Comparison of Renal Function Biomarkers of Serum Creatinine and Cystatin C in HIV-Infected People on Dolutegravir-Containing Therapy

Abstract

Objective(s) HIV-1-infected Chinese patients who were treated naïve with combination dolutegravir (DTG) and tenofovir disoproxil fumarate (TDF) group, DTG without TDF group, TDF without DTG, as well as patients switched to DTG-containing therapy from other drugs were included. Design The dynamics of serum creatinine, cystatin C (CysC) level, eGFR cr and eGFR CysC at the baseline, 4 w, 12w, 24w, 36w and 48w for different group of patients were collected and evaluated. Methods Changes in serum creatinine, levels, eGFR cr and eGFR CysC were analyzed among groups and in different time-points. Intra-group correlation coefficient and Bland–Altman plot were used to compare the results of eGFR cr and eGFR CysC . Results Thirty-seven treated-naïve HIV-patients in combined DTG and TDF group (group 1), 23 in DTG without TDF patients (group 2) and 47 patients on TDF without DTG group (control group, group 3) along with 31 patients whose ART switch to DTG-containing regimens (group 4) were collected. Serum creatinine was significantly elevated in the group 1 and group 2 instead of group 3 from baseline to 48w. Mean decreased change of eGFR calculated by serum creatinine proved the same conclusion. However, there were no differences in serum cystatin C and eGFR CysC between baseline and at 48 weeks in DTG-containing groups. Moreover, the proportion of eGFRcr decreased over 30% was significantly higher in DTG-treatment group. Conclusion We demonstrated the clinical benefits of CysC for assessing the glomerular filtration rate when evaluating renal function in HIV-1-infected patients treated with whether DTG combined with TDF or not.

A systematic review assessing the potential use of cystatin c as a biomarker for kidney disease in people living with HIV on antiretroviral therapy

“…Thus, it remains important to understand the relationship between serum cystatin C and eGFR to monitor the kidney function in PLWH on ART. In this study, evidence indicated that the creatinine-based GFR increased in PLWH taking tenofovir disoproxil fumarate-containing ART ( 42 , 45 ), but this was not observed in other studies ( 46 , 48 ). Moreover, switching to a dolutegravir-based ART regimen could improve the kidney function in PLWH, as measured using both creatinine- and cystatin C-based GFRs ( Table 1 ).…”

Drug Use Evaluation of Tenofovir/Lamivudine/Dolutegravir (TLD) Fixed-Dose Combination for Initiation and Transition Among HIV-Infected Individuals Attending Lumame Primary Hospital, North West Ethiopia

“…It is connected to how DTG affects the secretion of tubular creatinine and does not signify a deterioration in kidney function. 31 …”

Cystatin C should be routinely available for estimating kidney function

“…By comparison, vancomycin with piperacillin-tazobactam was not associated with changes in cystatin C nor with adverse clinical outcomes [30]. Dolutegravir, which blocks tubular secretion of creatinine, is used widely as first-line antiretroviral therapy and has been associated with significant early and sustained rises in serum creatinine over a 48-week treatment period [31]. Two recent reports [32,33] add to an expanding literature [34] describing cases where targeted systemic anticancer treatments lead to a rise in creatinine suggestive of acute kidney injury (AKI), in many cases leading to temporary or permanent cessation of treatment, and with major potential impacts on cancer progression and survival.…”

“…Across each of the scenarios described above, parallel increases in cystatin C were not observed, suggesting pseudo-AKI [30][31][32][33][34]. For drugs that competitively inhibit tubular creatinine excretion, use of creatinine alone makes it impossible to distinguish true AKI, potentially compromising clinical care.…”