Risk factors of chronic kidney disease in cisplatin-based hyperthermia intraperitoneal chemotherapy.

PURPOSE: Cisplatin is commonly prescribed in hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal malignancy. Acute kidney injury (AKI) is regarded as a common complication after HIPEC combined with cytoreductive surgery (CRS). However, post-HIPEC chronic kidney disease (CKD) is scarce and less investigated. This study aims to investigate the incidence of CKD following cisplatin-based HIPEC and to analyse the associated risk factors. MATERIALS AND METHODS: From January 2016 to August 2021, a total of 55 patients treated with CRS and cisplatin-based HIPEC for peritoneal carcinomatosis were categorized retrospectively into groups, with and without CKD. Demographics, comorbidity, surgery, postoperative management, and complications were collected to evaluate risk factors for cisplatin-based HIPEC-related CKD. Univariate and multivariate analyses were conducted to confirm the correlation between different variables and CKD occurrence. RESULTS: Of the 55 patients, 24 (43.6%) patients developed AKI and 17 (70.8%) patients of these AKI patients progressed to CKD. Multivariate regression analysis identified intraoperative use of parecoxib (Odds Ratio (OR) = 4.39) and intraoperative maximum temperature > 38.5°C (OR = 6.40) as major risk factors for cisplatin-based HIPEC-related CKD occurrence. Though type II diabetes mellitus and intraoperative complications were the independent risk factors of AKI following cisplatin-based HIPEC, but they were not shown in CKD analysis. CONCLUSION: Intraoperative use of parecoxib during cisplatin-based HIPEC emerged as a significant risk factor for postoperative CKD. Clinicians should exercise caution in prescribing parecoxib during HIPEC procedures. Additionally, maintaining intraoperative body temperature below 38.5°C might be crucial to mitigate the risk of CKD development. This study underscores the importance of identifying and preventing specific risk factors to improve long-term renal outcomes in patients undergoing cisplatin-based HIPEC.

Cardiothoracic ratio values and trajectories are associated with risk of requiring dialysis and mortality in chronic kidney disease.

BACKGROUND: The prognostic role of the cardiothoracic ratio (CTR) in chronic kidney disease (CKD) remains undetermined. METHODS: We conducted a retrospective cohort study of 3117 patients with CKD aged 18-89 years who participated in an Advanced CKD Care Program in Taiwan between 2003 and 2017 with a median follow up of 1.3(0.7-2.5) and 3.3(1.8-5.3) (IQR) years for outcome of end-stage renal disease (ESRD) and overall death, respectively. We developed a machine learning (ML)-based algorithm to calculate the baseline and serial CTRs, which were then used to classify patients into trajectory groups based on latent class mixed modelling. Association and discrimination were evaluated using multivariable Cox proportional hazards regression analyses and C-statistics, respectively. RESULTS: The median (interquartile range) age of 3117 patients is 69.5 (59.2-77.4) years. We create 3 CTR trajectory groups (low [30.1%], medium [48.1%], and high [21.8%]) for the 2474 patients with at least 2 CTR measurements. The adjusted hazard ratios for ESRD, cardiovascular mortality, and all-cause mortality in patients with baseline CTRs ≥0.57 (vs CTRs <0.47) are 1.35 (95% confidence interval, 1.06-1.72), 2.89 (1.78-4.71), and 1.50 (1.22-1.83), respectively. Similarly, greater effect sizes, particularly for cardiovascular mortality, are observed for high (vs low) CTR trajectories. Compared with a reference model, one with CTR as a continuous variable yields significantly higher C-statistics of 0.719 (vs 0.698, P = 0.04) for cardiovascular mortality and 0.697 (vs 0.693, P < 0.001) for all-cause mortality. CONCLUSIONS: Our findings support the real-world prognostic value of the CTR, as calculated by a ML annotation tool, in CKD. Our research presents a methodological foundation for using machine learning to improve cardioprotection among patients with CKD.

An enlarged heart occurs during various medical conditions and can result in early death. However, it is unclear whether this is also the case in patients with chronic kidney disease (CKD). Although the size of the heart can be measured on chest X-rays, this process is time consuming. We used artificial intelligence to quantify the heart size of 3117 CKD patients based on their chest X-rays within hours. We found that CKD patients with an enlarged heart were more likely to develop end-stage kidney disease or die. This could improve monitoring of CKD patients with an enlarged heart and improve their care.

Association of poorly controlled HbA1c with increased risk of progression to end-stage kidney disease and all-cause mortality in patients with diabetes and chronic kidney disease.

