BACKGROUND: Low-molecular weight (LMW) proteins, including albumin and novel urinary biomarkers of acute kidney injury (AKI) such as cystatin C and neutrophil gelatinase-associated lipocalin (NGAL), are normally absorbed from the glomerular filtrate by receptor-mediated transport. We evaluated the effect of albuminuria on urinary excretion of novel biomarkers. METHODS: Sprague-Dawley rats given four injections over 2 days of 5 mg/g body wt/day bovine serum albumin (BSA) in saline were compared with controls given saline alone. Urinary cystatin C, albumin and protein excretion rates were compared prior to treatment (Day -1), after treatment (Day 2) and 4 days later (Day 6). A preliminary assessment of the clinical effect of proteinuria on the filtered urinary biomarkers cystatin C and NGAL was made by comparison with the effect on urinary interleukin-18 (IL-18) that is not absorbed from the glomerular filtrate, in a cohort of intensive care unit patients. RESULTS: BSA induced transient increases in albuminuria, proteinuria and cystatinuria (P < 0.01, P < 0.001 and P < 0.001, respectively). Beyond a threshold 6-fold increase in albuminuria, cystatin C absorption was reduced by competitive inhibition. The excretion rates of all analytes returned to preinjection levels by Day 6. Clinical proteinuria was associated with increasing cystatin C and NGAL concentrations (n = 90, P < 0.0001) but not IL-18 (P = 0.12). CONCLUSIONS: Proteinuria may increase the threshold for detection of AKI by increasing the excretion of LMW protein biomarkers.
BACKGROUND: Low-molecular weight (LMW) proteins, including albumin and novel urinary biomarkers of acute kidney injury (AKI) such as cystatin C and neutrophil gelatinase-associated lipocalin (NGAL), are normally absorbed from the glomerular filtrate by receptor-mediated transport. We evaluated the effect of albuminuria on urinary excretion of novel biomarkers. METHODS:Sprague-Dawley rats given four injections over 2 days of 5 mg/g body wt/day bovineserum albumin (BSA) in saline were compared with controls given saline alone. Urinary cystatin C, albumin and protein excretion rates were compared prior to treatment (Day -1), after treatment (Day 2) and 4 days later (Day 6). A preliminary assessment of the clinical effect of proteinuria on the filtered urinary biomarkers cystatin C and NGAL was made by comparison with the effect on urinary interleukin-18 (IL-18) that is not absorbed from the glomerular filtrate, in a cohort of intensive care unit patients. RESULTS: BSA induced transient increases in albuminuria, proteinuria and cystatinuria (P < 0.01, P < 0.001 and P < 0.001, respectively). Beyond a threshold 6-fold increase in albuminuria, cystatin C absorption was reduced by competitive inhibition. The excretion rates of all analytes returned to preinjection levels by Day 6. Clinical proteinuria was associated with increasing cystatin C and NGAL concentrations (n = 90, P < 0.0001) but not IL-18 (P = 0.12). CONCLUSIONS:Proteinuria may increase the threshold for detection of AKI by increasing the excretion of LMW protein biomarkers.
Authors: Azrina Md Ralib; John W Pickering; Geoffrey M Shaw; Prasad Devarajan; Charles L Edelstein; Joseph V Bonventre; Zoltan H Endre Journal: J Am Soc Nephrol Date: 2011-11-17 Impact factor: 10.121
Authors: Marlies Ostermann; Lakhmir S Chawla; Lui G Forni; Sandra L Kane-Gill; John A Kellum; Jay Koyner; Patrick T Murray; Claudio Ronco; Stuart L Goldstein Journal: Br J Clin Pharmacol Date: 2017-12-01 Impact factor: 4.335
Authors: Maryam Nejat; John W Pickering; Prasad Devarajan; Joseph V Bonventre; Charles L Edelstein; Robert J Walker; Zoltán H Endre Journal: Kidney Int Date: 2012-03-14 Impact factor: 10.612