Randomized Trial on the Effect of an Oral Spleen Tyrosine Kinase Inhibitor in the Treatment of IgA Nephropathy.

Introduction: We reported increased spleen tyrosine kinase (SYK) expression in kidney biopsies of patients with IgA nephropathy (IgAN) and that inhibition of SYK reduces inflammatory cytokines production from IgA stimulated mesangial cells. Methods: This study was a double-blind, randomized, placebo-controlled phase 2 trial of fostamatinib (an oral SYK inhibitor) in 76 patients with IgAN. Patients were randomized to receive placebo, fostamatinib at 100 mg or 150 mg twice daily for 24 weeks on top of maximum tolerated dose of renin-angiotensin system inhibitors. The primary end point was reduction of proteinuria. Secondary end points included change from baseline in estimated glomerular filtration rate (eGFR) and kidney histology. Results: Although we could not detect significant reduction in proteinuria with fostamatinib overall, in a predetermined subgroup analysis, there was a trend for dose-dependent reduction in median proteinuria (from baseline to 24 weeks by 14%, 27%, and 36% in the placebo, fostamatinib 100 mg, and 150 mg groups, respectively) in patients with baseline urinary protein-to-creatinine ratios (UPCR) more than 1000 mg/g. Kidney function (eGFR) remained stable in all groups. Fostamatinib was well-tolerated. Side effects included diarrhea, hypertension, and increased liver enzymes. Thirty-nine patients underwent repeat biopsy showing reductions in SYK staining associated with therapy at low dose (-1.5 vs. 1.7 SYK+ cells/glomerulus in the placebo group, P < 0.05). Conclusions: There was a trend toward reduction in proteinuria with fostamatinib in a predefined analysis of high risk patients with IgAN despite maximal care, as defined by baseline UPCR greater than 1000 mg/g. Further study may be warranted.

Immune responses and safety of COVID-19 vaccination in atypical hemolytic uremic syndrome patients in Taiwan.

Atypical hemolytic uremic syndrome is a rare, life-threatening disorder which can be triggered by COVID 19 infection and COVID 19 vaccination then induce multiple organ failure. Our study is the first to evaluate immune responses to COVID-19 vaccination and safety in a cohort of patients in a local single-center study in Taiwan.. Results indicate that vaccines effectively shield aHUS patients from severe COVID-19 complications without significant safety concerns. A double booster dose for the third vaccine is essential for optimal efficacy. Anti-complement therapy did not influence vaccination effectiveness. Transplant aHUS patients had the lowest immune response titers, indicating a need for additional vaccine doses. Compared to healthcare workers, aHUS patients had poor T-cell responses. We noted a superior trend with mixed-type COVID-19 vaccinations in aHUS patients, while fixed-type mRNA demonstrated better results in healthcare workers. Our findings endorse COVID-19 vaccination as a potent strategy to safeguard aHUS patients from severe complications, emphasizing the importance of vigilant monitoring pre- and post-vaccination.

Dysregulation of Immune Cell Subpopulations in Atypical Hemolytic Uremic Syndrome.

Atypical hemolytic uremic syndrome (aHUS) is a rare, life-threatening thrombotic microangiopathy. Definitive biomarkers for disease diagnosis and activity remain elusive, making the exploration of molecular markers paramount. We conducted single-cell sequencing on peripheral blood mononuclear cells from 13 aHUS patients, 3 unaffected family members of aHUS patients, and 4 healthy controls. We identified 32 distinct subpopulations encompassing 5 B-cell types, 16 T- and natural killer (NK) cell types, 7 monocyte types, and 4 other cell types. Notably, we observed a significant increase in intermediate monocytes in unstable aHUS patients. Subclustering analysis revealed seven elevated expression genes, including NEAT1, MT-ATP6, MT-CYB, VIM, ACTG1, RPL13, and KLRB1, in unstable aHUS patients, and four heightened expression genes, including RPS27, RPS4X, RPL23, and GZMH genes, in stable aHUS patients. Additionally, an increase in the expression of mitochondria-related genes suggested a potential influence of cell metabolism on the clinical progression of the disease. Pseudotime trajectory analysis revealed a unique immune cell differentiation pattern, while cell-cell interaction profiling highlighted distinctive signaling pathways among patients, family members, and controls. This single-cell sequencing study is the first to confirm immune cell dysregulation in aHUS pathogenesis, offering valuable insights into molecular mechanisms and potential new diagnostic and disease activity markers.

