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Abstract: FR-PO1078

Urine Podocin to Nephrin mRNA Ratio Is Associated with Activity of Crescentic Necrotizing Glomerulonephritis

Session Information

Category: Glomerular Diseases

  • 1202 Glomerular Diseases: Immunology and Inflammation

Authors

  • Minakawa, Akihiro, University of Miyazaki, Miyazaki, Japan
  • Fukuda, Akihiro, Oita University, Yufu, Japan
  • Kikuchi, Masao, University of Miyazaki, Miyazaki, Japan
  • Sato, Yuji, University of Miyazaki, Miyazaki, Japan
  • Fujimoto, Shouichi, University of Miyazaki, Miyazaki, Japan
Background

Crescentic necrotizing glomerulonephritis (CNGN) rapidly leads to progressive glomerulonephritis syndrome, which then leads to irreversible renal failure without appropriate therapy. To estimate the severity of CNGN, renal biopsy is required. However, renal biopsy is sometimes not applied because of a severe general condition. If urine podocyte-specific mRNA predicts the severity of CNGN, it may be a useful tool.

Methods

A total of 28 patients with biopsy-proven CNGN (males: 16, mean age: 64.6±12.8 years) were enrolled during the past 7 years, with pathological data available for 27 patients. Kidney biopsy samples were used for immunostaining of podocytes and urine samples for podocyte mRNA with the patient’s consent by document.

Results


A blood test showed an estimated glomerular filtration rate of 24.9±18.7 mL/min and C-reactive protein level of 3.33±3.68 mg/dL. Histological analysis showed 3 patients with crescent class, 3 with sclerotic class, 9 with focal class and 12 with mixed class according to EUVAS classification. Immunostaining showed a podocyte number of 297.2±133/glom and podocyte density of 75.8±32/106µm3. A urinary mRNA study showed a urine podocin:nephrin mRNA ratio (PNR) of 1.46±0.80 and urine podocin mRNA:urine creatinine ratio (U-pod/CR) of 476.8±525.3. The podocyte number and density were lower, and the PNR and U-pod/CR were higher compared with those of healthy controls in our previous report (419±81/glom, 129±49/106µm3, 0.36±0.29, 4.3±4.6, respectively). Using EUVAS criteria, the podocyte number in the sclerotic class and podocyte density in the crescent and sclerotic classes tended to be lower compared with the other classes. The PNR and U-pod/CR in these classes, except for the sclerotic class, tended to be increased, which suggested a “podocyte-depleted” stage of sclerotic class. Remarkably, the PNR was significantly correlated with the percentage of glomeruli with acute crescents per unsolidified glomeruli (p<0.01, R2=0.28). Log10 of the U-pod/CR was also correlated with it, except for 6 severe crescentic cases (p<0.01, R2=0.40).

Conclusion

Urine podocyte mRNA, especially the PNR, might be a useful tool for evaluating activity of CNGN.