Predictive factors of renal function after robot-assisted partial nephrectomy in clinical T1b tumors.

Robot-assisted partial nephrectomy (RAPN) has been shown to be a safe and effective method for treatment of small renal tumors, including clinical T1b renal cell carcinoma (RCC); however, the impact of RAPN for cT1b renal tumors on renal function is not well understood. In this retrospective study, 50 patients who underwent RAPN for cT1b renal tumors were evaluated for pre- and post-operative renal function and perioperative clinical factors. Renal function was assessed using the estimated glomerular filtration rate (eGFR) at baseline and on postoperative days (POD) 1, 7, 30, and 180.A significant renal functional decline was defined as ≥ 15% reduction in eGFR at POD180 compared with eGFR at baseline. Logistic regression analyses were used to identify risk factors for renal function decline, including age, sex, RENAL nephrometry score, operative time, and estimated blood loss. The median patient age was 62 years, and the median tumor diameter and RENAL nephrometry score were 44 mm (IQR 43-50) and 8 (IQR 7-9), respectively. Of these patients, 16 (36%) showed a significant renal functional decline at POD 180. In the multivariate analysis, the L component of the RENAL nephrometry score and an estimated blood loss of 200 mL or more were identified as significant risk factors for renal functional decline. These findings suggest that the preoperatively definable L component of the RENAL nephrometry score and intraoperative blood loss, which may be modifiable factors, play significant roles in post-RAPN renal function decline.

Short sleep duration and smoking initiation in university students: a retrospective cohort study.

PURPOSE: The aim of this study was to clarify an association between short sleep duration and smoking initiation. METHODS: Participants eligible for this retrospective cohort study were university students who were admitted to a single national university in Japan between 2007 and 2015. Baseline sleep duration and smoking status were measured using general questionnaires at health checkups at admission. During a 6-year observation period, smoking initiation was assessed using general questionnaires at annual health checkups. Cox proportional hazards models adjusted for clinically relevant factors were used to assess the association between sleep duration and smoking initiation. RESULTS: Of 17,493 men, including 540, 5,568, 8,458, 2,507, and 420 men with sleep duration of < 5, 5-6, 6-7, 7-8, and ≥ 8 h, respectively, smoking initiation was observed in 16.1%, 12.5%, 11.2%, 10.0%, and 11.7%, respectively, during a median observation period of 3.0 years. Men with shorter sleep duration were at a higher risk of smoking initiation (adjusted hazard ratio 1.49 [95% confidence interval 1.19-1.85], 1.11 [1.01-1.22], 1.00 [reference], 0.92 [0.80-1.06], and 1.00 [0.75-1.34], respectively). Of 8,880 women, including 267, 3,163, 4,220, and 1,230 women with sleep duration of < 5, 5-6, 6-7, and ≥ 7 h, respectively, smoking initiation was observed in 4.9%, 2.3%, 2.0%, and 2.2%, respectively, during a median observation period of 3.0 years. A similar dose dependent association was ascertained in women (2.50 [1.39-4.49], 1.18 [0.86-1.62], 1.00 [reference], and 1.22 [0.79-1.89], respectively). CONCLUSION: This study clarified that university students with short sleep duration were vulnerable to smoking initiation.

Association between urinary uric acid excretion and kidney outcome in patients with CKD.

Inhibiting tubular urate reabsorption may protect the kidney from urate-induced tubular injury. However, this approach may promote intratubular uric acid crystallization, especially in acidified urine, which could be toxic to the kidney. To assess how tubular urate handling affects kidney outcomes, we conducted a retrospective cohort study including 1042 patients with estimated glomerular filtration rates (eGFR) of 15-60 mL/min/1.73 m2. The exposures were fractional excretion of uric acid (FEUA) and urinary uric acid-to-creatinine ratio (UUCR). The kidney outcome was defined as a halving of eGFR from baseline or initiating kidney replacement therapy. The median FEUA and UUCR were 7.2% and 0.33 g/gCre, respectively. During a median follow-up of 1.9 years, 314 kidney outcomes occurred. In a multivariate Cox model, the lowest FEUA quartile exhibited a 1.68-fold higher rate of kidney outcome than the highest FEUA quartile (95% confidence interval, 1.13-2.50; P = 0.01). Similarly, lower UUCR was associated with a higher rate of kidney outcome. Notably, patients in the highest quartile of FEUA and UUCR were at the lowest risk of kidney outcome even among those with aciduria. In conclusion, lower FEUA and UUCR were associated with a higher risk of kidney failure, suggesting that increased urate reabsorption is harmful to the kidney.