Atypical hemolytic uremic syndrome: Consensus of diagnosis and treatment in Taiwan.

Atypical hemolytic uremic syndrome (aHUS), characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury, is a rare but life-threatening systemic disorder caused by the dysregulation of the complement pathway. Current advances in molecular analysis and pathogenesis have facilitated the establishment of diagnosis and development of effective complement blockade. Based on this recent consensus, we provide suggestions regarding the diagnosis and management of aHUS in Taiwan. The diagnosis of aHUS is made by the presence of TMA with normal ADAMTS13 activity without known secondary causes. Although only 60% of patients with aHUS have mutations in genes involving the compliment and coagulation systems, molecular analysis is suggestive for helping establish diagnosis, clarifying the underlying pathophysiology, guiding the treatment decision-making, predicting the prognosis, and deciding renal transplantation. Complement blockade, anti-C5 monoclonal antibody, is the first-line therapy for patients with aHUS. Plasma therapy should be considered for removing autoantibody in patients with atypical HUS caused by anti-CFH or complement inhibitor is unavailable.

Peritoneal effluent MicroRNA profile for detection of encapsulating peritoneal sclerosis.

BACKGROUND: Encapsulating peritoneal sclerosis (EPS) is a catastrophic complication of peritoneal dialysis (PD) with high mortality. Our aim is to develop a novel noninvasive microRNA (miRNA) test for EPS. METHODS: We collected 142 PD effluents (EPS: 62 and non-EPS:80). MiRNA profiles of PD effluents were examined by a high-throughput real-time polymerase chain reaction (PCR) array to first screen. Candidate miRNAs were verified by single real-time PCR. The model for EPS prediction was evaluated by multiple logistic regression and machine learning. RESULTS: Seven candidate miRNAs were identified from the screening of PCR-array of 377 miRNAs. The top five area under the curve (AUC) values with 5 miRNA-ratios were selected using 127 samples (EPS: 56 vs non-EPS: 71) to produce a receiver operating characteristic curve. After considering clinical characteristics and 5 miRNA-ratios, the accuracies of the machine learning model of Random Forest and multiple logistic regression were boosted to AUC 0.97 and 0.99, respectively. Furthermore, the pathway analysis of miRNA associated targeting genes and miRNA-compound interaction network revealed that these five miRNAs played the roles in TGF-ß signaling pathway. CONCLUSION: The model-based miRNA expressions in PD effluents may help determine the probability of EPS and provide further therapeutic opinion for EPS.

The MicroRNA Prediction Models as Ancillary Diagnosis Biomarkers for Urothelial Carcinoma in Patients With Chronic Kidney Disease.

Urothelial carcinoma is a common urological cancer in chronic kidney disease patients. Cystoscopy and urine cytology are the clinical diagnostic tools for UC. However, cystoscopy is an invasive procedure, while urine cytology showed low sensitivity for low-grade urothelial tumors. High accuracy with non-invasive tools for UC is needed for CKD patients. Our study collected a total of 272 urine and 138 plasma samples to detect the miRNA expression levels for establishing UC signatures from CKD patients. Seventeen candidate miRNAs of biofluids were selected and confirmed by qRT-PCR. Our results showed that urinary miR-1274a and miR-30a-5p expression levels were significantly lower but miR-19a-5p expression levels were higher in UC when compared with CKD. In plasma samples, miR-155-5p, miR-19b-1-5p, miR-378, and miR-636 showed significantly lower expression in UC compared to those with CKD. The Kaplan-Meier curve showed that lower expression of miR-19a, miR-19b, miR-636 and miR-378, and higher expression of miR-708-5p were associated with poor prognosis in patients with bladder cancer. In addition, we produced classifiers for predicting UC by multiple logistic regression. The urine signature was developed with four miRNAs, and the AUC was 0.8211. Eight miRNA expression levels from both urine and plasma samples were examined, and the AUC was 0.8595. Two miRNA classifiers and the nomograms could improve the drawbacks of current UC biomarker screenings for patients with CKD.

