The impact of acute kidney injury with or without recovery on long-term kidney outcome in patients undergoing living liver transplantation.

BACKGROUND: Acute kidney injury (AKI) is associated with an increased incidence of poor liver graft and renal outcomes in patients who have undergone liver transplantation (LT). To date, no comprehensive study has compared patients with and without post-LT AKI and analyzed patients who recovered from AKI versus those who did not. METHODS: Patients who received living LT between January 2003 and January 2019 were enrolled. We diagnosed and classified AKI patients based on AKI-KDIGO guidelines by increment of creatinine after surgery when compared with serum creatinine on the day of surgery. The recovered AKI subgroup included recipients whose estimated glomerular filtration rate (eGFR) recovered more than 90% of baseline eGFR within 90 days after surgery. The risk of chronic kidney disease (CKD; eGFR <60 mL/min/1.73 m2) was investigated. RESULTS: A total of 392 patients, 77.3% men and mean ± standard deviation age 54.1 ± 8.4 years, met the eligible criteria and were divided into two groups (AKI vs non-AKI) and 243 (62%) patients developed AKI within 7 days after surgery. Compared with the non-AKI group, the AKI group was associated with an adjusted hazard ratio of 1.55 (95% CI 1.12-2.14) for the risk of incident CKD. Among AKI patients, 160 (65.8%) patients recovered renal function and 83 (34.2%) patients did not. Compared with the non-AKI group, the AKI non-recovery group was associated with an adjusted hazard ratio of 2.87 (95% CI 1.95-4.21) for the risk of incident CKD, while the AKI recovery group had no significant difference in the adjusted risk of incident CKD. CONCLUSIONS: Post-LT AKI is associated with subsequent risk of CKD development. Taking into account recovery status, AKI was no longer associated with a higher risk of CKD if renal function recovered within 90 days after surgery. Identification and implementation of targeted and individualized therapies for patients at risk for AKI, particularly non-recovery AKI, is of paramount importance to reduce incident CKD during follow-up.

Novel method for laparoscopic rectus sheath tunneling with Lin's tube in peritoneal dialysis catheter implantation.

Laparoscopic implantation of a catheter through rectus sheath tunnel minimizes the risks of catheter failure and reduces some complications like catheter migration, hernias, and leaks. We described a novel method for laparoscopic catheter rectus sheath tunneling using an aspiration tube and a silk tie (Lin's tube). This material is easily available and yields a small fascial defect with an equivalent cannula size to minimize tissue disruption. The technique is feasible, reproducible and it may reduce the risks of postoperative leakage and hemorrhage.

Predicting hyperkalemia in patients with advanced chronic kidney disease using the XGBoost model.

BACKGROUND: Hyperkalemia is a common complication of chronic kidney disease (CKD). Hyperkalemia is associated with mortality, CKD progression, hospitalization, and high healthcare costs in patients with CKD. We developed a machine learning model to predict hyperkalemia in patients with advanced CKD at an outpatient clinic. METHODS: This retrospective study included 1,965 advanced CKD patients between January 1, 2010, and December 31, 2020 in Taiwan. We randomly divided all patients into the training (75%) and testing (25%) datasets. The primary outcome was to predict hyperkalemia (K+ > 5.5 mEq/L) in the next clinic vist. Two nephrologists were enrolled in a human-machine competition. The area under the receiver operating characteristic curves (AUCs), sensitivity, specificity, and accuracy were used to evaluate the performance of XGBoost and conventional logistic regression models with that of these physicians. RESULTS: In a human-machine competition of hyperkalemia prediction, the AUC, PPV, and accuracy of the XGBoost model were 0.867 (95% confidence interval: 0.840-0.894), 0.700, and 0.933, which was significantly better than that of our clinicians. There were four variables that were chosen as high-ranking variables in XGBoost and logistic regression models, including hemoglobin, the serum potassium level in the previous visit, angiotensin receptor blocker use, and calcium polystyrene sulfonate use. CONCLUSIONS: The XGBoost model provided better predictive performance for hyperkalemia than physicians at the outpatient clinic.

Lupus nephritis with corticosteroid responsiveness: molecular changes of CD46-mediated type 1 regulatory T cells.

