Distinct phenotypes of kidney transplant recipients aged 80 years or older in the USA by machine learning consensus clustering.

Objectives: This study aimed to identify distinct clusters of very elderly kidney transplant recipients aged ≥80 and assess clinical outcomes among these unique clusters. Design: Cohort study with machine learning (ML) consensus clustering approach. Setting and participants: All very elderly (age ≥80 at time of transplant) kidney transplant recipients in the Organ Procurement and Transplantation Network/United Network for Organ Sharing database database from 2010 to 2019. Main outcome measures: Distinct clusters of very elderly kidney transplant recipients and their post-transplant outcomes including death-censored graft failure, overall mortality and acute allograft rejection among the assigned clusters. Results: Consensus cluster analysis was performed in 419 very elderly kidney transplant and identified three distinct clusters that best represented the clinical characteristics of very elderly kidney transplant recipients. Recipients in cluster 1 received standard Kidney Donor Profile Index (KDPI) non-extended criteria donor (ECD) kidneys from deceased donors. Recipients in cluster 2 received kidneys from older, hypertensive ECD deceased donors with a KDPI score ≥85%. Kidneys for cluster 2 patients had longer cold ischaemia time and the highest use of machine perfusion. Recipients in clusters 1 and 2 were more likely to be on dialysis at the time of transplant (88.3%, 89.4%). Recipients in cluster 3 were more likely to be preemptive (39%) or had a dialysis duration less than 1 year (24%). These recipients received living donor kidney transplants. Cluster 3 had the most favourable post-transplant outcomes. Compared with cluster 3, cluster 1 had comparable survival but higher death-censored graft failure, while cluster 2 had lower patient survival, higher death-censored graft failure and more acute rejection. Conclusions: Our study used an unsupervised ML approach to cluster very elderly kidney transplant recipients into three clinically unique clusters with distinct post-transplant outcomes. These findings from an ML clustering approach provide additional understanding towards individualised medicine and opportunities to improve care for very elderly kidney transplant recipients.

Explainable Preoperative Automated Machine Learning Prediction Model for Cardiac Surgery-Associated Acute Kidney Injury.

BACKGROUND: We aimed to develop and validate an automated machine learning (autoML) prediction model for cardiac surgery-associated acute kidney injury (CSA-AKI). METHODS: Using 69 preoperative variables, we developed several models to predict post-operative AKI in adult patients undergoing cardiac surgery. Models included autoML and non-autoML types, including decision tree (DT), random forest (RF), extreme gradient boosting (XGBoost), and artificial neural network (ANN), as well as a logistic regression prediction model. We then compared model performance using area under the receiver operating characteristic curve (AUROC) and assessed model calibration using Brier score on the independent testing dataset. RESULTS: The incidence of CSA-AKI was 36%. Stacked ensemble autoML had the highest predictive performance among autoML models, and was chosen for comparison with other non-autoML and multivariable logistic regression models. The autoML had the highest AUROC (0.79), followed by RF (0.78), XGBoost (0.77), multivariable logistic regression (0.77), ANN (0.75), and DT (0.64). The autoML had comparable AUROC with RF and outperformed the other models. The autoML was well-calibrated. The Brier score for autoML, RF, DT, XGBoost, ANN, and multivariable logistic regression was 0.18, 0.18, 0.21, 0.19, 0.19, and 0.18, respectively. We applied SHAP and LIME algorithms to our autoML prediction model to extract an explanation of the variables that drive patient-specific predictions of CSA-AKI. CONCLUSION: We were able to present a preoperative autoML prediction model for CSA-AKI that provided high predictive performance that was comparable to RF and superior to other ML and multivariable logistic regression models. The novel approaches of the proposed explainable preoperative autoML prediction model for CSA-AKI may guide clinicians in advancing individualized medicine plans for patients under cardiac surgery.

Machine Learning Consensus Clustering Approach for Patients with Lactic Acidosis in Intensive Care Units.

