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.

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.

Association between predialysis creatinine and mortality in acute kidney injury patients requiring dialysis.

BACKGROUND: Creatinine is widely used to estimate renal function, but this is not practical in critical illness. Low creatinine has been associated with mortality in many clinical settings. However, the associations between predialysis creatinine level, Sepsis-related Organ Failure Assessment (SOFA) score, fluid overload, and mortality in acute kidney injury patients receiving dialysis therapy (AKI-D) has not been fully addressed. METHODS: We extracted data for AKI-D patients in the eICU and MIMIC databases. We conducted a retrospective observational cohort study using the eICU dataset. The study cohort was divided into the high-creatine group and the low-creatinine group by the median value (4 mg/dL). The baseline patient information included demographic data, laboratory tests, medications, and comorbid conditions. The independent association of creatinine level with 30-day mortality was examined using multivariate logistic regression analysis. In sensitivity analyses, the associations between creatinine, SOFA score, and mortality were analyzed in patients with or without fluid overload. We also carried out an external validity using the MIMIC dataset. RESULTS: In all 1,600 eICU participants, the 30-day mortality rate was 34.2%. The crude overall mortality rate in the low-creatinine group (44.9%) was significantly higher than that in the high-creatinine group (21.9%; P < 0.001). In the fully adjusted models, the low-creatinine group was associated with a higher risk of 30-day mortality (odds ratio, 1.77; 95% confidence interval, 1.29-2.42; P < 0.001) compared with the high-creatinine group. The low-creatinine group had higher SOFA and nonrenal SOFA scores. In sensitivity analyses, the low-creatinine group had a higher 30-day mortality rate with regard to the BMI or albumin level. Fluid overloaded patients were associated with a significantly worse survival in the low-creatinine group. The results were consistent when assessing the external validity using the MIMIC dataset. CONCLUSIONS: In patients with AKI-D, lower predialysis creatinine was associated with increased mortality risk. Moreover, the mortality rate was substantially higher in patients with lower predialysis creatinine with concomitant elevation of fluid overload status.

Association of Hematuria with Renal Progression and Survival in Patients Who Underwent Living Donor Liver Transplant.

BACKGROUND: This study aimed to determine the association between episodic or persistent hematuria after liver transplantation and long-term renal outcomes. METHODS: Patients who underwent living donor liver transplantation between July 2005 and June 2019 were recruited and divided into two groups based on the finding of microscopic or gross hematuria after transplantation. All patients were followed up from the index date until the end date in May 2020. The risks of chronic kidney disease, death, and 30% and 50% declines in estimated glomerular filtration rate (eGFR) were compared between groups. RESULTS: A total of 295 patients underwent urinalysis for various reasons after undergoing transplantation. Hematuria was detected in 100 patients (group A) but was not present in 195 patients (group B). Compared with group B, group A had a higher risk of renal progression, including eGFR decline >50% [aHR = 3.447 (95%CI: 2.24~5.30), p < 0.001] and worse survival. In addition, patients who took non-steroidal anti-inflammatory drugs (NSAIDs) continuously for over seven days within six months before transplant surgery had high risks of rapid renal progression, including a >30% decline in eGFR [aHR = 1.572 (95%CI: 1.12~2.21), p = 0.009)]. CONCLUSION: Development of hematuria after surgery in patients who underwent living donor liver transplant and were exposed to NSAIDs before surgery were associated with worse long-term renal dysfunction and survival.

Superiority of albumin-globulin ratio over albumin to predict mortality in patients undergoing peritoneal dialysis.

There is increasing evidence showing that albumin-globulin ratio (AGR) can predict the survival of patients in many types of malignancies. However, no study was done to explore the value of AGR in peritoneal dialysis (PD) patients. A total of 554 incident patients undergoing PD from January 2001 through July 2016 were enrolled for this retrospective observational study. The outcomes of interest were all-cause mortality and cardiovascular disease (CVD) mortality. Baseline patient's socio-demographic data, pharmacotherapy, comorbidities, laboratory and PD-related parameters were collected and used in the multivariate Cox models. The predictive value of AGR on mortality risk was compared with other markers using area under the receiver operating characteristic curve (AUC) analysis. Among the study participants, there were 265 (47.83%) men and the mean follow-up time was 3.87 ± 3.15 years. Univariate Cox analysis showed that low AGR was significantly associated with worse outcomes in terms of all-cause and CVD mortality and it remained an independent predictor in the multivariate models. The fully adjusted hazard ratios for the low AGR group versus high AGR group were 2.12 (95% CI 1.34-3.35, p = 0.001) and 2.58 (95% CI 1.42-4.7, p = 0.002) for all-cause and CVD mortality, respectively. The predictive ability of AGR for mortality risk was superior to that of other biomarkers based on AUC calculations. In conclusion, low AGR was independently associated with higher all-cause and CVD mortality risks in patients undergoing PD.

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.

Cyclophilin A and CD147 associate with progression of diabetic nephropathy.

