Hyperuricemia often occurs in patients with chronic kidney disease and those on hemodialysis (HD). This study assessed the clinical efficacy and individual differences of the response to febuxostat, a non-purine selective xanthine oxidase inhibitor, in HD patients with hyperuricemia.Patients on maintenance HD who had a serum uric acid (SUA) level higher than 7.0 mg/dL were treated with febuxostat (10 mg/day). SUA levels were evaluated before and after 1 month of treatment in 27 patients, including 13 newly treated patients (new group) and 14 patients who were switched from allopurinol (switched group). In the new group, the SUA level decreased significantly from 9.7 mg/dL (7.4 – 11.9) to 5.0 mg/dL (3.4 – 7.1) with febuxostat treatment. In the switched group, the SUA level also decreased significantly from 9.1 mg/dL (7.0 – 10.0) to 6.1 mg/dL (5.1 – 10.0). However, the percent change of SUA after febuxostat administration was significantly smaller in the switched group than the new group. There was a significant negative correlation between the percent change of SUA and baseline blood urea nitrogen (BUN) in both groups. We divided the switched group into high responder and low responder based on the median percent change of SUA after febuxostat treatment (-22.7%), and found that the baseline BUN and normalized protein catabolic rate (nPCR) were significantly lower in low responder than high responder.The initial adequate dose of febuxostat for HD patients is 10 mg/day and caution is necessary to avoid a marked decrease of SUA. In patients switched from allopurinol, the response to febuxostat is good, but weaker than in newly treated patients. HD patients with a lower BUN or nPCR (both indicating poor nutritional status) may show a limited response to febuxostat.
[Purpose] To prevent acute rejection for renal transplantation, a combination immunosuppressive therapy of calucineurin inhibitors, antimetabolites, and steroids is usually provided. In the immunosuppressive therapy which uses high-dose mizoribine (MZ: 6 mg/ kg/ day) for antimetabolites, referred to as high-dose MZ therapy, it has been a problem that the individual difference of the blood concentration of MZ is large. MZ is a renal excretion drug, but the change between the individual of the absorption factor is remarkable, and the absorption of MZ becomes the factor which has an influence on the blood concentration following renal function. Therefore, we examined the influence which aging has on absorption of mizoribine.[Methods] The target population of our research was 50 patients who had received high-dose MZ therapy from April 2011 to September 2013. We divided the patients into two groups: the low age group (18-44 years: 25 patients), and the older age group (45 years and older: 25 patients).In two groups, we performed the comparison analysis of the blood concentration of MZ and the pharmacokinetic parameter. In addition, we examined the correlation between age and values of the area under the blood concentration time curve corrected for creatinine clearance and dose (AUC･Ccr/ Dose).[Results] The significant difference of the transplant renal function was not seen between two age groups. In the low age group, the trough level and AUC were significantly higher than that in the older age group. We also found a negative correlation between age and the AUC･Ccr/ Dose.[Discussion] It was supposed a drop of the absorption of MZ by the aging. Than this result, it was confirmed that enforcement of therapeutic drug monitoring was important to give high-dose MZ therapy appropriately. Moreover, we propose that when planning to administer MZ, we should take particular note of the age.
When we argue about proper use of drugs, it is essential to set appropriate dose levels for individual patients. Therefore, pharmacists need to obtain renal function data of patients. At community pharmacy, however, pharmacists have not been established a way to utilize renal function data. We conducted a survey of pharmacists working in community pharmacies. As a result, renal function data was ①considered (9.1%), ②considered partially (54.5%), ③ not considered partially (27.2%), ④ not considered (9.1%). Renal function data was gained from ① patient or its family (77.2%), ② medical doctor (4.5%), ③ nobody (9.1%). Based on these results, we have designed a seal put on the Medication Notebook to be able to share patients renal function data between hospital and community pharmacy. As a result, this eGFR labeled Medication Notebook was to be ① useful (50.0%), ② partially useful (36.3%). From this survey, it revealed that the community pharmacists cannot obtain the information about the patient’s renal function despite needing. Therefore, it is a very useful reminder for community pharmacists to consider of patients renal function data. This initiative can expect to avoid overdose of renal excretion drugs.
Sodium ozagrel is an antiplatelet drug administered for acute ischemic stroke. It is eliminated predominantly into the urine and may enhance the antiplatelet effect in patients with renal insufficiency or in patients who are elderly. However, few studies have investigated its use in such patients. Here, we evaluated the effects of sodium ozagrel on the antiplatelet effect in patients with renal insufficiency. The antiplatelet effect was retrospectively determined from the laboratory data of 23 patients receiving sodium ozagrel during the period March 2008 to April 2013. In patients who were not taking aspirin, the adenosine 5′-diphosphate disodium salt (ADP)-induced platelet aggregation threshold index (PATI) and the collagen-induced PATI were respectively 1 μM/mL and 0.7 μg/mL higher in those with renal insufficiency than in those with normal renal function. However, in patients who were taking aspirin, the ADP-induced PATI and the collagen-induced PATI were respectively 0.1 μM/mL lower and 0.2 μg/mL higher in those with renal insufficiency than in those with normal renal function.These findings indicate that sodium ozagrel enhances the antiplatelet effect in renal insufficiency. When administering it to patients with renal insufficiency, physicians should carefully monitor for adverse effects such as digestive hemorrhage and hemorrhagic stroke.
A male patient in his 40s received his second of two living donor kidney transplantations. The postoperative course was uneventful, and kidney function improved greatly. Tacrolimus (TAC) trough levels were 5.5 ng/mL on postoperative day 6 (POD6). However, the patient presented with diarrhea described as greater than five watery stools per day on POD7 after taking Minocycline (MINO) orally as postexposure prophylaxis for pertussis, and TAC trough levels were found to be subsequently elevated to 11.3 ng/mL on POD10. After the diarrhea stopped on discontinuation of MINO, TAC trough levels stabilized at 5.5-6.1 ng/mL. While the patient did present with transient palpitation and chest pain due to sinus tachycardia while TAC trough levels were elevated, no decline in transplanted kidney function was noted. Although TAC is typically poorly absorbable, previous studies have similarly reported that severe diarrhea caused an elevation in TAC trough levels due to increased absorption of TAC. Kidney transplant recipients often present with diarrhea due to various causes, including gastrointestinal infections, adverse effects of immunosuppressive drugs, and alteration of the intestinal flora due to antibiotic administration. We recommend careful monitoring of TAC levels in kidney transplant recipients with diarrhea to prevent adverse effects.