PCR analysis of human renal biopsies--renin gene regulation in glomerulonephritis

Animal studies show that the renin-angiotensin system contributes to hypertension, glomerulosclerosis and progressive chronic renal failure in renal disease. Direct data on the activity of the renal renin-angiotensin system (RAS) in human renal disease are scarce, however. The small amount of tissue in renal biopsies and insufficient sensitivity of analytical methods have precluded reliable measurements of the tissue components of the RAS in the past. Due to its highly sensitivity the quantitative polymerase chain reaction (QPCR) assay today allows the quantitation of gene transcription products in small tissue samples, for example, renal biopsies. The clinical applicability of the PCR has raised the interest in this methodology. We adopted quantitative PCR to study expression and regulation of the renin gene in patients with different forms of glomerulonephritis. For PCR a deletion mutant of the renin gene was used as an internal standard exhibiting the same primer binding sites as the human gene. The number of glomeruli per biopsy sample was counted by microscopic transillumination immediately after biopsy and was used as a reference base. Renin mRNA was expressed as fg per glomerulus. Compared to nonaffected tissue of tumor nephrectomy samples, renin gene expression was significantly lower in glomerulonephritic patients without converting enzyme inhibitor (CEI) treatment, that is, 63 +/- 20 (6) versus 250 +/- 50 (7) (P < 0.02), although plasma renin concentration was in the normal range. Significantly higher renin mRNA expression was found in patients with glomerulonephritis treated with CEI, that is, 210 +/- 50 (8) versus 63 +/- 20 (6) in patients not treated.(ABSTRACT TRUNCATED AT 250 WORDS)