We examined renal biopsy specimens from patients with mesangial IgA gl
omerulonephritis (n = 25; plasma creatinine 0.05-0.30 mmol/l) to ascer
tain whether the myofibroblast has a role in progressive renal interst
itial fibrosis. Myofibroblasts were identified by morphology and alpha
smooth muscle actin (a-SMA) immunostaining at the light and electron
microscope level. Results were related to staining for interstitial le
ukocytes and collagen III. A control group consisted of 6 normal renal
transplant donors from whom biopsy specimens were taken at the time o
f vascular anastomosis. The fractional volume of interstitial alpha-SM
A staining was greater in patients with mesangial IgA glomerulonephrit
is than in the control group (17.2 vs. 1.3%; p<0.001). alpha-SMA stain
ing was increased in areas of interstitial fibrosis with prominent per
iglomerular and peritubular distribution. Ultrastructural studies esta
blished that alpha-SMA staining in the renal interstitium was intracel
lular, cytoplasmic, and confined to myofibroblast-like cells and proce
sses. The a-SMA expression correlated with fractional volume of tubula
r atrophy/dilation (r = 0.79, p < 0.001), interstitial connective tiss
ue (r = 0.66, p<0.001), leucocytes (r = 0.72, p<0.005), and collagen I
II (r = 0.71, p<0.001). Staining correlated with renal function at the
time of biopsy (r = 0.64, p<0.005) and after 2 years of followup (r =
0.77, p<0.01). In conclusion, cells with a myofibroblast-like phenoty
pe have a significant role in the progression of tubulointerstitial in
jury.