BACKGROUND: Lactic acidosis is a heterogeneous condition with multiple underlying causes and associated outcomes. The use of multi-dimensional patient data to subtype lactic acidosis can personalize patient care. Machine learning consensus clustering may identify lactic acidosis subgroups with unique clinical profiles and outcomes. METHODS: We used the Medical Information Mart for Intensive Care III database to abstract electronic medical record data from patients admitted to intensive care units (ICU) in a tertiary care hospital in the United States. We included patients who developed lactic acidosis (defined as serum lactate ≥ 4 mmol/L) within 48 h of ICU admission. We performed consensus clustering analysis based on patient characteristics, comorbidities, vital signs, organ supports, and laboratory data to identify clinically distinct lactic acidosis subgroups. We calculated standardized mean differences to show key subgroup features. We compared outcomes among subgroups. RESULTS: We identified 1919 patients with lactic acidosis. The algorithm revealed three best unique lactic acidosis subgroups based on patient variables. Cluster 1 (n = 554) was characterized by old age, elective admission to cardiac surgery ICU, vasopressor use, mechanical ventilation use, and higher pH and serum bicarbonate. Cluster 2 (n = 815) was characterized by young age, admission to trauma/surgical ICU with higher blood pressure, lower comorbidity burden, lower severity index, and less vasopressor use. Cluster 3 (n = 550) was characterized by admission to medical ICU, history of liver disease and coagulopathy, acute kidney injury, lower blood pressure, higher comorbidity burden, higher severity index, higher serum lactate, and lower pH and serum bicarbonate. Cluster 3 had the worst outcomes, while cluster 1 had the most favorable outcomes in terms of persistent lactic acidosis and mortality. CONCLUSIONS: Consensus clustering analysis synthesized the pattern of clinical and laboratory data to reveal clinically distinct lactic acidosis subgroups with different outcomes.

Impact of Palliative Care Services on Treatment and Resource Utilization for Hepatorenal Syndrome in the United States.

Background: This study aimed to determine the rates of inpatient palliative care service use and assess the impact of palliative care service use on in-hospital treatments and resource utilization in hospital admissions for hepatorenal syndrome. Methods: Using the National Inpatient Sample, hospital admissions with a primary diagnosis of hepatorenal syndrome were identified from 2003 through 2014. The primary outcome of interest was the temporal trend and predictors of inpatient palliative care service use. Logistic and linear regression was performed to assess the impact of inpatient palliative care service on in-hospital treatments and resource use. Results: Of 5571 hospital admissions for hepatorenal syndrome, palliative care services were used in 748 (13.4%) admissions. There was an increasing trend in the rate of palliative care service use, from 3.3% in 2003 to 21.1% in 2014 (p < 0.001). Older age, more recent year of hospitalization, acute liver failure, alcoholic cirrhosis, and hepatocellular carcinoma were predictive of increased palliative care service use, whereas race other than Caucasian, African American, and Hispanic and chronic kidney disease were predictive of decreased palliative care service use. Although hospital admission with palliative care service use had higher mortality, palliative care service was associated with lower use of invasive mechanical ventilation, blood product transfusion, paracentesis, renal replacement, vasopressor but higher DNR status. Palliative care services reduced mean length of hospital stay and hospitalization cost. Conclusion: Although there was a substantial increase in the use of palliative care service in hospitalizations for hepatorenal syndrome, inpatient palliative care service was still underutilized. The use of palliative care service was associated with reduced resource use.

Use and outcomes of kidneys from donors with renal angiomyolipoma: A systematic review.

