Abstract:

Objective:To investigate whether calcineurin expression or not on podocytes of patients with focal segmental glomerulosclerosis (FSGS). Methodology: The renal calcineurin subunit A α, β, γ isoforms (CnAα，β, γ) were detected by immunohistochemistry in sixty-three adult nephrotic, biopsy-proven idopathic FSGS patients. 24 cases with minimal change disease (MCD) and 10 donor renal grafts were regarded as control. CnAα and synaptopodin by immunofluorescence double staining was performed. The precise location of CnAα in glomeruli was confirmed by colloidal gold immunoelectron microscopy. Immunostaining was scored by two pathologists in a double-blind manner. Results: Mild expressions of CnAα and CnAβ without CnAγ were found in renal tubules from donor renal grafts, while calcineurin wasn’t observed in glomeruli. CnAα expression was up-regulated on podocytes in cases with FSGS, but CnAβ without CnAγ was negative. CnAα expression in podocytes increased in 26 (41.3%) FSGS cases, while all MCD were negative (P<0.01). Serum creatinine, urinary rentiol binding protein, pathological variants were significant different between podocyte CnAα posivtie and negative FSGS cases (P<0.05). Podocyte CnAα posivte cases in Collapsing, Celluar, Tip, Hillar variant were 5 (83.3%), 10 (66.7%), 8 (61.5%)  and  2 (13.3% ), respectively, but none in NOS（P<0.001）. Serum creatinine (OR  4.855, P=0.007), collapsing variant (OR 11.069, P=0.040) were critical factors for CnAα overexpression in podocytes of FSGS by Logistic regression. Synaptopodin was decreased and discontinued in 69.2% cases with podocyte CnAα overexpression. Conclusion: We demonstrated that CnAα expresssion was upregulated in podocytes of some adult idopathic FSGS, which may be involved in the aggressive course. Differential expression of CnAα in podocytes suggests different pathogenic mechanism among FSGS variants and MCD. Detection of CnAα in podocytes is useful in distinction of FSGS versus MCD in renal biopsies without defining lesions.