Medications Influencing Serum Cystatin C Independent of Measured Glomerular Filtration Rate

BACKGROUND: Serum cystatin C is influenced by factors beyond glomerular filtration rate (GFR), and several medications have been hypothesized to alter its generation. Whether reported associations reflect effects on cystatin C independent of measured GFR (mGFR) or confounding by illness remains unclear. METHODS: We studied 5595 adults who underwent outpatient cystatin C (and creatinine) testing with mGFR determination using iohexol clearance in Stockholm healthcare. Associations between eight candidate medication classes and cystatin C were assessed using both inter- and intra-individual analyses, sequentially adjusting for mGFR, clinical variables, and ongoing medications. We further evaluated the effect of these medications on cystatin C-based eGFR (eGFRcys) bias compared with serum creatinine-based (eGFRcr) and combined (eGFRcr-cys) equations. RESULTS: After adjustment for mGFR and confounders, use of systemic glucocorticoids, opioids and loop diuretics was associated with higher cystatin C. The magnitude of increase was potentially clinically meaningful for glucocorticoid use, particularly for greater estimated daily dose categories, whereas the smaller increases observed with opioid and loop diuretic use likely reflect clinically non-meaningful effects. No associations were observed for use of allopurinol, immunosuppressants, thyroid hormone analogues, or antipsychotics, or for paracetamol after adjustment for concomitant medications. eGFRcys underestimated mGFR more in users than in non-users, while eGFRcr overestimated mGFR similarly in users and non-users. eGFRcr-cys provided the least biased GFR estimates. CONCLUSIONS: This study suggests that systemic glucocorticoids, opioids and loop diuretics may increase cystatin C independent of mGFR. Use of eGFRcr-cys was consistently more accurate than either eGFRcr or eGFRcys alone in patients using these treatments.