BACKGROUND: The engagement of the complement regulatory proteins CD46 and CD3 in human CD4+ T cells induces the type 1 regulatory T cells (Tr1) and interleukin-10 (IL-10) secretion. This study aimed to elucidate the molecular changes of Tr1 cells through CD46 cytoplasmic Cyt1 tail in lupus nephritis (LN) respond to intravenous methylprednisolone (ivMP) therapy. METHODS: We enrolled 40 pediatric patients with LN and 30 healthy controls. Clinical characteristics and peripheral blood mononuclear cells were collected before and 3 days after the administration of ivMP. Kidney specimens were taken from five LN and five minimal-change nephrotic syndrome patients. RESULTS: We found that defective CD46-mediated T-helper type 1 contraction (IL-10 switching) is present in active LN patients. The ivMP therapy enhanced LN remission, restored the production of IL-10, increased the CD46-Cyt1/Cyt2 ratio, AKT, and cAMP-responsive element-binding protein phosphorylation, and induced migration with the expression of chemokine receptor molecules CCR4, CCR6, and CCR7 of CD3/CD46-activated Tr1 cells. CONCLUSIONS: Pharmacologic interventions that alter the patterns of CD46-Cyt1/Cyt2 expression and the secretion of IL-10 by CD3/CD46-activated Tr1 cells can be used in patients with active LN. IMPACT: In patients with LN, ivMP was associated with increased IL-10 production and increased CD46-Cyt1/Cyt2 ratio and AKT phosphorylation by Tr1 cells, with enhanced potential to migration in response to CCL17. These results suggest that expression levels of CD46 isoforms Cyt1 and Cyt2 in CD4 + CD46 + Tr1 cells differ in patients with active LN but can be corrected by corticosteroid treatment. Enhancing the expression of functional CD4 + CD46 + Tr1 cells may be a useful therapeutic approach for LN.

Machine Learning Analysis of Time-Dependent Features for Predicting Adverse Events During Hemodialysis Therapy: Model Development and Validation Study.

BACKGROUND: Hemodialysis (HD) therapy is an indispensable tool used in critical care management. Patients undergoing HD are at risk for intradialytic adverse events, ranging from muscle cramps to cardiac arrest. So far, there is no effective HD device-integrated algorithm to assist medical staff in response to these adverse events a step earlier during HD. OBJECTIVE: We aimed to develop machine learning algorithms to predict intradialytic adverse events in an unbiased manner. METHODS: Three-month dialysis and physiological time-series data were collected from all patients who underwent maintenance HD therapy at a tertiary care referral center. Dialysis data were collected automatically by HD devices, and physiological data were recorded by medical staff. Intradialytic adverse events were documented by medical staff according to patient complaints. Features extracted from the time series data sets by linear and differential analyses were used for machine learning to predict adverse events during HD. RESULTS: Time series dialysis data were collected during the 4-hour HD session in 108 patients who underwent maintenance HD therapy. There were a total of 4221 HD sessions, 406 of which involved at least one intradialytic adverse event. Models were built by classification algorithms and evaluated by four-fold cross-validation. The developed algorithm predicted overall intradialytic adverse events, with an area under the curve (AUC) of 0.83, sensitivity of 0.53, and specificity of 0.96. The algorithm also predicted muscle cramps, with an AUC of 0.85, and blood pressure elevation, with an AUC of 0.93. In addition, the model built based on ultrafiltration-unrelated features predicted all types of adverse events, with an AUC of 0.81, indicating that ultrafiltration-unrelated factors also contribute to the onset of adverse events. CONCLUSIONS: Our results demonstrated that algorithms combining linear and differential analyses with two-class classification machine learning can predict intradialytic adverse events in quasi-real time with high AUCs. Such a methodology implemented with local cloud computation and real-time optimization by personalized HD data could warn clinicians to take timely actions in advance.

High particulate matter 2.5 levels and ambient temperature are associated with acute lung edema in patients with nondialysis Stage 5 chronic kidney disease.