BACKGROUND: Renal angiomyolipoma (AML) is the most frequent mesenchymal tumor of the kidney. Although there is a rare possibility of malignant transformation of AML, this risk has not been studied in immunosuppressed patients. The safety of donors with AML and their kidney transplant recipients has not been well established. METHODS: A literature search was conducted utilizing MEDLINE, EMBASE, and Cochrane databases from inception through May 15, 2018 (updated on October 2019). We included studies that reported the outcomes of kidney donors with AML or recipients of donor with AML. The protocol for this meta-analysis is registered with PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42018095157). RESULTS: Fourteen studies with a total of 16 donors with AML were identified. None of the donors had a diagnosis of tuberous sclerosis complex (TSC), pulmonary lymphangioleiomyomatosis (LAM), or epithelioid variant of AML. Donor age ranged from 35 to 77 years, and recipient age ranged from 27 to 62 years. Ninety-two percent of the donors were female. Only 8% were deceased donor renal transplant. The majority underwent ex vivo resection (65%) before transplantation, followed by no resection (18%), and the remaining had in vivo resection. Tumor size varied from 0.4 cm to 7 cm, and the majority (87%) were localized in the right kidney. Follow-up time ranged from 1 to 107 months. Donor creatinine prenephrectomy ranged 0.89-1.1 mg/dL and postnephrectomy creatinine 1.0-1.17 mg/dL. In those who did not have resection of the AML, tumor size remained stable. None of the donors with AML had end-stage renal disease or died at last follow-up. None of the recipients had malignant transformation of AML. CONCLUSION: These findings are reassuring for the safety of donors with AML (without TSC or LAM) as well as their recipients without evidence of malignant transformation of AML. As such, this can also positively impact the donor pool by increasing the number of available kidneys.

Thrombotic Microangiopathy among Hospitalized Patients with Systemic Lupus Erythematosus in the United States.

BACKGROUND: This study aimed to evaluate thrombotic microangiopathy's (TMA) incidence, risk factors, and impact on outcomes and resource use in hospitalized patients with systemic lupus erythematosus (SLE). METHODS: We used the National Inpatient Sample to construct a cohort of hospitalized patients with SLE from 2003-2014. We compared clinical characteristics, in-hospital treatments, outcomes, and resource use between SLE patients with and without TMA. RESULTS: Of 35,745 hospital admissions for SLE, TMA concurrently presented or developed in 188 (0.5%) admissions. Multivariable analysis showed that age ≥ 40 years and Hispanics were significantly associated with decreased risk of TMA, whereas Asian/Pacific Islanders and history of chronic kidney disease were significantly associated with increased risk of TMA. TMA patients required more kidney biopsy, plasmapheresis, mechanical ventilation, and renal replacement therapy. TMA was significantly associated with increased risk of in-hospital mortality and acute conditions including hemoptysis, glomerulonephritis, encephalitis/myelitis/encephalopathy, hemolytic anemia, pneumonia, urinary tract infection, sepsis, ischemic stroke, seizure, and acute kidney injury. The length of hospital stays and hospitalization cost was also significantly higher in SLE with TMA patients. CONCLUSION: TMA infrequently occurred in less than 1% of patients admitted for SLE, but it was significantly associated with higher morbidity, mortality, and resource use.

Impact of rhabdomyolysis on outcomes of hospitalizations for heat stroke in the United States.

BACKGROUND: The objective of this study was to evaluate the predictors and associated outcomes of rhabdomyolysis in admitted patients for heat stroke in the United States. METHODS: The National Inpatient Sample was utilized to identify hospitalized patients with a primary diagnosis of heat stroke from the years 2003-2014. Rhabdomyolysis was identified using hospital diagnosis code. We compared the clinical characteristics, in-hospital treatment, complications, outcomes, and resource utilization between patients with and without rhabdomyolysis. RESULTS: A total of 3,372 hospital admissions for heat stroke were studied. Of these, rhabdomyolysis occurred in 1049 (31%) admissions. The risk factors for rhabdomyolysis were age 20-39 years, male sex, African American race, history of alcohol drinking, whereas age ≥60 years, smoking, history of diabetes mellitus, and hypertension were associated with lower risk of rhabdomyolysis. Patients with rhabdomyolysis had greater requirements for mechanical ventilation, blood component transfusion, and renal replacement therapy. Rhabdomyolysis was significantly associated with increased risk of hyponatremia, hypernatremia, hyperkalemia, hypocalcemia, serum phosphorus and magnesium derangement, metabolic acidosis, sepsis, ventricular arrhythmia or cardiac arrest, renal failure, respiratory failure, liver failure, neurological failure, hematologic failure, and in-hospital mortality. Length of hospital stay and hospitalization cost were higher when rhabdomyolysis occurred during hospital stay. CONCLUSION: Rhabdomyolysis occurred in about one-third of hospitalized patients for heat stroke and was associated with increased morbidity, mortality, and resource utilization.

