Taiwan renal data report system: Framework, function, and development.

The world healthcare system is actively seeking possible solutions for the rapid growth of kidney disease threats. The Taiwan Renal Data System (TWRDS) was central in assisting kidney health and care policymaking to reduce end-stage kidney disease incidence and mortality. This article summarizes the TWRDS framework, recent applications, and developments to provide new insights for some international researchers to promote planetary kidney health. The TWRDS originated in 1987 for the accreditation and quality monitoring of dialysis units and was connected with enriched health claim databases after the implementation of universal national health insurance in Taiwan in 1995. As a healthcare information centre, TWRDS has published annual reports forming indispensable instructions for renal care improvement since 2014. The TWRDS possesses three main functions: (1) kidney disease surveillance; (2) offering rich materials for research purposes; (3) achieving precision prevention and care through complex algorithms. In the new era, TWRDS can help build a more resilient society against communicable disease threats by integrating remote sensor techniques for developing future remote healthcare structures, as well as identifying kidney health inequity populations and promoting healthcare resources distributed equity. The global healthcare system is facing escalating burdens of non-communicable disease care due to the rapidly growing elderly population. Therefore, a considerable-scale data system is an essential decision-supportive tool in promoting an evidence-based, resilient, sustainable, equity care environment. Undoubtedly, TWRDS experience is a practical example of leveraging healthcare providers' decisions, care outcomes, and renovation.

Trends in the incidence and prevalence of end-stage kidney disease requiring dialysis in Taiwan: 2010-2018.

BACKGROUND/PURPOSE: Taiwan has the highest incidence and prevalence of end-stage kidney disease (ESKD) worldwide. However, the epidemiologic features of ESKD requiring dialysis in Taiwan are unclear. METHODS: Our study population included all patients undergoing chronic dialysis (i.e., receiving dialysis treatment for at least three successive months) from the National Health Insurance Research Database from 2010 to 2018. Dialysis was defined using ICD-9-CM order codes for dialysis treatment. The age-standardized incidence and prevalence rates were calculated based on the World Health Organization standard population. RESULTS: The mean age was 47.7 ± 15.4 years at dialysis initiation. The incidence of ESKD requiring dialysis increased steadily during the study period, whereas the age-standardized incidence rate remained constant. The increased rate was particularly prevalent in men aged 65-74 and 75+ years. Additionally, the percentage of patients with estimated glomerular filtration rates > 10 mL/min/1.73 m2 at dialysis inception increased during the study period, especially in persons aged 75+ years. Most patients chose hemodialysis as the initial dialysis modality, including 86.8% in 2010 and 90.6% in 2018. The prevalence of dialysis increased substantially between 2010 and 2018, whereas the age-standardized prevalence of dialysis remained stable. The increasing trend was especially prominent in men aged ≥ 65 years. Among the patients on dialysis, the proportion of patients with mean dialysis times of more than 10 years has been increasing. CONCLUSION: The annual incidence and prevalence of dialysis increased steadily from 2010 to 2018, whereas the age-standardized incidence and prevalence of dialysis remained stable. The increased numbers of patients undergoing incident and prevalent dialysis were mostly elderly, especially men aged ≥65 years. Age-based prevention strategies and multidisciplinary care should be implemented to target the elderly population at risk of developing ESKD.

Hospitalization in patients with dialysis in Taiwan: A nationwide population-based observational study.

BACKGROUND: The hospitalization rate is higher in patients with end-stage kidney disease (ESKD) than in the general population. However, the national estimates in Taiwan remain unclear. Therefore, we investigated the hospitalization rates of ESKD patients in a disease-specific manner from 2010 to 2018 in Taiwan. METHODS: This population-based study was conducted using data from the National Health Insurance Research Database. We analyzed the hospitalization rates of patients with ESKD, defined as continuous dialysis for at least three successive months. The first diagnosis at discharge for each hospitalization was defined as the main diagnosis of hospitalization. The hospitalization rate in a certain year was calculated as the number of hospitalizations divided by the number of patients undergoing chronic dialysis in the respective year. RESULTS: Hospitalization occurred in half of all prevalent ESKD patients, with an increasing trend over time. The hospitalization rate increased from 964.1 per 1000 person-years in 2010 to 1037.9 per 1000 person-years in 2018. ESKD patients who were male, aged over 75 years, and receiving hemodialysis had higher hospitalization rates. Infection-related hospitalization was the main cause of hospitalization, followed by cardiovascular disease. The 30-day re-admission rate was 19%, and the in-hospital mortality rate was 9%. CONCLUSION: Hospitalization rates continued to increase from 2010 to 2018. The high hospitalization rates for infection-related diseases and hemodialysis patients call for further strategies to be developed that reduce the hospitalization burden.

