Dysregulation of apoptosis: a possible mechanism leading to chronic progressive renal histological changes in lupus nephritis

Objective To evaluate apoptosis in lupus nephritis and the relationship bet ween the existence of apoptotic cells in renal tissue and histopathological or clinical changes. Methods Apoptosis was detected by in situ nick-end labeling techniques (TUN EL) in renal biopsies from 25 patients with type IV lupus nephritis (LN), 1 2 patients with IgA nephropathy IgAN, 4 patients with idiopathic mesangiopr oliferative glomerulonephritis (MsPGN) and 3 patients with acute poststrept ococcal glomerulonephritis (APGN). Normal renal tissue obtained at nephrect omy for hypernephroma in 4 adults was used as control. Proliferating cells were identified by proliferating cell nuclear antigen (PCNA) in these patie nts. Results Compared to other proliferative glomerulonephritis and controls, th e patients with lupus nephritis had less apoptotic cells, a higher ratio of PCNA + cells/TdT + cells (P/T) in renal tissues; and their P/T ratio in gl omeruli and tubulointerstitium correlated with the chronicity index, r = 0. 4983 (P = 0.0132), r = 0.8399 (P < 0.001), r = 0.6614 (P = 0.0033), respect ively. P/T ratios in the glomerulus and tubule had a positive correlation w ith 24-hour urinary protein, r = 0.8554 (P < 0.001) and r = 0.7134 (P = 0.0 01); and a negative correlation with creatinine clearance (Ccr), r = - 0.48 80 (P = 0.0133) and r = - 0.7229 (P = 0.001), which in tubules positively c orrelated with serum creatinine (Scr), r = 0.4107 (P = 0.0414). Conclusions Apoptosis is reduced in proliferative lupus nephritis. Intense proliferation without a commensurate increase in apoptosis is a possible me chanism that leads to chronic progressive renal histopathological changes.