Clinical and Experimental Nephrology最新文献

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.

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: 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.

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: 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.

Background: Perioperative red blood cell transfusion (RBCT) and immunosuppressive therapy are critical factors influencing the risk of kidney transplantation (KT) rejection. In this study, we examined how RBCT volume, timing, and immunosuppressive therapy affect biopsy-proven rejection (BPR).

Methods: We analyzed 170 living donor KT recipients, assessing RBCT timing, volume, immunosuppressive therapy, and recipient characteristics. RBCT timing was classified as none, within 1 month, or over 1 month post-KT. Random forest and SHapley Additive explanation (SHAP) were used to identify risk factors for BPR. To mitigate overlearning, tenfold cross-validation was performed.

Results: The calcineurin inhibitor type was the most significant risk factor for BPR, with tacrolimus use associated with a lower risk than cyclosporine use. An RBCT exceeding 6 units and an RBCT administered more than 1 month post-KT were identified as critical thresholds for BPR risk. SHAP analysis indicated a nonlinear relationship between pre-transplant hemoglobin levels and BPR risk. RBCT timing and volume significantly influenced BPR risk. Late RBCT and those exceeding 6 units were linked to increased BPR risk. Additionally, tacrolimus may offer superior immunosuppressive control compared with that of cyclosporine regarding BPR. Stratified analysis using SHAP value showed that the high-risk group had significantly lower death-censored graft survival than the low-risk group.

Conclusion: RBCT volume and timing impact the rejection risk, with an increased risk observed for more than 6 units and over 1 month post-KT. Proper immunosuppressive management is crucial and warrants further research.

Background: Many older chronic kidney disease (CKD) patients with frailty do not tolerate renal replacement therapy (RRT). Although conservative kidney management (CKM) has become popular in Europe and America, end-of-life care systems, including palliative care intervention methods, have not been established.

Methods: We analyzed a total of 20 CKD patients aged 65 years or older who underwent comprehensive geriatric assessment (CGA), selected CKM based on advanced care planning (ACP), and died of end-stage renal disease.

Results: The mean age at death was 87.4 years. At the time of the CKM decision, BUN was 85.6 mg/dL, Cre was 5.2 mg/dL, eGFR was 10.9, clinical frailty scale (CFS) was 6.4, dementia assessment sheet for community-based care systems (DASC-21) was 55.6, and time from decision to death was 88 days. Eleven patients required sedatives for delirium and eight patients required narcotics for dyspnea or pain. Patients who required sedation were younger, had lower DASC-21, and were significantly more likely to have cardiovascular disease and diabetes than those who did not. Patients who required narcotics were younger, had lower CFS, and were significantly more likely to have cardiovascular disease than those who did not require narcotics.

Conclusions: ESRD patients who opted for CKM requiring palliative care narcotic or sedative intervention were characterized by young older patients with less dementia and frailty and those with cardiovascular disease. This study shows predictors of the need for palliative treatment at the end of life for CKM, which could be useful information for improving end-of-life care for CKM.

Background: The most prescribed oral glucose-lowering medication worldwide is biguanide (BG), which shows potential for further therapeutic applications. The coronavirus disease 2019 (COVID-19) pandemic is a global public health emergency. Nevertheless, low-cost treatments against COVID-19 have not been established, with varying morbidity and mortality rates in each country.

Methods: From the inpatient databases in Japan from September 2021 to March 2023, which includes the era following the development of COVID-19 vaccines, we extracted data from 168,370 patients with COVID-19 aged 20- < 80 years with diabetes mellitus treated with oral antidiabetic agents. The primary and secondary outcomes were 100-day in-hospital mortality and incidence of acute kidney injury (AKI) during hospitalisation, respectively. We compared outcomes in patients who received BG with those who did not using a logistic regression analysis and Cox proportional hazards under both propensity score-unmatched and matched cohorts.

Results: The incidence of in-hospital death was significantly lower in the BG group (1.18%) compared with the non-BG group (2.41%) (P < 0.001). Similarly, the incidence of AKI during hospitalisation was significantly lower in the BG group (0.66%) compared to the non-BG group (1.12%) (P < 0.001). Kaplan-Meier analysis from the propensity score-matched cohort showed a significantly better survival rate in the BG group (adjusted HR, 0.619; 95% CI, 0.545-0.702; P < 0.001).

Conclusion: In patients with COVID-19, oral biguanide use may be associated with reduced in-hospital mortality and AKI risk.