Abstract: FR-PO723

Thrombotic Microangiopathy in Pauci-Immune Glomerulonephritis

Session Information

Category: Glomerular

  • 1004 Clinical/Diagnostic Renal Pathology and Lab Medicine

Authors

  • Tao, Jianling, Stanford University, Stanford, California, United States
  • Troxell, Megan L., Stanford University School of Medicine, Stanford, California, United States
  • Lapasia, Jessica B., Kaiser Permanente, San Francisco, California, United States
  • Kambham, Neeraja, Stanford University School of Medicine, Stanford, California, United States
Background

Renal thrombotic microangiopathy (TMA) is occasionally seen in biopsies with pauci-immune necrotizing crescentic glomerulonephritis (NCGN). Recent studies indicate that NCGN patients with TMA have more severe renal injury and higher mortality rate.

Methods

Biopsies from 2 centers with diagnosis of NCGN and TMA changes were identified (5/2003- 4/2017) from Pathology records. Patients with connective tissue disorders, HBV, HCV, HIV, and monoclonal gammopathy were excluded. Biopsies were re-reviewed and detailed clinical and follow up data was documented.

Results

Ten patients met our inclusion criteria. Patients were predominantly female (9:1) and average age at biopsy was 48 years (range 10-72). Clinical presentation was nephritic syndrome +/- acute renal failure and 3 patients had nephrotic range proteinuria. ANCA was positive in 8 patients and schistocytes were noted on peripheral smear in 2 patients. Of 7 patients with available complement data, only 1 had low C3 at presentation; one patient with previously normal C3 developed hypocomplementemia and clinical TMA 3 years later. In addition to glomerular crescents and necrosis, prominent TMA changes (unrelated to GBM rupture or crescents) were seen in glomeruli/blood vessels on light microscopy in 6 patients and on EM in 4 patients. Glomerular mesangial C3 (+/- IgG) staining was documented in 3 patients, with ultrastructural confirmation of deposits in 2. The mean follow up was 40 months (range 0.5-156). At last follow up, 5 patients reached ESRD or died; 1 has mild chronic kidney disease and 2 have normal renal function. Treatment in most cases included steroids and Cytoxan, with a few receiving rituximab and plasmapheresis. One patient received anti-complement treatment after biopsy and another received it 3 years later; both were dialysis dependent at last follow-up.

Conclusion

NCGN patients rarely have clinical or biopsy-proven TMA. Based on this limited sample, the clinical outcome appears to be poor. The underlying mechanism has been postulated to be alternative complement pathway abnormality. The nephrologist should be alerted to the presence of TMA for potential therapeutic implications and further complement investigations.