Traditional Chinese medicine has received much attention as a source of novel therapeutic agents due to multiple beneficial effects and the absence of toxic and/or side effects. Traditional Chinese medicine influences changes at multi-system and multi-organ levels. The present study reports the therapeutic evidence for Kangen-karyu, one of our major compounds of interest among traditional Chinese medicine agents, from experimental models related to diabetic kidney. Firstly, we investigated the effects of Kangen-karyu on high glucose-induced oxidative stress using LLC-PK1 cells, renal tubular cells, which are the renal cells most vulnerable to oxidative stress. Kangen-karyu has exhibited promising therapeutic potential against pathological conditions associated with hyperglycemia-induced oxidative stress that occur in diabetes. Therefore, we investigated the effects of Kangen-karyu on damage to the kidney caused by diabetes-induced alterations such as advanced glycation endproduct formation and/or a fibrotic response in the kidney of type 2 diabetic db/db mice. Kangen-karyu showed renoprotective effects against the development of diabetic complications. To add to these findings, Kangen-karyu exhibited a pleiotropic effect on diabetes-induced alterations such as oxidative stress, inflammation, and morphological changes in the kidney of type 2 diabetic mice. These results provide important evidence that Kangen-karyu exerts a renoprotective effect against the development of diabetic nephropathy. They also provide scientific evidence that may explain the efficacy of traditional Chinese medicine at multi-system levels.
In Sakai City Medical Center, creatinine clearance (Ccr) is described on prescriptions. When drugs to be regulated in accordance with the kidney function are prescribed, the term “kidney” follows the drug name. Furthermore, the submission of PreAVOID reports is promoted in our hospital, and the number of reports has slightly increased. Many reports associated with the kidney function have also been submitted. In this study, we examined the influence of patient/drug information described on prescriptions on the accuracy of dispensing/surveillance and optimization of prescription surveillance, as well as the timing of PreAVOID -report submission and changes in the contents. A prescription surveillance involving pharmacists in our hospital and university pharmacy students was conducted by preparing sham prescriptions. On all sham prescriptions, Ccr was described, and prescriptions with “kidney” and without such a description were prepared. The accuracy of surveillance and time required were established as endpoints. Concerning PreAVOID reports, we compared reports on drugs for which kidney-function-based regulation is necessary between PreAVOID report groups in 2015 (“kidney”-describing group (2015)) and 2014 (non-“kidney”-describing group (2014)). The accuracy of auditing prescriptions with the “kidney” description was significantly higher than that of auditing prescriptions without such a description, and the time required for surveillance was significantly shortened. When comparing the number of kidney-function-associated PreAVOID reports between the above two groups, it was significantly greater in the “kidney”-describing group (2015). These results suggest that information on prescriptions contributes to an improvement in the accuracy of dispensing/surveillance and reduction of the time required, facilitating accurate, efficient surveillance. Thus, the description of “drugs to be regulated in accordance with the kidney function” on prescriptions may be useful for achieving prompt drug therapy.
Aiming to improve the quality of pharmaceutical interventions, the Drug Information centerat the Kansai Electric Power Hospital had built and was using a system (System) for checking contraindicated medicine prescriptions related to renal function from the hospital’s data warehouse, since 2014. This study deals with the utilization and issues faced while using the System for contraindicated drug prescriptions. The inpatients, who underwent a blood test within a month from the screening date, were targeted in this study. The creatinine clearance estimated by the Cockcroft-Gault formula (Ccr) was used as the screening parameter to select patients with decreasing Ccr levels of 60mL/minute or less. The patients were grouped into three based on their Ccr levels, which corresponded to Ccr levels of Ccr＜10mL/minute, Ccr＜30mL/minute, and Ccr＜60mL/minute. From the three groups, we selected those patients who were prescribed contraindication medicines (the Contraindication Medicine group) and discussed each case with a ward pharmacist before deciding the relevant countermeasure actions. A doctor from the Drug Information center was consulted in cases with doubtful references, as often as required. The System detected 104 contraindication cases; 41 cases, which represented a 39.4% of the total, had doubtful references requiring consultation with a doctor following discussions with a ward pharmacist. Finally, 24 cases qualified for prescription modifications. For the unmodified prescription cases, we consulted with a doctor and a ward pharmacist on the validity of the prescription. Additionally, we requested either an item inspection, or an implementation of Therapeutic Drug Monitoring (TDM), along with patient related consultations with a doctor from another department. Our system could effectively detect contraindication cases mechanically and cooperate with a ward pharmacist and a doctor for optimizing medication. Furthermore, it contributed to the rationalization of the prescribed medicines and improved drug treatment safety. Setting the correct border value in the Contraindication Medicine group was important, since it missed the consultations with the doctor and the ward pharmacist. The System could not often prohibit prescriptions of contraindicated drugs.
Diabetic nephropathy is one of the leading causes of end-stage renal disease (ESRD) and hemodialysis. Cardiovascular events and mortality rates increase in patients with ESRD and hemodialysis; therefore, it is important to delay ESRD and the onset of hemodialysis. The renal effects of liraglutide, a glucagon-like peptide-1 receptor agonist, have been reported. However, dulaglutide has only been shown to reduce albuminuria in other countries, and there is no report on the effect of dulaglutide on renal function in Japanese patients. We studied the effects of dulaglutide on glucose control and renal function. Forty-five patients started dulaglutide at Sapporo Medical University Hospital between September 2016 and September 2017 and 19 patients were ultimately included in the study. The primary outcomes were glycated hemoglobin (HbA1c) levels and the estimated glomerular filtration rate (eGFR) three months after starting dulaglutide. Changes in the eGFR were also analyzed. Of the patients included (mean age 57.4 years), 10 were men and 9 were women. Three months after the initial administration of dulaglutide, the mean HbA1c significantly decreased from 8.9 ± 0.4% (mean ± SE) to 8.0 ± 0.4% (p = 0.019), and the eGFR significantly increased from 60.2 ± 4.7 mL/min/1.73m2 (mean ± SE) to 65.3 ± 4.9 mL/min/1.73m2 (p = 0.011). However, the systolic blood pressure did not change significantly (from 123.6 ± 16.2 mmHg to 125.6 ± 16.6 mmHg (p = 0.919)). Three months before administering dulaglutide, the mean eGFR decreased by 2.1 ± 5.6 mL/min/1.73m2 and three months after the initiation of dulaglutide, the mean eGFR increased by 5.1 ± 7.9 mL/min/1.73m2 (p = 0.011). This study suggests that the administration of dulaglutide can result in lower rates of nephropathy progression and/or increases in eGFR in patients with type 2 diabetes.
A 34 years old woman had a convulsive seizure about 7 months after introduction of hemodialysis(HD), and convulsive seizure disappeared when Levetiracetam was administered. For the purpose of preventing dialysis amyloidosis, we changed from HD to on-line hemodiafiltration(on-line HDF), but after the change there was a strong appeal of drowsiness. Since the symptoms of strong drowsiness could not be taken, treatment was restored from on-line HDF to HD and the symptoms improved, so the possibility that Levetiracetam removal was less in on-line HDF than HD was suspected to have accumulated.