Predicting Acute Kidney Injury after Cardiac Surgery by Machine Learning Approaches.

Cardiac surgery-associated AKI (CSA-AKI) is common after cardiac surgery and has an adverse impact on short- and long-term mortality. Early identification of patients at high risk of CSA-AKI by applying risk prediction models allows clinicians to closely monitor these patients and initiate effective preventive and therapeutic approaches to lessen the incidence of AKI. Several risk prediction models and risk assessment scores have been developed for CSA-AKI. However, the definition of AKI and the variables utilized in these risk scores differ, making general utility complex. Recently, the utility of artificial intelligence coupled with machine learning, has generated much interest and many studies in clinical medicine, including CSA-AKI. In this article, we discussed the evolution of models established by machine learning approaches to predict CSA-AKI.

Recent Advances and Clinical Outcomes of Kidney Transplantation.

Recent advances in surgical, immunosuppressive and monitoring protocols have led to the significant improvement of overall one-year kidney allograft outcomes. Nonetheless, there has not been a significant change in long-term kidney allograft outcomes. In fact, chronic and acute antibody-mediated rejection (ABMR) and non-immunological complications following kidney transplantation, including multiple incidences of primary kidney disease, as well as complications such as cardiovascular diseases, infections, and malignancy are the major factors that have contributed to the failure of kidney allografts. The use of molecular techniques to enhance histological diagnostics and noninvasive surveillance are what the latest studies in the field of clinical kidney transplant seem to mainly focus upon. Increasingly innovative approaches are being used to discover immunosuppressive methods to overcome critical sensitization, prevent the development of anti-human leukocyte antigen (HLA) antibodies, treat chronic active ABMR, and reduce non-immunological complications following kidney transplantation, such as the recurrence of primary kidney disease and other complications, such as cardiovascular diseases, infections, and malignancy. In the present era of utilizing electronic health records (EHRs), it is strongly believed that big data and artificial intelligence will reshape the research done on kidney transplantation in the near future. In addition, the utilization of telemedicine is increasing, providing benefits such as reaching out to kidney transplant patients in remote areas and helping to make scarce healthcare resources more accessible for kidney transplantation. In this article, we discuss the recent research developments in kidney transplants that may affect long-term allografts, as well as the survival of the patient. The latest developments in living kidney donation are also explored.

Prevalence and associated factors influencing depression in older adults living in rural Thailand: A cross-sectional study.

AIM: Depression is a major disease burden in Thailand. In rural areas, young adults will leave home to work in cities, and older adults are left behind. Loneliness and comorbidities can lead to depression in older adults. The present study aimed to evaluate the prevalence and associated factors for geriatric depression. METHODS: A cross-sectional study was carried out. Questionnaires including the Thai Geriatric Depression Scale and family relationship were obtained by healthcare professions by face-to-face interviews of 584 older people aged ≥60 years in Ban Nayao community, Chachoengsao Province, Thailand. Geriatric depression can be defined as depressive syndromes that arise in adults aged ≥60 years. We excluded those who had visual or auditory disabilities or did not pass the Thai Mini-Mental Status Examination. The prevalence and associated factors for geriatric depression were obtained. Associated factors were analyzed by multivariate logistic regression. RESULTS: A total of 433 older people were eligible. The prevalence of geriatric depression was 18.5%. Of the participants, 54.1% lived in an imbalanced family type. Multivariate analysis showed the significance for female sex (adjusted OR 2.78, 95% CI 1.54-7.49, P = 0.01), illiteracy (adjusted OR 2.86, 95% CI 1.19-6.17, P-value 0.04), current smoker (adjusted OR 4.25, 95% CI 2.12-10.18, P = 0.009) and imbalanced family type (low attachment, low cooperation and poor alignment between each member; adjusted OR 4.52, 95% CI 2.14-7.86, P < 0.001) as risk factors for depression. CONCLUSIONS: The prevalence of geriatric depression in rural Thailand is high. Imbalanced family type is an important risk factor for geriatric depression in the rural community. Geriatr Gerontol Int 2019; 19: 1248-1253.