Associations of vitamin D receptor activators and calcimimetics with falls and effect modifications by physical activity: A prospective cohort study on the Japan Dialysis Outcomes and Practice Patterns Study.

INTRODUCTION: This study aimed to examine the associations of vitamin D receptor activators (VDRA) and calcimimetics use with falls. METHODS: This is a prospective cohort study on hemodialysis patients in the Japan Dialysis Outcomes and Practice Patterns Study. We excluded those who were unable to walk. The associations of VDRA or calcimimetics use with falls and effect modifications by physical activity were analyzed using marginal structural models. RESULTS: In total, 1875 patients were included. VDRA and calcimimetics use was not associated with falls (risk ratio [95% CI]: 1.13 [0.84-1.51] and 1.02 [0.72-1.44]). The risk ratio for falls associated with VDRA use was lower among those with poor physical activity (p for interaction <0.1). CONCLUSIONS: Although vitamin D receptor activators and calcimimetics use was not associated with falls, the lower risk ratio for falls with vitamin D receptor activators use among those with poor physical activity suggests that vitamin D receptor activators use might be beneficial among these patients.

External validation of the HACOR score and ROX index for predicting treatment failure in patients with coronavirus disease 2019 pneumonia managed on high-flow nasal cannula therapy: a multicenter retrospective observational study in Japan.

BACKGROUND: The HACOR score for predicting treatment failure includes vital signs and acid-base balance factors, whereas the ROX index only considers the respiratory rate, oxygen saturation, and fraction of inspired oxygen (FiO2). We aimed to externally validate the HACOR score and ROX index for predicting treatment failure in patients with coronavirus disease 2019 (COVID-19) on high-flow nasal cannula (HFNC) therapy in Japan. METHODS: This retrospective, observational, multicenter study included patients, aged ≥ 18 years, diagnosed with COVID-19 and treated with HFNC therapy between January 16, 2020, and March 31, 2022. The HACOR score and ROX index were calculated at 2, 6, 12, 24, and 48 h after stating HFNC therapy. The primary outcome was treatment failure (requirement for intubation or occurrence of death within 7 days). We calculated the area under the receiver operating characteristic curve (AUROC) and assessed the diagnostic performance of these indicators. The 2-h time-point prediction was considered the primary analysis and that of other time-points as the secondary analysis. We also assessed 2-h time-point sensitivity and specificity using previously reported cutoff values (HACOR score > 5, ROX index < 2.85). RESULTS: We analyzed 300 patients from 9 institutions (median age, 60 years; median SpO2/FiO2 ratio at the start of HFNC therapy, 121). Within 7 days of HFNC therapy, treatment failure occurred in 127 (42%) patients. The HACOR score and ROX index at the 2-h time-point exhibited AUROC discrimination values of 0.63 and 0.57 (P = 0.24), respectively. These values varied with temporal changes-0.58 and 0.62 at 6 h, 0.70 and 0.68 at 12 h, 0.68 and 0.69 at 24 h, and 0.75 and 0.75 at 48 h, respectively. The 2-h time-point sensitivity and specificity were 18% and 91% for the HACOR score, respectively, and 3% and 100% for the ROX index, respectively. Visual calibration assessment revealed well calibrated HACOR score, but not ROX index. CONCLUSIONS: In COVID-19 patients receiving HFNC therapy in Japan, the predictive performance of the HACOR score and ROX index at the 2-h time-point may be inadequate. Furthermore, clinicians should be mindful of time-point scores owing to the variation of the models' predictive performance with the time-point. Trial registration UMIN (registration number: UMIN000050024, January 13, 2023).

Concomitant severe traumatic brain injury is not associated with increased red blood cell transfusion volumes in patients with pelvic fractures: A retrospective observational study.

