pSTAT1 Is Activated during the Progression of IgA Nephropathy

Jianling Tao; Neeraja Kambham; Shirley Kwok; Richard A Lafayette

doi:10.1159/000526056

pSTAT1 Is Activated during the Progression of IgA Nephropathy

Glomerular Dis. 2022 Jul 26;3(1):12-18. doi: 10.1159/000526056. eCollection 2023 Jan-Dec.

Authors

Jianling Tao¹, Neeraja Kambham², Shirley Kwok², Richard A Lafayette¹

Affiliations

¹ Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Stanford University, Stanford, California, USA.
² Department of Pathology, Stanford University, Stanford, California, USA.

Abstract

Introduction: IgA nephropathy is the most common primary glomerular disease. Its pathogenesis is still poorly understood. Alterations of the Janus kinase signal transducer and activator of transcription (JAK-STAT) pathway may play an important role in IgA nephropathy.

Methods: We evaluated the clinical features, pathology, and tissue staining for lymphocytes and phosphorylated STAT1 (pSTAT1) in 43 patients with biopsy proven IgA nephropathy. They were followed to determine their disease outcomes. All had biopsy tissue and multiple laboratory measurements to assess their kidney disease progression. Sixteen patients underwent repeat kidney biopsy to further assess their clinical status.

Results: The median eGFR at baseline was 61 mL/min/1.73 m² and the median proteinuria was 2,600 mg/d. The median follow-up was 5 years with an average annual decline in eGFR of 2.25 mL/min/1.73 m². There was significant inflammation and atrophy seen in the first biopsy, which progressed among those who undertook a 2nd biopsy. Compared to healthy kidney tissue, glomeruli and tubulointerstitium demonstrated increased lymphocyte (CD3+) infiltrates and increased pSTAT1 staining by immunohistochemistry. Increased CD3 (p = 0.001) staining and increased pSTAT1 (p = 0.03) correlated with reduced eGFR levels. In repeat biopsy samples, increasing pSTAT1 staining correlated with loss of eGFR over time (p = 0.02).

Conclusion: These findings support the hypothesis that pSTAT1 is activated in IgA nephropathy and may play a role in the progression toward kidney failure.

Keywords: Biopsy; IgA nephropathy; Immunohistochemistry; Phosphorylated STAT1; Progression.

Grants and funding

The authors thank the contribution of the Sobrato Family Foundation and the Perlegos Family fund to this effort. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.