Clinical and Experimental Nephrology最新文献

Background: The validity of the International Classification of Diseases 10th Revision (ICD-10) codes for chronic kidney disease (CKD) in Japan have not been evaluated. In this study we evaluated the validity of CKD-related ICD-10 codes in Japan.

Methods: This retrospective cohort study used the JMDC hospital-based database, which comprises claims and laboratory data from over 1,000 medical institutions in Japan. Patients who underwent two serum creatinine measurements between April 2014 and August 2022 were identified; the second measurement was obtained 90-365 days after the first. The estimated glomerular filtration rate (eGFR) was calculated. CKD was defined by the Kidney Disease: Improving Global Outcomes (KDIGO) criteria: an eGFR < 60 mL/min/1.73 m² for both measurements. Markers of kidney damage such as albuminuria were unavailable. Patients assigned CKD-related ICD-10 codes (N183, N184, N185, N189, N19, E102, E112, E142, and I120) within 365 days of the initial serum creatinine measurement were identified. Subsequently, the positive predictive value (PPV), sensitivity, specificity, and negative predictive value (NPV) were calculated.

Results: Among the 618,208 included patients, 59,139 were assigned CKD-related ICD-10 codes and 172,657 met the KDIGO criteria. The overall PPV, sensitivity, specificity, and NPV were 57.9%, 19.8%, 94.4%, and 75.2%, respectively. In contrast, the PPVs of N183, N184, N185, and N189 exceeded 80%.

Conclusions: In Japan, the PPV of the ICD-10 codes for CKD was 57.9%, marginally lower than values reported in the United States (86.1%) and Canada (60.1%). Several ICD-10 codes may be useful for identifying patients with CKD, despite their limited sensitivity.

Background: Zinc-α2-glycoprotein (ZAG) is an adipokine, which may act locally to regulate adipocyte metabolism. Downregulation of ZAG expression in obesity has been reported in obesity in both mice and humans. In contrast, other studies revealed that serum ZAG levels were positively associated with renal dysfunction. We investigated whether serum ZAG levels serve as a biomarker for renal impairment in a general population, both cross-sectionally and longitudinally.

Methods: A total of 223 residents (85 men and 138 women, mean age 67.1 ± 9.7 years old) underwent health examinations in 2011. Baseline fasting blood samples were collected, including measurement of serum ZAG. Participants were followed annually for 13 years.

Results: Mean serum ZAG levels were 49.2 ± 13.7 μg/mL in males, and 41.7 ± 9.0 μg/mL in females. In univariate analysis, ZAG levels were significantly associated with male gender (p = 0.005), estimated glomerular filtration rate (eGFR p = 0.004, inversely), smoking habit (p = 0.031), and medication for hyperlipidemia (p = 0.024 inversely). In multiple logistic regression analysis, eGFR (p = 0.002, inversely), male gender (p = 0.003), and medication for hyperlipidemia (p = 0.038 inversely) remained significantly and independently associated with serum ZAG at baseline. During follow-up, 31 subjects developed chronic kidney diseases (CKD). However, baseline ZAG was not significantly associated with incident CKD over 13 years.

Conclusions: Serum ZAG levels were independently associated with renal function and may represent a novel biomarker of renal dysfunction in a general population. However, ZAG did not predict long-term CKD development.

Objective: This study aimed to investigate the role of B7-H3-an immune checkpoint implicated in inflammation and vascular remodeling-in uremic vascular calcification (UVC), particularly its effects on calcium deposition, vascular smooth muscle cell (VSMC) phenotype, and VSMC-macrophage crosstalk.

Methods: An in vitro UVC model was established using β-glycerophosphate (β-GP) treated human aortic VSMCs (HA-VSMCs). B7-H3 expression was silenced using siRNA. Calcification was assessed by Alizarin Red S staining, ALP activity, and calcium content assays. VSMCs phenotype switching was evaluated by Western blot for contractile and osteogenic markers. Macrophage recruitment, adhesion, and polarization (M1/M2) were assessed using THP-1 cells in co-culture systems and analyzed by qRT-PCR and flow cytometry. The effect of macrophage polarization on VSMCs calcification was investigated in the presence or absence of B7-H3 knockdown.