Healthcare utilization and expenditure among individuals with end-stage kidney disease in Taiwan.

BACKGROUND/PURPOSE: The prevalence of end-stage kidney disease (ESKD) in Taiwan has been increasing in recent decades. ESKD care and medical expenditures constitute an important part of the entire healthcare system. METHODS: This study analyzed data collected from the National Health Insurance (NHI) Research Database from 2010 to 2018. RESULTS: The annual medical cost increased by approximately 4% both in the entire Taiwanese population and in its ESKD population. The total medical expenditure in the ESKD population from 2010 to 2018 increased from 48.03 to 65.65 billion reimbursement points, with dialysis treatments costing higher than non-dialysis treatments. ESKD outpatient and inpatient costs accounted for 10.4%-11.1% and 4.8%-5.6% of the entire NHI expenditure, respectively. The leading cause of inpatient costs was circulatory diseases, accounting for 29.3% of the total ESKD inpatient costs in 2018. Furthermore, percutaneous coronary intervention had the highest cost followed by simple percutaneous transluminal angioplasty. In 2018, the hemodialysis population had the highest average monthly cost of 73 thousand points per person, while the kidney transplant population had the lowest average monthly cost of 39 thousand points per person. CONCLUSION: Medical expenditure, including both inpatient and outpatient costs, of the ESKD population continued to grow from 2010 to 2018. The non-dialysis cost in the ESKD population was mainly for cardiovascular disease management and vascular access care, for which prevention will always be challenging.

Trends of kidney transplantation from the 2020 annual report on kidney disease in Taiwan.

BACKGROUND: Renal transplantation (RTX) is the treatment of choice for end-stage kidney disease (ESKD). Taiwan has the highest incidence and prevalence of ESKD in this world. This is the first study to illustrate the national registry database of RTX. METHODS: All patients who received RTX in Taiwan between 2010 and 2018 were enrolled in this study. Demographic data and comorbidities were obtained from the National Health Insurance Research Database and Transplantation Society of Taiwan. Graft and patient survival rates were also analyzed. RESULTS: Men were more likely to receive RTX. During the observation periods, > 30% of the recipients were relatively young (20-44 years). The percentage of preemptive RTX (p = 0.014) and living RTX (p = 0.022) increased annually with statistical significance (linear regression model). Recently, recipients had more cardiovascular disease (p = 0.014), diabetes mellitus (p = 0.097), and hypertension (p = 0.021). The mean duration of graft survival increased yearly (p = 0.001). The proportion of patients surviving till age of ≧65 years increased significantly with time (2.2% in 2010, 33.1% in 2018) (p < 0.0001). Younger recipients (<44 years) had significantly better survival than the elderly (≧65 years). Patients with diabetes were more likely to have worse graft and patient survival rates. Recipients enrolled in pre-ESRD care program had better graft and patient survival rates than those not enrolled in these care program. CONCLUSION: The proportion of preemptive and livingdonor RTX increased but was still low. Despite increased number of commodities in recipients, graft and patient survival have increased recently. Enrolling patients with CKD in pre-ESRD care program was associated with better graft and patient survival.

Trends of treated hepatitis B, hepatitis C, and tuberculosis infection in long-term hemodialysis patients in Taiwan: A nationwide survey in 2010-2018.