Glycosylated hemoglobin (HbA1c) targets for patients with chronic kidney disease (CKD) and type 2 diabetes remain controversial. To evaluate whether baseline HbA1c and HbA1c trajectories are associated with the risk of end-stage kidney disease (ESKD) and all-cause mortality, we recruited adult patients with CKD and type 2 diabetes from a "Pre-ESKD Program" at a medical center in Taiwan from 2003 to 2017. Group-based trajectory modeling was performed to identify distinct patient groups that contained patients with similar longitudinal HbA1c patterns. Cox proportional hazard models were used to estimate hazard ratios (HRs) of ESKD and mortality associated with baseline HbA1c levels and HbA1c trajectories. In the analysis related to baseline HbA1c (n = 4543), the adjusted HRs [95% confidence interval (CI)] of all-cause mortality were 1.06 (0.95-1.18) and 1.25 (95% CI, 1.07-1.46) in patients with an HbA1c level of 7%-9% (53-75 mmol/mol) and >9% (>75 mmol/mol), respectively, as compared with those with an HbA1c level < 7% (<53 mmol/mol). In the trajectory analysis (n = 2692), three distinct longitudinal HbA1c trajectories were identified: nearly optimal (55.9%), moderate to stable (34.2%), and poor control (9.9%). Compared with the "nearly optimal" HbA1c trajectory group, the "moderate-to-stable" group did not have significantly higher mortality, but the "poorly controlled" group had 35% higher risk of mortality (adjusted HR = 1.35, 95% CI = 1.06-1.71). Neither baseline levels of HbA1c nor trajectories were associated with ESKD risk. In conclusion, in patients with CKD and type 2 diabetes, poor glycemic control was associated with an elevated risk of mortality but not associated with a risk of progression to ESKD.

Dyslipidemia and coronary artery calcium: From association to development of a risk-prediction nomogram.

BACKGROUND AND AIMS: The associations between dyslipidemia and coronary artery calcium (CAC) are controversial. We investigated their cross-sectional relationships and developed a predictive scoring system for prognostically significant coronary calcification (PSCC). METHODS AND RESULTS: This study evaluated the lipid profiles and the CAC score (CACS) measured through multidetector computed tomography (MDCT) among Taiwanese adult patients in a tertiary hospital between 2011 and 2016. Patients with CACS higher than 100 were classified as having PSCC. Dyslipidemia for each lipid component was defined based on the clinical cutoffs or the use of the lipid-lowering agents. Multivariable logistic regression was used to assess the association between dyslipidemia and PSCC and the model performance was assessed using calibration plot, discrimination, and a decision curve analysis. Of the 3586 eligible patients, 364 (10.2%) had PSCC. Increased age, male sex, higher body mass index (BMI), and higher level of triglyceride (TG) were associated with PSCC. The adjusted odds ratios (95% confidence intervals) of PSCC was 1.15 (0.90-1.47) for dyslipidemia defined by total cholesterol (TC) ≥200 mg/dL, 1.06 (0.83-1.35) for low-density-lipoprotein-cholesterol (LDL-C) ≥130 mg/dL, and 1.36 (1.06-1.75) for TG ≥ 200 mg/dL. The positive association between TG ≥ 200 mg/dL and PSCC was not modified by sex. Incorporating hypertriglyceridemia did not significantly improve the predictive performance of the base model comprising of age, sex, BMI, smoking, hypertension, diabetes, estimated glomerular filtration rate, and fasting glucose. CONCLUSIONS: Hypertriglyceridemia was significantly associated with the prevalent odds of PSCC. Our proposed predictive model may be a useful screening tool for PSCC.

Insomnia and Poor Sleep in CKD: A Systematic Review and Meta-analysis.