Results: β-GP treatment induced HA-VSMC calcification, osteogenic differentiation, and upregulated B7-H3 expression. Silencing B7-H3 attenuated calcification, restored contractile markers, and reduced osteogenic markers in VSMCs. B7-H3 knockdown also suppressed the recruitment and adhesion of macrophages to HA-VSMCs, inhibited M1 polarization of co-cultured macrophages, and promoted their shift toward the M2 phenotype. Furthermore, silencing B7-H3 mitigated M1 macrophage-induced VSMC calcification and enhanced the protective effects of M2 macrophages.

Conclusion: B7-H3 promotes UVC directly by inducing osteogenic transformation of VSMCs and indirectly by enhancing macrophage recruitment and favoring pro-calcific M1 polarization. Thus, targeting B7-H3 may represent a promising therapeutic strategy to mitigate UVC.

Background: Exercise therapy is recommended for patients with chronic kidney disease (CKD), but evidence for its effectiveness in older adults with pre-dialysis CKD is limited.

Methods: This single-center randomized controlled trial examined the effects of a six-month home-based exercise program with monthly counseling in 29 patients aged ≥ 65 years with stage 3-5 pre-dialysis CKD. Participants were randomly assigned to an exercise group (n = 15) or control group (n = 14). Primary outcomes were physical function, measured by 6-min walk distance (6MWD), and health-related quality of life (HRQOL), assessed using the Kidney Disease Quality of Life Short Form (KDQOL-SF). Secondary outcomes included depressive symptoms, nutritional status, and renal function.

Results: 6MWD significantly improved in the exercise group, while no significant change was observed in the control group (p < 0.05). The change in 6MWD was significantly greater in the exercise group than in the control group (p < 0.05). In KDQOL-SF, the role-physical score significantly improved in the exercise group and declined in the control group (p < 0.05). No significant changes were observed in secondary outcomes.

Conclusions: A six-month home-based exercise program with counseling improved physical function and HRQOL in older patients with pre-dialysis CKD.

Background: Post-transplant malignancies are the leading causes of death in patients after kidney transplant (KT) and significantly contribute to death with a functioning graft (DWFG). The incidence of such malignancies is 3-5 times higher than in the general population, with various reported risk factors. However, the association between ABO-incompatible KT and post-transplant malignancies has not yet been thoroughly investigated. We evaluated the association between ABO incompatibility and the development of malignancies in living-donor KT recipients.

Methods: This study included 605 of 643 patients who underwent living-donor KT at six facilities in the Tohoku region of Japan, part of the Michinoku Renal Transplant Network (MRTN), between May 1998 and November 2021, with exclusion of those with missing data. The primary endpoint was the incidence of first post-transplant malignancy. Patients were divided into ABO-compatible (ABOc) and ABO-incompatible (ABOi) groups, and analyses were conducted to compare these groups.

Results: The mean patient age was 47.1 years. The ABOc group included 464 patients (76.7%), whereas the ABOi group included 141 patients (23.3%). During the observation period, 67 patients (11.1%) developed post-transplant malignancies, with gastrointestinal and genitourinary cancers being the most common (median observation period, 77.0 months). There was no significant difference in the incidence of the first post-transplant malignancy between the two groups. Multivariate analysis identified age as the only factor associated with the development of a first post-transplant malignancy.

Conclusion: This study demonstrates ABOi living-donor KT is not associated with an increased risk of post-transplant malignancy in the mid to long term.

Aims: We investigated the efficacy of dapagliflozin, which is a sodium-glucose cotransporter 2 inhibitor, on uric acid (UA) in individuals with moderate-to-severe chronic kidney disease (CKD) (stage G3-4).

Methods: We retrospectively studied 46 patients (mean age: 66.6 ± 14.1 years; 32 men and 14 women) after 12 months of dapagliflozin treatment. We recorded the change in UA and urine protein. All of the patients had moderate-to-severe CKD (mean estimated glomerular filtration rate: 35.9 ± 10.9 mL/min/1.73 m²; stage G3, n = 32; G4, n = 14). The data of 46 matched patients with similar propensity scores (who did not take dapagliflozin) were analyzed as a control group.

Results: UA concentrations significantly decreased from baseline to 12 months in the dapagliflozin group (6.4 ± 1.2 mg/dL to 5.6 ± 1.4 mg/dL, probability (p) < 0.05) but UA concentrations did not change in the control group. In addition, UA concentrations were significantly lower in the dapagliflozin group than in the control group at 12 months (5.6 ± 1.4 mg/dL vs. 6.4 ± 1.4 mg/dL, p < 0.05). UA concentrations significantly decreased from baseline to 12 months in patients with CKD stage G3 in the dapagliflozin group at 12 months (6.4 ± 0.9 mg/dL to 5.4 ± 1.0 mg/dL, p < 0.05) but UA concentrations did not change in patients with CKD stage G4.