BACKGROUND: Numerous studies have shown that exposure to air pollution, especially particulate matter (PM) with a diameter <2.5 µm (PM2.5), was associated with various diseases. We tried to determine the impact of PM2.5 and other weather factors on acute lung edema in patients with Stage 5 nondialysis chronic kidney disease (CKD Stage 5-ND). METHODS: In total, 317 CKD Stage 5-ND (estimated glomerular filtration rate 6.79 ± 4.56 mL/min) patients residing in central Taiwan who developed acute lung edema and initiated long-term dialysis were included in this case-crossover study. Pearson's correlation test was used to examine the relationship of acute lung edema cases with PM2.5 levels and ambient temperature separately. RESULTS: The average PM2.5 level within the 7-day period correlated with acute lung edema incidence in the fall [adjusted odds ratio (OR) 3.23, P = 0.047] and winter (adjusted OR 1.99, P < 0.001). In winter, even a 3-day exposure to PM2.5 was associated with increased risk (adjusted OR 1.55, P < 0.001). The average temperatures within 3 days in spring and summer were correlated positively with the risk (adjusted OR 2.77 P < 0.001 and adjusted OR 2.72, P < 0.001, respectively). In the fall and winter, temperatures were correlated negatively with the risk (adjusted OR 0.36, P < 0.001 and adjusted OR 0.54, P < 0.001, respectively). CONCLUSIONS: A high PM2.5 level was associated with an increased risk of acute lung edema. High ambient temperature in hot seasons and low ambient temperature in cold seasons were also associated with increased risk. It is essential to educate these patients to avoid areas with severe air pollution and extreme ambient temperature.

Favourable renal outcomes after intravenous thrombolytic therapy for acute ischemic stroke: Clinical implication of kidney-brain axis.

AIM: Recombinant tissue plasminogen activator (rt-PA) administration is the most prevalent treatment for acute ischemic within golden time. However, the effects of rt-PA on the kidney function in such patients remain unknown. This study determined long-term renal outcomes in patients with acute ischemic stroke receiving systemic rt-PA. METHODS: We enroled patients who were hospitalized for acute ischemic stroke from January 2001 to January 2017. We applied 1:2 propensity score matching to eliminate various confounding variables. We defined surrogate renal outcomes as declining of estimated glomerular filtration rate (eGFR) greater than 30% and 50%, and chronic kidney disease (CKD) with eGFR less than 60 mL/min. We then compared the 1-year eGFR with paired t-test in patients treated with or without rt-PA. RESULTS: Overall, 343 of 1739 patients received rt-PA within golden time. After 1:2 propensity score matching, their baseline characteristics were grouped as treated with rt-PA (n = 235) or not (n = 394). rt-PA-treated patients exhibited slower renal progression, including the risk of eGFR declining greater than 30% (hazard ratio (HR), 0.72; P = 0.03), risk of declining eGFR greater than 50% (HR, 0.63; P = 0.046) and risk of CKD (HR, 0.61; P = 0.005). After 1-year cohort, the rt-PA group exhibited an improved renal outcome by the paired t-test (propensity match: ΔGFR = 9.1 (95% confidence interval: 6.3, 11.8), P < 0.001 in rt-PA group; ΔGFR = -1.1 (95% confidence interval: -2.9, 0.7), P = 0.23 in non-rt-PA group). In patients with eGFR less than 45 mL/min (n = 34), intracerebral haemorrhage was not reported. CONCLUSION: Patients receiving rt-PA for acute ischemic stroke exhibit favourable renal outcomes, and no increased incidence of intracerebral haemorrhage occurs in rt-PA patients with advanced CKD.

Urinary cell-free mitochondrial and nuclear deoxyribonucleic acid correlates with the prognosis of chronic kidney diseases.

INTRODUCTION: Cell-free deoxyribonucleic acid DNA (cf-DNA) in urine is promising due to the advantage of urine as an easily obtained and non-invasive sample source over tissue and blood. In clinical practice, it is important to identify non-invasive biomarkers of chronic kidney disease (CKD) in monitoring and surveillance of disease progression. Information is limited, however, regarding the relationship between urine and plasma cf-DNA and the renal outcome in CKD patients. METHODS: One hundred and thirty-one CKD patients were enrolled between January 2016 and September 2018. Baseline urine and plasma cell-free mitochondrial DNA (cf-mtDNA) and cell-free nuclear DNA (cf-nDNA) were isolated using quantitative real-time PCR. Estimated glomerular filtration rate (eGFR) measurement was performed at baseline and 6-month follow-up. Favorable renal outcome was defined as eGFR at 6 months minus baseline eGFR> = 0. Receiver operator characteristics (ROC) curve analysis was performed to assess different samples of cf-DNA to predict favorable renal outcomes at 6 months. A multivariate linear regression model was used to evaluate independent associations between possible predictors and different samples of cf-DNA. RESULTS: Patients with an advanced stage of CKD has significantly low plasma cf-nDNA and high plasma neutrophil gelatinase-associated lipocalin (NGAL) levels. Low urine cf-mtDNA, cf-nDNA levels and low plasma NGAL were significantly correlated with favorable renal outcomes at 6 months. The urine albumin-creatinine ratio (ACR) or urine protein-creatinine ratio (PCR) level is a robust predictor of cf-mtDNA and cf-nDNA in CKD patients. Baseline urine levels of cf-mtDNA and cf-nDNA could predict renal outcomes at 6 months. CONCLUSIONS: Urinary cf-mtDNA and cf-nDNA may provide novel prognostic biomarkers for renal outcome in CKD patients. The levels of plasma cf-nDNA and plasma NGAL are significantly correlated with the severity of CKD.