BACKGROUND/PURPOSE: Hepatitis B virus (HBV), hepatitis C virus (HCV), and tuberculosis (TB) infections affect patient morbidity and mortality and challenge infection control procedures within dialysis facilities. Thus, updated information on the yearly infection trends in the dialysis population is pivotal to preventing and improving the management of these infectious diseases. METHODS: This study used reimbursement data from the Taiwan National Health Insurance Research Database. Long-term hemodialysis (HD) patients were defined as those receiving regular HD for more than 3 months. Treated HBV, HCV, and TB cases were defined according to the diagnosis codes, together with specified prescriptions. Liver malignancy and liver-related mortality were determined by the disease diagnosis. RESULTS: The long-term HD population in Taiwan grew from 57,539 in 2010 to 74,203 in 2018. The mean number of treated HBV, HCV, and TB cases in the HD population was 254 (3.9 per thousand HD patients), 136 (2.0 per thousand), and 165 (2.6 per thousand), respectively. An increasing trend of treated viral hepatitis and a mildly decreasing trend in treated TB were observed. Liver outcome showed an increasing trend in liver malignancy prevalence and a stationary trend of liver-related mortality. Treated HBV and TB, liver malignancy, and liver-associated mortality were higher in men than women (all p < 0.001). The burden of liver complications was higher in southern Taiwan. CONCLUSION: The increasing yearly trend of treated HBV and HCV and a stable trend of treated TB provide evidence for further infection control management and risk population identification of the HD population.

Trends of medication used in patients with pre-ESKD from 2010 to 2018 in Taiwan.

BACKGROUND/PURPOSE: The burden of end-stage kidney disease (ESKD) continues to grow globally. Information on medication prescribed to advanced chronic kidney disease (CKD) patients can help formulate further CKD prevention policies. This study aimed to review and assess several major medications routinely prescribed to pre-ESKD patients. METHODS: Medication information of advanced CKD patients one year before regular dialysis was collected from the National Health Insurance Research Database from 2000 to 2018 in Taiwan. Usages of major medication were comprehensively analyzed. RESULTS: During 2000-2018, trends in medication usage evolved gradually in the pre-ESKD population in Taiwan. The use of erythropoietin had increased (48.3% in 2000 to 71.0% in 2018) with decreased blood transfusion rate (70.9% in 2003 to 52.1% in 2018). The use of non-steroidal anti-inflammatory drugs had also dropped (43.5% in 2004 to 25.5% in 2018). These changes were more evident for patients enrolled in the pre-ESKD prevention program. The most frequently used blood pressure-lowering and glucose-lowering agents were calcium channel blockers (90.6%) and insulin (78.1%), but usage of metformin was unexpectedly high (38.4% in 2018). The most frequently used blood thinner was aspirin (49.5%), with considerably increased use of direct oral anticoagulant (16.5% in 2018). CONCLUSION: An overview of the trends of major medication usage and blood transfusion represented the continuously improving care quality in pre-ESKD patients in Taiwan. These trends were especially evident in patients enrolled in the pre-ESKD prevention program. This report also indirectly indicated the potential and long-term benefits of implementing CKD and pre-ESKD prevention programs.

Clinical characteristics and outcomes of patients requiring incident dialysis in Taiwan.

BACKGROUND: Despite having a well-established pre-end-stage kidney disease (pre-ESKD) care program, Taiwan has a high incidence of ESKD. Unrecovered incident dialysis may lead to the maintenance of dialysis. Contrast medium (CM) or general anesthesia (GA) may also induce dialysis. We aimed to examine the trends for incident dialysis, use of CM or GA, and its long-term trajectory outcomes. METHODS: Patients who received at least one dialysis intervention between 2010 and 2017 were identified using the National Health Insurance Research Database. We collected information on age, sex, comorbidities, causes of dialysis in outpatient or inpatient settings, use of CM or GA or pre-ESKD program enrolment before incident dialysis, and trajectory outcomes. RESULTS: Incident dialysis occurred more frequently in elderly inpatients with infectious diseases or previous chronic kidney disease (CKD). The number of patients who had a pre-ESKD care plan before incident dialysis increased from 25% in 2010 to 41% in 2017 (P < 0.001). In general, CM or GA exposure related with a higher mortality rate. Over the five-year longitudinal follow-up, patients without a history of CKD had a higher mortality rate than those with a history of CKD. CONCLUSION: Enrolment in the pre-ESKD care program increased, and inpatient incident dialysis decreased. The long-term survival of patients with CKD was higher than that of non-CKD patients after incident dialysis. CM or GA exposure appears to be related to dialysis-induced mortality, and further investigations are warranted.

