Possible liposomal amphotericin B-induced nephrogenic diabetes insipidus.

OBJECTIVE: To report the development of nephrogenic diabetes insipidus (NDI) associated with the use of high-dose liposomal amphotericin B. CASE SUMMARY: A 38-year-old white man with relapsed acute myelogenous leukemia underwent a matched unrelated donor allogeneic bone marrow transplant with adequate engraftment and mild graft-versus-host disease responding to corticosteroids. Approximately 11 months after transplant, the patient was admitted to the hospital with suspected fungal pneumonia and started on liposomal amphotericin B (baseline serum creatinine 1.4-1.5 mg/dL). The dose was increased due to his immunosuppression and poor response, as the fungal etiology was identified as Torulopsis glabrata. The patient required mechanical ventilation due to biopsy-proven bronchiolitis olbiterans organizing pneumonia. Additionally, he developed diffuse alveolar hemorrhage and received intravenous desmopressin, with a reduction in bloody secretions. He also developed hypernatremia (serum sodium 155 mEq/L) on day 3 of the desmopressin and had an inappropriately increased urine output consistent with NDI. The most likely etiology for the NDI was liposomal amphotericin B and its associated hypokalemia. DISCUSSION: The observation of worsening hypernatremia (serum sodium increased from 135 to 164 mEq/L) with polyuria was associated with an increasing cumulative dosage of liposomal amphotericin B for fungal pneumonia despite the concurrent use of intravenous desmopressin. Aggressive water replacement was an effective treatment option in this patient. The Naranjo probability scale classified this as a possible adverse reaction because of the temporal sequence of NDI after high-dose liposomal amphotericin B and previously reported cases of NDI associated with amphotericin B desoxycholate. CONCLUSIONS: Amphotericin B desoxycholate has been implicated as an etiology for NDI, and the use of the newer liposomal amphotericin B reportedly avoids this rare complication. We observed the development of NDI despite the use of liposomal amphotericin B in a critically ill patient with bone marrow transplant.

Steps toward mapping the human vasculature by phage display.

The molecular diversity of receptors in human blood vessels remains largely unexplored. We developed a selection method in which peptides that home to specific vascular beds are identified after administration of a peptide library. Here we report the first in vivo screening of a peptide library in a patient. We surveyed 47,160 motifs that localized to different organs. This large-scale screening indicates that the tissue distribution of circulating peptides is nonrandom. High-throughput analysis of the motifs revealed similarities to ligands for differentially expressed cell-surface proteins, and a candidate ligand-receptor pair was validated. These data represent a step toward the construction of a molecular map of human vasculature and may have broad implications for the development of targeted therapies.