INTRODUCTION: Traumatic brain injury (TBI)-associated coagulopathy significantly influences survival outcomes in patients with multiple injuries. Severe TBI can potentially affect systemic hemostasis due to coagulopathy; however, there is limited evidence regarding whether the risk of hemorrhage increases in patients with pelvic fractures complicated with TBI. Therefore, through multivariable analysis, we aimed to examine the association between severe TBI and increased blood transfusion requirements in patients with pelvic fractures. MATERIALS AND METHODS: This retrospective observational study was conducted at a tertiary care facility in Japan. Patients aged 16 years or older with pelvic fractures who were admitted to our intensive care unit between April 2014 and December 2021 were included in the analysis. The patients were categorized into no to mild and severe TBI groups according to whether the Head Abbreviated Injury Scale (AIS) score was 3 or higher. The primary outcome was the number of red blood cell (RBC) units transfused within 24 h after arrival at the hospital. The primary outcome was analyzed using univariable and multivariable linear regression analyses. The covariates used for the multivariable linear regression analysis were age, sex, antithrombotic therapy, mechanism of injury, Pelvic AIS score, and extravasation on contrast-enhanced computed tomography on admission. RESULTS: We identified 315 eligible patients (221 and 94 in the no to mild and severe TBI groups, respectively). In the univariable analysis, the RBC transfusion volume within 24 h after arrival was significantly higher in the severe TBI group than in the no to mild TBI group (2.53-unit increase; 95 % confidence interval [CI]: 0.46-4.61). However, in the multivariable analysis, no statistically significant association was detected between severe TBI and the RBC transfusion volume within 24 h after arrival at the hospital (0.87-unit increase; 95 % CI: -1.11-2.85). CONCLUSIONS: Concomitant severe TBI was not associated with increased RBC transfusion volumes in patients with pelvic fractures on multivariable analysis.

Seasonal variations of the prevalence of metabolic syndrome and its markers using big-data of health check-ups.

BACKGROUND: It is crucial to understand the seasonal variation of Metabolic Syndrome (MetS) for the detection and management of MetS. Previous studies have demonstrated the seasonal variations in MetS prevalence and its markers, but their methods are not robust. To clarify the concrete seasonal variations in the MetS prevalence and its markers, we utilized a powerful method called Seasonal Trend Decomposition Procedure based on LOESS (STL) and a big dataset of health checkups. METHODS: A total of 1,819,214 records of health checkups (759,839 records for men and 1,059,375 records for women) between April 2012 and December 2017 were included in this study. We examined the seasonal variations in the MetS prevalence and its markers using 5 years and 9 months health checkup data and STL analysis. MetS markers consisted of waist circumference (WC), systolic blood pressure (SBP), diastolic blood pressure (DBP), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), fasting plasma glucose (FPG). RESULTS: We found that the MetS prevalence was high in winter and somewhat high in August. Among men, MetS prevalence was 2.64 ± 0.42 (mean ± SD) % higher in the highest month (January) than in the lowest month (June). Among women, MetS prevalence was 0.53 ± 0.24% higher in the highest month (January) than in the lowest month (June). Additionally, SBP, DBP, and HDL-C exhibited simple variations, being higher in winter and lower in summer, while WC, TG, and FPG displayed more complex variations. CONCLUSIONS: This finding, complex seasonal variations of MetS prevalence, WC, TG, and FPG, could not be derived from previous studies using just the mean values in spring, summer, autumn and winter or the cosinor analysis. More attention should be paid to factors affecting seasonal variations of central obesity, dyslipidemia and insulin resistance.

The association between embedded catheter implantation and hospitalization costs for peritoneal dialysis initiation: a retrospective cohort study.

BACKGROUND: Compared with the conventional peritoneal dialysis (PD) catheter insertion, embedding PD catheter implantation is one of the procedures for planned PD initiation. However, facilities where embedded PD catheter implantation is available are limited, and the impact of embedded PD catheter implantation on hospitalization cost and length of hospitalization is unknown. METHODS: This retrospective single-center cohort study included 132 patients with PD initiation between 2005 and 2020. The patients were divided into two groups: 64 patients in the embedding group and 68 patients in the conventional insertion group. We created a multivariable generalized linear model (GLM) with the gamma family and log-link function to evaluate the association among catheter embedding, the duration and medical costs of hospitalization for PD initiation. We also evaluated the effect modification between age and catheter embedding. RESULTS: Catheter embedding (ß coefficient - 0.13 [95% confidence interval - 0.21, - 0.05]) and age (per 10 years 0.08 [0.03, 0.14]) were significantly associated with hospitalization costs. Catheter embedding (- 0.21 [- 0.32, - 0.10]) and age (0.11 [0.03, 0.19]) were also identified as factors significantly associated with length of hospitalization. The difference between the embedding group and the conventional insertion group in hospitalization costs for PD initiation (P for interaction = 0.060) and the length of hospitalization (P for interaction = 0.027) was larger in young-to-middle-aged patients than in elderly patients. CONCLUSIONS: Catheter embedding was associated with lower hospitalization cost and shorter length of hospitalization for PD initiation than conventional PD catheter insertion, especially in young-to-middle-aged patients.