The Risk of Tuberculosis Infection in Non-dialysis Chronic Kidney Disease Patients.

Background: Patients with chronic kidney disease (CKD) receiving maintenance renal replacement therapy are at higher risk of tuberculosis (TB) infection. The risk of TB infection in CKD patients not receiving dialysis is unknown. Aim: We conduct this study to test the hypothesis that TB infection is negatively correlated to renal function. Design: Non-dialysis CKD stage 1-5 patients, admitted in China Medical University Hospital from January of 2003 to May of 2014, were enrolled in this study and were prospectively followed up to the diagnosis of TB, death, loss to follow-up, or December 2014. The risk factors of TB infection were analyzed using competing-risks regression analysis with time-varying covariates. The initiation of dialysis and patients' death were considered as competing events. Patients' estimated glomerular filtration rate (eGFR) and body mass index (BMI) were recorded at enrollment. Results: They were followed-up for a median duration of 1.4 years. Of the 7221 patients, TB infection was identified in 114 patients. Higher eGFR was associated with lower risk of TB infection (P < 0.01). The adjusted subdistribution hazard ratio (aSHR) was 0.82 [95% confidence interval (CI), 0.72 to 0.94] for every 5 ml/min/1.73 m2 increase in eGFR. In addition, higher BMI (p = 0.01) was associated with a lower risk of TB infection and the aSHR was 0.91 (95% CI, 0.85 to 0.98) for every 1 kg/m2 increase in BMI. Conclusion: Renal function and body mass index are independently associated with the risk of tuberculosis infection in patients with chronic kidney disease not receiving dialysis.

Effect of Whole-Body Vibration Training on Physical Fitness and Postural Control in Working-Age Patients on Haemodialysis.

OBJECTIVE: To evaluate the effect of whole-body vibration training on working-age people on haemodialysis. DESIGN: Consecutive case series study. SUBJECTS: Seventeen working-age participants on maintenance haemodialysis were enrolled. METHODS: A 12-week whole-body vibration training programme, including different postures, was designed. The study evaluated and compared physical fitness, including a list of tests such as the 5-repetition sit-to-stand test, hand grip test, 2-min step test, and 8-foot up-and-go test; modified Berg balance scale; static and dynamic balance function; and quality of life, using a quality of life questionnaire before and after the training. RESULTS: All physical fitness parameters, except grip strength on the left side, improved after whole-body vibration training. For balance, the modified Berg balance scale demonstrated enhanced scores for equilibrium, with eyes closed on a stable surface and eyes open on an unstable surface, and movement velocity under the fast condition along the left and right directions (p=0.011). No significant improvements in quality of life were found. CONCLUSION: Whole-body vibration exercise training enhanced physical fitness and static and dynamic balance control in working-age participants on haemodialysis.

Discovery of Novel Protein Biomarkers in Urine for Diagnosis of Urothelial Cancer Using iTRAQ Proteomics.

Urothelial carcinoma (UC) is the ninth most prevalent malignancy worldwide. Noninvasive and efficient biomarkers with high accuracy are imperative for the surveillance and diagnosis of UC. CKD patients were enrolled as a control group in this study for the discovery of highly specific urinary protein markers of UC. An iTRAQ-labeled quantitative proteomic approach was used to discover novel potential markers. These markers were further validated with 501 samples by ELISA assay, and their diagnostic accuracies were compared to those of other reported UC markers. BRDT, CYBP, GARS, and HDGF were identified as novel urinary UC biomarkers with a high discrimination ability in a population comprising CKD and healthy subjects. The diagnostic values of the four novel UC markers were better than that of a panel of well-known or FDA-approved urinary protein markers CYFR21.1, Midkine, and NUMA1. Three of our discovered markers (BRDT, HDGF, GARS) and one well-known marker (CYFR21.1) were finally selected and combined as a marker panel having AUC values of 0.962 (95% CI, 0.94-0.98) and 0.860 (95% CI, 0.83-0.89) for the discrimination between UC and normal groups and UC and control (healthy + CKD) groups, respectively.