To find the associations of circulating cyclophilin A (CyP A) and CD147/EMMPRIN with renal outcomes in type 2 diabetes patients and possible pathogenesis involved. Total 131 patients were recruited since 2004. Glycated hemoglobin, blood glucose and urine albumin-creatinine ratio levels at baseline and every 3 months were measured. Plasma CyP A and CD147 were also measured at baseline. Patients were divided into two groups based upon the median level of the baseline plasma CyP A value: < 93.64 ng/mL (group A, n = 65), ≥ 93.64 ng/mL (group B, n = 66). The estimated glomerular filtration rate was calculated at each follow-up visit. Besides, mitochondrial function assay by cellular mitochondrial energy utility was studied when cells were exposed to glucose or exogenous CyP A or both. Multivariate analysis, using median level (93.64) ng/mL as the cut-off value, revealed that circulating CyP A and CD147 levels at baseline were associated with the baseline estimated glomerular filtration rate (eGFR) (p = .042 and p = .001 separately) in cross-sectional analysis. Longitudinally, higher baseline plasma CyP A level was also correlated to a rapid decline in eGFR (p = .016). The results were also significant when using the continuous plasma CyP A level (p = .003). In cells exposed to glucose, results of oxygen consumption rate (OCR) showed a significant reduction in basal respiration, maximal respiration and ATP production. Depressed OCR further occurred when incubated with both of CyP A and glucose. Plasma CyP A and CD147 can serve as indicators of renal disease progression in type 2 diabetes patients.

Increased chronic kidney disease development and progression in diabetic patients after appendectomy: a population-based cohort study.

BACKGROUND: The vermiform appendix serves as a "safe house" for maintaining normal gut bacteria and appendectomy may impair the intestinal microbiota. Appendectomy is expected to profoundly alter the immune system and modulate the pathogenic inflammatory immune responses of the gut. Recent studies have shown that a dysbiotic gut increases the risk of cardiovascular disease and chronic kidney disease (CKD). Therefore, we hypothesized that appendectomy would increase the risk of CKD. METHODS: This nationwide, population-based, propensity-score-matched cohort study included 10,383 patients who underwent appendectomy and 41,532 propensity-score-matched controls. Data were collected by the National Health Insurance Research Database of Taiwan from 2000 to 2013. We examined the associations between appendectomy and CKD and end-stage renal disease (ESRD). The major outcome was a new diagnosis of CKD based on an outpatient diagnosis made at least three times or hospital discharge diagnosis made once during the follow-up period. ESRD was defined as undergoing dialysis therapy for at least 90 days, as in previous studies. RESULTS: The incidence rates of CKD and ESRD were higher in the appendectomy group than in the control cohort (CKD: 6.52 vs. 5.93 per 1,000 person-years, respectively; ESRD: 0.49 vs. 0.31 per 1,000 person-years, respectively). Appendectomy patients also had a higher risk of developing CKD (adjusted hazard ratio [aHR] 1.13; 95% CI [1.01-1.26]; P = 0.037) and ESRD (aHR 1.59; 95% CI [1.06-2.37]; P = 0.024) than control group patients. Subgroup analysis showed that appendectomy patients with concomitant diabetes mellitus (aHR 2.08; P = 0.004) were at higher risk of incident ESRD than those without diabetes mellitus. The interaction effects of appendectomy and diabetes mellitus were significant for ESRD risk (P = 0.022); no interaction effect was found for CKD risk (P = 0.555). CONCLUSIONS: Appendectomy increases the risk of developing CKD and ESRD, especially in diabetic patients. Physicians should pay close attention to renal function prognosis in appendectomy patients.

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.

Long-term renal outcomes in patients with traumatic brain injury: A nationwide population-based cohort study.

BACKGROUND: Traumatic brain injury (TBI) is an important cause of death and disability worldwide. The relationship between TBI and kidney diseases is largely unknown. METHODS: We aimed to determine whether TBI is associated with long-term adverse renal outcomes. We performed a nationwide, population-based, propensity score-matched cohort study of 32,152 TBI patients and 128,608 propensity score-matched controls. Data were collected by the National Health Insurance Research Database of Taiwan from 2000 to 2012. Our clinical outcomes were chronic kidney disease (CKD), end-stage renal disease (ESRD) and the composite endpoint of ESRD or all-cause mortality. RESULTS: The incidence rate of CKD was higher in the TBI than in the control cohort (8.99 vs. 7.4 per 1000 person-years). The TBI patients also showed higher risks of CKD (adjusted hazard ratio [aHR] 1.14, 95% confidence interval [CI] 1.08-1.20; P < 0.001) and composite endpoints (aHR 1.08, 95% CI 1.01-1.15; P = 0.022) than the control groups, but the ESRD was not significantly different between the groups. In subgroup analyses, the risks of incident CKD and composite endpoints were significantly raised in TBI patients aged < 65 years and/or without comorbidities. However, the risks of both CKD and composite outcome were little affected by the severity of TBI. CONCLUSIONS: TBI has a modest but significant effect on incident CKD and composite endpoint, but not on ESRD alone. TBI patients under 65 are at greater risk of CKD and composite outcome than their older counterparts.