Multidisciplinary care program in pre-end-stage kidney disease from 2010 to 2018 in Taiwan.

BACKGROUND: The Taiwanese government launched a universal pay-for-performance (P4P) program in 2006 to promote multidisciplinary care for patients with stage 3b-5 chronic kidney disease (CKD). This study aimed to understand the enrollments, care processes, and outcomes of the P4P program between 2010 and 2018. METHODS: We conducted a population-based study using the Taiwan National Health Insurance Research Data. We divided the incident dialysis population into joining and not joining P4P groups based on whether patients had joined the pre-ESRD program before dialysis or not. Trends in the medications prescribed, anemia correction, vascular access preparation before dialysis initiation, and cumulative survival rate were compared. RESULTS: The program included more than 100,000 patients with late-stage CKD. Enrollment increased by almost 100% from 2010 to 2018, with increases seen in those over 75 years old (127.5%), male (96.7%), and earlier CKD stages (≥35% stage 3b in 2018). Females were more likely to stay being enrolled. The joining P4P group was prescribed more appropriate medications, such as erythropoietin-stimulating agents and statins. However, a high number of patients were still prescribed metformin (≥40%) and non-steroidal anti-inflammatory drugs (≥20%). Compared to the not joining P4P group, the patients in the P4P group had better anemia management, dialysis preparation, and post-dialysis survival. CONCLUSION: The patients in the joining P4P program group were delivered more appropriate CKD care and were associated with better survival outcomes. Polices and action plans are needed to extend the coverage of and enrollment in the P4P program.

Mortality rate of end-stage kidney disease patients in Taiwan.

BACKGROUND/PURPOSE: End-stage kidney disease (ESKD) is a global burden that reflects each country's unique condition. We used the National Health Insurance Research Database (NHIRD) of Taiwan to decipher changes in the mortality and international survival rates and to determine the effectiveness of the pre-end-stage renal disease care program (pre-ESRD care program) to guide future health policies for ESKD. METHODS: We conducted a retrospective cohort analysis of the NHIRD data along with records from the catastrophic illness certificate program of ESKD patients from 2010 to 2018. RESULTS: From 2010 to 2018, the annual dialysis-related mortality rate in Taiwan increased from 10.6 to 11.8 deaths per hundred patient-years. The mortality rate for patients below 40 years appears to be decreasing, reflecting the improved quality of care for ESKD patients. Patients above 75 years showed increasing mortality, indicating the prolonged survival and aging of the ESKD population. Patients undergoing dialysis who participated in the pre-ESRD care program had a higher post-dialysis initiation life expectancy than those who did not participate. Among the program enrollees, the post-dialysis initiation life expectancy was higher in patients who had participated for more than one year. Taiwan has one of the highest ESKD patient survival rates globally. CONCLUSION: From 2010 to 2018, the reduced mortality in young patients and aging of the ESKD population might indicate that the quality of care in Taiwan for ESKD has improved. Furthermore, a better survival rate after dialysis initiation was observed in the pre-ESRD care program participants.

Effect of Renin-Angiotensin-Aldosterone System Blockade on Long-Term Outcomes in Postacute Kidney Injury Patients With Hypertension.

OBJECTIVES: Renal replacement therapy-requiring acute kidney injury frequently occurs in ICUs, which require evidence-based medical attention. However, in the postacute kidney injury patient population, the evidence regarding effective therapies to improve patient outcomes is lacking. Therefore, we aimed to examine whether the renin-angiotensin-aldosterone system blockade is effective in improving renal outcomes in postacute kidney injury patients who experienced temporary renal replacement therapy and have hypertension. DESIGN: A retrospective cohort study. SETTING: A nationwide database in Taiwan. PATIENTS: From January 1, 2000, to December 31, 2013, we identified 8,558 acute kidney injury patients with hypertension in the national registry database. All these patients experienced an acute kidney injury episode, which required temporary renal replacement therapy for at least once. INTERVENTIONS: Users (n = 3,885) and nonusers (n = 4,673) of angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers. MEASUREMENTS AND MAIN RESULTS: We used Cox proportional hazards regression models to analyze hazard ratios for the commencement of end-stage renal disease and all-cause mortality for angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker users (n = 3,885) and nonusers (n = 4,673).In a median follow-up of 4.3 years, 5,880 patients (68.7%) required long-term dialysis, and 4,841 patients (56.6%) died. Compared with postacute kidney injury patients who did not use angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker, angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker users are marginally less likely to progress to end-stage renal disease (adjusted hazard ratio 0.95; 95% CI 0.90-1.01; p = 0.06) and significantly less likely to suffer from all-cause mortality (adjusted hazard ratio 0.93; 95% CI 0.87-0.98; p = 0.011). CONCLUSIONS: In patients who experienced renal replacement therapy-requiring acute kidney injury and have hypertension, angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker use is associated with better survival outcomes compared with nonuser.

