A machine learning-based approach for predicting renal function recovery in general ward patients with acute kidney injury

Acute kidney injury (AKI) is a significant challenge in healthcare. While there are considerable researches dedicated to AKI patients, a crucial factor in their renal function recovery, is often overlooked. Thus, our study aims to address this issue through the development of a machine learning model to predict restoration of kidney function in patients with AKI. Methods: Our study encompassed data from 350,345 cases, derived from three hospitals. AKI was classified in accordance with the Kidney Disease: Improving Global Outcomes. Criteria for recovery were established as either a 33% decrease in serum creatinine levels at AKI onset, which was initially employed for the diagnosis of AKI. We employed various machine learning models, selecting 43 pertinent features for analysis. Results: Our analysis contained 7,041 and 2,929 patients’ data from internal cohort and external cohort respectively. The Categorical Boosting Model demonstrated significant predictive accuracy, as evidenced by an internal area under the receiver operating characteristic (AUROC) of 0.7860, and an external AUROC score of 0.7316, thereby confirming its robustness in predictive performance. SHapley Additive exPlanations (SHAP) values were employed to explain key factors impacting recovery of renal function in AKI patients. Conclusion: This study presented a machine learning approach for predicting renal function recovery in patients with AKI. The model performance was assessed across distinct hospital settings, which revealed its efficacy. Although the model exhibited favorable outcomes, the necessity for further enhancements and the incorporation of more diverse datasets is imperative for its application in real- world.

Genome-wide association study and fine-mapping on Korean biobank to discover renal trait-associated variants

Chronic kidney disease is a significant health burden worldwide, with increasing incidence. Although several genome- wide association studies (GWAS) have investigated single nucleotide polymorphisms (SNP) associated with kidney trait, most studies were focused on European ancestry. Methods: We utilized clinical and genetic information collected from the Korean Genome and Epidemiology Study (KoGES). Results: More than five million SNPs from 58,406 participants were analyzed. After meta-GWAS, 1,360 loci associated with estimated glomerular filtration rate (eGFR) at a genome-wide significant level (p = 5 × 10–8) were identified. Among them, 399 loci were validated with at least one other biomarker (blood urea nitrogen [BUN] or eGFRcysC) and 149 loci were validated using both markers. Among them, 18 SNPs (nine known ones and nine novel ones) with 20 putative genes were found. The aggregated effect of genes estimated by MAGMA gene analysis showed that these significant genes were enriched in kidney-associated pathways, with the kidney and liver being the most enriched tissues. Conclusion: In this study, we conducted GWAS for more than 50,000 Korean individuals and identified several variants associated with kidney traits, including eGFR, BUN, and eGFRcysC. We also investigated functions of relevant genes using computational methods to define putative causal variants.

Pericoronary fat attenuation index in computed tomography angiography is associated with mortality in end-stage renal disease

An increased pericoronary fat attenuation index (FAI) on computed tomography angiography (CTA) is associated with increased all-cause and cardiac mortality in the general population. However, the ability of pericoronary FAI to predict long-term outcomes in chronic kidney disease (CKD) patients is unknown. Methods: In this single-center retrospective longitudinal cohort study, we assessed the utility of CTA-based pericoronary FAI measurement to predict mortality of CKD patients, including those with end-stage renal disease (ESRD). Mapping and analysis of pericoronary FAI involved three major proximal coronary arteries. The prognostic value of pericoronary FAI for long-term mortality was assessed with multivariable Cox regression models. Results: Among 268 CKD participants who underwent coronary CTA, 209 participants with left anterior descending artery (LAD) FAI measurements were included. The pericoronary FAI measured at the LAD was not significantly associated with adjusted risk of allcause mortality (hazard ratio [HR], 2.08; 95% confidence interval [CI], 0.94–3.51) in any CKD group. However, ESRD patients with elevated pericoronary FAI values had a greater adjusted risk of all-cause mortality compared with the low-FAI group (HR, 2.26; 95% CI, 1.11–4.61). Conclusion: The pericoronary FAI measured at the LAD predicted long-term mortality in patients with ESRD, which could provide an opportunity for early primary intervention in ESRD patients.

