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Katsunori Yanai, Keiji Hirai, Shohei Kaneko, Yuko Mutsuyoshi, Taisuke Kitano, Haruhisa Miyazawa, Kiyonori Ito, Yuichiro Ueda, Susumu Ookawara, Yoshiyuki Morishita Division of Nephrology, First Department of Integrated Medicine, Saitama Medical Center, Jichi Medical University, Saitama, JapanCorrespondence: Keiji Hirai, Division of Nephrology, First Department of Integrated Medicine, Saitama Medical Center, Jichi Medical University, 1-847 Amanuma-cho, Omiya-ku, Saitama-shi, Saitama-ken, 330-8503, Japan, Tel +81-48-647-2111, Fax +81-48-647-6831, Email keijihirai@kfy.biglobe.ne.jpObjective: We investigated the efficacy and safety of dotinurad, a selective urate reabsorption inhibitor, in hyperuricemic patients with advanced chronic kidney disease (CKD) (stage G3-5).Patients and Methods: We retrospectively analyzed the cases of 34 patients (mean age, 68.6 ± 13.3 years; 17 men and 17 women) after 12 months of dotinurad treatment based on the changes in uric acid (UA) and the urine protein-to-creatinine ratio (UPCR) plus the annual change in estimated glomerular filtration rate (eGFR). Hyperuricemia (UA ≥ 6.0 mg/dL) and advanced CKD (mean eGFR: 32.0 ± 13.3 mL/min/1.73m2; stage G3, n=17; G4, n=13; G5, n=4) were present in all of the patients. The cases of 34 matched individuals with similar propensity scores (who were not taking dotinurad) were analyzed as a control group.Results: UA values decreased significantly in the dotinurad group (7.1 ± 0.8 mg/dL to 5.9 ± 1.0 mg/dL, p< 0.05) but those did not change in the control group. UPCR did not change in either group. Low-density lipoprotein cholesterol also decreased significantly in the dotinurad group (98.8 ± 43.4 mg/dL to 82.9 ± 33.1 mg/dL, p< 0.05). With the 12-month dotinurad treatment, the annual change in the patients’ eGFR was significantly improved from − 6.0 ± 12.9 mL/min/1.73 m2/year to − 0.9 ± 4.6 mL/min/1.73 m2/year (p< 0.05), but there was no change in the control group.Conclusion: Dotinurad can decrease UA levels and might attenuate renal function decline in individuals with hyperuricemia and advanced CKD.Keywords: chronic kidney disease, dotinurad, hyperuricemia, uric acid, renal function

Keiji Hirai, Junki Morino, Saori Minato, Shohei Kaneko, Katsunori Yanai, Yuko Mutsuyoshi, Hiroki Ishii, Momoko Matsuyama, Taisuke Kitano, Akinori Aomatsu, Haruhisa Miyazawa, Kiyonori Ito, Yuichiro Ueda, Susumu Ookawara, Yoshiyuki Morishita Division of Nephrology, First Department of Integrated Medicine, Saitama Medical Center, Jichi Medical University, Saitama, JapanCorrespondence: Keiji HiraiDivision of Nephrology, First Department of Integrated Medicine, Saitama Medical Center, Jichi Medical University, 1-847 Amanuma-cho, Omiya-ku, Saitama-shi, Saitama-ken 330-8503, JapanTel +81-48-647-2111Fax +81-48-647-6831Email keijihirai@kfy.biglobe.ne.jpPurpose: The objective of this study was to determine factors associated with the change in carotid maximum intima-media thickness (IMT), an established surrogate marker of atherosclerosis, in moderate-to-advanced stage chronic kidney disease (CKD) patients.Methods: In total, 130 moderate-to-advanced stage CKD patients (mean age: 67.6 ± 11.0 years old; 91 men and 39 women) were included in this retrospective, single-center, observational study. Relationships between the change in carotid maximum IMT and clinical and laboratory data were analyzed by using multivariate linear regression analyses.Results: Mean observation period was 2.9 ± 1.6 years. Mean carotid maximum IMT at baseline was 2.2 ± 1.0 mm, and the annual change in carotid maximum IMT was 0.06 ± 0.22 mm/year. Low-density lipoprotein (LDL)-cholesterol (β = 0.173, p < 0.05) and annual change in triglyceride (β = 0.175, p < 0.05) independently correlated with the annual change in carotid maximum IMT.Conclusion: Increases in LDL-cholesterol and triglyceride were associated with the rate of progression of carotid maximum IMT in moderate-to-advanced stage CKD patients.Keywords: atherosclerosis, carotid maximum intima-media thickness, chronic kidney disease

