excretion of C5b-9 (p<0.005). All three regimens abolished the excretion of C5b-9. Thus this study suggests that uC5b-9 is a marker of ongoing immunological insult in IMN and can be used in the selection of patients for treatment and monitoring efficacy. Membranes in the urine from six IMN patients known to excrete C5b-9 were isolated and characterised: S-protein and CD59 were detected. The cytokines IL-1, IL-6, TNF-α and TGF-β1 were assayed by ELISA in plasma and urine samples of twenty IMN patients. Of the cytokines studied, only plasma IL-1β and urinary IL-6 were significantly elevated in the IMN group compared to healthy controls (p<0.05), but it did not correlate with uC5b-9. C5b-9 does not appear to release inflammatory cytokines in the glomerular injury of IMN.

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