Emotional and cognitive changes in chronic kidney disease

Chronic kidney disease (CKD) leads to cognitive impairment and emotional changes. However, the precise mechanism underlying the crosstalk between the kidneys and the nervous system is not fully understood. Inflammation and cerebrovascular disease can influence the development of depression in CKD. CKD is one of the strongest risk factors for cognitive impairment. Moreover, cognitive impairment occurs in CKD as patients experience the dysregulation of several brain functional domains due to damage caused to multiple cortical regions and to subcortical modulatory neurons. The differences in structural brain changes between CKD and non-CKD dementia may be attributable to the different mechanisms that occur in CKD. The kidney and brain have similar anatomical vascular systems, which may be susceptible to traditional risk factors. Vascular factors are assumed to be involved in the development of cognitive impairment in patients with CKD. Vascular injury induces white matter lesions, silent infarction, and microbleeds. Uremic toxins may also be directly related to cognitive impairment in CKD. Many uremic toxins, such as indoxyl sulfate, are likely to have an impact on the central nervous system. Further studies are required to identify therapeutic targets to prevent changes in the brain in patients with CKD.

Urinary exosomal microRNA profiling in type 2 diabetes patients taking dipeptidyl peptidase-4 inhibitor compared with sulfonylurea

Background@#Dipeptidyl peptidase-4 (DPP-4) inhibitor has been reported to have kidney-protective benefits. To elucidate how antidiabetic agents prevent diabetic kidney disease progression, it is important to investigate their effect on the kidney environment in type 2 diabetes mellitus (DM) patients. Herein, we investigated the expression pattern of urinary exosome-derived microRNA (miRNA) in patients taking a combination of DPP-4 inhibitor and metformin (DPP-4 inhibitor group) and compared them with patients taking a combination of sulfonylurea and metformin (sulfonylurea group). @*Methods@#This was a prospective study involving 57 patients with type 2 DM (DPP-4 inhibitor group, n = 34; sulfonylurea group, n = 23) and healthy volunteers (n = 7). We measured urinary exosomal miRNA using the NanoString nCounter miRNA array (NanoString Technologies) across the three groups (n = 4 per each group) and validated findings using real-time polymerase chain reaction. @*Results@#Twenty-one differentially expressed candidate miRNAs were identified, and six (let-7c-5p, miR-23a-3p, miR-26a-3p, miR-30d, miR-205, and miR-200a) were selected for validation. Validation showed no significant difference in miRNA expression between the DPP-4 inhibitor and sulfonylurea groups. Only miR-23a-3p was significantly overexpressed in the diabetes group compared with the control group (DPP-4 inhibitor vs. control, p = 0.01; sulfonylurea vs. control, p = 0.007). This trend was consistent even after adjusting for age, sex, and body mass index. @*Conclusion@#There was no significant difference in urine exosome miRNA expression between diabetic participants taking DPP-4 inhibitor and those taking sulfonylurea. The miR-23a levels were higher in diabetic participants than in nondiabetic controls.

Severe Case of Hypermagnesemia Caused by Ingesting Magnesium Containing Fertilizer

Hypermagnesemia is a rare condition that is usually iatrogenic in patients with elderly or renal failure. Severe hypermagnesemia is uncommon in patients with a normal renal function. Symptoms due to hypermagnesemia can range from mild symptoms, such as nausea, to severe symptoms, such as cardiac and respiratory arrest. This paper describes a case of a 49-year-old woman who ingested a magnesium-containing fertilizer with normal renal function. Cardiac arrest occurred eight hours after poisoning.Electrocardiography changed from a narrow QRS to a wide QRS and then to a complete atrioventricular block. Her hemodynamic state was unstable. Continuous renal replacement therapy was performed to remove magnesium from the blood, with the subsequent resolution of arrhythmia and hemodynamic stabilization. This paper reviews the pathophysiologic effects of magnesium on the cardiovascular system, clinical manifestation, and treatment of hypermagnesemia.