Rationale & Objective: Poor sleep quality and insomnia are pervasive among patients with advanced chronic kidney disease (CKD); however, these health issues have not been systematically evaluated. Study Design: Systematic review and meta-analysis. Setting & Study Populations: Adult patients with CKD not receiving kidney replacement therapy (KRT), as well as adults receiving KRT, including hemodialysis, peritoneal dialysis, and kidney transplantation. Selection Criteria for Studies: A systematic literature search using PubMed, Embase, and PsycNET, was conducted for articles published between January 1, 1990, and September 28, 2018. Data Extraction: Data on the prevalences of poor sleep quality and insomnia in patients with CKD, including those receiving and not receiving KRT, were extracted. Analytical Approach: Pooled prevalences were estimated using a random-effects meta-analysis and were stratified according to age, CKD stage, World Health Organization region, risk of bias, Pittsburgh Sleep Quality Index score, and the different criteria for insomnia that were used at diagnosis. Results: Of 3,708 articles, 93 were selected, and significant methodological heterogeneity was present. The pooled prevalences of poor sleep quality for CKD without KRT, hemodialysis, peritoneal dialysis, and kidney transplantation were 59% (95% CI, 44%-73%), 68% (95% CI, 64%-73%), 67% (95% CI, 44%-86%), and 46% (95% CI, 34%-59%), respectively. The corresponding prevalences of insomnia were 48% (95% CI, 30%-67%), 46% (95% CI, 39%-54%), 61% (95% CI, 41%-79%), and 26% (95% CI, 9%-49%), respectively. Insomnia was significantly more prevalent among patients aged 51-60 years and those aged >60 years than among those aged <50 years. The prevalence of insomnia in the European region was the lowest of all World Health Organization regions. Limitations: High interstudy heterogeneity. Conclusions: Approximately half of the patients with advanced CKD had poor sleep quality or insomnia, and the prevalence was even higher among those who received KRT. Kidney transplantation may reduce the burden of poor sleep quality and insomnia.

Paradoxical mortality of high estimated glomerular filtration rate reversed by 24-h urine creatinine excretion rate adjustment: sarcopenia matters.

BACKGROUND: Muscle wasting may explain the paradoxical mortality of patients with high estimated glomerular filtration rates (eGFRs) derived from equation methods. However, empirical evidence and solutions remain insufficient. METHODS: In this retrospective cohort study, we compared the performance of equation methods for predicting all-cause mortality; we used 24-h creatinine clearance (24-h CrCl), equation-based eGFRs, and a new eGFR estimating equation weighting for population 24-h urine creatinine excretion rate (U-CER). From 2003 to 2018, we identified 4986 patients whose data constituted the first 24-h CrCl measurement data in the Clinical Research Data Repository of China Medical University Hospital and were followed up for at least 5 years after careful exclusion. Three GFR estimation equations [the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), Modification of Diet in Renal Disease (MDRD) Study, and Taiwanese MDRD], 24-h CrCl, and 24-h U-CER-adjusted eGFR were used. RESULTS: A high correlation was observed among the eGFR levels derived from the equation methods (0.995-1.000); however, the correlation decreased to 0.895-0.914 when equation methods were compared with the 24-h CrCl or 24-h U-CER-adjusted equation-based eGFR. In the Bland-Altman plots, the average discrepancy between the equation methods and the 24-h CrCl method was close to zero (maximal bias range: 5.12 for the Taiwanese MDRD equation vs. 24-h CrCl), but the range in limit of agreement was wide, from ±43.7 mL/min/1.73 m2 for the CKD-EPI equation to ±54.3 mL/min/1.73 m2 for the Taiwanese MDRD equation. A J-shaped dose-response relationship was observed between all equation-based eGFRs and all-cause mortality. Only 24-h CrCl exhibited a non-linear negative dose-response relationship with all-cause mortality. After adjustment for 24-h U-CER in the statistical model, the paradoxical increase in mortality risk for an eGFR of >90 mL/min/1.73 m2 returned to null. When 24-h U-CER was used directly to correct eGFR, the monotonic non-linear negative relationship with all-cause mortality was almost identical to that of 24-h CrCl. CONCLUSIONS: The 24-h U-CER-adjusted eGFR and 24-h CrCl are viable options for informing mortality risk. The 24-h U-CER adjustment method can be practically implemented to eGFR-based care and effectively mitigate the inherent confounding biases from individual's muscle mass amount due to both sex and racial differences.

Associations between Myocardial Diastolic Dysfunction and Cardiovascular Mortality in Chronic Kidney Disease: A Large Single-Center Cohort Study.