Living Arrangements Predict Frequent Alcohol Consumption Among University Students: A Retrospective Cohort Study.

PURPOSE: This study aimed to confirm the clinical impact of living arrangements on incidence of frequent alcohol consumption in university students. DESIGN: A retrospective cohort study. SETTING: A national university in Japan. SUBJECTS: 17,774 university students. MEASURES: The association between living arrangements on admission and the incidence of frequent alcohol consumption (≥4 days/week) was assessed using multivariable-adjusted Cox proportional-hazards models. RESULTS: Among 5,685, 692, and 5,151 male students living with family, living in the dormitory, and living alone, 5.0%, 6.2%, and 5.8% reported frequent alcohol consumption during the median observational period of 3.0 years, respectively. Living in the dormitory and living alone were identified as significant predictors of frequent alcohol consumption (multivariable-adjusted hazard ratios: 1.00 [reference], 1.39 [1.01-1.92], and 1.21 [1.03-1.42], respectively). On the contrary, living arrangements were not associated with the incidence of frequent alcohol consumption among of 6,091 female students, partly because of low incidence of frequent alcohol consumption (2.3%, 1.4%, and 2.6%, respectively). CONCLUSIONS: Living arrangements predicted frequent alcohol consumption among male university students, whereas not among female university students.

Challenges hindering emergency physicians; involvement in multicenter collaborative studies in Japan: A nationwide survey analysis.

Aim: Multicenter collaborative research accelerates patient recruitment and strengthens evidence. Nevertheless, the factors influencing emergency and critical care physicians' involvement in such research in Japan remain unclear. Methods: A nationwide web-based survey conducted in early 2023 targeted emergency physicians working a minimum of 3 days per week in Japan. The survey descriptively assessed their backgrounds, work and research environments, experiences, and perceived impediments and motivators for multicenter research. Results: Of the 387 respondents, 348 were included in the study, yielding a 5.1% response rate. Women comprised 11% of the participants; 33% worked in university hospitals, 65% served in both emergency departments and intensive care units, and 54% did shift work. Only 12% had designated research time during working hours, with a median of 1 hour per week (interquartile range 0-5 h), including time outside of work. While 73% had participated in multicenter research, 58% noted barriers to participation. The key obstacles were excessive data entry (72%), meeting time constraints (59%), ethical review at each facility (50%), and unique sample collection, such as bronchoalveolar lavage specimens or pathological tissues (51%). The major incentives were networking (70%), data sets reuse (65%), feedback on research results (63%), and recognition from academic societies (63%). Financial rewards were not highly prioritized (38%). Conclusions: While valuing clinical research, emergency physicians face barriers, especially data entry burden and limited research time. Networking and sharing research findings motivate them. These insights can guide strategies to enhance collaborative research in emergency and critical care in Japan.

BRCA2 Frameshift Mutation in de novo Small-Cell Neuroendocrine Carcinoma of the Prostate: A Case Report.

