Individual effect of renin-angiotensin system inhibition and corticosteroid therapy in IgA glomerulonephritis: results of a pilot study.
BACKGROUND
The impact of different therapy modalities on the outcome of Immunoglobulin A glomerulonephritis (IgAGN) in individual patient is not clear. We present preliminary results from the sequential application of renin-angiotensin system (RAS) inhibition and corticosteroids to discriminate the individual effect of both therapies.


METHODS
Regardless of the degree of proteinuria, renal function and histological grading, patients with biopsy-proven IgAGN were treated with a standardized protocol. RAS inhibition was performed for 3 months. Thereafter, immunosuppressive therapy with prednisone (0.5 mg/kg body weight) on alternate days for 6 months was started. The primary endpoint was a maximal reduction of proteinuria (spot urine protein/ creatinine ratio (uPCR)), by RAS inhibition and by the combination of RAS inhibition and steroids.


RESULTS
10 patients were treated according to the protocol. During a median follow-up of 18 months, uPCR decreased from initial 230 mg/mmol (2 g/g) (median, interquartile range (IQR) 146 - 396) to 154 mg/mmol (1.4 g/g) (IQR 88 - 190) at 3 months during the RAS inhibition period (33% reduction, p = 0.01) and further to 31 mg/mmol (0.3 g/g) (IQR 21 - 71) until end of the steroid period at 9 months (80% reduction compared to uPCR at 3 month, p < 0.001). At the last F/U, uPCR (median) remained stable at 41 mg/mmol (0.4 g/g). The estimated glomerular filtration rate was stable during the whole observation period.


CONCLUSIONS
Sequential RAS inhibition and steroid treatment leads to a continuous decrease in proteinuria, beyond the decrease produced by isolated RAS inhibition. Our data suggest independent effects of both, RAS inhibition and steroids, on the reduction of proteinuria in a small, non selected group of patients with IgAGN. The hypothesis that patients with IgAGN, regardless of the degree of proteinuria, renal function and histological grading, may benefit from combination therapy with maximal RAS inhibition and low dose corticosteroids now has to be confirmed in a randomized study.
Clinic for Transplantation Immunology and Nephrology, University Hospital Basel, Basel, Switzerland.
M J
MJ
Kim
H
H
Hopfer
M T
MT
Koller
O
O
Giannini
M J
MJ
Mihatsch
M
M
Mayr
D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001706:Biopsy; D001794:Blood Pressure / Q000187:drug effects; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate / Q000187:drug effects; D005922:Glomerulonephritis, IGA / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D012084:Renin-Angiotensin System / Q000187:drug effects*; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome
D000806:Angiotensin-Converting Enzyme Inhibitors; D005938:Glucocorticoids