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Research article
Yunhao Xun
Xixi Hospital of Hangzhou
Corresponding Author
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Background
Estimated glomerular filtration rate (eGFR) trajectory in HIV-1-infected patients on tenofovir disoproxil fumarate (TDF) therapy has been widely estimated using linear models, but this linearity assumption is not well validated and the nonlinearity of eGFR change remains unknown in Asians with initially normal renal function.
Methods
Estimated GFR trajectories were compared by one-linear and piecewise-linear mixed effects models, before and after propensity matching, respectively. Whether the incidence of renal dysfunction (reduced renal function RRF, eGFR < 90 mL/min/1.73 m² and rapid kidney function decline RKFD, eGFR > -3 mL/min/1.73 m²/year) follows nonlinearity was assessed by logistic regression.
Results
In this Chinese observational cohort, we examined 823 (299 of TDF users and 524 of non-TDF users) treatment-naïve HIV-1-infected participants (age≥17 years) with first eGFR greater than 90 mL/min/1.73m². The median follow-up time was 10 (interquartile range IQR, 2-20) months, during which 178 (21.6%) experienced RRF, and 451 (54.8%) experienced RKFD. In nonlinear adjusted model, the eGFR of TDF users decreased over time before 1.40 years (-5.31 mL/min/1.73 m²/year; 95% CI: -6.57, -4.06), and after 2.30 years (-3.71 mL/min/1.73 m²/year; 95% CI: -5.97, -1.45). However, the eGFR significantly increased from years 1.40 to 2.30 (4.83 mL/min/1.73 m²/year; 95% CI:1.38, 8.28). Within this particular time frame, each year of TDF exposure was associated with a 78% decreased risk of RKFD (95% CI: -91%, -49%). In comparison, eGFR increased slightly at the initiation of antiviral therapy, declined after 2.15 years (-4.96 mL/min/1.73 m²/year; 95% CI: -5.76, -4.17) among non-TDF users. Such a progression nonlinear trajectory was missed on the assumption of one-linearity, whether in TDF or non-TDF users.
Conclusion
For HIV-1-infected Asians initiated antiviral therapy with normal renal function, the nonlinearity of renal function do exist. Routine screen based on nonlinear progression of eGFR could be helpful for clinical management and patient care.
Keywords
Nonlinear Trajectory, Human Immunodeficiency Virus-1, Estimated Glomerular Filtration Rate, Renal Function, Tenofovir
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A new preprint design is coming!
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This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Research article
Yunhao Xun
Xixi Hospital of Hangzhou
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 02 Aug, 2019
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Urology & Nephrology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
Estimated glomerular filtration rate (eGFR) trajectory in HIV-1-infected patients on tenofovir disoproxil fumarate (TDF) therapy has been widely estimated using linear models, but this linearity assumption is not well validated and the nonlinearity of eGFR change remains unknown in Asians with initially normal renal function.
Methods
Estimated GFR trajectories were compared by one-linear and piecewise-linear mixed effects models, before and after propensity matching, respectively. Whether the incidence of renal dysfunction (reduced renal function RRF, eGFR < 90 mL/min/1.73 m² and rapid kidney function decline RKFD, eGFR > -3 mL/min/1.73 m²/year) follows nonlinearity was assessed by logistic regression.
Results
In this Chinese observational cohort, we examined 823 (299 of TDF users and 524 of non-TDF users) treatment-naïve HIV-1-infected participants (age≥17 years) with first eGFR greater than 90 mL/min/1.73m². The median follow-up time was 10 (interquartile range IQR, 2-20) months, during which 178 (21.6%) experienced RRF, and 451 (54.8%) experienced RKFD. In nonlinear adjusted model, the eGFR of TDF users decreased over time before 1.40 years (-5.31 mL/min/1.73 m²/year; 95% CI: -6.57, -4.06), and after 2.30 years (-3.71 mL/min/1.73 m²/year; 95% CI: -5.97, -1.45). However, the eGFR significantly increased from years 1.40 to 2.30 (4.83 mL/min/1.73 m²/year; 95% CI:1.38, 8.28). Within this particular time frame, each year of TDF exposure was associated with a 78% decreased risk of RKFD (95% CI: -91%, -49%). In comparison, eGFR increased slightly at the initiation of antiviral therapy, declined after 2.15 years (-4.96 mL/min/1.73 m²/year; 95% CI: -5.76, -4.17) among non-TDF users. Such a progression nonlinear trajectory was missed on the assumption of one-linearity, whether in TDF or non-TDF users.
Conclusion
For HIV-1-infected Asians initiated antiviral therapy with normal renal function, the nonlinearity of renal function do exist. Routine screen based on nonlinear progression of eGFR could be helpful for clinical management and patient care.
Figure 1
Figure 2
This is a list of supplementary files associated with this preprint. Click to download.
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