Risk Factors to Predict Acute Respiratory Failure in Patients with Acute Pesticide Poisoning

Acute respiratory failure is an important risk factor for mortality in patients with acute pesticide poisoning. Therefore, it is necessary to investigate the risk factors to predict respiratory failure in these patients. This study retrospectively investigated the clinical features of respiratory failure among patients with acute pesticide poisoning requiring mechanical ventilation. This study included patients who were admitted with intentional poisoning by pesticide ingestion from January 2017 to December 2019. Paraquat intoxication was excluded. Among 469 patients with acute pesticide poisoning, 398 patients were enrolled in this study. The respiratory failure rate was 30.4%. The rate of respiratory failure according to the type of pesticide was carbamate (75.0%), organophosphate (52.6%), glufosinate (52.1%), glyphosate (23%), pyrethroid (8.9%), and others (17%). The mortality was 25.6% in the respiratory failure group. The risk factors for respiratory failure were old age, low body mass index, and ingestion of more than 300 mL. In conclusion, respiratory failure is a risk factor for mortality in pesticide poisoning. Old age, low body mass index, and ingestion of more than 300 mL are the risk factors for predicting respiratory failure.

Severe Case of Hypermagnesemia Caused by Ingesting Magnesium Containing Fertilizer

Hypermagnesemia is a rare condition that is usually iatrogenic in patients with elderly or renal failure. Severe hypermagnesemia is uncommon in patients with a normal renal function. Symptoms due to hypermagnesemia can range from mild symptoms, such as nausea, to severe symptoms, such as cardiac and respiratory arrest. This paper describes a case of a 49-year-old woman who ingested a magnesium-containing fertilizer with normal renal function. Cardiac arrest occurred eight hours after poisoning.Electrocardiography changed from a narrow QRS to a wide QRS and then to a complete atrioventricular block. Her hemodynamic state was unstable. Continuous renal replacement therapy was performed to remove magnesium from the blood, with the subsequent resolution of arrhythmia and hemodynamic stabilization. This paper reviews the pathophysiologic effects of magnesium on the cardiovascular system, clinical manifestation, and treatment of hypermagnesemia.

Risk Factors to Predict Acute Respiratory Failure in Patients with Acute Pesticide Poisoning

Acute respiratory failure is an important risk factor for mortality in patients with acute pesticide poisoning. Therefore, it is necessary to investigate the risk factors to predict respiratory failure in these patients. This study retrospectively investigated the clinical features of respiratory failure among patients with acute pesticide poisoning requiring mechanical ventilation. This study included patients who were admitted with intentional poisoning by pesticide ingestion from January 2017 to December 2019. Paraquat intoxication was excluded. Among 469 patients with acute pesticide poisoning, 398 patients were enrolled in this study. The respiratory failure rate was 30.4%. The rate of respiratory failure according to the type of pesticide was carbamate (75.0%), organophosphate (52.6%), glufosinate (52.1%), glyphosate (23%), pyrethroid (8.9%), and others (17%). The mortality was 25.6% in the respiratory failure group. The risk factors for respiratory failure were old age, low body mass index, and ingestion of more than 300 mL. In conclusion, respiratory failure is a risk factor for mortality in pesticide poisoning. Old age, low body mass index, and ingestion of more than 300 mL are the risk factors for predicting respiratory failure.

Evaluation of Cerebral Blood Flow Using Arterial Spin Labeling in Patients with Chronic Kidney Disease

Purpose@#This study aimed to compare the brain perfusion status of patients with chronic kidney disease to a normal control group to identify any significant differences. @*Materials and Methods@#The perfusion state of the brain was measured by MRI using the arterial spin labeling technique in 36 patients undergoing hemodialysis due to chronic kidney disease and 36 normal controls. Images were then analyzed in a voxel-wise manner to detect brain areas showing significant perfusion differences between the two groups. @*Results@#Patients with chronic kidney disease showed increased perfusion in the form of large clusters across the right fronto-parieto-temporal lobe and the left parieto-occipital lobe. In addition, perfusion increased in the bilateral thalami, midbrain, pons, and cerebellum (p < 0.01, familywise error corrected). @*Conclusion@#Brain perfusion appears to increase in patients with chronic kidney disease compared to normal controls. Uremic toxicity is thought to be the cause of this increase as it can cause damage to the microscopic blood vessels and their surrounding structures.