Keiji Hirai, Junki Morino, Saori Minato, Shohei Kaneko, Katsunori Yanai, Yuko Mutsuyoshi, Hiroki Ishii, Momoko Matsuyama, Taisuke Kitano, Mitsutoshi Shindo, Akinori Aomatsu, Haruhisa Miyazawa, Kiyonori Ito, Yuichiro Ueda, Susumu Ookawara, Yoshiyuki Morishita Division of Nephrology, First Department of Integrated Medicine, Saitama Medical Center, Jichi Medical University, Saitama, JapanCorrespondence: Keiji HiraiDivision of Nephrology, First Department of Integrated Medicine, Saitama Medical Center, Jichi Medical University, 1-847 Amanuma-Cho, Omiya-Ku, Saitama City, Saitama 330-8503, JapanTel +81-48-647-2111Fax +81-48-647-6831Email keijihirai@kfy.biglobe.ne.jpIntroduction and Objectives: We investigated the efficacy and safety of sodium-glucose cotransporter-2 (SGLT-2) inhibitors as an add-on therapy in patients with advanced-stage diabetic kidney disease taking renin-angiotensin system (RAS) blockers.Materials and Methods: Changes in glycated hemoglobin (HbA1c), urine protein-to-creatinine ratio (UACR), body weight, systolic blood pressure, and annual change in estimated glomerular filtration rate (eGFR) were retrospectively analyzed in 20 patients after 12 months of SGLT-2 inhibitor administration (mean eGFR: 22.8 ± 9.7 mL/min/1.73 m2). All patients had advanced-stage diabetic kidney disease and were taking RAS blockers. Twenty patients matched with similar propensity scores who were not taking SGLT-2 inhibitors served as the control group.Results: The annual change in eGFR improved significantly from − 8.6 ± 12.5 mL/min/1.73 m2/year to − 2.6 ± 5.0 mL/min/1.73 m2/year after 12 months by SGLT-2 inhibitor administration (p < 0.05), but did not change in the control group. Other clinical parameters, such as HbA1c, UACR, body weight, blood pressure, serum lipids, and electrolytes did not change in either group. No adverse effects were observed by taking SGLT-2 inhibitors.Conclusion: Using SGLT-2 inhibitors as an add-on therapy may have beneficial effects on renal function in patients with advanced-stage diabetic kidney disease taking RAS blockers without any adverse effects.Keywords: advanced-stage diabetic kidney disease, renin-angiotensin system blocker, sodium-glucose cotransporter-2 inhibitor

Saori Minato, Keiji Hirai, Junki Morino, Shohei Kaneko, Katsunori Yanai, Yuko Mutsuyoshi, Hiroki Ishii, Momoko Matsuyama, Taisuke Kitano, Mitsutoshi Shindo, Akinori Aomatsu, Haruhisa Miyazawa, Kiyonori Ito, Yuichiro Ueda, Taro Hoshino, Susumu Ookawara, Yoshiyuki Morishita Division of Nephrology, First Department of Integrated Medicine, Saitama Medical Center, Jichi Medical University, Saitama, JapanCorrespondence: Keiji HiraiDivision of Nephrology, First Department of Integrated Medicine, Saitama Medical Center, Jichi Medical University, 1-847 Amanuma-cho, Omiya-ku, Saitama, Saitama 330-8503, JapanTel +81-48-647-2111Fax +81-48-647-6831Email keijihirai@kfy.biglobe.ne.jpAim: The aim of this study was to investigate different intensities of uremic pruritus in the daytime and nighttime, as well as contributing factors, in patients undergoing peritoneal dialysis (PD).Methods: A total of 46 patients (31 males, 15 females) with a mean age of 59.4± 14.7 years and mean PD vintage of 29.2± 25.2 months were enrolled in this single-center, prospective, cross-sectional study. The intensity of uremic pruritus in the daytime and nighttime was assessed using a visual analog scale (VAS). The relationships between intensity and various clinical and laboratory parameters were analyzed using multiple linear regression analyses.Results: The most common site of uremic pruritus was on the back (70%), followed by lower limbs (67%), chest and abdomen (59%), upper limbs (28%), and head and neck (22%). Mean VAS scores were higher in the nighttime compared with the daytime (4.5± 3.3 vs. 3.5± 2.7, P=0.02). Only male sex was correlated with higher uremic pruritus intensity in the daytime (standard coefficient [β]=0.310, P=0.036). PD vintage (β=0.415, P=0.004) and topical medicines, including moisturizer and topical corticosteroid use (β=0.345, P=0.019), were independently correlated with higher uremic pruritus intensity in the nighttime.Conclusion: Uremic pruritus intensity was greater in the nighttime than in the daytime in PD patients. Male sex was associated with higher uremic pruritus intensity in the daytime, whereas PD vintage and topical medicine use were associated with higher uremic pruritus intensity in the nighttime.Keywords: uremic pruritus, peritoneal dialysis

Kaori Yanai,1 Jane Huang,1 Kazuaki Kadonosono,2 Eiichi Uchio1 1Department of Ophthalmology, Fukuoka University School of Medicine, Fukuoka, Japan; 2Department of Ophthalmology, Yokohama City University Medical Center, Yokohama, Japan Purpose: To evaluate the safety of bromfenac sodium eye drops from the standpoint of corneal sensitivity and tear secretion in healthy controls following instillation for 1 month. Methods: A prospective single-blind parallel clinical study was conducted in 20 eyes of ten healthy volunteers with no history of ocular or systemic allergic disease, dry eye, contact lens wear, or ocular surgery. Participants were instructed to instill either bromfenac sodium or artificial tears in each eye twice daily for 28 days. Corneal sensitivity tested using a Cochet–Bonnet esthesiometer was evaluated before and immediately after instillation at 7, 14, and 28 days after the initiation of treatment. Tear secretion was also evaluated by Schirmer's eye test before and at 28 days. Results: No significant difference in mean corneal sensitivity and tear-secretion rate was observed between the bromfenac and artificial-tear treatment groups at any time. Conclusion: These results indicate that bromfenac sodium eye drops are safe with respect to corneal sensitivity and tear secretion in subjects with a normal ocular surface condition. Further evaluation is still necessary to determine whether bromfenac is safe in pathological conditions, such as inflammatory disorders and postsurgical cases. Keywords: bromfenac sodium, cornea, sensitivity, tear, nonsteroidal anti-inflammatory drug