A Matrix Metalloproteinase-2-Based Nomogram to Assess the Risk of Encapsulating Peritoneal Sclerosis in Peritoneal Dialysis Patients.

BACKGROUND: Encapsulating peritoneal sclerosis (EPS) is a rare but serious complication of peritoneal dialysis (PD). So far, there is no biomarker-based prediction tool available for EPS. Matrix metalloproteinase-2 (MMP-2) is a protein involved in the breakdown of the extracellular matrix, and the effluent MMP-2 can be a potential biomarker of EPS. This study is aimed at developing a nomogram for EPS based on effluent MMP-2 levels. Patients and Methods. We enrolled 18 EPS patients and 90 gender-matched PD patients without EPS in this cross-sectional case-controlled study. The effluent MMP-2 levels and possible risk factors for EPS were analyzed using multivariable logistic regression, and a nomogram was developed. The nomogram was validated using 200 bootstrap resamples to reduce overfit bias. RESULTS: The effluent MMP-2 levels in EPS patients were significantly higher than those in normal PD patients (p < 0.001, Manny-Whitney U test). Effluent MMP-2 levels and PD duration were independently associated with EPS risks (p < 0.001 and p = 0.001) in multivariate logistic regression. A nomogram based on MMP-2 levels and PD duration was proposed. The AUC of MMP-2 was 0.824, and the AUC of the nomogram was 0.907 (p = 0.05). CONCLUSION: A nomogram based on effluent MMP-2 levels and PD duration may predict EPS with high accuracy.

Urine phthalate metabolites are associated with urothelial cancer in chronic kidney disease patients.

BACKGROUND: Di(2-ethylhexyl) phthalate (DEHP) is one of the most widely used phthalates and is associated with breast cancer. Ths association between DEHP and other types of cancer is not clear. DEHP may increase matrix metalloproteinase-9 that is critical for the development of urothelial cancer (UC). We examined the association between urinary phthalate metabolites and UC. CKD patients were selected as a control group because CKD patients are more at risk of UC than the general population. METHODS: In this cross-sectional study, we measured seven urinary phthalate metabolites that are abundant and can be measured using HPLC-MS/MS in Taiwan CKD patients between Jul 2013 and Dec 2015. MiBP (a urinary metabolite of Dibutyl phthalates[DBP]) and MEHHP (a urinary metabolite of DEHP) were described because they are the most abundant phthalate metabolites. The association of phthalate (log-transformed) and UC were analyzed using logistic regression with adjustments for age, gender, renal function, use of traditional Chinese medicine, toxins (dye, organic solvent), and non-steroidal anti-inflammatory drugs. RESULTS: We measured the urinary MEHHP and MiBP of 496 patients (224 UC and 272 CKD patients). The urinary MEHHP was associated with UC but MiBP was not. Medical history including the use of non-steroid anti-inflammatory drugs, exposure to environmental toxins (dye, paint, and organic solvent), and the use of traditional Chinese medicine was independently associated with UC. The adjusted odds ratio of MEHHP was 1.42 (95% confidence interval: 1.21-1.68). CONCLUSION: Phthalate urinary metabolite(MEHHP) may be associated with UC in CKD patients and the association is independent of well-known risk factors of UC.

Association between regional economic status and renal recovery of dialysis-requiring acute kidney injury among critically ill patients.

The association between regional economic status and the probability of renal recovery among patients with dialysis-requiring AKI (AKI-D) is unknown. The nationwide prospective multicenter study enrolled critically ill adult patients with AKI-D in four sampled months (October 2014, along with January, April, and July 2015) in Taiwan. The regional economic status was defined by annual disposable income per capita (ADIPC) of the cities the hospitals located. Among the 1,322 enrolled patients (67.1 ± 15.5 years, 36.2% female), 833 patients (63.1%) died, and 306 (23.1%) experienced renal recovery within 90 days following discharge. We categorized all patients into high (n = 992) and low economic status groups (n = 330) by the best cut-point of ADIPC determined by the generalized additive model plot. By using the Fine and Gray competing risk regression model with mortality as a competing risk factor, we found that the independent association between regional economic status and renal recovery persisted from model 1 (no adjustment), model 2 (adjustment to basic variables), to model 3 (adjustment to basic and clinical variables; subdistribution hazard ratio, 1.422; 95% confidence interval, 1.022-1.977; p = 0.037). In conclusion, high regional economic status was an independent factor for renal recovery among critically ill patients with AKI-D.

