Simultaneous manifestation of pleural effusion and acute renal failure associated with dasatinib: a case report

Abstract

PE is the most common extra-haematological toxicity observed during dasatinib treatment whose pathogenesis is still unclear. A possible role of cytokines, such as platelet-derived growth factor receptor (PDGFR)-β and vascular endothelial growth factor (VEGF), in causing endothelial permeability has been suggested. The aetiology of renal failure is also unclear in these patients, but two different possible mechanisms have been suggested such as tumour lysis syndrome and toxic tubular damage. In conclusion, here we describe the first case of simultaneous manifestation of PE and ARF associated with dasatinib. Thus, in patients treated with tyrosine kinase inhibitors, especially those with predisposing nephrological or haematological factors, serum creatinine levels should be monitored routinely.

Effects of Bosutinib Treatment on Renal Function in Patients With Philadelphia Chromosome-Positive Leukemias

“…Renal dysfunction has been reported with other TKIs, including imatinib, [6][7][8][9][10]14,[34][35][36] nilotinib, [37][38][39] and dasatinib, 6,9,[11][12][13][14][40][41][42][43] suggesting a possible drug class effect. This is supported by the similar frequency and characteristics of renal decline observed with imatinib and bosutinib treatment in our analyses.…”

“…Tumor lysis and toxic tubular damage have been proposed as possible mechanisms for renal failure with TKI therapy. 7,13 Imatinib-induced tubular damage might be related to the off-target inhibition of platelet-derived growth factor receptor (PDGF-R), which regulates the proliferation and regeneration of proximal tubular cells in the kidney and is notably not targeted by bosutinib. 44,45 However, findings from a recent study suggested that long-term treatment with imatinib, but not dasatinib or nilotinib, might cause a significant decline in eGFR.…”

“…Although generally well tolerated, tyrosine kinase inhibitors (TKIs) are associated with adverse events (AEs). [1][2][3][4][5] Renal toxicity has been reported during TKI treatment for Philadelphia chromosome-positive (Ph þ ) leukemias 2,[6][7][8][9][10][11][12][13] ; however, information is mostly limited to case reports. [7][8][9][11][12][13][14] Because of the long-term nature of TKI therapy and the different kinetics observed, particularly with regard to nonhematologic toxicities, a better understanding of the renal safety profiles of TKIs is important for optimizing patient management.…”

Renal Toxicities of Targeted Therapies

“…In addition to BCR-ABL and Src, dasatinib has been shown to inhibit LCK, YES, FYN, c-KIT, ephrin (EPH) receptor-A2, and PDGFRβ [60]. The data on nephrotoxicity with dasatinib are limited, with only three case reports of acute renal failure reported with this agent [61][62][63]. However, neither case was a definite link with dasatinib demonstrated nor was a mechanism of toxicity established.…”

“…The second case was associated with the development of acute gastroenteritis, although the authors felt that the cause of the renal failure was not related to hypovolemia [62], while the third patient had simultaneous development of a pulmonary embolus [63]. These reports notwithstanding, dasatinib is well-tolerated and does not call for dose reductions or interruptions in relation to nephrotoxicity [63].…”