Apoptosis and proliferating cell nuclear antigen in lupus nephritis (class IV) and membranoproliferative glomerulonephritis

Abstract

Background: The role of apoptosis in the pathogenesis of renal diseases has not been clearly established. Proliferating cell nuclear antigen (PCNA) is also a proliferation marker. In this study, we investigated the relationship between clinical course and PCNA apoptosis on baseline renal biopsy in patients with Lupus nephritis (LN) and membranoproliferative glomerulonephritis (MPGN). Methods: Thirty-nine patients with proliferative glomerulonephritis [lupus nephritis (LN)[21] and MPGN[18]] were included in this study. PCNA and apoptosis on renal biopsies were detected by immunohistochemical and terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (TUNEL) methods, respectively. We calculated the ratios of intraglomerular apoptotic cells and PCNA positive cells per glomeruli, and total numbers of apoptotic tubular cells and PCNA positive tubular cells among the 100 tubular cells, and PCNA positive cell and apoptotic cell on two different tubulointerstitial areas (40 x 10). Results: In LN: Apoptotic indexes of glomerulus and tubulus were 1.08 ± 0.49 and 3.71 ± 1.38, respectively. PCNA positivities were found at 16.76 ± 11.34%, 46.57 ± 22.54%, and 40.28 ± 23.14% on glomerulus, tubulus, and interstitium, respectively. The activity index was 11.23 ± 3.41, and the chronicity index was 3.81 ± 1.99. In MPGN: Apoptotic indexes were found at 0.83 ± 0.25 and 3.55 ± 1.75 on glomerulus and tubulus, respectively. PCNA positivities were found at 21.33 ± 18.42%, 35.5 ± 25.99%, and 34.66 ± 26.84% on glomerulus, tubulus, and interstitium, respectively. In controls, apoptosis was not found. In LN: PCNA positivity on tubulus and interstitium were correlated with the activity index (r = 0.768, p < 0.001, r = 0.721, and p < 0.001, respectively). Glomerular PCNA and apoptosis on interstitium and glomerulus were not correlated with the activity index. The activity index also was not correlated with creatinine clearance and daily proteinuria (p = 0.35 for both). At the end of the first year, patients with recovered or stabilized renal function had higher interstitial and tubular PCNA than others in G1 and G2. Conclusion: It can be said that expression of PCNA on renal biopsy was correlated with activity indexes in LN. PCNA may be a prognostic indicator in MPGN and LN. However, apoptosis does not have a predictive value for MPGN and LN.