Mannitol - a new-old marker for measuring glomerular filtration rate

Abstract

Mannitol – a new-old marker for measuring glomerular filtration rate

ABSTRACT Acute kidney injury is a serious complication in critically ill patients, associated with increased morbidity and mortality. Furthermore, chronic kidney disease (CKD) is a growing global health-care concern. In many clinical situations, assessing kidney function through glomerular filtration rate (GFR) may significantly improve patient care. However, access to standard GFR measurement methods is often limited, particularly in patients in the intensive care units (ICU). Thus, GFR is typically estimated (eGFR), using equations based on blood levels of creatinine and/or cystatin C, which can potentially introduce various sources of error.

This research project revisits an older concept: using mannitol as a potential marker for measuring GFR. Mannitol fulfils essential criteria for such use, as it is filtered by the kidneys without being metabolized or reabsorbed. It is inexpensive, easy to use, and has no known adverse effects. The recent availability of a highly sensitive analysis method, liquid chromatography–tandem mass spectrometry (LC-MS/MS) enables accurate measurements of plasma mannitol.

Patients and methods: In Study I, GFR was assessed using mannitol and 51Cr-EDTA clearances with bolus injection technique in outpatients with normal GFR or CKD stages 1–4 (n=41). In Study II, eGFR using the CKD-EPI or Lund-Malmö formulas was compared to GFR measured with 51CrEDTA or iohexol in two groups: ICU patients (n=43) and outpatients (n=48). In Study III, mannitol GFR and iohexol GFR were compared in 2 groups, ICU (n=20) and outpatients with CKD stages 3-4 (n=20). Mannitol concentrations were analyzed using an enzymatic method in Study I and mass-spectrometry (LC-MS/MS) in study III.

Results: A good agreement and very good accuracy were observed when mannitol and 51Cr-EDTA clearance were compared in an outpatient group (Study I). The generally used estimation equations, based on creatinine and cystatin C, alone or in combination, using the CKD-EPI or Lund-Malmö formulas performed poorly in the ICU patient cohort. In comparison, in a group of outpatients the formulas showed a good agreement and accuracy when using combination of creatinine and cystatin C (Study II). Mannitol performed well as a clearance marker in an ICU patient cohort in comparison with iohexol clearance as a reference method, showing good agreement and accuracy, despite two outliers. The agreement and accuracy in the outpatient group with CKD stages 3-4, was excellent (Study III).

Conclusion: The studies support the use of mannitol plasma clearance as a promising, reliable and practical alternative for assessing measured GFR, particularly when using LC-MS/MS. Further studies in larger, diverse patient cohorts are warranted to validate this method.

Keywords: mannitol, glomerular filtration rate, measured GFR, estimated GFR, LC-MS/MS, clearance, creatinine, cystatin C, kidney function, chronic kidney disease.