Creatinine (Cr) is one of the main intrinsic hydroxyl radical (•OH) scavengers. We estimated how much Cr could scavenge •OH in human and rats, and compared such estimated values with corresponding ones for well-known deoxyguanosine (dG). Daily urinary excretions of some reaction products with •OH have been used to estimate the amount of •OH produced daily. For such a purpose, we have used Cr-related metabolites such as creatol (CTL: 5-hydroxycreatinine), an •OH adduct of Cr, plus its metabolite, methylguanidine (MG), and/or their molar sum (CTL + MG), whereas the amount of 8-hydroxydeoxyguanosine (8-OHdG), a well-known marker of •OH, in the body is negligible (103-fold less than Cr-related metabolites). The daily amounts of •OH scavenged in healthy subjects and normal rats are steady: Cr scavenges circa (ca.) 20-25 μmole and ca. 200 pmole of •OH, respectively; (CTL + MG)/Cr has been reported to be ca. 2.2 and 3.0 mmole/mole (spot urine or 24-h urine); 0.2 and 0.3% of Cr in healthy subjects are used in order to scavenge •OH, respectively. In patients with chronic renal failure (CRF) or chronic kidney disease (CKD) at stages 3-5 (glomerular filtration rate <60 mL/min/1.73 m³), •OH levels increase in proportion to the severity of CKD: up to ca. 3% of Cr is used daily in order to scavenge •OH. Novel intrinsic and natural •OH scavengers, such as 5-hydroxy-1-methylhydantoin and magnesium lithospermate B, respectively, decrease the amount of •OH, and prevent the progression of CRF in rats.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by muscle atrophy involving the entire body. Therefore, in ALS patients, a method for evaluating renal function that does not depend on muscle mass, such as the glomerular filtration rate (eGFRcys), estimated by serum cystatin C (CysC), is preferred. However, it is more difficult to use this method than calculation of the estimated glomerular filtration rate (eGFRcreat) or estimated creatinine clearance (eCCr) using serum creatinine (SCr) in clinical practice. The purpose of this study was to determine the most accurate method for estimating eGFRcreat and eCCr compared to eGFRcys in patients with ALS. Among ALS patients who visited Kansai Electric Power Hospital from May 2014 to November 2019, the subjects whose SCr and CysC levels were measured were included in the study. Patients were divided into two groups: modified Rankin Scale (mRS) 0-2 and mRS 3-6 groups. Furthermore, (a) eGFRcreat and eCCr levels obtained by the methods (b) to (f) were compared with eGFRcys.

(b) Actual SCr value by an enzymatic method, (c) + 0.2 correction method, in which the enzymatic SCr value is converted via the Jaffe rate assay, (d) roundup method, in which the SCr value is adjusted to 1.0 mg/dL if lower than 1.0 mg/dL, (e) Furukubo method, 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, and (f) Dooley method, in which the SCr value is rounded up to 0.06 mmol/L if below 0.06 mmol/L. The comparison of prediction accuracy as a percentage of patients with eGFRcreat or eCCr values within ±30% of eGFRcys values showed that group (c) had the highest accuracy with both 100% in the mRS 0-2 group and 71.4% in the mRS 3-6 group. A comparison of eGFRcys and eGFRcreat or eCCr values obtained by different methods showed that consistency between eGFRcreat or eCCr and eGFRcys was the greatest when the SCr value was adjusted by the + 0.2 correction method, adding 0.2 mg/dL to the enzymatically measured SCr value.

Rivaroxaban has no specific monitoring index, such as the PT-INR for warfarin. Thus, we investigated whether PT and renal function were useful monitoring indices for rivaroxaban.

