Clotrimazole increases tacrolimus blood levels: a drug interaction in kidney transplant patients

In order to substantiate a previous case report of a drug interaction between tacrolimus and clotrimazole, we randomly assigned tacrolimus-treated renal allograft recipients to therapy with either clotrimazole or nystatin for oral thrush prophylaxis immediately following transplantation. Patients receiving other agents known to interact with cytochrome P450 were excluded from the study. The clotrimazole group consisted of 17 patients and the nystatin group, which served as the control group, consisted of 18 patients. An oral loading dose (approximately 0.3 mg/kg) of tacrolimus was given pre-operatively. Post-transplant, tacrolimus (approximately 0.15 mg/kg) was orally administered twice daily. Clotrimazole therapy consisted of a 10-mg troche administered three times daily. Nystatin therapy consisted of the oral suspension (5 mL) administered as a 'swish and swallow' four times daily. We evaluated tacrolimus trough blood levels and tacrolimus doses on days 1, 3, 5, and 7 following transplantation. On post-transplant day 1, mean tacrolimus trough levels did not differ between clotrimazole- and nystatin-treated patients. Mean tacrolimus blood trough levels were significantly higher in clotrimazole-treated patients on days 3, 5, and 7 post-transplant, 42+/-14, 53+/-7, and 33+/-17 ng/mL, respectively, compared to 15+/-8, 15+/-7, and 14+/-6 ng/mL in nystatin-treated patients (p<0.05). The mean tacrolimus dose was significantly lower in the clotrimazole group by day 7 post-transplant (p<0.05). We conclude that clotrimazole therapy may cause a significant rise in tacrolimus trough blood levels. Recognition of this potential drug interaction is essential to minimize tacrolimus-associated toxicities in the early post-transplant period.     

A thromboxane synthetase antagonist ameliorates progressive renal disease of Dahl-S rats

Recent studies have suggested a role for thromboxane in the progression of renal disease. The current study evaluated the role of this arachidonic acid metabolite in a model of renal disease which bears many biologic similarities to that in the kidneys of patients with chronic progressive renal failure. The model is that induced by ferritin-anti-ferritin immune complex nephritis in Dahl-salt sensitive rats rendered hypertensive by a high salt intake. Rats with this model of renal disease were chronically given a thromboxane synthetase antagonist OKY-046 or a placebo treatment from 16 to 29 weeks of age. Sequential observations of serum creatinine and 24-hour urinary protein excretion showed an ameliorating effect of OKY-046 on these renal parameters. Histologic examination of the kidneys also showed significantly less glomerular sclerosis in OKY-046 treated animals. The efficacy of OKY-046 was monitored by measurements of serum TXB2 levels and of glomerular production of TXB2 (and other prostaglandins); amounts of TXB2 were significantly reduced in the OKY-046 group. It is concluded that blockade of thromboxane generation has been successful in ameliorating the functional and structural lesions in this model of renal disease, providing further support to the thesis that thromboxane is an important mediator in events leading to eventual chronic renal failure and sclerosis.     

Physician communication styles in initial consultations for hematological cancer

Objective

To characterize practices in subspecialist physicians’ communication styles, and their potential effects on shared decision-making, in second-opinion consultations.

Methods

Theme-oriented discourse analysis of 20 second-opinion consultations with subspecialist hematologist-oncologists.

Results

Physicians frequently “broadcasted” information about the disease, treatment options, relevant research, and prognostic information in extended, often-uninterrupted monologs. Their communicative styles had one of two implications: conveying options without offering specific recommendations, or recommending one without incorporating patients’ goals and values into the decision. Some physicians, however, used techniques that encouraged patient participation.

Conclusions

Broadcasting may be a suboptimal method of conveying complex treatment information in order to support shared decision-making. Interventions could teach techniques that encourage patient participation.

Practice implications

Techniques such as open-ended questions, affirmations of patients’ expressions, and pauses to check for patient understanding can mitigate the effects of broadcasting and could be used to promote shared decision-making in information-dense subspecialist consultations.     

Idiopathic pediatric chronic kidney disease: can genomic technology crack the case?

In children, chronic kidney disease (CKD) that results from structural abnormalities and glomerular injury is readily diagnosed; however, most cases of pediatric CKD are of unknown etiology. In this issue of the JCI, Verbitsky and colleagues used chromosomal microarrays to evaluate genomic variation in children with CKD. Compared with control individuals, a substantial proportion of children with idiopathic CKD had clearly identifiable genomic imbalances. Moreover, in some cases, detailed analysis of these imbalances identified pathogenic alterations that were unsuspected based on clinical presentation. The results of this study support genome-wide evaluation for pediatric cases of CKD; however, more work will need to be done before such an approach is widely available in the clinic.