An effective and safe drug therapy for elderly bedridden patients requires an accurate assessment of renal function, since aging affects drug pharmacokinetics in patients. In Japan, based on the enzymatically measured serum creatinine (SCr) value, estimated glomerular filtration rate (eGFR) and estimated creatinine clearance (eCCr) calculated using the Cockcroft-Gault (CG) formula have been used as indicators of patients’ kidney function in routine practice. However, there are some limitations to using eGFR or eCCr directly for elderly patients, because the CG formula is based on data from a non-Japanese population, and uses SCr values measured colorimetrically by the Jaffe method. To overcome these issues, various adjustment protocols for determining the SCr value have been proposed. The purpose of this study was to determine the most accurate adjustment method for SCr values to calculate the eCCr when compared with measured 24-h CCr (mCCr) in elderly bedridden patients.The mCCr was measured by urine collected for 24 h from 45 patients aged 65 years or above, hospitalized at the Naruto Yamakami Hospital between August 2014 and May 2015. The eCCr value was estimated using the CG formula based on SCr value determined by the following methods: (a) actual SCr value by the enzymatic method; (b) + 0.2 correction method, in which the enzymatic SCr value is converted into the Jaffe rate assay; (c) Dooley, in which the SCr value is rounded up to 0.06 mmol/L if below 0.06 mmol/L; (d) Smythe, in which the SCr value is adjusted to 1.0 mg/dL if lower than 1.0 mg/dL; and (e) Furukubo, in which the SCr value is adjusted to 0.8 mg/dL if lower than 0.8 mg/dL in males and to 0.6 mg/dL if lower than 0.6 mg/dL in females.Comparison of mCCr (control group) with the eCCr of each group by the Dunnett test revealed a significant difference between them in the (a) and (d) groups (p < 0.05). Bland-Altman analysis showed a consistency in eCCr and mCCr values in groups (b), (c), and (e). Finally, comparison of prediction accuracy as a percentage of patients with eCCr values within ±30% of mCCr values showed that group (b) had the highest accuracy at 75.6%, followed by group (c) at 71.1%.A comparison of mCCr and eCCr values obtained by different methods showed that consistency between eCCr and mCCr was greatest when the SCr value was adjusted by the + 0.2 correction method, adding 0.2 mg/dL to the enzymatically measured SCr value.
Polypharmacy in elderly patients represents a potential increase in the use of inappropriate drugs that may lead to an increased risk of adverse events. In this study, we aimed to clarify the relationship between the stages of chronic kidney disease (CKD) and use of inappropriate drugs that can result in polypharmacy in elderly CKD patients. Patients aged 65 years or older, who were hospitalized between January 2016 and June 2016 (n = 647), were classified according to their CKD stages determined by the categories of glomerular filtration rate (GFR). The regular medications that patients were taking at the time of hospital admission were examined in terms of dosage regimen, and polypharmacy was defined as the use of six or more of these drugs. In addition, we examined the potential risk factors for adverse events associated with polypharmacy in elderly patients or patients with decreased kidney function, and whether the drugs were discontinued or changed during hospitalization. The results showed that the rate of polypharmacy was 42.0% in patients with stage G1/2, while it was 84.1 and 90.5% in those with stage G4 and G5D, respectively. The usage of different dosage regimens significantly increased in patients with stage G4 or more severe CKD compared to patients with stage G1/2. The proportion of prescribed drugs that were considered potential risk factors for adverse events in elderly patients was significantly higher in patients with stage G4 (84.1%) and G5D (71.4%) than in patients with stage G1/2 (50.7%). Meanwhile, the proportion of prescribed drugs that were considered potential risk factors for adverse events in patients with decreased kidney function was 33–50% in each GFR category. However, this proportion was relatively small and no significant differences were observed. The characteristics of different drugs were identified according to the GFR categories. The proportion of drugs that were discontinued or changed during hospitalization was higher in patients with stages G4 and G5 than in other GFR categories. This study demonstrated that with the progression of CKD, elderly patients tended to show an increased rate of polypharmacy as well as intake of drugs, which can be potential risk factors for adverse events. In addition, the results of study suggest that the pharmacological management of prescription drugs, which are considered potential risk factors for adverse events, according to the CKD stage of the patient is important.
The Therapeutic Drug Monitoring (TDM) guidelines recommend the administration of initial loading dose of vancomycin to patients with normal renal function (i.e., an estimated glomerular filtration rate (eGFR) > 80 mL/min/1.73 m2), because the optimum concentration of vancomycin in the blood is >10 mg/L. This TDM guideline determines the initial dosage of vancomycin. However, because the clinical safety of vancomycin is limited in patients with reduced renal function (i.e., eGFR < 80 mL/min/1.73 m2), initial loading dose of vancomycin is not recommended. However, the initial loading dose of vancomycin should be recommended to patients with decreased renal function because the attainment of steady state is delayed by pharmacokinetics. Therefore, we surveyed the nephrotoxicity and efficacy that resulted from the administration of initial loading dose vancomycin in patients with reduced renal function. We retrospectively examined the medical records of patients who were administered vancomycin at our hospital between January 2015 and December 2016. During the study period, the trough values and eGFR were calculated for 22 cases: load-administered group, 6 cases; standard treatment group, 16 cases. We compared the rate of therapeutic range and kidney injury between both groups. The rate of therapeutic range was 83.3% (load-administered group) and 50% (standard treatment group). It tends to be higher in the load-administered group than in the standard treatment group. Kidney impairment was observed to be 0% in the load-administered group and 12.5% in the standard treatment group.In patients with decreased renal function, safety of the initial dosage of vancomycin TDM is comparable with that of the standard treatment group.