A Facile NMR Method for Pre-MRI Evaluation of Trigger-Responsive T1 Contrast Enhancement.

There is a growing interest in developing paramagnetic nanoparticles as responsive magnetic resonance imaging (MRI) contrast agents, which feature switchable T1 image contrast of water protons upon biochemical cues for better discerning diseases. However, performing an MRI is pragmatically limited by its cost and availability. Hence, a facile, routine method for measuring the T1 contrast is highly desired in early-stage development. This work presents a single-point inversion recovery (IR) nuclear magnetic resonance (NMR) method that can rapidly evaluate T1 contrast change by employing a single, optimized IR pulse sequence that minimizes water signal for "off-state" nanoparticles and allows for sensitively measuring the signal change with "switch-on" T1 contrast. Using peptide-induced liposomal gadopentetic acid (Gd3+ -DTPA) release and redox-sensitive manganese oxide (MnO2 ) nanoparticles as a demonstration of generality, this method successfully evaluates the T1 shortening of water protons caused by liposomal Gd3+ -DTPA release and Mn2+ formation from MnO2 reduction. Furthermore, the NMR measurement is highly correlated to T1 -weighted MRI scans, suggesting its feasibility to predict the MRI results at the same field strength. This NMR method can be a low-cost, time-saving alternative for pre-MRI evaluation for a diversity of responsive T1 contrast systems.

Visualization of rodent brain tumor angiogenesis and effects of antiangiogenic treatment using 3D ΔR2-µMRA.

Understanding of structural and functional characteristics of the vascular microenvironment in gliomas and the impact of antiangiogenic treatments is essential for developing better therapeutic strategies. Although a number of methods exist in which this process can be studied experimentally, no single noninvasive test has the capacity to provide information concerning both microvascular function and morphology. The purpose of present study is to demonstrate the feasibility of using a novel three-dimensional ΔR2-based microscopic magnetic resonance angiography (3D ΔR2-µMRA) technique for longitudinal imaging of tumor angiogenesis and monitoring the effects of antiangiogenic treatment in rodent brain tumor models. Using 3D ΔR2-µMRA, a generally consistent early pattern of vascular development in gliomas was revealed, in which a single feeding vessel was visualized first (arteriogenesis), followed by sprouting angiogenesis. Considerable variability of the tumor-associated vasculature was then noted at later stages of tumor evolution. ΔR2-µMRA revealed that anti-vascular endothelial growth factor treatment induced a rapid and significant alteration of the intratumoral angiogenic phenotype. In summary, 3D ΔR2-µMRA enables high-resolution visualization of tumor-associated vessels while simultaneously providing functional information on the tumor microvasculature. It can serve as a useful tool for monitoring both the temporal evolution of tumor angiogenesis and the impact of antiangiogenic therapies.

Manganese-enhanced MRI of rat brain based on slow cerebral delivery of manganese(II) with silica-encapsulated Mn x Fe(1-x) O nanoparticles.