Stroke and Risks of Development and Progression of Kidney Diseases and End-Stage Renal Disease: A Nationwide Population-Based Cohort Study.

BACKGROUND: There is little information about the association between stroke and kidney diseases. We aimed to investigate the impact of stroke on long-term renal outcomes. METHODS: In this large population-based retrospective cohort study, we identified 100,353 subjects registered in the National Health Insurance Research Database of Taiwan from January 1, 2000, through December 31, 2012, including 33,451 stroke patients and 66,902 age-, sex- and Charlson's comorbidity index score-matched controls. RESULTS: The incidence rate of chronic kidney disease (CKD) was higher in the stroke than in the control cohort (17.5 vs. 9.06 per 1000 person-years). After multivariate adjustment, the risk of developing CKD was significantly higher in patients with stroke (adjusted hazard ratio [aHR] 1.43, 95% confidence interval [CI] 1.36-1.50, P<0.001). Subgroup analysis showed that stroke patients <50 years (aHR 1.61, P<0.001) and those with concomitant diabetes mellitus (aHR 2.12, P<0.001), hyperlipidemia (aHR 1.53, P<0.001) or gout (aHR 1.84, P<0.001) were at higher risk of incident CKD. Additionally, the risks of progression to advanced CKD and end-stage renal disease (ESRD) were significantly higher for stroke patients (aHRs, 1.22 and 1.30; P = 0.04 and P = 0.008, respectively), independent of age, sex, comorbidities and long-term medications. CONCLUSIONS: Stroke is associated with higher risks for incident CKD, decline in renal function and ESRD. Younger stroke patients, as well as those with concomitant diabetes mellitus, hyperlipidemia or gout are at greater risk for kidney diseases.

Trajectories of Serum Albumin Predict Survival of Peritoneal Dialysis Patients: A 15-year Follow-Up Study.

Although initial serum albumin level is highly associated with overall and cardiovascular mortality in peritoneal dialysis (PD) patients, we consider that the dynamic change and trend of albumin after initiation of PD are also essential.We enrolled patients who received PD for more than 3 months from January 1999 to March 2014. We categorized these patients into 2 groups by the difference in serum albumin level (Δalbumin = difference between peak with initial albumin level = peak albumin level - initial albumin level) after PD. The patients with Δalbumin < 0.2 g/dL (median level) were considered as group A (n, number = 238) and those with Δalbumin ≥ 0.2 g/dL were considered as group B (n = 278). Further, we stratified these patients into quartiles: Q1 Δalbumin < -0.2 g/dL; Q2, -0.2 ≦∼ <0.2 g/dL; Q3, 0.2 ≦∼ <0.6 g/dL; and Q4, ≥0.6 g/dL. Regression analysis was performed to determine the correlation of initial albumin and Δalbumin.Group A patients presented with higher levels of serum albumin (3.71 ±â€Š0.54 vs 3.04 ±â€Š0.55 g/dL; P < 0.001) and hematocrit as well as better initial residual renal function. However, those in group A had lower serum albumin increment and downward-sloped trends after dialysis. In contrast, the albumin trend was upward sloped and the increment of albumin was remarkable in group B, despite the high prevalence of cardiovascular diseases and diabetes. Overtime, group A patients had poorer survival and experienced more frequent and longer hospitalizations. Group Q1 patients with least albumin increment had worst survival. Group Q4 patients with lowest initial albumin also had poor survival. Age, diabetes, cardiovascular diseases, BMI, initial albumin, and Δalbumin could affect patient outcomes independently. Regression analysis showed a better outcome can be obtained if the initial albumin level is at least above 3.15 g/dL. (Initial albumin level = -0.61 × Δalbumin + 3.50.)The increment and trend of albumin especially during early period of PD may be a more crucial determinant for survival.

An alternative root for the eukaryote tree of life.

The root of the eukaryote tree of life defines some of the most fundamental relationships among species. It is also critical for defining the last eukaryote common ancestor (LECA), the shared heritage of all extant species. The unikont-bikont root has been the reigning paradigm for eukaryotes for more than 10 years but is becoming increasingly controversial. We developed a carefully vetted data set, consisting of 37 nuclear-encoded proteins of close bacterial ancestry (euBacs) and their closest bacterial relatives, augmented by deep sequencing of the Acrasis kona (Heterolobosea, Discoba) transcriptome. Phylogenetic analysis of these data produces a highly robust, fully resolved global phylogeny of eukaryotes. The tree sorts all examined eukaryotes into three megagroups and identifies the Discoba, and potentially its parent taxon Excavata, as the sister group to the bulk of known eukaryote diversity, the proposed Neozoa (Amorphea + Stramenopila+Alveolata+Rhizaria+Plantae [SARP]). All major alternative hypotheses are rejected with as little as ∼50% of the data, and this resolution is unaffected by the presence of fast-evolving alignment positions or distant outgroup sequences. This "neozoan-excavate" root revises hypotheses of early eukaryote evolution and highlights the importance of the poorly studied Discoba for understanding the evolution of eukaryotic diversity and basic cellular processes.