Severity of foot process effacement is associated with proteinuria in patients with IgA nephropathy

Background@#Proteinuria is a significant risk factor for progression of IgA nephropathy (IgAN) and has a positive correlation with severity of foot process effacement (FPE). We evaluated the relationship of FPE with proteinuria and histologic characteristics, including the Oxford classification. @*Methods@#Patients who underwent renal biopsy and were diagnosed with IgAN at a single center were retrospectively reviewed. Patients aged less than 18 years and those with the possibility of secondary causes were excluded from the study. Subsequently, we evaluated the association between degree of proteinuria, severity of FPE, and histologic characteristics, including the Oxford classification and other immunofluorescence stains. @*Results@#A total of 805 cases of renal biopsy was performed at our institution, and 327 patients were diagnosed with IgAN. Among them, 82 patients were excluded. Severity of FPE had an impact on the degree of proteinuria. Notably, the group with diffuse FPE had more than about 1.3 g/day of urine protein compared to those with rare FPE. Among the histologic characteristics, M1 score and immune deposition of IgG affected severity of FPE (hazard ratios [95% confidence interval], 1.90 [1.10 to 3.26], and 3.77 [1.66 to 8.54], respectively). @*Conclusion@#Severity of FPE had an impact on the degree of proteinuria and may be associated with the pathogenesis of IgAN.

Association of proton pump inhibitor use with renal outcomes in patients with coronary artery disease

BACKGROUND: Several studies have suggested that proton pump inhibitor (PPI) use is associated with adverse renal outcomes, but obvious evidence for this association is lacking. We investigated the association between PPI use and adverse renal outcomes in patients who had undergone percutaneous coronary intervention. METHODS: Of the 1,284 patients hospitalized for percutaneous coronary intervention between January 2007 and May 2012, 934 patients with baseline estimated glomerular filtration rate greater than 60 mL/min/1.73 m2 were enrolled. Multivariable Cox models were used to examine whether PPI use was associated with acute and chronic adverse renal outcomes. RESULTS: In adjusted time-dependent Cox models, PPI use was associated with acute kidney injury (hazard ratio [HR], 1.46; 95% confidence interval [95% CI], 1.05–2.02), especially in patients aged 65 years or younger (HR, 2.08; 95% CI, 1.09 3.96) or in patients with diabetes (HR, 2.00; 95% CI, 1.23–3.25). In multivariable Cox models, the association between duration of PPI use and chronic kidney disease development was not statistically significant (HR of heavy users, 1.50; 95% CI, 0.61–3.67), but a longer duration of PPI use was associated with mild renal progression in patients younger than 65 years (HR of heavy users, 2.24; 95% CI, 1.09–4.60). CONCLUSION: Our results suggest that PPI use increases the risk of AKI development, and that PPI use is more significantly associated with acute and chronic renal injuries in younger patients.

Urine Methyl Hippuric Acid Levels in Acute Pesticide Poisoning: Estimation of Ingested Xylene Volume and Association with Clinical Outcome Parameters

To determine the relationship between the oral ingestion volume of xylene and methyl hippuric acid (MHA) in urine, we measured MHA in 11 patients whose ingested xylene volume was identified. The best-fit equation between urine MHA and ingested amount of xylene was as follows: y (ingested amount of xylene, mL/kg) = −0.052x² + 0.756x (x = MHA in urine in g/g creatinine). From this equation, we estimated the ingested xylene volume in 194 patients who had ingested pesticide of which the formulation was not available. Our results demonstrated that oxadiazole, dinitroaniline, chloroacetamide, organophosphate, and pyrethroid were xylene-containing pesticide classes, while the paraquat, glyphosate, glufosinate, synthetic auxin, fungicide, neonicotinoid, and carbamate classes were xylene-free pesticides. Sub-group univariate analysis showed a significant association between MHA levels in urine and ventilator necessity in the pyrethroid group. However, this association was not observed in the organophosphate group. Our results suggest that MHA in urine is a surrogate marker for xylene ingestion, and high urine MHA levels may be a risk factor for poor clinical outcome with some pesticide poisoning.

Long-Term Functional Outcome of Peripheral Neuropathy in Microscopic Polyangiitis with Poor Prognostic Factors: 3-Year Clinical Follow-up

Microscopic polyangiitis (MPA) is a systemic small vessel vasculitis with few or no immune deposits and no granulomatous inflammation. Peripheral neuropathy occurs in approximately 20%–30% of patients with MPA. We report a case of a 66-year-old woman who presented with paresthesia and motor weakness of the extremities and rapidly progressive glomerulonephritis. She was later diagnosed with MPA based on the findings of positive perinuclear antineutrophil cytoplasmic antibody along with findings on kidney biopsy. Nerve conduction study showed symmetric sensorimotor polyneuropathy. We followed the patient for 3 years, and she showed good functional outcome after immune-modulating therapy although Five-Factor Score more than 2 at diagnosis.