BACKGROUND: The clinical burden and prognostic role of diastolic dysfunction (DD), on the basis of the latest (2016) American Society of Echocardiography guidelines, remain unclear in patients with chronic kidney disease (CKD). Moreover, risk mapping of concomitant systolic dysfunction and DD to evaluate the hazard of cardiovascular (CV) mortality in patients with CKD remains unexplored. METHODS: This retrospective cohort study identified 20,257 adult patients who underwent comprehensive echocardiography between 2008 and 2016 at a tertiary medical center in central Taiwan. The patients were stratified by CKD stage, and 3-year CV mortality risk in each CKD stratum was estimated through multivariable Cox proportional-hazards modeling using left ventricular ejection fraction (LVEF) and DD grades on the basis of the 2016 American Society of Echocardiography guidelines as the main risk factors. RESULTS: Compared with patients with stages 1 and 2 CKD, those with stages 4 and 5 CKD had significantly lower left ventricular ejection fractions and more severe DD. Both left ventricular ejection fraction (<40% vs ≥60%; adjusted hazard ratio, 3.17; 95% CI, 2.54-3.97) and DD grade (severe DD vs normal diastolic function; adjusted hazard ratio, 3.33; 95% CI, 2.33-4.76) were independently associated with 3-year CV mortality in the entire study population and had comparable effect sizes. The corresponding adjusted hazard ratios further increased to 4.20 (95% CI, 2.45-7.21) and 4.54 (95% CI, 2.20-9.38) in patients with stages 4 and 5 CKD. Systolic dysfunction and DD demonstrated mutually augmentative effects on CV mortality. CONCLUSIONS: These findings suggest that the current practice of cardioprotection for patients with CKD should be prioritized at an early stage along with conventional nephroprotection.

Prediction of non-responsiveness to pre-dialysis care program in patients with chronic kidney disease: a retrospective cohort analysis.

The responsiveness of patients with chronic kidney disease (CKD) to nephrologists' care is unpredictable. We defined the longitudinal stages (LSs) 1-5 of estimated glomerular filtration rate (eGFR) by group-based trajectory modeling for repeated eGFR measurements of 7135 patients with CKD aged 20-90 years from a 13-year pre-end-stage renal disease (ESRD) care registry. Patients were considered nonresponsive to the pre-dialysis care if they had a more advanced eGFR LS compared with the baseline. Conversely, those with improved or stable eGFR LS were considered responsive. The proportion of patients with CKD stage progression increased with the increase in the baseline CKD stage (stages 1-2: 29.2%; stage 4: 45.8%). The adjusted times to ESRD and all-cause mortality in patients with eGFR LS-5 were 92% (95% confidence interval [CI] 86-96%) and 57% (95% CI 48-65%) shorter, respectively, than in patients with eGFR LS-3A. Among patients with baseline CKD stages 3 and 4, the adjusted times to ESRD and all-cause death in the nonresponsive patients were 39% (95% CI 33-44%) and 20% (95% CI 14-26%) shorter, respectively, than in the responsive patients. Our proposed Renal Care Responsiveness Prediction (RCRP) model performed significantly better than the conventional Kidney Failure Risk Equation in discrimination, calibration, and net benefit according to decision curve analysis. Non-responsiveness to nephrologists' care is associated with rapid progression to ESRD and all-cause mortality. The RCRP model improves early identification of responsiveness based on variables collected during enrollment in a pre-ESRD program. Urgent attention should be given to characterize the underlying heterogeneous responsiveness to pre-dialysis care.

The ratio and difference of urine protein-to-creatinine ratio and albumin-to-creatinine ratio facilitate risk prediction of all-cause mortality.

The role of the difference and ratio of albuminuria (urine albumin-to-creatinine ratio, uACR) and proteinuria (urine protein-to-creatinine ratio, uPCR) has not been systematically evaluated with all-cause mortality. We retrospectively analyzed 2904 patients with concurrently measured uACR and uPCR from the same urine specimen in a tertiary hospital in Taiwan. The urinary albumin-to-protein ratio (uAPR) was derived by dividing uACR by uPCR, whereas urinary non-albumin protein (uNAP) was calculated by subtracting uACR from uPCR. Conventional severity categories of uACR and uPCR were also used to establish a concordance matrix and develop a corresponding risk matrix. The median age at enrollment was 58.6 years (interquartile range 45.4-70.8). During the 12,391 person-years of follow-up, 657 deaths occurred. For each doubling increase in uPCR, uACR, and uNAP, the adjusted hazard ratios (aHRs) of all-cause mortality were 1.29 (95% confidence interval [CI] 1.24-1.35), 1.12 (1.09-1.16), and 1.41 (1.34-1.49), respectively. For each 10% increase in uAPR, it was 1.02 (95% CI 0.98-1.06). The linear dose-response association with all-cause mortality was only observed with uPCR and uNAP. The 3 × 3 risk matrices revealed that patients with severe proteinuria and normal albuminuria had the highest risk of all-cause mortality (aHR 5.25, 95% CI 1.88, 14.63). uNAP significantly improved the discriminative performance compared to that of uPCR (c statistics: 0.834 vs. 0.828, p-value = 0.032). Our study findings advocate for simultaneous measurements of uPCR and uACR in daily practice to derive uAPR and uNAP, which can provide a better mortality prognostic assessment.

