Cystatin C as a Marker of Renal Function is Affected by HIV Replication Leading to an Underestimation of Kidney Function in HIV Patients

Abstract

Background Broad use of tenofovir and an ageing HIV-infected population have created an interest in renal function in HIV patients. Serum cystatin C is a newer marker of renal function and might be more sensitive than creatinine. Methods Patients were enrolled consecutively in an observational study. HIV-seropositive patients naive to antiretroviral therapy ( n=261) were compared with healthy volunteers undergoing check-up procedures ( n=193). Estimated glomerular filtration rate (eGFR) was derived using creatinine-based Modification of Diet in Renal Disease (MDRD) and Cockcroft–Gault formulas or cystatin C-based calculations. HIV-seropositive patients starting antiretroviral therapy ( n=92) were followed prospectively after enrolment. Results MDRD showed a higher median eGFR in antiretroviral- naive HIV-seropositive patients compared with controls (104 versus 93 ml/min; P<0.001). Cockcroft–Gault gave similar results (118 versus 106 ml/min; P<0.001). By contrast, cystatin C levels in HIV-seropositive individuals were higher, resulting in a lower median eGFR compared with controls (99 versus 120 ml/min; P<0.001). Cystatin C was positively correlated with HIV RNA ( r=0.33, P<0.01) and inversely correlated with CD4+ T-cell count ( r=-0.29, P<0.01). Initiating antiretroviral therapy ( n=92) decreased cystatin C levels and led to an increased cystatin C-based eGFR from median 84 to 103 ml/min at week 24 ( P<0.001). Serum creatinine was not substantially altered. Conclusions Correlation of cystatin C with HIV RNA and CD4+ T–cell count, plus decrease of cystatin C after suppression of HIV replication, suggest an increase of cystatin C levels by active HIV infection. This might result in overestimation of renal impairment, particularly in treatment-naive patients. Therefore, use of cystatin C to calculate GFR in HIV-seropositive individuals should not be recommended without further validation.

Clinical Practice Guideline for the Management of Chronic Kidney Disease in Patients Infected With HIV: 2014 Update by the HIV Medicine Association of the Infectious Diseases Society of America

“…inflammatory markers in the general population [19,20], and has been reported to be correlated with HIV RNA levels, hepatitis C coinfection, and T-cell activation indices in HIV-infected persons [21][22][23]. In both the general population and in HIVinfected persons, cystatin C is a stronger predictor of mortality and cardiovascular events than creatinine or creatinine-based GFR estimates [24][25][26][27].…”

Cystatin C in addition to creatinine for better assessment of glomerular renal function decline in people with HIV receiving antiretroviral therapy

“…The present study focused on PWH treated with antiretroviral drugs aged around 60 (AE10.7) years without significant difference between groups for age and BMI, which could have impacted creatinine levels [32] and with suppressed HIV viral load to avoid impact on cystatin C [29]. As a current hypothesis, overestimation of plasma creatinine because of ICS exposure would erroneously decrease the eGFR.…”

“…For instance, increased levels are encountered in the general population in hyperthyroidism or under glucocorticoids use [27,28]. In PWH, increased levels had been reported in cases of uncontrolled viral load [29]. Otherwise, decreased levels occur notably in hypothyroidism and in several cancers [27,30,31].…”

Association between Serum Cys C and PTB Cavitation

“…Recent studies have shown that Cys C plays a crucial role in regulating antigen presentation, protecting the host from microbial invasion, and inhibiting viral replication and growth [ 20 – 23 ]. Elevated Cys C levels associated with high viral loads have been found in HIV patients [ 24 ]. We boldly hypothesized that elevated serum Cys C might be a function of the immune defense against the high load of Mtb in cavitary PTB.…”