Prospective associations between environmental heavy metal exposure and renal outcomes in adults with chronic kidney disease.

AIM: In Taiwan, Changhua County residents were exposed to high heavy metal pollution and exhibited high heavy metal levels in blood and urine. We examined associations between heavy metals in residential soil and renal outcomes of residents with chronic kidney disease (CKD). METHOD: From 1 January 2003 to 30 June 2015, we retrospectively identified CKD patients with an estimated glomerular filtration rate of <60 mL/min per 1.73 m2 at one tertiary care centre. We linked data displaying heavy metal concentrations from farm soil adjacent to the patients' residences to clinical outcomes. We included 2343 CKD patients (533 with progression to end-stage renal disease [ESRD] and 1810 without]. We followed these patients for 3.49 ± 2.27 years, until death or initiation of maintenance dialysis. RESULTS: There were high correlations among the concentrations of the eight metals: arsenic, cadmium, chromium, mercury, copper, lead, nickel, and zinc. After factor analysis, chromium, copper, nickel, and zinc were grouped and labelled Factor 1. High Factor 1 concentration near the patients' residences was associated with diagnoses of hypertension, diabetes mellitus, and cerebral vascular accident. Patients living in areas with high Factor 1 concentrations were at higher risk of ESRD. After multivariate adjustment [adjusted hazard ratio: 1.08, 95% Confidence interval: 1.01-1.14, P = 0.02], only zinc and nickel were risk factors for progression to ESRD. CONCLUSION: Patients with CKD, with long-term exposure to soil-based heavy metals, had rapid progression to ESRD. Groups of minerals from the same source of contamination may accumulate and lead to additional harm.

Urinary glycated uromodulin in diabetic kidney disease.

Advanced glycation end-products (AGEs) form during oxidative stress, which is increased in diabetes mellitus (DM). Uromodulin is a protein with a renal protective effect, and may be subject to glycation. The implications of uromodulin glycation and AGEs in the urine are not understood. Here, immunoprecipitation and liquid chromatography-mass spectrometry identified glycated uromodulin (glcUMOD) in the urine of 62.5% of patients with diabetic kidney disease (DKD), 20.0% of patients with non-diabetic chronic kidney disease (CKD), and no DM patients with normal renal function or healthy control participants; a finding replicated in a larger cohort of 84 patients with CKD in a case-control study (35 with DM, 49 without). Uromodulin forms high molecular weight polymers that associate with microvesicles and exosomes. Differential centrifugation identified uromodulin in the supernatant, microvesicles, and exosomes of the urine of healthy participants, but only in the supernatant of samples from patients with DKD, suggesting that glycation influences uromodulin function. Finally, the diagnostic and prognostic utility of measuring urinary glcUMOD concentration was examined. Urinary glcUMOD concentration was substantially higher in DKD patients than non-diabetic CKD patients. Urinary glcUMOD concentration predicted DKD status, particularly in patients with CKD stages 1-3a aged <65 years and with urine glcUMOD concentration ≥9,000 arbitrary units (AU). Urinary uromodulin is apparently glycated in DKD and forms AGEs, and glcUMOD may serve as a biomarker for DKD.

The role of uric acid in chronic kidney disease patients.