Joint Longitudinal Low Calcium High Phosphorus Trajectory Associates with Accelerated Progression, Acute Coronary Syndrome and Mortality in Chronic Kidney Disease.

The effects of long-term disturbance of the mineral metabolism on patients with chronic kidney disease (CKD) are unclear. We investigated whether the longitudinal Ca-P (joint calcium and phosphorus) trajectories are associated with incident end-stage renal disease (ESRD), acute coronary syndrome (ACS), and all-cause mortality in patients with CKD. We conducted a prospective cohort study by using data from a 13-year multidisciplinary pre-ESRD care registry. The final study population consisted of 4,237 CKD patients aged 20-90 years with data gathered from 2003 to 2015. Individuals' Ca-P trajectories were defined using group-based multi-trajectory modeling into three distinct patterns: reference, moderately abnormal, and severely abnormal. Times to ESRD, ACS, and death were analyzed using multiple Cox regression. Compared with those with a "reference" Ca-P trajectory, the adjusted hazard ratios (aHRs) (95% confidence interval [CI]) for incidental ESRD were 5.92 (4.71-7.44) and 15.20 (11.85-19.50) for "moderately abnormal" and "severely abnormal" Ca-P trajectories, respectively. The corresponding aHRs for ACS were 1.94 (1.49-2.52) and 3.18 (2.30-4.39), and for all-cause mortality, they were 1.88 (1.64-2.16) and 2.46 (2.05-2.96) for "moderately abnormal" and "severely abnormal" Ca-P trajectories, respectively. For outcomes of progression to ESRD, the detrimental effects of abnormal Ca-P trajectories were more substantial in patients with CKD stage 3 than those with CKD stage 4 or 5 (p-value for interaction < 0.001). Future studies should validate reliable longitudinal cut-offs of serum phosphorus and consider the "lowering phosphorus- the lower the better, the earlier the better" approach to phosphorus control in CKD.

Dialysis timing may be deferred toward very late initiation: An observational study.

The optimal timing to initiate dialysis among patients with an estimated glomerular filtration rate (eGFR) of <5 mL/min/1.73 m2 is unknown. We hypothesized that dialysis initiation time can be deferred in this population even with high uremic burden. A case-crossover study with case (0-30 days before dialysis initiation [DI]) and control (90-120 days before DI) periods was conducted in 1,079 hemodialysis patients aged 18-90 years at China Medical University Hospital between 2006 and 2015. The uremic burden was quantified based on 7 uremic indicators that reached the predefined threshold in case period, namely hemoglobin, serum albumin, blood urea nitrogen, serum creatinine, potassium, phosphorus, and bicarbonate. Dialysis timing was classified as standard (met 0-2 uremic indicators), late (3-5 indicators), and very late (6-7 indicators). Median eGFR-DI of the 1,079 patients was 3.4 mL/min/1.73 m2 and was 2.7 mL/min/1.73 m2 in patients with very late initiation. The median follow-up duration was 2.42 years. Antibiotics, diuretics, antihypertensive medications, and non-steroidal anti-inflammatory drugs (NSAIDs) were more prevalently used during the case period. The fully adjusted hazards ratios of all-cause mortality for the late and very late groups were 0.97 (95% confidence interval 0.76-1.24) and 0.83 (0.61-1.15) compared with the standard group. It is safe to defer dialysis initiation among patients with chronic kidney disease (CKD) having an eGFR of <5 mL/min/1.73 m2 even when patients having multiple biochemical uremic burdens. Coordinated efforts in acute infection prevention, optimal fluid management, and prevention of accidental exposure to NSAIDs are crucial to prolong the dialysis-free survival.

24-hour Serum Creatinine Variation Associates with Short- and Long-Term All-Cause Mortality: A Real-World Insight into Early Detection of Acute Kidney Injury.

