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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) – based therapy has been widely assessed using linear models, but this linearity assumption is disputable and the nonlinearity of eGFR change remains unknown in patients with initially normal renal function.
Methods This is a retrospective, observational cohort study in treatment-naïve HIV-1-infected patients in Hangzhou, China. Estimated GFR (calculated by MDRD equation) 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 We examined 823 (299 of TDF users and 524 of non-TDF users) treatment-naïve HIV-1-infected participants (age≥17 years) with initial eGFR greater than 90 mL/min/1.73m² . The median follow-up time was 10 (interquartile range, 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 improved 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 Chinese initiated antiviral therapy with normal renal function, the nonlinear trajectory of renal function do exist, as revealed by the piecewise mixed effects model with advantage of speaking to the true nature of the exposure outcome relationships. Routine screen based on this nonlinear progression of eGFR, could be helpful for patient management.
Keywords
Nonlinear Trajectory, Human Immunodeficiency Virus-1, Estimated Glomerular Filtration Rate, Renal Function, Tenofovir
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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 26 Nov, 2019
No community comments so far
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Comments: 0
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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) – based therapy has been widely assessed using linear models, but this linearity assumption is disputable and the nonlinearity of eGFR change remains unknown in patients with initially normal renal function.
Methods This is a retrospective, observational cohort study in treatment-naïve HIV-1-infected patients in Hangzhou, China. Estimated GFR (calculated by MDRD equation) 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 We examined 823 (299 of TDF users and 524 of non-TDF users) treatment-naïve HIV-1-infected participants (age≥17 years) with initial eGFR greater than 90 mL/min/1.73m² . The median follow-up time was 10 (interquartile range, 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 improved 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 Chinese initiated antiviral therapy with normal renal function, the nonlinear trajectory of renal function do exist, as revealed by the piecewise mixed effects model with advantage of speaking to the true nature of the exposure outcome relationships. Routine screen based on this nonlinear progression of eGFR, could be helpful for patient management.
Figure 1
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