Conclusions: Dapagliflozin can decrease UA concentrations in patients with moderate CKD. This finding suggests that dapagliflozin has a beneficial effect on UA metabolism in patients with moderate CKD.

Background: Hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitors have been used for the treatment of anemia in patients with chronic kidney disease not receiving dialysis since 2020. In September 2020, the Japanese Society of Nephrology published recommendations for the appropriate use of HIF-PH inhibitors, which emphasized monitoring iron indices. However, real-world adherence to these recommendations remains unclear.

Methods: We retrieved the data of new users of erythropoietin-stimulating agents (ESAs) or HIF-PH inhibitors from a large Japanese claims database (DeSC, Tokyo, Japan) between 2018 and 2022. Adherence to iron testing before and after the treatments was analyzed using modified Poisson regression and Cox models. Facility-level variations were assessed via mixed-effects models.

Results: We identified 105,346 patients who had a new prescription of ESAs (n = 86,263) or HIF-PH inhibitors (n = 19,083) and did not have kidney failure with replacement therapy. The proportion of HIF-PH inhibitor use increased from 3.6% in 2020 to 42.7% in 2022. During the study period, testing frequency for serum iron, serum TIBC or UIBC, and ferritin ranged from 57.2-59.8%, 39.2-42.8%, and 50.6-52.6%, respectively. Multivariate analysis showed that adherence to testing was significantly higher in university hospitals, Diagnosis Procedure Combination-affiliated DPC hospitals, and non-DPC hospitals compared with clinics. A similar tendency was observed in testing after the index date.

Conclusions: The type of facility was the primary determinant of adherence to the recommendation for iron indices testing before the initiation of ESAs or HIF-PH inhibitors. Targeted educational interventions in low-adherence settings may help improve adherence rates and optimize patient care.

Sedentary behavior (SB) has gained attention as one of the behavioral risk factors, independent of physical inactivity. Patients with chronic diseases, such as hypertension and type 2 diabetes, tend to have longer SB, and prolonged SB is reported as a risk factor for adverse outcomes. Recently, these concerns have also been increasingly recognized in patients with chronic kidney disease (CKD). Despite growing interest, the role of SB in this population is still not well understood. This review aims to summarize the existing evidence on the association between SB and the risk of CKD. A total of 17 studies (9 cross-sectional and 8 longitudinal) were reviewed, indicating that longer SB is associated with an increasing risk of CKD. Through this review, we suggest that reducing SB may play a role in preventing the onset and slowing the progression of CKD. However, evidence remains limited, such as regarding the effective approaches to reduce SB in daily life among patients with CKD, and the causality between CKD and SB. Further high-quality studies, including randomized controlled trials, are warranted to explore these issues in this population.

Background: Selenium is an essential trace element, and its deficiency is associated with thyroid dysfunction, which is known as a cardiovascular risk factor. Hemodialysis (HD) patients are particularly prone to selenium deficiency, and this nutritional factor may increase the risk of thyroid dysfunction and subsequently cardiovascular disease (CVD). Therefore, we investigated selenium deficiency in HD patients and tried to analyze the effect of selenium deficiency on thyroid dysfunction and its correlation with CVD.

Methods: A cross-sectional study was conducted with 183 chronic HD patients. Selenium deficiency was defined as a serum selenium level below 90 µg/L. Patients were categorized into subgroups based on selenium status and/or thyroid hormone dysfunction. CVD prevalence was assessed.

Results: Of the 183 subjects, 79 (43.2%) had selenium deficiency, which was associated with a trend toward higher thyroid dysfunction and increased CVD. In the subgroup analysis, the group with both selenium deficiency and thyroid dysfunction showed a significantly higher CVD prevalence of 68.1% compared to other groups. Additionally, in the logistic regression analysis for CVD risk factors, selenium deficiency/thyroid dysfunction was found to have a significant odds ratio of 3.171.

Conclusions: This study demonstrates that selenium deficiency is associated with thyroid dysfunction and an increased CVD risk in chronic HD patients. Moreover, a negative synergistic effect on CVD was observed when both selenium deficiency and thyroid dysfunction were present.