URINARY-EXCRETION OF CYTOKINES AND COMPLEMENT SC5B-9 IN IDIOPATHIC MEMBRANOUS GLOMERULONEPHRITIS

Idiopathic membranous glomerulonephritis (iMGN) has previously been sh own to be associated with urinary excretion of terminal complement com plexes while increased urinary levels of cytokines have been reported in mesangial proliferative glomerulonephritis. In the present cross-se ctional study urinary excretion of IL-1 beta, TNF-alpha, IL-6, and sol uble C5b-9 (SC5b-9) was examined for 23 patients with iMGN, 16 patient s with diabetic nephropathy (DNP), and 17 healthy subjects. IL-1 beta excretion (pg/mg crea) was significantly higher in iMGN patients (375, range 162-11 000) than in DNP patients (39, range 22-59, P < 0.001) o r healthy controls (151, range 23-481, P < 0.001). TNF-alpha excretion rate (pg/mg crea) was clearly higher (38, range 21-700) in iMGN patie nts than in DNP patients (14, range 8-52, P < 0.001) or healthy subjec ts (11, range 7-26, P < 0.001). Median IL-6 excretion (pg/mg crea) was only marginally higher in iMGN patients (73, range 0-850) than in hea lthy subjects (64, range 3-158, P = 0.02) but significantly higher tha n in DNP patients (29, range 17-47, P < 0.001). No significant correla tion with corresponding serum values was observed for urinary IL-6 or TNF-alpha excretion. Urinary IL-1 beta and TNF-alpha correlated with d ecreased renal function. Five of 23 patients showed progression of iMG N over a follow-up of 6 months. The excretion of all cytokines, TNF-al pha in particular, was significantly higher in patients with a progres sive disease than in the other patients. High TNF-alpha excretion (>57 pg/mg crea) was detected in 4/5 patients with progression but in none of the stable patients (P < 0.001). Seventy-seven per cent of the iMG N patients and 94% of DNP patients, but none of the healthy subjects h ad detectable SC5b-9 excretion. In DNP patients the urinary SC5b-9 lev els correlated with proteinuria whereas in iMGN the SC5b-9 excretion c ould not be accounted for by proteinuria alone. Urinary excretion of S C5b-9 correlated with decreased renal function and had a relationship to urinary IL-1 beta and TNF-alpha excretion in iMGN patients. Moreove r the median excretion rate of SC5b-9 was higher in patients with than in those without progression of iMGN. The results suggest that increa sed urinary IL-1 beta, TNF-alpha, and SC5b-9 excretion are detected in patients having iMGN. They may be indicators of a progressive renal d isease in iMGN.