In this work, we report a monodisperse bifunctional nanoparticle system, MIO@SiO2 -RITC, as an MRI contrast agent [core, manganese iron oxide (MIO); shell, amorphous silica conjugated with rhodamine B isothiocyanate (RITC)]. It was prepared by thermal decomposition and modified microemulsion methods. The nanoparticles with varying iron to manganese ratios displayed different saturated magnetizations and relaxivities. In vivo MRI of rats injected intravenously with MIO@SiO2-RITC nanoparticles exhibited enhancement of the T1 contrast in brain tissue, in particular a time-delayed enhancement in the hippocampus, pituitary gland, striatum and cerebellum. This is attributable to the gradual degradation of MIO@SiO2-RITC nanoparticles in the liver, resulting in the slow release of manganese(II) [Mn(II)] into the blood pool and, subsequently, accumulation in the brain tissue. Thus, T1-weighted contrast enhancement was clearly detected in the anatomic structure of the brain as time progressed. In addition, T2*-weighted images of the liver showed a gradual darkening effect. Here, we demonstrate the concept of the slow release of Mn(II) for neuroimaging. This new nanoparticle-based manganese contrast agent allows one simple intravenous injection (rather than multiple infusions) of Mn(II) precursor, and results in delineation of the detailed anatomic neuroarchitecture in MRI; hence, this provides the advantage of the long-term study of neural function.

Association of anemia and iron parameters with mortality among prevalent peritoneal dialysis patients in Taiwan: the AIM-PD study.

In 1996, the National Health Insurance Administration of Taiwan applied a restrictive reimbursement criteria for erythropoiesis-stimulating agents (ESAs) use in patients with chronic kidney disease. The maximal ESAs dosage allowed by insurance is capped at 20,000 U of epoetin per month. Nephrologists avoided the use of high ESA dosages to achieve a hemoglobin level of 10-11 g/dL using iron supplementation. We assessed the association of anemia and iron parameters with mortality among peritoneal dialysis (AIM-PD) patients. A retrospective cohort study was conducted based on the Taiwan Renal Registry Data System. From January 1, 2000 to December 31, 2008, we enrolled 4356 well-nourished PD patients who were older than 20 years and had been receiving PD for more than 12 months. All patients were divided into subgroups according to different hemoglobin, ferritin and transferrin saturation (TSAT) values. Patients were followed until death or December 31, 2008. In a median 2.9-year study period, 694 (15.9%) patients died. By multivariate adjustment, a hemoglobin level lower than 10 g/dL was significantly associated with a higher risk for all-cause and cardiovascular deaths. Moreover, a serum ferritin level higher than 800 ng/mL was associated with a higher risk for all-cause deaths, and a TSAT value between 20 and 50% was associated with the lowest all-cause mortality. In conclusions, we recommend avoiding a low hemoglobin level and a serum ferritin level of more than 800 ng/mL and maintaining a TSAT value between 20 and 50%, as these conditions were associated with lower risks of all-cause mortality in the AIM-PD study.

A Gadolinium DO3A Amide m-Phenyl Boronic Acid MRI Probe for Targeted Imaging of Sialated Solid Tumors.

We developed a new probe, Gd-DO3A-Am-PBA, for imaging tumors. Our results showed active targeting of Gd-DO3A-Am-PBA to sialic acid (SA) moieties, with increased cellular labeling in vitro and enhanced tumor accumulation and retention in vivo, compared to the commercial Gadovist. The effectiveness of our newly synthesized probe lies in its adequate retention phase, which is expected to provide a suitable time window for tumor diagnosis and a faster renal clearance, which will reduce toxicity risks when translated to clinics. Hence, this study can be extended to other tumor types that express SA on their surface. Targeting and MR imaging of any type of tumors can also be achieved by conjugating the newly synthesized contrast agent with specific antibodies. This study thus opens new avenues for drug delivery and tumor diagnosis via imaging.

Hypoperfusion of the infrapatellar fat pad and its relationship to MRI T2* relaxation time changes in a 5/6 nephrectomy model.

The purpose of present study was to longitudinally investigate the alterations in infrapatellar fat pad (IPFP) vascularity in 5/6 nephrectomized rats by using dynamic contrast enhanced (DCE) MRI and IPFP degeneration by using MRI T2* relaxation time. Twelve male Sprague-Dawley rats were assigned to a control group and a 5/6 nephrectomy CKD group. The right knees of all rats were longitudinally scanned by 4.7 T MRI, and serial changes in the IPFP were assessed at 0, 8, 16, 30, and 44 weeks by DCE-MRI (parameters A, kel and kep) and MRI T2* mapping. After MRI measurements, knee specimens were obtained and evaluated histologically. The CKD group had IPFPs with lower blood volume A and lower permeability kep values from 16 weeks (p < 0.05), lower venous washout kel value from 30 weeks (p < 0.001), and significantly higher T2* values reflecting adipocyte degeneration beginning at 16 weeks (p < 0.05). The histopathological results confirmed the MRI findings. Hypoperfusion and adipocytes degeneration related to CKD were demonstrated in a rodent 5/6 nephrectomy model. DCE parameters and MRI T2* can serve as imaging biomarkers of fat pad degeneration during CKD progression.