2018 Kidney Disease: Improving Global Outcomes (KDIGO) Hepatitis C in Chronic Kidney Disease Guideline Implementation: Asia Summit Conference Report.

In 2018, Kidney Disease: Improving Global Outcomes (KDIGO) published a clinical practice guideline on the prevention, diagnosis, evaluation, and treatment of hepatitis C virus (HCV) infection in chronic kidney disease (CKD). The guideline synthesized recent advances, especially in HCV therapeutics and diagnostics, and provided clinical recommendations and suggestions to aid healthcare providers and improve care for CKD patients with HCV. To gain insight into the extent that the 2018 guideline has been adopted in Asia, KDIGO convened an HCV Implementation Summit in Hong Kong. Participants included nephrologists, hepatologists, and nurse consultants from 8 Southeast Asian countries or regions with comparable high-to-middle economic ranking by the World Bank: mainland China, Hong Kong, Japan, Malaysia, Singapore, South Korea, Taiwan, and Thailand. Through presentations and discussions, meeting participants described regional practice patterns related to the KDIGO HCV in CKD guideline, identified barriers to implementing the guideline, and developed strategies for overcoming the barriers in Asia and around the world.

A comparison of quality of life between patients treated with different dialysis modalities in Taiwan.

PURPOSE: This study compared the quality of life (QOL) of hemodialysis (HD) and peritoneal dialysis (PD) patients in Taiwan. METHODS: This cross-sectional study recruited end-stage renal disease patients from 34 Taiwanese hospitals or clinics. Patient characteristics, diagnoses, and laboratory data were extracted from charts. The Chinese version of the Quality of Life Index-Dialysis version (QLI-D) was used. Multiple linear regression analysis showed the effects of dialysis modality on QOL. P<0.05 indicated statistical significance. RESULTS: In total, 600 HD and 387 PD patients were included. The mean health and functioning, social and economic, psychological/spiritual, and family subscale scores and total QOL scores were significantly lower in HD patients than PD patients. After adjusting for region, hospital level, age, education level, marital status, and Karnofsky Performance Scale, the total QOL was 2.81 points higher for PD patients than for HD patients visiting medical centers (p<0.001). The total QOL was 2.53 points lower in PD patients than in HD patients for those visiting clinics. CONCLUSION: Compared to HD patients, PD patients had better QOL in Taiwanese medical centers. The current survey improves our understanding of the QOL of patients undergoing different dialysis modalities in Taiwan.

Plasma miRNA profile is a biomarker associated with urothelial carcinoma in chronic hemodialysis patients.

The incidence of urothelial carcinoma (UC) is higher in patients undergoing chronic dialysis than in the general population. This study investigated plasma miRNA profiling as the ancillary diagnosis biomarker associated with UC in patients undergoing chronic hemodialysis. We successfully screened out and detected miRNA expression from plasma in eight patients undergoing dialysis through quantitative real-time PCR array analysis and identified eight candidate miRNAs. The candidate miRNAs were then validated using single quantitative RT-PCR assays from 52 plasma samples. The miRNA classifier for ancillary UC detection was developed by multiple logistic regression analyses. Moreover, we validated the classifier by testing another nine samples. Expression levels of miR-150-5p, miR-150-5p/miR-155-5p, miR-378a-3p/miR-150-5p, miR-636/miR-150-5p, miR-150-5p/miR-210-3p, and miR-19b-1-5p/miR-378a-3p were shown to be significantly different between UC and non-UC samples (P = 0.035, 0.0048, 0.016, 0.024, 0.038, and 0.048). Kaplan-Meier curve analysis also showed that low miR-19b-1-5p expression was associated with a worse prognosis (P = 0.0382). We also developed a miRNA classifier based on five miRNA expression levels to predict UC and found that the area under curve was 0.882. The classifier had a sensitivity of 80% (95% confidence interval: 0.5191% to 0.9567%) and a specificity of 83.7% (95% confidence interval: 0.6799% to 0.9381%). This classifier was tested by nine samples with 100% accuracy. The miRNA classifier offers higher sensitivity and specificity than the existing makers. Thus, this approach will improve the prospective diagnosis of UC in patients undergoing chronic hemodialysis.

