PCR ANALYSIS OF HUMAN RENAL BIOPSIES - RENIN GENE-REGULATION IN GLOMERULONEPHRITIS

PCR analysis of human renal biopsies-Renin gene regulation in glomerul onephritis. Animal studies show that the renin-angiotensin system cont ributes to hypertension, glomerulosclerosis and progressive chronic re nal failure in renal disease. Direct data on the activity of the renal renin-angiotensin system (RAS) in human renal disease are scarce, how ever. The small amount of tissue in renal biopsies and insufficient se nsitivity of analytical methods have precluded reliable measurements o f the tissue components of the RAS in the past. Due to its high sensit ivity the quantitative polymerase chain reaction (QPCR) assay today al lows the quantitation of gene transcription products in small tissue s amples, for example, renal biopsies. The clinical applicability of the PCR has raised the interest in this methodology. We adopted quantitat ive PCR to study expression and regulation of the renin gene in patien ts with different forms of glomerulonephritis. For PCR a deletion muta nt of the renin gene was used as an internal standard exhibiting the s ame primer binding sites as the human gene. The number of glomeruli pe r biopsy sample was counted by microscopic transillumination immediate ly after biopsy and was used as a reference base. Renin mRNA was expre ssed as fg per glomerulus. Compared to nonaffected tissue of tumor nep hrectomy samples, renin gene expression was significantly lower in glo merulonephritic patients without converting enzyme inhibitor (CEI) tre atment, that is, 63 +/- 20 (6) versus 250 +/- 50 (7) (P < 0.02), altho ugh plasma renin concentration was in the normal range. Significantly higher renin mRNA expression was found in patients with glomerulonephr itis treated with CEI, that is, 210 +/- 50 (8) versus 63 +/- 20 (6) in patients not treated. The data document (i) that quantitative PCR ass ays permit determination of renin gene expression in human renal disea se, and that (ii) expression of the renin gene is low early in the cou rse of glomerulonephritis.