Tubular stress test detects subclinical reduction in renal functioning mass

Background. To develop a test that would disclose subclinical impairment in renal function, we studied the increment in tubular secretion of creatinin e (TSCr) induced by intravenous creatinine administration. Methods. Studies were done in 14 normal individuals, 7 kidney donors (KDs), and 11 transplant recipients (Tx), all of whom had normal creatinine level s (P-Cr <133 <mu>mol/L). Creatinine infusion studies determined that maxima l stimulation of TSCr resulted from P-Cr levels of 500 to 700 mu mol/L. The refore, in the tubular stress test, clearances, urinary excretion of creati nine (UCrV) and TSCr were determined before and after (15 to 105 min) a sin gle bolus injection of 88.4 mmol/kg body wt, which resulted in the target P -Cr levels. Results. Baseline determinations of P-Cr, UCrV, and TSCr were not significa ntly different in the study groups. Stimulated UCrV (nmol/kg/min) was highe r in normals (426 +/- 82) than in KDs (338 +/- 72, P < 0.05) and Tx patient s (311 +/- 66, P < 0.01). Similarly, TSCr (nmol/kg/min) was higher (P < 0.0 01) in normals (180 +/- 60) than in KDs (155 +/- 54) and Tx patients (86 +/ - 35). Furthermore, the transplanted kidney responded worse than the solita ry normal kidney (P < 0.05), despite having similar levels of glomerular fi ltration rate (GFR). The tubular stress test increased TSCr 11.3 +/- 6.2 ti mes in normals, 4.3 +/- 1.2 times in KDs (P < 0.01), and 2.5 times in Tx (P < 0.001). Conclusions. Impaired tubular secretory response to a creatinine load is a more sensitive index of reduced functioning renal mass than levels of P-Cr and GFR. The tubular stress test may be useful in following the natural his tory of kidney disease and the results of therapeutic interventions.