Abstract: SA-OR110

Kidney Tubular Dysfunction among HIV-Negative Persons Receiving Tenofovir-Based Pre-Exposure Prophylaxis

Session Information

  • What Happens After AKI
    November 04, 2017 | Location: Room 295, Morial Convention Center
    Abstract Time: 05:30 PM - 05:42 PM

Category: Acute Kidney Injury

  • 003 AKI: Clinical and Translational

Authors

  • Jotwani, Vasantha, UCSF, San Francisco, California, United States
  • Scherzer, Rebecca, UCSF, San Francisco, California, United States
  • Glidden, David V., UCSF, San Francisco, California, United States
  • Coca, Steven G., Icahn School of Medicine at Mount Sinai, New York, New York, United States
  • Parikh, Chirag R., Yale University and VAMC, New Haven, Connecticut, United States
  • Grant, Robert M, UCSF, San Francisco, California, United States
  • Shlipak, Michael, San Francisco VA Medical Center, San Francisco, California, United States
Background

Pre-exposure prophylaxis (PrEP) with once-daily tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) has been adopted by the World Health Organization and the United States Centers for Disease Control as a global strategy for HIV prevention. Tenofovir can cause proximal tubular damage and chronic kidney disease in HIV-infected persons, but little is known regarding its nephrotoxicity in persons without HIV. We evaluated the effects of PrEP on kidney health using a panel of urinary biomarkers.

Methods

Biomarker levels were measured in urine specimens collected before and after PrEP initiation in 109 HIV seronegative participants of the iPrEx-OLE study, a longitudinal cohort of former PrEP trial participants who received open-label TDF/FTC. Cross-sectional correlations of hair drug concentrations with post-TDF urine biomarker levels were evaluated.

Results

After 24 weeks on PrEP, we observed statistically significant increases in proteinuria and α1-microglobulin, a marker of proximal tubule dysfunction, whereas monocyte chemoattractant protein-1 (MCP-1), a marker of renal repair, and eGFR declined (112 ml/min/1.73m2 pre-TDF vs 108 ml/min/1.73m2 post-TDF). Higher tenofovir concentrations, measured in hair, were associated with lower concentrations of uromodulin (r=-0.404; p<0.001), a protein secreted by healthy tubular cells.

Conclusion

PrEP with TDF/FTC was associated with changes in renal tubular health, captured by urine biomarker levels. Urine biomarkers may be useful indicators of nephrotoxicity in PrEP users.

Biomarkers levels before and after initiation of PrEP
BiomarkerPre-TDF
Median (IQR)
Post-TDF
Median (IQR)
Relative changeP-value
Proteinuria (mg/g)72.0 (53.1, 97.8)85.3 (65.0, 110.8)14%0.002
Albuminuria (mg/g)5.2 (3.4, 8.6)4.8 (3.2, 7.6)1.0%0.77
α1-microglobulin (mg/dL)0.50 (0.50, 0.80)0.70 (0.50, 1.10)26%<0.001
β2-microglobulin (ng/mL)87.9 (60.3, 139)101 (48.4, 167)7.2%0.48
Interleukin-18 (pg/mL)44.1 (25.5, 70.4)36.6 (17.2, 72.6)-19%0.12
Kidney injury molecule-1 (pg/mL)995 (355, 1711)715 (315, 1659)-12%0.48
Neutrophil gelatinase-associated lipocalin (ng/mL)18.2 (10.0, 37.7)13.1 (5.9, 39.7)-14%0.20
Monocyte chemoattractant protein-1 (pg/mL)200 (103, 308)169 (74, 292)-15%0.04
Uromodulin (µg/mL)7.7 (3.9, 12.8)7.5 (3.3, 14.6)-5.6%0.70

P-values from Wilcoxon Signed-Rank test.

Funding

  • NIDDK Support