Interstitial myofibroblasts in IgA glomerulonephritis.
We examined renal biopsy specimens from patients with mesangial IgA glomerulonephritis (n = 25; plasma creatinine 0.05-0.30 mmol/l) to ascertain whether the myofibroblast has a role in progressive renal interstitial fibrosis. Myofibroblasts were identified by morphology and alpha smooth muscle actin (alpha-SMA) immunostaining at the light and electron microscope level. Results were related to staining for interstitial leukocytes and collagen III. A control group consisted of 6 normal renal transplant donors from whom biopsy specimens were taken at the time of vascular anastomosis. The fractional volume of interstitial alpha-SMA staining was greater in patients with mesangial IgA glomerulonephritis than in the control group (17.2 vs. 1.3%; p < 0.001). alpha-SMA staining was increased in areas of interstitial fibrosis with prominent periglomerular and peritubular distribution. Ultrastructural studies established that alpha-SMA staining in the renal interstitium was intracellular, cytoplasmic, and confined to myofibroblast-like cells and processes. The alpha-SMA expression correlated with fractional volume of tubular atrophy/dilation (r = 0.79, p < 0.001), interstitial connective tissue (r = 0.66, p < 0.001), leucocytes (r = 0.72, p < 0.005), and collagen III (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 follow-up (r = 0.77, p < 0.01). In conclusion, cells with a myofibroblast-like phenotype have a significant role in the progression of tubulointerstitial injury.
Hewitson
T D
TD
Department of Nephrology, Royal Melbourne Hospital, Australia.
Becker
G J
GJ
D000199:Actins / Q000032:analysis; D001706:Biopsy; D016022:Case-Control Studies; D005347:Fibroblasts / Q000648:ultrastructure; D005922:Glomerulonephritis, IGA / Q000473:pathology*; D006801:Humans; D007124:Immunoenzyme Techniques; D007678:Kidney Glomerulus / Q000737:chemistry / Q000473:pathology*; D008854:Microscopy, Electron; D016253:Microscopy, Immunoelectron
D000199:Actins