Development and validation of a nomogram for urothelial cancer in patients with chronic kidney disease.

Urothelial cancer (UC) is a common kidney cancer in Taiwan and patients with chronic kidney disease (CKD) are more at risk for UC than the general population. The diagnostic value of urine analysis and urine cytology is limited, especially in CKD patients. The aim of the study is to develop a nomogram to predict the risk of UC in CKD patients. We enrolled 169 UC patients and 1383 CKD patients from 9 hospitals in Taiwan between 2012 and 2015. CA125, HE4, clinical characteristics, and medical history were analyzed using multivariable logistic regression for its association with UC. A nomogram was developed to predict the risk of UC and was validated using Bootstrap. CA125 was associated with UC in CKD patients (OR: 5.91, 95% CI: 3.24-10.77) but HE4 was not (OR: 1.29, 95% CI: 0.67-2.35). A nomogram based on patients' age, estimated glomerular filtration rate, CA125 (log transformed), smoking, exposure of environmental toxin, use of nonsteroid anti-inflammatory drugs, and use of traditional Chinese medicine was conducted. The AUC of the nomogram was 0.90 (95% CI: 0.86-0.92, p < 0.01). Serum CA125 may identify UC patients from CKD patients but has limited diagnostic value due to low sensitivity. The diagnostic value of serum CA125 level can be improved by the combination with clinical characteristics including age, renal function, and medical history.

Maximum Glomerular Filtration Decline Rate is Associated with Mortality and Poor Renal Outcome in Chronic Kidney Disease Patients.

BACKGROUND: Glomerular filtrate rate (GFR) decline is associated with increased risk of dialysis in patients with chronic kidney disease (CKD). It is unclear whether the maximum, the minimum, or the average of GFR decline rate is associated with the risk of mortality and the initiation of renal replacement therapy (RRT). We investigated prognostic role of the maximum, the minimum, and the average of GFR decline rate in patients with CKD not yet on dialysis. METHODS: Patients, enrolled in the CKD program of China Medical University Hospital between July 2004 and Aug 2013, with CKD stages 3-5 (estimated GFR [eGFR] < 60 mL/min/1.73 m2) not yet on dialysis were analyzed. Primary outcome was a composite of mortality and RRT. The association between 3 readings of GFR decline rate and primary outcome was analyzed using Cox proportional hazard regression. RESULTS: We analyzed 815 patients aged 75 (interquartile range [IQR] 65-82) years with a median follow-up of 5.2 years (IQR 3.9-6.9). The maximum of eGFR decline rate was associated with the primary outcome (hazard ratio 2.19, 95% CI 1.16-4.12, p = 0.015), independent of age, gender, diabetes, cerebrovascular accident, smoking, baseline eGFR, serum albumin, calcium, urine protein/creatinine ratio, usage of renin-angiotensin system blockade. The minimum and the average of eGFR decline rate were not associated with the primary outcome. CONCLUSIONS: The maximum of GFR decline rate was associated with mortality and poor renal outcome in CKD patients, independent of other contributive confounders.

Abdominal aortic calcification score predicts the occurrence of coronary artery disease in middle-aged peritoneal dialysis patients.