Patients taking rivaroxaban (10 mg) when they were admitted to the Sapporo Medical University Hospital from November 1, 2013 to April 30, 2018 were included in this study. The primary outcomes were the presence or absence of bleeding, PT, creatinine clearance (CCr), and estimated glomerular filtration rate cystatin C (eGFRcys). Forty patients were included (mean age 71.5 ± 8.1 years) and 14 were women. A positive result for fecal occult blood test was indicative of bleeding. Nine patients exhibited bleeding and were placed in the bleeding group, in which the PT was significantly longer (17.0 ± 2.1 s vs 15.3 ± 1.9 s; p = 0.031) and renal function was lower (CCr: 44.6 ± 15.7 mL/min vs 59.5 ± 20.1 mL/min, p = 0.047; eGFRcys: 39.4 ± 12.6 mL/min vs 57.6 ± 18.5 mL/min, p = 0.009) than those in the non-bleeding group. We investigated cut-off values of bleeding using a receiver operating characteristic analysis. The values were as follows: PT 16.1 s (sensitivity: 77.8%, specificity: 61.3%), CCr 42.1 mL/min (sensitivity: 66.7%, specificity: 77.4%), and eGFRcys 46.1 mL/min (sensitivity: 77.8%, specificity: 74.2%).　These results suggested that not only CCr, but also PT and eGFRcys could be used as monitoring indices in patients administered rivaroxaban.

The sulfamethoxazole-trimethoprim (ST) combination is the first choice as a prophylactic agent for Pneumocystis pneumonia. Although ST combination is known to inhibit the renal tubular transporters and increase serum creatinine (sCr) and potassium (K) levels, there is no information on the variations in these levels in patients with chronic kidney disease (CKD). The objective of this study was to clarify the criteria for the evaluation of adverse events by administering ST combination to patients with CKD, and to investigate the relationship between changes in sCr and sK levels and renal function at the start of administration.

Patients who received the ST combination from April 2016 to March 2018 were divided into the normal renal function group (eGFR ≥ 60 mL/min/1.73m²) [n=34], a moderate renal dysfunction group (30≦eGFR < 60 mL/min/1.73m²) [n=23], and the severe renal dysfunction group (eGFR < 30 mL/min/1.73m²) [n = 9]; the changes in sCr and sK levels were measured for each group from day 1 to day 14. The factors affecting the variations in sCr and sK levels were examined by simple and multiple regression analysis.

Although the ST combination significantly increased the levels of sCr and sK in the normal renal function group, there were no significant changes in the severe renal dysfunction group. The change in sCr level was positively affected by eGFR (mL/min/1.73m²) before administration, whereas the change in sK value was not affected. The value of eGFR (β=0.16), weekly dose of the ST combination (β=0.24) for changes in sCr levels, renal disease (β=0.20), and the renin-angiotensin-aldosterone inhibitor (β=0.23) were detected as significant factors for changes in sK levels. That is, the increase in sCr levels in patients with severe renal dysfunction was shown to be minimal. And, it should be noted that the degree of increase in both sCr and sK levels is affected not only by renal function, but also by the dose of ST combination, the underlying disease, and multiple factors of concomitant drugs.

We report a suspected case of transient remaining of lanthanum carbonate OD tablet at middle the esophagus in patient with hemodialysis. The patient was 70s woman with 28 years dialysis vintage. After she came to our dialysis clinic, she had a lunch then took two calcium carbonate OD tablets (Caltan® OD 500mg tablet) and one lanthanum carbonate OD tablet (Fosrenol® OD 250mg tablet). The day was a scheduled day of chest X-ray examination prior to hemodialysis. In the X-ray image, a tablet-like circular shade was identified in middle the esophagus. Physician confirmed that there were no foreign objects on the patient’s clothing or skin and another X-ray radiograph was taken. The following images revealed that the shade was gradually disintegrating. The physician instructed her to drink additional water and to hold in sitting position for 10 minutes, then another X-ray was taken. In the final image, the shade was completely disappeared. In this case, the shade that existed in the esophagus was considered to be a lanthanum carbonate OD tablet. To avoid sticking OD tablet to esophagus, if taken without disintegration in oral cavity, it is necessary to require at least same amount of water to drink as taking regular tablets was suggested.