Real-world evidence describing the variation in serum creatinine (S-Cre) within 24 hours and its prognostic value is unknown. We enrolled 14 912 adults who received two S-Cre measurements within 24 hours at a tertiary hospital between 2003 and 2016. The study population was divided into four groups according to the hospital service settings where the baseline and second S-Cre were measured: Group 1, Outpatient-to-Outpatient; Group 2, Outpatient-to-ED (emergency department) or Inpatient; Group 3, ED-to-ED or Inpatient; and Group 4, Inpatient-to-Inpatient. The main predictors were the difference between the two S-Cre measurements (ΔS-Cre) and the percent change (ΔS-Cre%). The main outcomes were 30-day, 1-year, or 3-year all-cause mortality. A total of 6753 and 8159 patients with an increase and a decrease within-day ΔS-Cre, respectively. Among 6753 patients who had deteriorating ΔS-Cre or ΔS-Cre%, the adjusted hazard ratio (aHR) for 1-year all-cause mortality for each 0.1 mg/dL or 5% change in S-Cre was 1.09 (95% confidence interval [CI]: 1.07, 1.11) and 1.03 (95% CI: 1.03, 1.04). In 8159 patients with improving ΔS-Cre%, the aHR was 0.97 (95% CI: 0.94, 1.00). Groups 3 and 4 had statistically significant positive linear relationships between deteriorating ΔS-Cre% and 30-day and 3-year mortality. The optimal cut-offs for deteriorating ΔS-Cre% for predicting 30-day mortality were approximately 22% for Group 3 and 20% for Group 4. Inpatient within-day deteriorating ΔS-Cre or ΔS-Cre% above 0.2 mg/dL or 20%, respectively, is associated with all-cause mortality. Monitoring 24-hour S-Cre variation identifies acute kidney injury earlier than the conventional criteria.

Blood Transfusion and Risk of Venous Thromboembolism: A Population-Based Cohort Study.

BACKGROUND: The risk of venous thromboembolism (VTE) in generally ill patients, both under outpatient and inpatient care, following blood transfusion has not been determined. METHODS: This retrospective population-based cohort study was conducted using the National Health Insurance Research Database. We studied patients who received blood transfusion, defined as red blood cell transfusion of any type, from January 1, 2000 to December 31, 2011. The index date was defined as the date of blood transfusion. The primary outcome was VTE. Propensity score matching and Cox proportional hazard models were used. RESULTS: A total of 41,866 patients who underwent blood transfusion and 41,866 matched controls were studied. Generally, the blood transfusion cohort has 2.98 times higher risk of VTE than the control cohort (95% confidence interval [CI] = 1.23-7.22). The blood transfusion cohort had respectively 1.99 and 1.64 times higher risk of deep vein thrombosis (DVT) and pulmonary embolism (PE) compared with the control cohort (DVT, 95% CI = 1.65-2.41; PE, 95% CI = 1.19-2.26). Patients in the blood transfusion cohort who did not use warfarin were 1.95 times more likely to develop VTE than those in the control cohort (adjusted hazard ratio [HR]: 1.95, 95% CI = 1.65-2.31). Patients in the blood transfusion cohort were 1.74 times more likely to die than those in the control cohort (adjusted HR: 1.74, 95% CI = 1.48-2.05). CONCLUSION: Blood transfusion is associated with an increased risk of VTE. The risk of VTE decreased in those who took warfarin.

Acute Kidney Injury in the Outpatient Setting Associates with Risk of End-Stage Renal Disease and Death in Patients with CKD.

Current acute kidney injury (AKI) diagnostic criteria are restricted to the inpatient setting. We proposed a new AKI diagnostic algorithm for the outpatient setting and evaluate whether outpatient AKI (AKIOPT) modifies the disease course among patients with chronic kidney disease (CKD) enrolled in the national predialysis registry. AKIOPT was detected when a 50% increase in serum creatinine level or 35% decline in eGFR was observed in the 180-day period prior to enrollment in the predialysis care program. Outcomes were progression to end-stage renal disease (ESRD) and all-cause mortality. Association analyses were performed using multiple Cox regression and coarsened exact matching (CEM) analysis. Among 6,046 patients, 31.5% (1,905 patients) had developed AKIOPT within the 180-day period before enrollment. The adjusted hazard ratios of the 1-year and overall risk of ESRD among patients with preceding AKIOPT compared with those without AKIOPT were 2.61 (95% CI: 2.15-3.18) and 1.97 (1.72-2.26), respectively. For 1-year and overall risk of all-cause mortality, patients with AKIOPT had respectively a 141% (95% CI: 89-209%) and 84% (56-117%) higher risk than those without AKIOPT. This statistical inference remained robust in CEM analysis. We also discovered a complete reversal in the eGFR slope before and after the AKIOPT from -10.61 ± 0.32 to 0.25 ± 0.30 mL/min/1.73 m2 per year; however, the loss of kidney function is not recovered. The new AKIOPT diagnostic algorithm provides prognostic insight in patients with CKD.

Association of Transfusion With Risks of Dementia or Alzheimer's Disease: A Population-Based Cohort Study.

