Acute renal failure following massive mannitol infusion. Appropriate response of tubuloglomerular feedback?

Two patients suffered reversible acute oligoanuric renal failure following massive mannitol infusion (400 to 900 g/day) given as treatment for intracranial hypertension. We believe this to be a previously unreported complication. Both patients had normal renal function before therapy. Serum creatinine level rose to 7.4 mg/dL (654 mumole/L) in patient 1 and to 2.7 mg/dL (238 mumole/L) in patient 2. Measured and calculated serum osmolality were 362 and 301 mOsm/kg, respectively, in patient 1 and 333 and 220 mOsm/kg, respectively, in patient 2. Other causes of renal failure were excluded. We postulate that the mannitol-induced increase in solute delivery to the macula densa may have triggered an intense tubuloglomerular feedback response resulting in a marked fall in glomerular filtration rate. Alternatively, mannitol infusion may have caused tubular cell swelling with luminal obstruction.