MARKED ENZYMURIA AFTER BONE-MARROW TRANSPLANTATION - A CORRELATE OF VENOOCCLUSIVE DISEASE-INDUCED HEPATORENAL-SYNDROME

During the first month after bone marrow transplantation, approximatel y 15% of patients develop acute renal failure (ARF). This usually occu rs in the setting of hepatic veno-occlusive disease (VOD). Prior clini cal data have suggested that this form of ARF has a hemodynamic basis, analogous to the hepatorenal syndrome (HRS). If so, then proximal tub ular injury would not be expected, To directly test this hypothesis, e nzymuria (N-acetyl-beta-D-glucosaminidase (NAG)) was quantitated in th e following groups of patients within the first 35 days after BMT: ( I ) VOD + ARF (serum creatinine level > 1.5 mg/dL; N = 10); (2) VOD with relatively normal renal function (serum creatinine level < 1.5 mg/dL; N = 11); and (3) patients without hepatic or renal complications (BMT controls; N = 12). For comparison, NAG was also quantitated in the fo llowing groups of non-BMT patients: (I) toxic/ischemic acute tubular n ecrosis (ATN) (N = 10); (2) jaundice without azotemia (N = 5); and (3) HRS (N = 6). Urine samples from eight healthy subjects established no rmal NAG concentrations (2.5 +/- 0,5 mu U/mg urinary creatinine; mean +/- SE). All non-BMT patients with ATN had markedly elevated NAG level s (61 +/- 12; P < 0,001), validating the test as a marker of tubular d amage. NAG concentrations were significantly elevated in all of the co ntrol BMT patients (24 +/- 3; P < 0.01), and the presence of VOD was a ssociated with further striking increments (approximately 50 times nor mal). However, the degree of enzymuria was virtually identical for VOD patients with (125 +/- 27) and without (122 +/- 17) ARF, Jaundice in a non-BMT setting was associated with only mild NAG elevations (11 +/- 2), However, striking enzymuria was noted in all HRS patients (61 +/- 20), equaling the levels seen with ATN. The following conclusions wer e derived: (I) subclinical tubular injury, as defined by enzymuria, ap pears to be ubiquitous after BMT; (2) VOD dramatically increases the e xtent of enzymuria; (3) the degree of enzymuria in VOD patients is not correlated with renal dysfunction, implying that the associated ARF h as a large hemodynamic component; and (4) HRS and ATN manifest compara ble degrees of enzymuria, suggesting that substantial tubular damage e xists in both of these forms of ARF.