Purpose: The association between neurodegenerative diseases and transfusion remains to be investigated. Methods: The study population comprised 63,813 patients who underwent a blood transfusion and 63,813 propensity score-matched controls between 2000 and 2010. Data were obtained from the Taiwan National Health Insurance Research Database, which is maintained by the National Health Research Institutes. A Cox regression analysis was conducted to elucidate the relationship between blood transfusions and the risk of dementia. Results: A multivariate Cox regression analysis of factors, such as age, sex, cardiovascular ischemia disease, and depression, revealed that patients who underwent a blood transfusion showed a 1.73-fold higher risk of dementia [95% confidence interval (CI) = 1.62-1.84] and a 1.37-fold higher risk of Alzheimer's disease (AD) [95% CI = 1.13-1.66] than those who did not. Patients who received a transfusion of washed red blood cells showed a 2.37-fold higher risk of dementia (95% CI = 1.63-3.44) than those who did not. Conclusion: Blood transfusion, especially transfusion of any type of red blood cells is associated with an increased risk of dementia.

Variability of red blood cell size predicts all-cause mortality, but not progression to dialysis, in patients with chronic kidney disease: A 13-year pre-ESRD registry-based cohort.

BACKGROUND: Prognostic role of red blood cell distribution width (RDW) in patients with chronic kidney disease (CKD) is unclear. Little evidence provides a comprehensive predictive analysis considering both baseline values and longitudinal trajectories of RDW along with mean corpuscular volume (MCV). METHODS: We conducted a comprehensive risk assessment of RDW and MCV in a registry-based cohort of 4621 patients with CKD (age, 20-90 y) receiving multidisciplinary care during 2003 to 2015. Both baseline and longitudinal trajectories of RDW and MCV were modeled as predictors for end-stage renal disease (ESRD) and mortality by using multiple Cox proportional hazards regression models, incorporating time-varying covariates and adjustments for imperative confounding variables. RESULTS: Fully adjusted hazard ratio (HR; 95% CI) of progression to ESRD for each unit increase in RDW and MCV at baseline was 0.97 (0.93-1.02) and 1.00 (0.99-1.01), respectively. Longitudinally, neither RDW nor MCV trajectory was associated with progression to ESRD. For all-cause mortality, fully adjusted HRs (95%CI) were 1.09 (1.04-1.14) for each percent increase in RDW with a linear dose-response relationship and 1.95 (1.47-2.59) for a stable-high RDW trajectory compared with normal RDW trajectory. The effects of RDW on mortality were further augmented in patients with concomitantly high MCV status. Incorporating point-of-care RDW significantly improves the discrimination performance quantified using Harrell C statistics into the existing CKD mortality predictive equation (from 0.770 to 0.784, P = .018). CONCLUSIONS: We support the clinical utility of RDW in predicting all-cause mortality among patients with CKD. The mechanism underlying our findings is critical for CKD risk assessment and management, particularly from malnutrition, inflammation, and atherosclerosis perspectives.

Longitudinal progression trajectory of random urine creatinine as a novel predictor of ESRD among patients with CKD.

BACKGROUND: The clinical importance of random urine creatinine concentration in CKD population remains undetermined. Earlier studies found that lower 24-h urine creatinine excretion was associated with the risk of ESRD and all-cause mortality among CKD patients. METHODS: We modeled the longitudinal trajectories of serial random urine creatinine among 4689 CKD patients enrolled in a national registry-based pre-ESRD program between 2003 and 2015 at a tertiary medical center. Other biochemical parameters including kidney function and serum albumin were regularly evaluated. Primary study outcomes were ESRD requiring maintenance dialysis and all-cause mortality. RESULTS: By group-based trajectory modeling, the urine creatinine trajectories were characterized into three patterns: (1) stable low; (2) medium; and (3) high-declining. The adjusted hazard ratio of incident ESRD and all-cause mortality increased by 6% (95% CI: 1-12%) and 9% (95% CI: 2-17%), respectively, for each 20 mg/dL reduction in baseline random urine creatinine concentration. Consistently, there was a significant inverse linear dose-response relationship between baseline random urine creatinine and incident ESRD, but not all-cause mortality. Compared to patients with "medium" and "high-declining" urine creatinine trajectories combined, the adjusted hazard ratio for incidental ESRD among patients with a "stable-low" trajectory who had serial random urine creatinine concentrations stably below 100 mg/dL was 1.46 (95% CI: 1.00-2.12) after considering the competing risk of death. CONCLUSIONS: Random urine creatinine not only serves as a common urinary concentration corrector but has its own clinical significance in risk stratification and outcome prediction in patients with advanced CKD.

Sitagliptin and Fractures in Type 2 Diabetes: A Nationwide Population-Based Propensity-Matching Study.

