Study Reinforces Need To Monitor Kidney Function In Long-Term PrEP Users

In people taking tenofovir-based pre-exposure prophylaxis (PrEP), established biomarkers of kidney injury may be elevated in patients with and without clinical evidence of kidney injury, suggesting the potential for subclinical kidney injury with long-term use of tenofovir-based PrEP, researchers say.

"These findings should serve as a reminder to monitor routine measures of kidney function in patients who are on long-term PrEP," Dr. Christina Wyatt of Duke University School of Medicine and Duke Clinical Research Institute, in Durham, North Carolina, told Reuters Health by email.

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In a report in the journal AIDS, the researchers note that PrEP with emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF) has been shown to reduce the risk of HIV infection in high-risk individuals.

In people with HIV, TDF has been linked to proximal tubulopathy and decreased glomerular filtration rate (eGFR). FTC/TDF PrEP has also been shown to cause a "small but significant" decline in eGFR.

Although proximal tubulopathy was rare in clinical trials, Dr. Wyatt and colleagues previously found a higher rate of non-albumin proteinuria in people randomized to FTC/TDF PrEP (versus placebo) in the Partners PrEP Study.

In the current study, they sought to determine whether established biomarkers of subclinical kidney injury may help in the early identification of people at risk for clinically evident kidney injury with TDF.

The nested case-control study included 139 participants in the FTC/TDF PrEP arm of the Partners PrEP study. Kidney injury was defined as an eGFR decline of 25% or more from baseline at any time-point or proximal tubulopathy or non-albumin proteinuria at 24 months.

They compared 73 kidney injury cases to 66 randomly selected controls without non-albumin proteinuria or proximal tubulopathy at 24 months and in whom eGFR declined by less than 10% from baseline throughout follow-up.

Neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule 1 (KIM-1), established biomarkers of tubular injury, were measured in stored urine collected at 12 months. Urine NGAL >100 ng/mL and urine KIM-1 >2 ng/mL were considered clinically meaningful elevations.

At 12 months, urine NGAL and KIM-1 levels did not differ significantly between people who subsequently developed clinically evident kidney injury and those who did not.

"Notably, more than one-third of subjects had a clinically meaningful elevation in at least one of the biomarkers, while a smaller number had elevations in both," the researchers report in their paper.

"The biomarkers studied do not identify those who are at risk for clinically relevant changes in kidney function," Dr. Wyatt told Reuters Health.

However, the finding of elevated kidney injury biomarker levels in a substantial number of cases "reinforces the need for kidney injury monitoring in this setting," the researchers conclude in their paper.

The Partners PrEP Study was funded by the Bill and Melinda Gates Foundation. This work was also supported by the National Institutes of Health. Dr. Wyatt serves as a consultant for Epividian. Two authors and Columbia Irving University Medical Center hold patents for the use of NGAL as a diagnostic marker.

—Megan Brooks

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