A 66-year-old male was diagnosed with cT4N0M1b small-cell neuroendocrine carcinoma of the prostate. Four months after the administration of combined androgen blockade, multiple novel metastatic regions in the lung and liver and progression of bone metastasis were observed. The patient was referred to our hospital because of biochemical and radiographic progression after four cycles of docetaxel as a first-line therapy for castration-resistant prostate cancer. Transurethral resection of the prostate and hepatic biopsy revealed small-cell carcinoma with positive expression of neuroendocrine markers. The FoundationOne CDx next-generation sequencing test revealed several pathogenic variants, including BRCA2 (W1692fs*3), KEAP1 (R320W), and TP53 (C2385) mutation. After four cycles of chemotherapy with carboplatin plus etoposide (CE), the metastatic regions regressed markedly. The prostate-specific antigen (PSA) and neuron-specific enolase (NSE) level decreased by 96.9% and 91.6%, respectively. However, 2 months after the completion of four cycles of CE, elevation of tumor marker levels, and re-growth of the metastatic regions were observed. Although olaparib, a poly (ADP-ribose) polymerase inhibitor (PARPi), achieved a 45.2% decrease in NSE, the patient rejected to continue therapy because of G2 adverse events. After receiving an additional two cycles of CE and one cycle of cabazitaxel, the patient died because of cancer progression 24 months after the initial treatment for prostate cancer. Here, we present a case of BRCA2-altered small-cell neuroendocrine prostate cancer treated with both platinum-containing chemotherapy and PARPi. Both therapies achieved an initial response; however, durable responses were not obtained. Additional discussion regarding the optimal treatment strategy for BRCA-altered small-cell/neuroendocrine prostate cancer is required.

Poor Social Functioning: A Potentially Modifiable Risk Factor for Pneumonia in the Elderly.

Background Most risk factors for developing community-acquired pneumonia (CAP) are age-related and chronic medical conditions; modifying these factors can be challenging, especially in the elderly. Poor social functioning, however, has a negative impact on medical conditions but can be improved through interventions. Therefore, the social functioning domain of health-related quality of life (HRQOL) may be a modifiable risk factor for the development of CAP. This study investigated the association between poor social functioning and the incidence of CAP in elderly individuals. Methodology We conducted a retrospective cohort study using a dataset from 2018 to 2021, derived from an annual questionnaire-based survey of a cohort of community-dwelling people aged 75 years or older (the Sukagawa Study). The dataset included social functioning subscale scores of HRQOL obtained from the Eight-Item Short Form (SF-8) questionnaire. Health insurance claims data were matched with these HRQOL data. For each participant, the exposure (HRQOL) was measured, and outcomes (incidence of CAP) were observed yearly from 2018 through 2021. Results The four observation years had a total of 17,016 observation periods among 6,513 participants. The annual incidence rate of CAP was 0.90-1.77%. Lower social functioning was associated with a higher risk of CAP. Specifically, for each standard deviation difference in social functioning score, the adjusted rate ratio for CAP incidence was 1.26 (95% confidence interval (CI) = 1.08-1.48). In a subgroup analysis, the association between social functioning and CAP differed by sex (p = 0.037). Specifically, the adjusted rate ratio for CAP incidence was 1.41 (95% CI = 1.17-1.70) in men and 1.00 (95% CI = 0.76-1.35) in women. Conclusions Poor social functioning is an important risk factor for CAP in the elderly, especially in men. Interventions that improve social functioning may help to prevent CAP.

Effect of the post-learning period on the accuracy and self-efficacy of measuring the joint range of motion.

[Purpose] To verify the effects of the differences in the post-learning period on the accuracy and self-efficacy of measuring the range of passive flexion of the knee and elbow of students. [Participants and Methods] Thirty-six physical therapy students were classified into three groups (short-term, medium-term, and long-term) based on the interval since learning to measure the range of motion. Participants were asked to self-evaluate their efficacy in appropriately measuring the range of motion for knee and elbow flexion using a 10-point Likert scale. Subsequently, the flexion range of the left knee and elbow was measured using a universal goniometer and compared to the measurements obtained using an electronic accelerometer. [Results] Absolute errors in measuring knee flexion were significantly smaller in the medium- and long-term groups than in the short-term group. No other significant main effects or correlations were observed. [Conclusion] Although the accuracy of measuring the range of motion by students improved while they were in school, it did not improve sufficiently based on the joint being assessed. Furthermore, the post-learning period did not affect a student's self-efficacy for measuring the range of motion and did not reflect its accuracy.

Androgen deprivation therapy caused a drastic proliferation of B-cell lymphoma with IgG4-related disease in patients with prostate cancer: a case report.