Background: Sitagliptin, a dipeptidyl peptidase-4 inhibitor possibly affects bone turnover. We conducted this cohort study to determine whether sitagliptin is associated with an increased risk of fracture. Methods: The sitagliptin cohort included 1,578 patients aged 20 years and above. The nonsitagliptin cohort comprised propensity-score matched patients at a ratio of 1:1. The primary outcome was the incidence of fractures, which was evaluated using Kaplan-Meier survival analysis and proportional hazards modeling. Results: The mean age of patients in the sitagliptin and nonsitagliptin cohorts was 63.1 and 63.3 years, respectively. The incidence of fractures in the sitagliptin cohort was 46 per 1,000 person-years and that in the nonsitagliptin cohort was 40.8 per 1,000 person-years. Compared with patients in the nonsitagliptin cohort, those in the sitagliptin cohort who received sitagliptin for ≥250 days had a higher risk of fracture (aHR = 1.32, 95% CI = 1.06-1.64). Conclusion: Using sitaglipin ≥250 days was associated with an increased risk of fracture.

Comparative effectiveness of allopurinol, febuxostat and benzbromarone on renal function in chronic kidney disease patients with hyperuricemia: a 13-year inception cohort study.

Background: Direct comparisons of the effectiveness of allopurinol with that of other urate-lowering agents in chronic kidney disease (CKD) populations, as well as guideline recommendations for clinical practice, are lacking. Methods: We constructed a pharmacoepidemiology cohort study by including patients from Taiwan's long-term integrated CKD care program to compare the effectiveness among allopurinol, febuxostat and benzbromarone in reducing the risk of progression to dialysis. A total of 874 patients with hyperuricemia who were newly treated with allopurinol, febuxostat or benzbromarone were included. The primary and secondary outcomes were incident end-stage renal disease (ESRD) and the serum uric acid (SUA) changes from baseline, respectively. The results were analyzed using multiple Cox proportional models adjusted for multinomial propensity scores. For subgroup analyses, we further stratified patients according to whether their latest SUA level reached the therapeutic target. Results: Compared with allopurinol, benzbromarone therapy was associated with a reduced risk of progression to dialysis, the adjusted hazard ratio was 0.50 (95% confidence interval, 0.25-0.99). Patients who received allopurinol or febuxostat exhibited a comparable risk of ESRD [adjusted hazard ratio, 0.99 (0.40-2.44)]. Febuxostat was significantly more potent than allopurinol or benzbromarone in lowering SUA levels in the fully adjusted model. Among patients who reached the therapeutic target, those with febuxostat and benzbromarone initiation had a significantly lower risk of ESRD. Conclusions: In conclusion, compared with conventional allopurinol, febuxostat and benzbromarone may be more effective in reducing the risk of progression to dialysis and in lowering SUA levels in CKD populations.

Uric acid predicts adverse outcomes in chronic kidney disease: a novel insight from trajectory analyses.

Background: Very little is known about longitudinal trajectories of serum uric acid (SUA) over the course of chronic kidney disease (CKD). We aimed to determine whether longitudinal SUA trajectories are associated with the risk of end-stage renal disease (ESRD) and all-cause mortality among CKD patients. Methods: We conducted a prospective cohort study from a 13-year multidisciplinary pre-ESRD care registry. The final study population consisted of 5090 CKD patients aged 20-90 years between 2003 and 2015. An individual's SUA trajectory was defined by group-based trajectory modeling in four distinct patterns: high, moderate-high, moderate and low. Time to ESRD and death was analyzed by multiple Cox regression. Results: A total of 948 ESRD events and 472 deaths occurred with incidence rates of 57.9 and 28.7 per 1000 person-years, respectively. Compared with those with a low SUA trajectory, the adjusted hazard ratio of patients for incident ESRD was in a dose-response manner as follows: moderate, 1.89 [95% confidence interval (CI), 1.37-2.60]; moderate-high, 2.49 (1.75-3.55); and high, 2.84 (1.81-4.47); after considering the competing risk of death. For all-cause mortality, the corresponding risk estimate of the same SUA trajectory was 1.38 (95% CI, 0.89-2.12), 1.95 (1.22-3.10) and 4.52 (2.48-8.26), respectively. The unfavorable effect of elevated SUA trajectories on progression to ESRD was differentially higher among CKD patients without using urate-lowering agents at baseline (P for interaction = 0.018). Conclusions: Elevated SUA trajectories are associated with accelerated kidney failure and all-cause mortality in CKD patients. Adequate experimental evidence is urgently needed to inform when and how to optimize SUA in this population.