Association between serum uric acid and chronic kidney disease in patients with hypertension: A multicenter nationwide cross-sectional study.

INTRODUCTION: Current data on the role of hyperuricemia as a risk factor for renal progression in patients with hypertension is inconclusive. This study aimed to assess the association of uric acid and chronic kidney disease (CKD) in hypertensive patients using a nationwide patient sample. METHODS: We conducted a nationwide cross-sectional study based on the DM/HT study of the Medical Research Network of the Consortium of Thai Medical Schools. This study evaluated adult patients with hypertension from 831 Thailand public hospitals in the year 2014. Serum uric acid (SUA) was categorized into quintiles (≤4.5, 4.6 to 5.4, 5.5 to 6.2, 6.3 to 7.4, ≥7.5 mg/dL). CKD was defined as estimated glomerular filtration rate of ≤ 60 mL/min/1.73 m2 . Multivariate logistic regression was performed to assess the association between SUA and CKD using uric acid of ≤4.5 mg/dL as the reference group. RESULTS: A total of 9776 hypertensive patients with available SUA were included in the analysis. The mean SUA was 6.1±1.8 mg/dL. The prevalence of CKD in hypertensive patients was 31.8%. SUA of 4.6 to 5.4, 5.5 to 6.2, 6.3 to 7.4, and ≥7.5 mg/dL were associated with an increased CKD with ORs of 1.57 (95% CI 1.28 to 1.92), 2.15 (95% CI 1.74 to 2.66), 3.31 (95% CI 2.72 to 4.04), and 7.11 (95% CI 5.76 to 8.78), respectively. The restricted cubic spline showed significant increased CKD prevalence when uric acid ≥4.6 mg/dL. CONCLUSION: Higher SUA was associated with increased CKD prevalence in patients with hypertension. SUA should be monitored in hypertensive patients for CKD prevention.

Incidence and Mortality of Renal Cell Carcinoma after Kidney Transplantation: A Meta-Analysis.

BACKGROUND: The incidence and mortality of renal cell carcinoma (RCC) after kidney transplantation (KTx) remain unclear. This study's aims were (1) to investigate the pooled incidence/incidence trends, and (2) to assess the mortality/mortality trends in KTx patients with RCC. METHODS: A literature search was conducted using the MEDLINE, EMBASE and Cochrane databases from inception through October 2018. Studies that reported the incidence or mortality of RCC among kidney transplant recipients were included. The pooled incidence and 95% CI were calculated using a random-effect model. The protocol for this meta-analysis is registered with PROSPERO; no. CRD42018108994. RESULTS: A total of 22 observational studies with a total of 320,190 KTx patients were enrolled. Overall, the pooled estimated incidence of RCC after KTx was 0.7% (95% CI: 0.5-0.8%, I2 = 93%). While the pooled estimated incidence of de novo RCC in the native kidney was 0.7% (95% CI: 0.6-0.9%, I2 = 88%), the pooled estimated incidence of RCC in the allograft kidney was 0.2% (95% CI: 0.1-0.4%, I2 = 64%). The pooled estimated mortality rate in KTx recipients with RCC was 15.0% (95% CI: 7.4-28.1%, I2 = 80%) at a mean follow-up time of 42 months after RCC diagnosis. While meta-regression analysis showed a significant negative correlation between year of study and incidence of de novo RCC post-KTx (slopes = -0.05, P = 0.01), there were no significant correlations between the year of study and mortality of patients with RCC (P = 0.50). Egger's regression asymmetry test was performed and showed no publication bias in all analyses. CONCLUSIONS: The overall estimated incidence of RCC after KTX was 0.7%. Although there has been a potential decrease in the incidence of RCC post-KTx, mortality in KTx patients with RCC has not decreased over time.

Effects of denosumab on bone metabolism and bone mineral density in kidney transplant patients: a systematic review and meta-analysis.