BACKGROUND: We report a case of diffuse large B-cell lymphoma that progressed rapidly after androgen deprivation therapy for prostate cancer in a patient with a history of IgG4-related disease. Estrogen has been reported to be a possible cause of acute exacerbations of malignant lymphoma only in mouse models. Therefore, its clinical significance has not been clarified. CASE PRESENTATION: This case report describes a 75-year-old man with prostate cancer who had IgG4-related disease. Hormone therapy was initiated to treat prostate cancer, but he developed dyspnea and back pain. A diagnosis was made of diffuse large B-cell lymphoma. Immunohistochemistry was positive for estrogen receptor ß, which led us to suspect rapid progression of diffuse large B-cell lymphoma due to estrogen suppression by gonadotropin-releasing hormone antagonists. Hormone therapy was discontinued, and the patient received R-CHOP therapy. Subsequently, the lymphoma masses shrunk, and the patient obtained remission. CONCLUSION: This case is the first report of clinical significance regarding the crucial role of estrogen and estrogen receptor ß in malignant lymphoma in a patient with IgG4-related disease. Our report aims to raise awareness of the need to carefully select treatment options for prostate cancer patients with IgG4-related disease or lymphoma.

Association of secondhand smoke exposure and health-related lifestyle behaviors among male university employees in Japan.

Secondhand smoke (SHS) exposure causes various health problems associated with an unhealthy lifestyle. However, the lifestyles of individuals exposed to SHS have not been characterized extensively. Therefore, this cross-sectional study aimed to investigate the association between SHS exposure and lifestyle behaviors. The participants were 2379 healthy male employees at Osaka University who underwent health examinations. Physical and biochemical parameters and lifestyle behavior data were obtained from all the participants. Participants with SHS exposure had significantly higher body mass index, waist circumference, and serum levels of triglycerides and uric acid than that of those without SHS exposure. SHS exposure was significantly correlated with several lifestyle behaviors, including TV time, frequency of breakfast consumption and fried food consumption, vegetable and fruit intake, alcohol consumption frequency and daily alcohol intake, and smoking status. Thus, SHS exposure may be associated with an unhealthy lifestyle. The lifestyle behaviors of the smoke-excluded population were assessed further; however, SHS exposure was still associated with dietary and drinking habits. Since participants with SHS exposure are likely to have an unhealthy life and combined unhealthy lifestyle behaviors, the confounding effect of these factors should be considered when assessing the impact of SHS exposure on health.

Real clinical outcomes of nivolumab plus ipilimumab for renal cell carcinoma in patients over 75 years old.

BACKGROUND: Although nivolumab plus ipilimumab is the standard treatment for metastatic renal cell carcinoma (RCC), its efficacy and safety in older patients remain unclear. Therefore, this study aimed to assess the clinical outcomes of nivolumab plus ipilimumab for metastatic RCC in patients aged ≥ 75 years. METHODS: We enrolled 120 patients with metastatic RCC treated with nivolumab plus ipilimumab from August 2015 to January 2023. Objective response rates (ORRs) were compared between patients aged < 75 and ≥ 75 years. Progression-free survival (PFS), overall survival (OS), and adverse events were compared between the groups. Adverse events were evaluated according to the Response Evaluation Criteria in Solid Tumors 1.1. RESULTS: Among the patients, 57 and 63 were classified as intermediate and poor risk, respectively, and one could not be classified. The median follow-up duration after the initiation of treatment was 16 months. The patient characteristics between the groups, except for age, were not significantly different. Intergroup differences in ORR (42% vs. 40%; p = 0.818), PFS (HR: 0.820, 95% CI 0.455-1.479; p = 0.510), and median OS (HR: 1.492, 95% CI 0.737-3.020; p = 0.267) were not significant. The incidence of adverse events (50% vs. 67%; p = 0.111) and nivolumab plus ipilimumab discontinuation due to adverse events was not significantly different between the groups (14% vs. 13%; p = 0.877). CONCLUSIONS: The effectiveness of nivolumab plus ipilimumab was comparable between patients with metastatic RCC aged < 75 and those ≥ 75 years with respect to their ORRs, PFS, OS, and adverse event rates.

Interstitial Eosinophilic Aggregates and Kidney Outcome in Patients with CKD.