AIM: Chronic kidney disease (CKD) is always associated with hyperuricaemia. However, the studies evaluating the clinical implications of hyperuricaemia have shown conflicting results in these patients. METHODS: A retrospective observational study was conducted in 2408 stage 3-5 CKD patients. Instead of one baseline uric acid (UA) level, the averaged level of the two consecutive measurements for each participant was used as the predictor for the outcomes of the study, which included mortality, renal outcomes, and hospitalization risk. A multivariate Cox proportional hazards model and logistic regression model were performed to determine the independent risk factor. RESULTS: The mean UA level was 0.46 ± 0.106 mmol/L. Of the 2408 patients, there were 563 (23.3%) deaths, 143 (5.9%) cardiovascular deaths, 652 (27%) subjects commencing renal replacement therapy (RRT), 664 (27.5%) subjects with rapid renal progression, 1937 (58%) patients requiring hospitalization and 404 (16.7%) patients with CVD hospitalization during a mean follow-up of approximately 3.03 years. After multivariate adjustments, a 1-mg/dL increase in uric acid level was associated with a hazard ratio (HR) of 1.26 for RRT (P = 0.002), an odds ratio (OR) of 1.27 for rapid renal progression (P = 0.001), an HR of 1.19 for all-cause hospitalization (P < 0.001), and an HR of 1.12 for cardiovascular disease (CVD) hospitalization (P = 0.02), but not significantly with all-cause mortality and cardiovascular death at the end of follow-up. CONCLUSIONS: In stage 3-5 CKD patients, hyperuricaemia was associated with a higher risk of renal replacement therapy, rapid renal progression and hospitalization for all causes or CVD, but not with all-cause mortality or cardiovascular mortality.

U-shaped relationship between uric acid and residual renal function decline in continuous ambulatory peritoneal dialysis patients.

AIM: There is little information on the relationship between uric acid (UA) and residual renal function (RRF) in continuous ambulatory peritoneal dialysis (CAPD). The aim of this research is to study the influence of UA on RRF decline in CAPD patients. METHODS: A retrospective observational cohort study of 304 patients who started CAPD without anuria between 2001 and 2010 was conducted at a single medical center. The outcomes measured in the study included the rate of RRF decline and anuria. A multiple ordinal logistic regression model with backward elimination was conducted to determine the independent factors of the slope of RRF decline. A Cox proportional hazard model was conducted to determine the independent variables of time to anuria. RESULTS: The average rate of RRF decline was -0.12 ± 0.22 mL/min per month. Multivariate analysis showed that lower UA group (<0.372 mmol/L), higher UA group (≧0.421 mmol/L), male gender, diabetes mellitus (DM), the use of calcium channel blocker (CCB), and RRF at baseline were linked positively with the rate of RRF decline; on the other hand, independence in dialysate exchanges and BUN were negatively associated with the risk of RRF decline. In addition, male gender, DM, diuretics, and CCB were associated with a higher risk of progression to anuria, whereas 24-h urine amount at baseline conferred a protective role in the development of anuria. CONCLUSIONS: A U-shaped relationship was found between UA levels and the rate of RRF decline in patients on CAPD, with a faster decline rate in those of higher and lower UA groups.

Lower-dose warfarin delays renal progression and prolongs patient survival in patients with stage 3 - 5 chronic kidney disease and nonvalvular atrial fibrillation: a 12-year follow-up study.

BACKGROUND: Anticoagulants are used to reduce the risk of stroke in patients with atrial fibrillation (Af) and chronic kidney disease (CKD). Warfarin is one of the commonly used anticoagulants; however, its effect on renal function remains unclear. METHODS: In a retrospective cohort study (January 2001 - July 2013), we surveyed data charts from 2,450 patients with stage 3 - 5 CKD, and enrolled 159 patients with Af. In total, 104 patients had a CHADS2 score of >= 2 (congestive heart failure, hypertension, >= 75 years old, diabetes, 1 point; prior stroke or transient ischemic attack or thromboembolism, 2 points). These patients were categorized into groups A and B based on warfarin treatment. Group A included 73 patients and was not undergoing warfarin treatment and group B included 31 patients undergoing warfarin treatment. The baseline demographic and biochemical data as well as changes in estimated glomerular filtration rate (eGFR) after 6, 12, and 18 months of warfarin treatment were analyzed. We also studied censored patient survival over 12 years using Kaplan-Meier model. RESULTS: The mean international normalization ratio (INR) of warfarin treatment in group B was 1.92 ± 1.04. Moreover, group B showed a significant increase in eGFR. The maximum improvement was at 6 months (mean eGFR increased from 25.97 to 31.12 mL/min; p = 0.01) and lasted for up to 18 months (eGFR 28.65 mL/min). Despite higher initial CHADS2 scores, group B showed a superior survival rate compared with group A (p = 0.02). CONCLUSION: Lower doses of warfarin may protect against renal dysfunction and could be beneficial for treatment of stage 3 - 5 CKD with Af.