The Anion Gap is a Predictive Clinical Marker for Death in Patients with Acute Pesticide Intoxication

Pesticide formulation includes solvents (methanol and xylene) and antifreeze (ethylene glycol) whose metabolites are anions such as formic acid, hippuric acid, and oxalate. However, the effect of the anion gap on clinical outcome in acute pesticide intoxication requires clarification. In this prospective study, we compared the anion gap and other parameters between surviving versus deceased patients with acute pesticide intoxication. The following parameters were assessed in 1,058 patients with acute pesticide intoxication: blood chemistry (blood urea nitrogen, creatinine, glucose, lactic acid, liver enzymes, albumin, globulin, and urate), urinalysis (ketone bodies), arterial blood gas analysis, electrolytes (Na+, K+, Cl- HCO3 -, Ca++), pesticide field of use, class, and ingestion amount, clinical outcome (death rate, length of hospital stay, length of intensive care unit stay, and seriousness of toxic symptoms), and the calculated anion gap. Among the 481 patients with a high anion gap, 52.2% had a blood pH in the physiologic range, 35.8% had metabolic acidosis, and 12.1% had acidemia. Age, anion gap, pesticide field of use, pesticide class, seriousness of symptoms (all P < 0.001), and time lag after ingestion (P = 0.048) were significant risk factors for death in univariate analyses. Among these, age, anion gap, and pesticide class were significant risk factors for death in a multiple logistic regression analysis (P < 0.001). In conclusions, high anion gap is a significant risk factor for death, regardless of the accompanying acid-base balance status in patients with acute pesticide intoxication.

The Poisoning Information Database Covers a Large Proportion of Real Poisoning Cases in Korea

The poisoning information database (PIDB) provides clinical toxicological information on commonly encountered toxic substances in Korea. The aim of this study was to estimate the coverage rate of the PIDB by comparing the database with the distribution of toxic substances that real poisoning patients presented to 20 emergency departments. Development of the PIDB started in 2007, and the number of toxic substances increased annually from 50 to 470 substances in 2014. We retrospectively reviewed the medical records of patients with toxic exposure who visited 20 emergency departments in Korea from January to December 2013. Identified toxic substances were classified as prescription drug, agricultural chemical, household product, animal or plant, herbal drug, or other. We calculated the coverage rate of the PIDB for both the number of poisoning cases and the kinds of toxic substances. A total of 10,887 cases of intoxication among 8,145 patients was collected. The 470 substances registered in the PIDB covered 89.3% of 8,891 identified cases related to poisoning, while the same substances only covered 45.3% of the 671 kinds of identified toxic substances. According to category, 211 prescription drugs, 58 agricultural chemicals, 28 household products, and 32 animals or plants were not covered by the PIDB. This study suggested that the PIDB covered a large proportion of real poisoning cases in Korea. However, the database should be continuously extended to provide information for even rare toxic substances.

Toxicokinetics of paraquat in Korean patients with acute poisoning

To conduct a kinetic study of paraquat (PQ), we investigated 9 patients with acute PQ intoxication. All of them ingested more than 20 ml of undiluted PQ herbicide to commit suicide and arrived at our hospital early, not later than 7 h after PQ ingestion. The urine dithionite test for PQ in all of the nine patients was strongly positive at emergency room. Blood samples were obtained every 30 min for the first 2~3 h and then every 1 or 2 h, as long as the clinical progression was stable among the patients for 30 h after PQ ingestion. The area under the plasma concentration-time curve (AUCinf), which was extrapolated to infinity, was calculated using the trapezoidal rule. Toxicokinetic parameters, such as the terminal elimination half-life, apparent oral clearance, and apparent volume of distribution (Vd/F) were calculated. The maximum PQ concentration (Cmax) and the time to reach maximum PQ concentration (Tmax) were also obtained. Plasma PQ concentrations in nine patients were well described by a bi-exponential curve with a mean terminal elimination half-life of 13.1+/-6.8 h. Cmax and AUCinf were 20.8+/-25.7 mg/l and 172.5+/-160.3 h.mg/l, respectively. Apparent volume of distribution and apparent oral clearance were 50.9+/-61.3 l/kg and 173.4+/-111.2 l/h, respectively. There were a significant correlation (r =0.84; p<0.05) between the PQ amount ingested and Cmax. AUCinf also showed a significant correlation (r =0.83; p<0.05) with the PQ amount ingested. These correlations provide evidence that PQ has dose-linear toxicokinetic characteristics.