OBJECTIVE: The use of immunosuppressive agents, especially glucocorticoids, are associated with increased risks of bone loss in kidney transplant patients. Denosumab, a potent antiresorptive agent, has been shown to increase bone mineral density (BMD) in patients with CKD. However, its effects on bone metabolism and BMD in kidney transplant patients remain unclear. METHODS: A literature search was conducted using MEDLINE, EMBASE, and Cochrane Database from inception through April 2018 to identify studies evaluating denosumab's effect on changes in bone metabolism and BMD from baseline to post-treatment course in kidney transplant patients. Study results were pooled and analyzed utilizing random-effects model. The protocol for this systematic review is registered with PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42018095055). RESULTS: Five studies (a clinical trial and four cohort studies) with a total of 162 kidney transplant patients were identified. The majority of patients had a baseline eGFR ≥ 30 mL/min/1.73 m2. After treatment (≥ 6 to 12 months), there were significant increases in BMD with standardized mean differences (SMDs) of 3.26 (95% CI 0.88-5.64) and 1.83 (95% CI 0.43 to 3.22) for lumbar spine and femoral neck, respectively. There were also significant increases in T scores with SMDs of 0.92 (95% CI 0.58 to 1.25) and 1.14 (95% CI 0.17 to 2.10) for lumbar spine and femoral neck, respectively. After treatment, there were no significant changes in serum calcium (Ca) or parathyroid hormone (PTH) from baseline to post-treatment course (≥ 6 months) with mean differences (MDs) of 0.52 (95% CI, - 0.13 to 1.16) mmol/L and - 13.24 (95% CI, - 43.85 to 17.37) ng/L, respectively. The clinical trial data demonstrated more asymptomatic hypocalcemia in the denosumab (12 episodes in 39 patients) than in the control (1 episode in 42 patients) group. From the cohort studies, the pooled incidence of hypocalcemia following denosumab treatment was 1.7% (95% CI 0.4 to 6.6%). All reported hypocalcemic episodes were mild and asymptomatic, but the majority of patients required Ca and vitamin D supplements. CONCLUSION: Among kidney transplant patients with good allograft function, denosumab effectively increases BMD and T scores in the lumbar spine and femur neck. From baseline to post-treatment, there are no differences in serum Ca and PTH. However, mild hypocalcemia can occur following denosumab treatment, requiring monitoring and titration of Ca and vitamin D supplements.

Acute Kidney Injury in Patients Undergoing Total Hip Arthroplasty: A Systematic Review and Meta-Analysis.

BACKGROUND: The number of total hip arthroplasties (THA) performed across the world is growing rapidly. We performed this meta-analysis to evaluate the incidence of acute kidney injury (AKI) in patients undergoing THA. METHODS: A literature search was performed using MEDLINE, EMBASE and Cochrane Database from inception until July 2018 to identify studies assessing the incidence of AKI (using standard AKI definitions of RIFLE, AKIN, and KDIGO classifications) in patients undergoing THA. We applied a random-effects model to estimate the incidence of AKI. The protocol for this meta-analysis is registered with PROSPERO (no. CRD42018101928). RESULTS: Seventeen cohort studies with a total of 24,158 patients undergoing THA were enrolled. Overall, the pooled estimated incidence rates of AKI and severe AKI requiring dialysis following THA were 6.3% (95% CI: 3.8%⁻10.2%) and 0.5% (95% CI: 0.1%⁻2.3%). Subgroup analysis based on the countries by continent was performed and demonstrated the pooled estimated incidence of AKI following THA of 9.2% (95% CI: 5.6%⁻14.8%) in Asia, 8.1% (95% CI: 4.9%⁻13.2%) in Australia, 7.4% (95% CI: 3.2%⁻16.3%) in Europe, and 2.8% (95% CI: 1.2%⁻17.0%) in North America. Meta-regression of all included studies showed significant negative correlation between incidence of AKI following THA and study year (slope = -0.37, p <0.001). There was no publication bias as assessed by the funnel plot and Egger's regression asymmetry test with p = 0.13 for the incidence of AKI in patients undergoing THA. CONCLUSION: The overall estimated incidence rates of AKI and severe AKI requiring dialysis in patients undergoing THA are 6.3% and 0.5%, respectively. There has been potential improvement in AKI incidence for patients undergoing THA over time.