Multidisciplinary care improves clinical outcome and reduces medical costs for pre-end-stage renal disease in Taiwan.

AIM: Multidisciplinary care (MDC) for patients with chronic kidney disease (CKD) may help to optimize disease care and improve clinical outcomes. Our study aimed to evaluate the effectiveness of pre-end-stage renal disease (ESRD) patients under MDC and usual care in Taiwan. METHOD: In this 3-year retrospective observational study, we recruited 822 ESRD subjects, aged 18 years and older, initiating maintenance dialysis more than 3 months from five cooperating hospitals. The MDC (n = 391) group was cared for by a nephrologists-based team and the usual care group (n = 431) was cared for by sub-specialists or nephrologists alone more than 90 days before dialysis initiation. Patient characteristics, dialysis modality, hospital utilization, hospitalization at dialysis initiation, mortality and medical cost were evaluated. Medical costs were further divided into in-hospital, emergency services and outpatient visits. RESULTS: The MDC group had a better prevalence in peritoneal dialysis (PD) selection, less temporary catheter use, a lower hospitalization rate at dialysis initiation and 15% reduction in the risk of hospitalization (P < 0.05). After adjusting for gender, age and Charlson Comorbidity Index score, there were lower in-hospital and higher outpatient costs in the MDC group during 3 months before dialysis initiation (P < 0.05). In contrast, medical costs (NT$ 146,038 vs 79,022) and hospitalization days (22.4 vs 15.5 days) at dialysis initiation were higher in the usual care group. Estimated medical costs during 3 months before dialysis till dialysis initiation, the MDC group yielded a reduction of NT$ 59,251 for each patient (P < 0.001). Patient mortality was not significantly different. CONCLUSION: Multidisciplinary care intervention for pre-ESRD patients could not only significantly improve the quality of disease care and clinical outcome, but also reduce medical costs.

Efficacy and Safety of Acupuncture for Restless Legs Syndrome in Patients with End-Stage Renal Disease: A Randomized-Controlled Trial at Hospital-Based Hemodialysis Center.

Background: Restless legs syndrome (RLS) is frequent in patients with hemodialysis (HD) and occurs predominantly in its most severe forms. The study was conducted to evaluate the efficacy and safety of acupuncture for RLS in patients with end-stage renal disease (ESRD) at hospital-based HD center. Methods: This single-blind, randomized controlled trial was performed on patients with HD and RLS who were randomly assigned to the experimental group and control group. Data were collected using the International Restless Legs Syndrome Rating Scale (IRLSRS), Insomnia Severity Index (ISI), and heart rate variability (HRV) records at baseline, after the therapeutic course (12 times/4 weeks), and 1-week follow-up. Result: A total of 47 patients were evaluated with IRLSRS score from 11 to 30 in this study. There were 41 patients enrolled in the study based on inclusion/exclusion criteria and allocated randomly into two groups. A total of 35 participants completed the trial, including 18 subjects in the experimental group and 17 subjects in the control group. The comparison of IRLSRS and ISI showed a significant reduction between two groups after acupuncture treatment (p = 0.002, p = 0.003). The ISI after 1-week follow-up also revealed significant decrease (p = 0.003). This HRV results showed that high frequency (HF%) increased significantly (p = 0.021) and low frequency (LF%) decreased significantly in the acupuncture group (p = 0.021). The generalized estimating equation showed that the IRLSRS improved by 2.902 points (p < 0.001) in the acupuncture group compared with the control group and by 1.340 points (p = 0.003) after 1-week follow-up. There were no adverse effects observed during HD in this study. Discussion: The authors conclude that acupuncture could effectively improve the symptoms of RLS significantly. The results from this study provide clinical evidence on the efficacy and safety of acupuncture to treat the patients with RLS at the HD center.

Effectiveness of multidisciplinary care for chronic kidney disease in Taiwan: a 3-year prospective cohort study.

