Angiotensin-converting enzyme inhibition in experimental in-situ immune complex glomerulonephritis: influence on renal function, proteinuria, and morphology.
BACKGROUND
Converting enzyme inhibition (CEI) ameliorates progressive loss of function in non-immune-mediated renal diseases and experimental hypertension. Little, however, is known on the potential role of CEI in established experimental chronic glomerular immune injury. We therefore studied the effect of the CEI ramipril on renal function and morphology in a model of immune mediated glomerular injury.


METHODS
The immune complex glomerulonephritis was induced in uninephrectomized rats by intrarenal perfusion with the cationized antigen followed by an intravenous application of the antibody. This disease is characterized by the development of progressive albuminuria and a nephrotic syndrome (albuminuria: immune complex glomerulonephritis 342 +/- 58, control 76 +/- 18 mg/24h; P < 0.001). The CEI by ramipril, dissolved in the drinking water, was given 28 weeks after induction of the disease and treatment was continued for 12 weeks.


RESULTS
In these experiments ramipril significantly reduced albumin excretion (immune complex glomerulonephritis + CEI 109 +/- 16 mg/24h; P < 0.01) when compared with untreated nephritic rats. Ramipril, however, did not significantly change inulin clearances (immune complex glomerulonephritis 224 +/- 67, immune complex glomerulonephritis + CEI 278 +/- 48 microliters/min/100 g bw). Glomerular structural damage expressed as glomerular damage index was significantly greater in rats with immune complex glomerulonephritis when compared with controls (immune complex glomerulonephritis 0.91 +/- 0.13; control 0.60 +/- 0.08; P < 0.05), but was uneffected by the treatment with the CEI (immune complex) glomerulonephritis + CEI 1.02 +/- 0.26; control + CEI 0.63 +/- 0.11).


CONCLUSIONS
These data demonstrate that ramipril reduced albuminuria in a model of immune complex glomerulonephritis; however, it failed to alter GFR and glomerular damage index. The study suggests that ramipril ameliorates proteinuria independently of obvious glomerular histological changes. The reduction of proteinuria is, however, associated with a significant decrease in filtration fraction and therefore is at least partially haemodynamically mediated.
Thaiss
F
F
University Hospital Eppendorf, Department of Internal Medicine, Hamburg, Germany.
Haas
C
C
Helmchen
U
U
Wenzel
U
U
Stahl
R A
RA
D000419:Albuminuria / Q000188:drug therapy / Q000378:metabolism*; D000704:Analysis of Variance; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D005921:Glomerulonephritis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D007677:Kidney Function Tests; D008055:Lipids / Q000097:blood; D008297:Male; D009929:Organ Size; D017257:Ramipril / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012083:Renin / Q000097:blood / Q000187:drug effects; D012709:Serum Albumin / Q000378:metabolism*
D000806:Angiotensin-Converting Enzyme Inhibitors; D008055:Lipids; D012709:Serum Albumin; D012083:Renin; D017257:Ramipril