Plasma proenkephalin-a facilitates measurement of human kidney functional reserve: From healthy kidney donors to polymorbid patients.

Reduced kidney functional reserve, KFR, predicts poor outcomes in kidney diseases. We compared plasma proenkephalin-A, plasma cystatin C, and creatinine clearance for kidney functional reserve measurement. KFR was measured preoperatively in 40 patients undergoing cardiac surgery and 22 healthy participants, including 14 kidney donors. Plasma proenkephalin-A, cystatin C, and creatinine levels were compared before and after a protein meal for KFR calculation. Baseline creatinine clearance correlated poorly with baseline estimated glomerular filtration rate measured by any method. Cystatin C and proenkephalin-A nadir after protein occurred earlier. The proenkephalin-A-based KFR had a greater dynamic range than cystatin C- and creatinine clearance-based KFR (median [IQR] fractional KFR: proenkephalin-A 44.2% [35.5; 58.0]; cystatin C 10.5% [4.4; 16.2]; creatinine clearance 30.0% [8.4; 68.9], p < 0.0001). Measurements were more homogeneous with cystatin C- and proenkephalin-A-estimated glomerular filtration rate than creatinine clearance (higher intraclass correlation: 0.98 for cystatin C; 0.86 for proenkephalin-A, and 0.63 for creatinine clearance). The median [IQR] absolute proenkephalin-A- and cystatin C-based KFR were higher in healthy participants (proenkephalin-A-KFR: 33.8 [26.6; 59.0], cystatin C-KFR: 11.6 [6.6; 15.1] mL/min/1.73m2) than cardiac surgery patients (proenkephalin-A-reserve: 28.5 [19.9; 40.6], cystatin C-reserve: 5.0 [0.3; 8.7] mL/min/1.73m2, p < 0.05). Creatinine clearance-KFR did not differ between groups and mostly reflected tubular secretion of creatinine than change in glomerular filtration rate. In conclusion, proenkephalin-A provided a brief, homogeneous measure of KFR with wide dynamic range, encouraging wider use of this kidney stress test.