BACKGROUND: Previous studies have demonstrated that multidisciplinary pre-dialysis education and team care may slow the decline in renal function for chronic kidney disease (CKD). Our study compared clinical outcomes of CKD patients between multidisciplinary care (MDC) and usual care in Taiwan. METHODS: In this 3-year prospective cohort study from 2008 to 2010, we recruited 1056 CKD subjects, aged 20-80 years, from five hospitals, who received either MDC or usual care, had an estimated glomerular filtration rate (eGFR) <60 mL/min, were matched one to one with the propensity score including gender, age, eGFR and co-morbidity diseases. The MDC team was under-cared based on NKF K/DOQI clinical practice guidelines and the Taiwanese pre-end-stage renal disease (ESRD) care program. The incidence of progression to ESRD (initiation of dialysis) and mortality was compared between two groups. We also monitored blood pressure control, the rate of renal function decline, lipid profile, hematocrit and mineral bone disease control. RESULTS: Participants were prone to be male (64.8%) with a mean age of 65.1 years and 33.1 months of mean follow-up. The MDC group had higher prescription rates of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB), phosphate binder, vitamin D3, uric acid lower agents and erythropoietin-stimulating therapy and better control in secondary hyperparathyroidism. The decline of renal function in advanced stage CKD IV and V was also slower in the MDC group (-5.1 versus -7.3 mL/min, P = 0.01). The use of temporary dialysis catheter was higher in the usual care group, and CKD patients under MDC intervention exhibited a greater willingness to choose peritoneal dialysis modality. A Cox regression revealed that the MDC group was associated with a 40% reduction in the risk of hospitalization due to infection, and a 51% reduction in patient mortality, but a 68% increase in the risk of initiation dialysis when compared with the usual care group. CONCLUSIONS: MDC patients were found to have more effective medication prescription according to K/DOQI guidelines and slower renal function declines in advanced/late-stage CKD. After MDC intervention, CKD patients had a better survival rate and were more likely to initiate renal replacement therapy (RRT) instead of mortality.

Serum globulin is a novel predictor of mortality in patients undergoing peritoneal dialysis.

Serum globulin, which is composed mainly of immunoglobulins and acute phase proteins, can be considered as reflecting the inflammatory state. We conducted the present study to investigate the role of globulin in mortality risk in patients undergoing peritoneal dialysis (PD). The study participants were categorized by the median globulin value (2.8 g/dL) as the high globulin group (≥ 2.8 g/dL), and low globulin group (< 2.8 g/dL). Serum globulin is calculated by the equation: (serum total protein-serum albumin). The area under the curve (AUC) by the receiver operating characteristics curve analysis was calculated to compare the mortality prediction capacity of globulin with that of ferritin, and WBC counts. Among the 554 patients, 265 (47.83%) were men, the mean age was 52.91 ± 15.54 years and the body mass index was 23.44 ± 3.88 kg/m2. Multivariate Cox models showed the high globulin group had higher mortality risks of all-cause and cardiovascular disease (CVD), compared with the low globulin group with adjusted HRs of 2.06 (95% CI 1.39-3.05) and 1.94 (95% CI 1.18-3.16), respectively. The AUC of univariate and multivariate models for all-cause mortality resulted in higher AUC values for globulin than for ferritin and white blood cell (WBC) counts. In patients undergoing PD, the serum globulin can serve as a novel and independent determinant of predicting overall and CVD- associated mortality.

Can chronic kidney disease staging early predict outcome of large-artery ischemic stroke with impaired renal function?

Background: Ischemic stroke poses a major threat to human beings, and a prompt intravenous thrombolytic management remains the gold standard protocol for stroke sufferers. Although the role of thrombolytic therapy (r-tPA) for ischemic stroke patients and those with underlying impaired renal function has been advocated as effective treating strategy, there is still a lack of investigation as to finding out baseline important variables that are capable of early outcome prediction. Objectives: In this project, we hypothesize that the change of clinical chronic kidney disease (CKD) staging (delta stage = CKD stage after 3-month follow-up - CKD stage at admission) could serve as a crucial predictor of the prognosis of patients. Design: This is a cohort longitudinal retrospective study. Sources and Methods: A total of 765 cerebral artery ischemic stroke patients with impaired renal function were recruited and followed up for 1 year. Among them, 116 had received the thrombolytic treatment (r-tPA) after being evaluated at the triage in the emergency department and the rest had not (non-r-tPA). Propensity-matching was applied to compare the mortality between the r-tPA and non-r-tPA groups. Multiple logistic regression (LR) and decision tree (DT) algorithm were used to identify important prediction factors for mortality as well as the improvement in neurological function. Results: The 1-year mortality rates for r-tPA and non-r-tPA groups were 32.8% and 44.4%, respectively. The propensity-matched odds ratio of mortality for the r-tPA group compared with the non-r-tPA group is 0.469, with p = 0.003. Logistic regressions suggest that age, Hct, diabetes mellitus type 2, coronary artery disease, and delta stage are important factors for mortality for the non-r-tPA group, whereas age, diabetes mellitus type 2, chronic heart failure, hospital day, and delta stage are important factors for the r-tPA group. On the usage of antihypertensive drugs, ACEI/ARB was not associated with mortality (p = 0.198), whereas the diuretic was, with odds ratio at 1.619 (p = 0.025), indicating higher mortality after administration. Both LR and DT analyses indicate that delta stage is the most important predictor. For the r-tPA group, patients with delta stage ⩽0 had a 24% mortality, while that for delta stage >0 the mortality is 75%. For non-r-tPA patients, the corresponding mortalities were 30.9 and 66.3, respectively. Delta stage is also useful for predicting patients' improvement of neurological function, assessed by NIHSS, mRS, and Barthel Index. The areas under the curve for the three assessments are 0.83, 0.835, and 0.663, respectively. Conclusion: Large-artery ischemic stroke patients who received thrombolytic treatment had significantly lower mortality, even when presenting underlying impaired renal function. The change of CKD staging (delta stage) is capable of acting as a powerful clinical baseline surrogate for both r-tPA and non-r-tPA patients in terms of early outcome prediction. Long-term use of diuretics could be potentially harmful to this group of patients. Moreover, delta stage correlates well with clinical long-term neurological functionality assessment (NIHSS, mRS, and Barthel index), which is helpful in aiding urgent clinical decision-making.