pH Mapping of Skeletal Muscle by Chemical Exchange Saturation Transfer (CEST) Imaging.

Magnetic resonance imaging (MRI) is extensively used in clinical and basic biomedical research. However, MRI detection of pH changes still poses a technical challenge. Chemical exchange saturation transfer (CEST) imaging is a possible solution to this problem. Using saturation transfer, alterations in the exchange rates between the solute and water protons because of small pH changes can be detected with greater sensitivity. In this study, we examined a fatigued skeletal muscle model in electrically stimulated mice. The measured CEST signal ratio was between 1.96 ppm and 2.6 ppm in the z-spectrum, and this was associated with pH values based on the ratio between the creatine (Cr) and the phosphocreatine (PCr). The CEST results demonstrated a significant contrast change at the electrical stimulation site. Moreover, the pH value was observed to decrease from 7.23 to 7.15 within 20 h after electrical stimulation. This pH decrease was verified by 31P magnetic resonance spectroscopy and behavioral tests, which showed a consistent variation over time.

In vivo cerebromicrovasculatural visualization using 3D DeltaR2-based microscopy of magnetic resonance angiography (3DDeltaR2-mMRA).

This study proposed a novel methodology for depicting cerebral small vessels including veins, arterioles, and venules, called 3DDeltaR(2)-mMRA (three-dimensional, steady-state DeltaR(2)-based, and flow-independent microscopic magnetic resonance angiography). The DeltaR(2) map calculated by a fast spin-echo imaging technique before and after the injection of an iron-oxide contrast agent was used to delineate the relative cerebral blood volume, primarily to microvasculature. The proposed 3DDeltaR(2)-mMRA method, which employs 3D reconstruction techniques, can simultaneously provide high-resolution 3D information on the cerebral anatomy, in vivo microvascular architecture, and hemodynamic response, which can be used to evaluate pathological microvascular changes over time in cerebromicrovascular disease. Since spin-echo-based DeltaR(2) imaging was applied, the inflow effects, susceptibility artifacts, and the overestimation of vessel size in brain were reduced. A well-defined three-vessel occlusion model in the rat was performed to evaluate the capability of the proposed method in evaluating alterations to the microvasculature.

Cancer and mTOR inhibitors in kidney transplantation recipients.

BACKGROUND: Previous studies show that mTOR inhibitors decrease the risk of cancer development after kidney transplantation. However, the effect of cumulative doses of mTOR inhibitors on cancer after kidney transplantation is not well known. METHODS: In the current study, patients were registered into a national database in Taiwan. Between year 2000 and 2013, 4,563 patients received kidney transplantation. They were divided into two groups, according to mTOR inhibitors usage. The cumulative dose of mTOR inhibitors was recorded. Patients were followed-up until de novo cancer development, death, or the end of 2014. RESULTS: Patients were divided into two groups: mTOR inhibitors users (study group, n = 828) and mTOR inhibitors non-users (control group, n = 3,735). The median follow-up duration was 7.8 years. The risk of de novo cancer (hazards ratio (HR) 0.80, 95% CI [0.60-1.09], p = 0.16) and risk of death (HR 1.14, 95% CI [0.82-1.60], p = 0.43) was not different between mTOR inhibitor user and non-user groups. Neither high- nor low-dose exposure to mTOR inhibitors was associated with increased risk of cancer or mortality. Analysis of cancer subtypes showed no influence by mTOR inhibitors. In addition, the cause of mortality was not significantly different between the two groups. DISCUSSION: We could not find the association of mTOR inhibitors use and risk of de novo cancer development or mortality in patients with kidney transplantation in Chinese patients. Cumulative exposure to mTOR inhibitors did not change the results.