Development of Renal Calculi and Imatinib Therapy in CML: Is There an Association?.

Abstract

Abstract Reports are accumulating regarding the altered bone and mineral metabolism caused by imatinib (IM) therapy (Berman E, et al 2006 NEJM). This probably occurs through in vivo inhibition of PDGF receptors. It has been proposed that prolonged use of IM may cause some potentially serious metabolic pathological disorders. Compensatory rise in parathyroid hormone level may cause renal pathologies in these patients. In this observational study we came across a few patients on imatinib therapy for CML who experienced prolonged dyspepsia, abdominal and bone pain (suggestive of groans, moans, bones and stones features) and abdominal ultrasonography revealed renal calculi. This has led to collection of clinical data. So far, no systematic evaluation with radiological or biochemical have been undertaken in our cohort of 177 of CML on imatinib therapy. At the time of this report we have noted development of renal calculi (all symptomatic) in 7 patients of CML on imatinib therapy. All these patients have been on imatinib therapy 400 mg daily for more than 1 month before symptoms developed. In all but one, no surgical intervention has been necessary so far. Biochemical evaluation for altered bone metabolism revealed hyperphosphatemia in one and normal in another. Analysis of renal stone in one showed a composition of calcium phosphate and oxalate. Imatinib was not discontinued but reduced to 300 mg in 3 patients. It is possible that prolonged use of IM may alter calcium and phosphate metabolism leading to renal calculi formation. The proposed mechanisms could be, interference with bone and mineral metabolism coupled with parathyroid dysfunction which in turn leads to renal tubular abnormalities or availability of excess oxalate for intestinal absorption brought about by low calcium ingestion. Well designed cohort studies may throw more light in this area.