Abstract: FR-PO672

Urinary CD80 as a Biomarker for Nephrotic Syndrome

Session Information

Category: Glomerular

  • 1001 Glomerular: Basic/Experimental Immunology and Inflammation

Authors

  • Hogan, Marie C., Mayo Clinic, Rochester, Minnesota, United States
  • Gonzalez guerrico, Anatilde M, Mayo Clinic , Rochester, Minnesota, United States
  • Wright, Adam M, Mayo Clinic , Rochester, Minnesota, United States
  • Troost, Jonathan P., University of Michigan, Ann Arbor, Michigan, United States
  • Fervenza, Fernando C., Mayo Clinic , Rochester, Minnesota, United States
  • Lieske, John C., Mayo Clinic , Rochester, Minnesota, United States
  • Klee, George G, Mayo Clinic , Rochester, Minnesota, United States
Background

The immune system appears to play a significant role in the pathogenesis of certain nephrotic syndrome (NS) patients with minimal change disease (MCD) and focal segmental glomerular sclerosis (FSGS). CD80/B7-1, a co-stimulatory receptor expressed on activated antigen presenting cells, has been implicated in certain cases. However, CD80 assays have suffered from lack of sensitivity and specificity.

Methods

Use a newly-validated ELISA to determine association of urinary CD80 with renal histology and disease status in biopsy proven MCD, FSGS, or other renal diseases (lupus nephritis, diabetic nephropathy, IgA, membranous nephropathy (MN), or polycystic kidney disease. We modified commercial CD80 ELISAs assays to increase sensitivity (biotinyl tyramide amplification) and analytically validated the assay for urine (uCD80). Cases were recruited from the Mayo and NEPTUNE cohorts(Table). Data is expressed as (mean, median (IQR)) and analyzed by t-test or GEE.

Results

uCD80 levels associated with MCD and FSGS compared to other pathologies, and also was higher in disease relapse (table). Using a GEE model of CD80 levels in all diagnsoses versus MCD we observed strong separation by disease type (MN β= -269; CI -469 to-69; p<0.01; FSGS β=-228,CI -429 to-27, p=0.03; IgA β=-289; CI-489 to-89, p<0.01).

Conclusion

Our results confirm that uCD80 excretion correlates with MCD and FSGS disease status. Further study (ongoing) is warranted to determine whether uCD80 is a useful biomarker for diagnosis, prognosis, and predictor of response to immunosuppression. These results also suggest that uCD80 may reflect immune pathways involved in the pathogenesis of certain MCD and FSGS cases, and further research is needed to understand its cellular source.

Table 1. Description of MCD and FSGS and comparison cohort samples
 RemissionRelapse 
 nCD80/CreatUP/CreatnCD80/CreatUP/Creatp
Paired samples       
MCD2344 (22 to 103)0.1 (0.02 to 0.2)23141 (83 to 232)6.9 (3.3 to 11.7)<0.01
FSGS1626 (9 to 75)0.4 (0.1 to 0.9)1690 (55 to 116)4.2 (3.3 to 7.7)<0.01
Unpaired samples       
MCD4749 (27 to 86)0.1 (0.1, 0.2)34140 (82, 224)6.2 (3.4, 10.6)<0.01
FSGS1925 (8, 74)0.3 (0.1, 0.9)4280 (30 to 98)4.0 (2.8, to 5.7)<0.01
MN1338 (23 to 45)0.2 (0.1 to 0.2)2946 (31 to 74)2.6 (1.5 to 3.6)0.10
Lupus1030 (8 to 64)0.2 (0.2 to 0.5)9116 (70 to 293)3.3 (1.7 to 11)0.03
IgA834 (12 to 41)0.8 (0.3 to 0.9)1136 (21 to 57)2.3 (1.1 to 3.1)0.70
Diabetic389 (21, 132)1.1 (0.6 to 6.4)6234 (123, 334)8.1 (6.0, 10.2)0.20

Funding

  • NIDDK Support