Abstract: TH-PO507

The Nephropathy Studied in the African American Study of Kidney Disease (AASK) May Be an Atypical Tubulopathy

Session Information

Category: Chronic Kidney Disease (Non-Dialysis)

  • 305 CKD: Clinical Trials and Tubulointerstitial Disorders

Authors

  • Almaani, Salem, University Hospital Network - The University of Toronto, Toronto, Ontario, Canada
  • Birmingham, Daniel J., Ohio State University, Columbus, Ohio, United States
  • Rovin, Brad H., Ohio State University, Columbus, Ohio, United States
  • Hebert, Lee A., Ohio State University, Columbus, Ohio, United States
Background

It has been suggested that the nephropathy associated with patients enrolled in the AASK (AASK-N) may be a primary tubulopathy (and not a glomerulopathy or a vasculopathy related to hypertension) because it progresses at levels of proteinuria below that of progressive glomerulopathy. However, studying this in AASK-N urine samples has been hampered due to protein degradation because of the presence of acetic acid as a preservative. This report addresses this question by studying urine samples from patients enrolled in the Chronic Renal Insufficiency Cohort (CRIC) who met criteria for AASK enrollment.

Methods

Urine samples were obtained from 43 African American CRIC patients with urine protein-to-creatinine ratios (uPCRs) of 0.2 to 1.1 and eGFRs ranging from 65 to 20. Six kidney injury markers were measured in these samples by a multiplex platform (Meso Scale Discovery, MSD) that uses a capture and detection antibody pair for each analyte. For comparison, urine samples from 20 lupus nephritis (LN) patients with the same uPCR range were also tested.

Results

There were no differences in albumin-to-protein ratios (uAPR) between the CRIC cohort (mean 0.59) and the LN cohort (0.54). The results of the MSD analysis are shown in the table. Notably, levels of B2M, a classic marker of proximal tubule injury/dysfunction, were 8-fold higher in CRIC, while levels of cystatin C, another marker of proximal tubule dysfunction, were no different between the two cohorts. Decreased EGF levels in the CRIC cohort reflect their lower GFRs.

Conclusion

The 8-fold increase in urine B2M levels in the CRIC cohort compared to the LN cohort in the face of similar levels of uAPRs and other indicators of proximal tubular injury suggest that AASK-N is not a typical tubulopathy, but may involve unique proximal tubular damage.

AnalyteCRIC (N=43)LN (N=20)P value
Beta-2 -micorglobulin (B2M)768940.013
Cystatin C53660.364
Epidermal growth factor (EGF)1.46.5<0.001
Neutrophil gelatinase-associated lipocalin (NGAL)50460.746
Osteopontin (OPN)4206280.154
Uromodulin (UMOD)7,44010,7500.032

Analyte levels = median ng/mg urine creatinine

Funding

  • NIDDK Support