Romain Palich1,2, Roland Tubiana1,2, Besma Abdi3, Fouzi Mestari4, Marguerite Guiguet2, Françoise Imbert-Bismut4, Christine Katlama1,2, Dominique Bonnefont-Rousselot4,5, Corinne Isnard-Bagnis6. 1. Infectious Diseases Department, Pitié-Salpêtrière University Hospital, AP-HP, Paris, France. 2. Pierre Louis Institute of Epidemiology and Public Health (IPLESP, UMRS 1136), Paris, France. 3. Virology Department, Pitié-Salpêtrière University Hospital, AP-HP, Paris, France. 4. Metabolic Biochemistry Department, Pitié-Salpêtrière University Hospital, AP-HP, Paris, France. 5. Biochemistry Department, Faculty of Pharmacology, CNRS UMR8258 - INSERM U1022, Paris Descartes University, Paris, France. 6. Nephrology Department, Pitié-Salpêtrière University Hospital, AP-HP, Paris Sorbonne University, Paris, France.
Abstract
Objectives: Inhibition of the organic cation transporter-2 renal tubule transporter by dolutegravir leads to serum creatinine increase. Serum cystatin C is a non-organic cation transporter-2-dependent marker, possibly enabling glomerular filtration rate (GFR) estimation under dolutegravir. Our goal was to evaluate the changes in creatinine- and cystatin C-based estimated GFR values before and after dolutegravir initiation. Methods: Creatinine and cystatin measurements were carried out on frozen plasma samples from HIV-1-infected patients, before and after dolutegravir initiation, between October 2016 and March 2017 at Pitié-Salpêtrière Hospital. CKD-EPI equations were used to estimate mean GFR from creatinine and cystatin C values. Variations were analysed by paired t-test. Results: Forty-four patients were included [median age = 48 years (IQR 36-58) and median CD4 count = 592 cells/mm3 (IQR 388-728)], including 6 ART-naive patients and 38 on switch strategies [72% with viral load <50 copies/mL and median ART duration = 13 years (IQR 5-20)]. Before dolutegravir initiation (median time = 41 days), 19 patients (43%) had creatinine-based estimated GFR <90 mL/min/1.73 m2 and 11 (25%) had cystatin C-based estimated GFR <90 mL/min/1.73 m2. After dolutegravir initiation, serum creatinine values significantly increased (+8.6 μmol/L, 95% CI +5.8; +11.4, P < 0.001) and associated estimated GFR significantly decreased (-7.7 mL/min/1.73 m2, 95% CI -10.4; -5.1, P < 0.001). In contrast, there was no significant change in cystatin C value variation and associated estimated GFR. The same results were observed regardless of renal function at baseline. Conclusions: Creatinine values increased after dolutegravir initiation, whereas no change was observed for cystatin C values. Use of cystatin C may enable better understanding of plasma creatinine fluctuations after dolutegravir initiation, particularly in high-risk renal patients.
Objectives: Inhibition of the organic cation transporter-2 renal tubule transporter by dolutegravir leads to serum creatinine increase. Serum cystatin C is a non-organic cation transporter-2-dependent marker, possibly enabling glomerular filtration rate (GFR) estimation under dolutegravir. Our goal was to evaluate the changes in creatinine- and cystatin C-based estimated GFR values before and after dolutegravir initiation. Methods:Creatinine and cystatin measurements were carried out on frozen plasma samples from HIV-1-infectedpatients, before and after dolutegravir initiation, between October 2016 and March 2017 at Pitié-Salpêtrière Hospital. CKD-EPI equations were used to estimate mean GFR from creatinine and cystatin C values. Variations were analysed by paired t-test. Results: Forty-four patients were included [median age = 48 years (IQR 36-58) and median CD4 count = 592 cells/mm3 (IQR 388-728)], including 6 ART-naive patients and 38 on switch strategies [72% with viral load <50 copies/mL and median ART duration = 13 years (IQR 5-20)]. Before dolutegravir initiation (median time = 41 days), 19 patients (43%) had creatinine-based estimated GFR <90 mL/min/1.73 m2 and 11 (25%) had cystatin C-based estimated GFR <90 mL/min/1.73 m2. After dolutegravir initiation, serum creatinine values significantly increased (+8.6 μmol/L, 95% CI +5.8; +11.4, P < 0.001) and associated estimated GFR significantly decreased (-7.7 mL/min/1.73 m2, 95% CI -10.4; -5.1, P < 0.001). In contrast, there was no significant change in cystatin C value variation and associated estimated GFR. The same results were observed regardless of renal function at baseline. Conclusions: Creatinine values increased after dolutegravir initiation, whereas no change was observed for cystatin C values. Use of cystatin C may enable better understanding of plasma creatinine fluctuations after dolutegravir initiation, particularly in high-risk renal patients.
Authors: Thomas Theo Brehm; Marleen Franz; Anja Hüfner; Sandra Hertling; Stefan Schmiedel; Olaf Degen; Benno Kreuels; Julian Schulze Zur Wiesch Journal: Medicine (Baltimore) Date: 2019-08 Impact factor: 1.817