AIM: Abdominal aortic calcification (AAC) score in dialysis patients was associated with coronary artery disease (CAD) in cross-sectional study, but the use of AAC score in the CAD prediction was not clear. We aimed to use AAC score in the estimation of CAD occurrence in middle-aged peritoneal dialysis (PD) patients. METHODS: Middle-aged (45-65 years old) PD patients were recruited and followed up until CAD occurrence, patient mortality, or PD failure. We quantified AAC score by lateral lumbar radiography, and used receiver operation curve (ROC) analysis to find the cut-off value for CAD prediction. RESULTS: There were 187 patients recruited for study with a mean follow-up of 1027 ± 427 days. AAC score in patients with CAD during follow-up period (9.7 ± 7.6, n = 41) was higher than in patients without CAD occurrence (5.5 ± 6.1, n = 146) (P < 0.001). Multivariate hazard ratio of AAC score for CAD was 1.07 (P = 0.044). ROC showed that AAC score of 5.5 had a sensitivity of 0.667 and a specificity of 0.581 in the prediction of CAD occurrence. Patients with AAC score above 5.5 had significantly higher cumulative incidence of CAD than patients with AAC score below 5.5 (Log-rank test, P = 0.003). Age (P = 0.002), diabetes (P = 0.002), hypertension (P = 0.032), longer dialysis vintage (P < 0.001) and lower serum potassium (P = 0.012) were parameters significantly associated with higher AAC score. CONCLUSION: AAC score can predict CAD occurrence in PD patients. Age, diabetes, hypertension, dialysis vintage and serum potassium level are factors associated with higher AAC score.

Abdominal aortic calcification score can predict future coronary artery disease in hemodialysis patients: a 5-year prospective cohort study.

BACKGROUND: Abdominal aortic calcification (AAC) has been known to be associated with cardiovascular mortality in hemodialysis. However, the association between AAC and future coronary artery disease (CAD) occurrence is not clear. We aimed to clarify the association of AAC severity and the occurrence of future CAD events in hemodialysis patients. METHODS: Hemodialysis (HD) patients were recruited in this prospective cohort study. AAC severity was quantified by AAC score, which was measured by lateral lumbar radiography. We used receiver operation curve (ROC) analysis to find the cutoff AAC value for CAD prediction. CAD-free survival was analyzed by Kaplan-Meier study. RESULTS: There were 303 patients recruited for study with a median (interquartile range) follow-up of 95 (65-146) months. The AAC score in patients with occurrence of new CAD [9 (3-15.25), n = 114] was higher than in patients without new CAD occurrence [5 (1-9) n = 189], p < 0.001. Multivariate hazard ratio of AAC score for CAD was 1.039 (p = 0.016). ROC study showed that an AAC score of 5.5 had a sensitivity of 0.658 and a specificity of 0.587 in the prediction of new CAD occurrence. Patients with AAC score above 5.5 had significantly higher cumulative incidence of CAD than patients with AAC score below 5.5. Age, diabetes, prior history of CAD, and longer dialysis vintage were major factors associated with higher AAC score. CONCLUSIONS: AAC score can predict the occurrence of future CAD events in HD patients. The best cut-off value of AAC score is 5.5. AAC score greater than 5.5 is a reliable abdominal aortic calcification marker, and can predict future CAD in ESRD patients. Major contributive factors for higher AAC score were age, presence of diabetes, prior history of CAD, and longer dialysis vintage.

Norepinephrine Administration Is Associated with Higher Mortality in Dialysis Requiring Acute Kidney Injury Patients with Septic Shock.

(1) Background: Norepinephrine (NE) is the first-line vasoactive agent used in septic shock patients; however, the effect of norepinephrine on dialysis-required septic acute kidney injury (AKI-D) patients is uncertain. (2) Methods: To evaluate the impact of NE on 90-day mortality and renal recovery in septic AKI-D patients, we enrolled patients in intensive care units from 30 hospitals in Taiwan. (3) Results: 372 patients were enrolled and were divided into norepinephrine users and non-users. After adjustment by Inverse probability of treatment weighted (IPTW), there was no significant difference of baseline comorbidities between the two groups. NE users had significantly higher 90-day mortality rate and using NE is a strong predictor of 90-day mortality in the multivariate Cox regression (HR = 1.497, p = 0.027) after adjustment. The generalized additive model disclosed norepinephrine alone exerted a dose⁻dependent effect on 90-day mortality, while other vasoactive agents were not. (4) Conclusion: Using norepinephrine in septic AKI-D patients is associated with higher 90-day mortality and the effect is dose-dependent. Further study to explore the potential mechanism is needed.