Proteinuria due to suboptimal hydration with high-dose methotrexate therapy

Extended duration of prehydration does not prevent nephrotoxicity or delayed drug elimination in high-dose methotrexate infusions: A prospectively randomized cross-over study

“…When hydration was initially employed, it significantly decreased the incidence of renal toxicity and increased the clearance of MTX . The ideal length of prehydration has never been determined; as a consequence prehydration time varies from a couple of hours to more than 24 hours between ALL treatment protocols . It has been suggested that extended prehydration (i.e., 12–24 hours) can prevent renal toxicity in patients who have had delayed MTX elimination in previous HDMTX infusions .…”

Influence of high‐dose methotrexate therapy (HD‐MTX) on glomerular and tubular kidney function

“…Tubular obstruction by crystal deposits of MTX and its main metabolite, 7-OH-MTX, is assumed to be the significant mechanism of serious MTX excretion disturbance [8][9][10][11]. An indirect evidence for this hypothesis is the clinical observation that providing sufficient hydration and improving the solubility of MTX by means of urine alkalization can significantly reduce the frequency of MTX toxicity [10,[12][13][14]. In spite of proper hydration and urine alkalization, serious renal dysfunction seldom occurs after the administration of HD-MTX.…”

“…In spite of proper hydration and urine alkalization, serious renal dysfunction seldom occurs after the administration of HD-MTX. Therefore it can be assumed that a disturbance in preglomerular vascular resistance [7,15], direct damage to the glomeruli [5,12], or direct tubular toxicity [11,16] are further nephrotoxic mechanisms.…”