BACKGROUND: Interstitial eosinophilic aggregates are observed in various kidney diseases, but their clinical implications remain unknown. We assessed the association between interstitial eosinophilic aggregates and kidney outcomes and further analyzed the association between blood eosinophil count, as a surrogate for interstitial eosinophilic aggregates, and the risk of kidney failure in patients with advanced CKD. METHODS: We analyzed datasets from two retrospective cohort studies: ( 1 ) the kidney biopsy cohort including 563 patients who underwent native kidney biopsy at Osaka University Hospital between 2009 and 2021 and ( 2 ) the retrospective CKD cohort including 2877 patients with an eGFR of 10-60 ml/min per 1.73 m 2 referred to the nephrology outpatient center at Osaka University Hospital between 2005 and 2018. Interstitial eosinophilic aggregates were defined as ≥5 interstitial eosinophils in the high-power field on hematoxylin and eosin staining. This study outcome was initiation of KRT or ≥40% decline in eGFR. RESULTS: In the kidney biopsy cohort, interstitial eosinophilic aggregates were found in 17% of patients, most frequently in those with diabetic nephropathy (50%). Interstitial eosinophilic aggregates were associated with a higher rate of the composite kidney outcome after adjustment for clinical and histological variables (hazard ratio, 3.61; 95% confidence interval, 2.47 to 5.29; P < 0.001). LASSO revealed that blood eosinophil count was the strongest predictor of interstitial eosinophilic aggregates. In the retrospective CKD cohort, higher baseline and time-updated blood eosinophil counts were significantly associated with a higher rate of KRT initiation in Cox proportional hazards models and marginal structural models. CONCLUSIONS: Interstitial eosinophilic aggregates were associated with a higher risk of a composite of KRT initiation or ≥40% decline in eGFR. PODCAST: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_12_08_CJN0000000000000277.mp3.

Chapter 2:indications and dosing of anticancer drug therapy in patients with impaired kidney function, from clinical practice guidelines for the management of kidney injury during anticancer drug therapy 2022.

This comprehensive review discusses the dosing strategies of cancer treatment drugs for patients with impaired kidney function, specifically those with chronic kidney disease (CKD), undergoing hemodialysis, and kidney transplant recipients. CKD patients often necessitate dose adjustments of chemotherapeutic agents, e.g., platinum preparations, pyrimidine fluoride antimetabolites, antifolate agents, molecularly targeted agents, and bone-modifying agents, to prevent drug accumulation and toxicity due to diminished renal clearance of the administered drugs and their metabolites. In hemodialysis patients, factors such as drug removal from hemodialysis and altered pharmacokinetics demand careful optimization of anticancer drug therapy, including dose adjustment and timing of administration. While free cisplatin is removed by hemodialysis, most of the tissue- and protein-bound cisplatin remains in the body and rebound cisplatin elevations are observed after hemodialysis. It is not recommended hemodialysis for drug removal, regardless of timing. Kidney transplant patients encounter unique challenges in cancer treatment, as maintaining the balance between reduction of immunosuppression, switching to mTOR inhibitors, and considering potential drug interactions with chemotherapeutic agents and immunosuppressants are crucial for preventing graft rejection and achieving optimal oncologic outcomes. The review underscores the importance of personalized, patient-centric approaches to anticancer drug therapy in patients with impaired kidney function.

Chapter 1: Evaluation of kidney function in patients undergoing anticancer drug therapy, from clinical practice guidelines for the management of kidney injury during anticancer drug therapy 2022.

The prevalence of CKD may be higher in patients with cancer than in those without due to the addition of cancer-specific risk factors to those already present for CKD. In this review, we describe the evaluation of kidney function in patients undergoing anticancer drug therapy. When anticancer drug therapy is administered, kidney function is evaluated to (1) set the dose of renally excretable drugs, (2) detect kidney disease associated with the cancer and its treatment, and (3) obtain baseline values for long-term monitoring. Owing to some requirements for use in clinical practice, a GFR estimation method such as the Cockcroft-Gault, MDRD, CKD-EPI, and the Japanese Society of Nephrology's GFR estimation formula has been developed that is simple, inexpensive, and provides rapid results. However, an important clinical question is whether they can be used as a method of GFR evaluation in patients with cancer. When designing a drug dosing regimen in consideration of kidney function, it is important to make a comprehensive judgment, recognizing that there are limitations regardless of which estimation formula is used or if GFR is directly measured. Although CTCAEs are commonly used as criteria for evaluating kidney disease-related adverse events that occur during anticancer drug therapy, a specialized approach using KDIGO criteria or other criteria is required when nephrologists intervene in treatment. Each drug is associated with the different disorders related to the kidney. And various risk factors for kidney disease associated with each anticancer drug therapy.