Vitamin C affects the expression of hepcidin and erythropoietin receptor in HepG2 cells.

BACKGROUNDS: Hepcidin modulates the de novo absorption of iron from the duodenum and the recycling of iron released from the reticuloendothelial system. In patients with chronic renal failure, administration of higher doses of erythropoietin (EPO) or vitamin C (Vit C) can correct the functional iron deficiency. While EPO-regulated hepcidin expression within hepatocytes has been recently identified, the relation between vitamin C with hepcidin expression is still uncertain. METHODS: Hepcidin-producing HepG2 cells (a human liver carcinoma cell line) were cultured with 50- to 100-µg/mL vitamin C or 0.25- to 1.0-U/mL EPO for 6 hours. Reverse transcription polymerase chain reaction was performed for quantitative measurements of hepcidin, EPO, and EPO receptor (EPOR) expression. RESULTS: EPO and vitamin C inhibited hepcidin expression within HepG2 cells; the EPO effect was dose dependent. EPO downregulated EPOR and vitamin C and upregulated EPOR. However, vitamin C had little effect on the expression of EPO. CONCLUSIONS: EPO is capable of downregulating EPOR when it acts early. Vitamin C directly inhibits hepcidin expression within HepG2 cells. Moreover, by enhancing EPOR production, vitamin C may correct the downregulating EPOR from EPO, which has additional effect with EPO in treating anemia.

Association of Albumin and Globulin with Mortality Risk in Incident Peritoneal Dialysis Patients.

Background: Nutrition and inflammation have been implicated in predicting mortality in patients on peritoneal dialysis (PD). Serum albumin and globulin can be regarded for the nutritional and inflammatory status. However, there is lack of data to evaluate the synergistic effect of albumin and globulin on mortality prediction. Methods: In 554 patients initiating PD from January 2001 to July 2016, we divided them into four groups by the combination of two categories of low vs. high albumin and low vs. high globulin. The median values for albumin and globulin were chosen to classify them into low or high groups. Their associations with all-cause and cardiovascular (CV) mortality were examined in Cox regression models adjusted for confounding clinical and laboratory data. Results: Patients, 52.91 ± 15.2 years old and 47.8% men, had a median (interquartile range) value of 3.3 (2.9−3.8) g/dL for albumin and 2.8 (2.5−3.2) g/dL for globulin, respectively. Patients with low albumin and high globulin had the highest all-cause mortality and CV mortality, with adjusted hazard ratios of 3.87 (95% CI 1.83−8.20, p < 0.001) and 5.65 (95% CI 2.23−14.34, p < 0.001), respectively, compared with those with a high albumin and low globulin having the lowest mortality rate. Sensitivity analyses further confirmed this relationship. Conclusions: A patient profile of either low albumin or high globulin is linked to a higher risk for mortality, particularly for a profile of both low albumin and high globulin compared with one without either of them. Further studies are needed to explore the mechanisms underlying this phenomenon and how to improve clinical outcomes in those high-risk patients.