Expression of Cell Membrane Antigens in Cells Excreted in the Urinary Sediment Predicts Progression of Renal Disease in Patients with Focal Segmental Glomerulosclerosis

Abstract

Background/Aims: A link between the number of podocytes excreted in the urine and activity of glomerular disease has been established. The aim of this study was to investigate possible correlations between urinary cells' phenotype and the progression of focal segmental glomerulosclerosis (FSGS). Methods: Forty patients with newly diagnosed FSGS were included. Cells were isolated from urine by adherence to collagen-coated cover slips and assessed for the expression of podocalyxin (PDX), CD68 and Ki67 antigens by indirect immunofluorescence. In addition, double-staining procedures were performed in combinations of the above antigens plus cytokeratin, WT1 and CD-105. Twenty-two patients in whom urinary protein to creatinine ratio exceeded 2.0 at diagnosis were followed for 36 months, with assessments of renal function and proteinuria every 3 months. During observation, patients were subjected to standard therapy. Results: Significantly higher numbers of Ki67 positive cells at the onset of the study were observed in patients who have doubled serum creatinine (SCr) in follow-up, than in those who have not (p = 0.0149). By logistic regression analysis, both CD68 and Ki67, but not anti-PDX positive cell numbers at diagnosis were found to be predictors of doubling SCr concentration in 36 months' follow-up. Results of double staining indicate that PDX positive cells could be identified as podocytes or their precursors and parietal epithelial cells. Conclusion: Urinary sediment PDX positive cell numbers do not predict the progression of FSGS, whereas CD68 and Ki67 phenotype of urinary podocytic lineage clearly has a prognostic significance in 36 months' observation of primary FSGS.

Glomerulosclerosis predicts poor renal outcome in patients with idiopathic membranous nephropathy

“…Glomerulosclerosis is characterized by loss of glomerular cells, increased synthesis of extracellular matrix of the glomerulus, and reduced Fig. 3 Renal survival curve analysis in both groups (Kaplan-Meier survival analysis) Table 5 Cox regression analysis of glomerular sclerosis proportion in renal prognosis of patients with IMN The composite endpoint was defined as a 20% reduction in the eGFR or development of ESRD Model 0: Unadjusted Model 1: was adjusted for age, gender, BMI, systolic blood pressure (BP), Immunosuppressant Model 2: was adjusted for model 1plus serum creatinine, 24-h urinary protein Model 3: was adjusted for mode 2 plus renal interstitial inflammatory cell infiltration, renal tubular atrophy, renal degradation, resulting in excessive accumulation of extracellular matrix [7,15,16]. Dumoulin et al [17] hypothesized that the deposition of immune complexes on the glomerular epithelial side leads to the detachment of glomerular podocytes and glomerular basement membrane, resulting in glomerular segmental sclerosis and sclerosis [18,19].…”

“…Approximately 20% of patients with IMN progress to end-stage renal disease within 5-15 years or die from related complications [3][4][5]. In recent years, the morphological changes of renal tissue and glomerulosclerosis have gradually attracted attention as the influencing factors of prognostic evaluation of patients with IMN, but significant differences in their research conclusions are observed [5][6][7][8]. IMN pathology related with glomerulosclerosis is closely associated with the patient's prognosis [9][10][11].…”

CD44 is required for the pathogenesis of experimental crescentic glomerulonephritis and collapsing focal segmental glomerulosclerosis

“…Apparently, the number of glomerular proliferating cells is a more sensitive parameter that can be related to albuminuria rather than to histology in the 2 tested models of glomerular scarring, as was suggested recently for proliferating cells in the urine of FSGS patients. 47 The number of glomerular proliferating cells also was related to cortical collagen I expression in both models. Notably, collagen IV is the type of collagen expressed in both normal and diseased glomeruli (sclerosis), whereas collagen I is normally not expressed in the glomerulus, but several studies have shown glomerular collagen I expression in various glomerulopathies.…”

Glomerular podocytes in diabetic renal disease

“…35,36 It was soon demonstrated that assessment of podocyte antigen expression immediately after the recovery of the cells from urinary sediment by adhesion to a plastic surface provides a useful tool to investigate the importance of podocytes in the progression of glomerular diseases. 37 The concentration of proteins secreted to the urinary space by damaged podocytes can be measured using the western blot technique. In patients with diabetes, the urinary podocalyxin concentration is higher than the cut-off value in patients at the normoalbuminuric, microalbuminuric and macroalbuminuric stage.…”