Effects of Probiotics on Inflammation and Uremic Toxins Among Patients on Dialysis: A Systematic Review and Meta-Analysis.

BACKGROUND/OBJECTIVES: We performed this systematic review and meta-analysis to evaluate effects of probiotics on inflammation, uremic toxins, and gastrointestinal (GI) symptoms in end-stage renal disease (ESRD) patients. METHODS: A literature search was conducted utilizing MEDLINE, EMBASE, and Cochrane Database from inception through October 2017. We included studies that assessed assessing effects of probiotics on inflammatory markers, protein-bound uremic toxins (PBUTs), and GI symptoms in ESRD patients on dialysis. Effect estimates from the individual study were extracted and combined utilizing random effect, generic inverse variance method of DerSimonian and Laird. The protocol for this meta-analysis is registered with PROSPERO; No. CRD42017082137. RESULTS: Seven clinical trials with 178 ESRD patients were enrolled. There was a significant reduction in serum C-reactive protein (CRP) from baseline to post-probiotic course (≥ 2 months after treatment) with standardized mean difference (SMD) of - 0.42 (95% CI - 0.68 to - 0.16, p = 0.002). When compared to control, patients who received probiotics also had a significant higher degree of reduction in CRP level with SMDs of - 0.37 (95% CI - 0.72 to 0.03, p = 0.04). However, there were no significant changes in serum TNF-alpha or albumin with SMDs of - 0.32 (95% CI - 0.92 to 0.28, p = 0.29) and 0.16 (95% CI - 0.20 to 0.53, p = 0.39), respectively. After probiotic course, there were also significant decrease in PBUTs and improvement in overall GI symptoms (reduction in GI symptom scores) with SMDs of - 0.61 (95% CI - 1.16 to - 0.07, p = 0.03) and - 1.04 (95% CI - 1.70 to - 0.38, p = 0.002), respectively. CONCLUSION: Our study demonstrates potential beneficial effects of probiotics on inflammation, uremic toxins, and GI Symptoms in ESRD patients. Future large-scale clinical studies are required to assess its benefits on other important clinical outcomes including patient mortality.

Safety and efficacy of apixaban versus warfarin in patients with end-stage renal disease: Meta-analysis.

BACKGROUND: At the present, apixaban is the only nonvitamin K oral anticoagulant approved by the Food and Drug Administration for use with patients with creatinine clearance <15 mL/min or end-stage renal disease (ESRD). However, the recommendations are based on pharmacokinetic and pharmacodynamic data and there was lack of clinical trial evidence. We aimed to assess safety and efficacy of apixaban in patients with advanced chronic kidney disease (CKD) or ESRD. METHODS: Databases were searched through November 2017. Studies that reported incidence or odd ratios of bleeding complications or thromboembolic events in the use of apixaban in patients with CKD stage 4-5 or ESRD on dialysis were included. Effect estimates from the individual study were extracted and combined using random-effect, generic inverse variance method of DerSimonian and Laird. RESULTS: Five studies were included into the analysis consisting of 43,850 patients in observational cohort studies. The majority of patients (87%) used apixaban for atrial fibrillation. The pooled estimated incidence of any bleeding complications on apixaban was 17.4% (95% confidence interval [CI]: 13.0%-23.0%). Compared to warfarin, apixaban was significantly associated with reduced risk of major bleeding (pooled odds ratio [OR], 0.42; 95% CI, 0.28-0.61). In studies in ESRD patients on dialysis, the pooled OR of major bleeding was 0.27 (95% CI, 0.07-0.95). There was no significant difference in risk of thromboembolic events in advanced CKD or ESRD patients on apixaban versus vitamin K antagonists (pooled OR, 0.56; 95% CI, 0.23-1.39). CONCLUSIONS: Among patients with advanced CKD and ESRD, the use of apixaban was associated with lower risk of major bleeding compared to warfarin, and was found to be relatively effective with no excess risk of thromboembolic events.