Bidirectional Crosstalk between Kidney and Lung / 대한내과학회지

Data reported recently suggest that acute kidney injury (AKI) is a systemic disease that adversely affects the function of other organs-including the heart, lung, liver, brain and immune system-which is related to the high mortality rate of affected patients. Kidney and lung function are closely related in both health and disease. Data support deleterious bidirectional crosstalk between the lung and kidney. AKI is a common complication in patients with acute respiratory distress syndrome, and has been reported to exert adverse effects on the lungs. Mortality rates for AKI combined with acute lung injury (ALI) can be up to 80% in critically ill patients. Although AKI-associated ALI presents clinically as increased pulmonary edema, the mechanism of AKI-associated ALI extends beyond simple volume overload. Data from animal studies suggest that AKI-induced pulmonary edema is related to both cardiogenic edema (due to elevated hydrostatic pressure) and non-cardiogenic edema (due to pulmonary endothelial and epithelial cell injury caused by inflammation, oxidative stress, and apoptosis). ALI with mechanical ventilation causes a decline in renal hemodynamic function and apoptosis. Elucidation of the mechanisms of kidney-lung crosstalk would facilitate development of effective therapies and reduce the mortality rate of AKI combined with respiratory failure.

Common Pesticides Used in Suicide Attempts Following the 2012 Paraquat Ban in Korea

To determine the change in pesticides used during suicide attempts after the 2012 paraquat (PQ) ban, we evaluated the annual number of suicide attempts by pesticide ingestion between 2011 and 2014. We extracted demographic, clinical outcome, and pesticide class data from the medical records of 1,331 patients that attempted suicide by pesticide ingestion. Pesticides were sorted into 5 groups: herbicides, insecticides, fungicides, other pesticides, and combined pesticides. Each group was subdivided into various classes based on publications by the respective Resistance Action Committees. The chi-square test for trends was used to compare the annual incidence of categorical variables. The total number of suicide attempts decreased each year, from 399 in 2011 to 245 in 2014. Simultaneously, PQ ingestion decreased from 253 patients in 2011 to 60 in 2014. The proportion of PQ to pesticides also decreased from 63.4% in 2011 to 24.5% in 2014. Furthermore, the rate of decrease in the proportion of PQ to all herbicide categories increased by calendar year. In conclusion, there is a significant trend in increased annual number of suicides and proportion of suicides using glyphosates and glufosinates versus total herbicides. However, the number of suicide attempts using glyphosate and glufosinate is lower than that using PQ. The ratio of persons completing suicide to those attempting suicide after pesticide ingestion has decreased every year after the PQ ban.

Idiopathic erythrocytosis in a patient on chronic hemodialysis

A 78-year-old man on hemodialysis presented to our hospital with erythrocytosis. He had started hemodialysis 4 years previously, with a hemoglobin level of 9.8 g/dL, and was administered erythropoiesis stimulating agents and ferrous sulfate. Two years previously, his hemoglobin level increased to 14.5 g/dL and the treatment for anemia was discontinued. He continued hemodialysis thrice weekly; however, the hemoglobin level had increased to 17.0 g/dL at the time of presenting to our hospital. His serum erythropoietin level was 31.4 mIU/mL (range, 3.7-31.5 mIU/mL), carboxyhemoglobin level was 0.6% (range, 0-1.5%), and oxygen saturation in ambient air was 95.4%. The JAK2 V617F mutation was not observed and other bone marrow abnormalities were not identified. The patient was diagnosed with bladder cancer and a transurethral resection was performed. Eight months after the treatment of bladder cancer, his hemoglobin level was 15.1 g/dL, and he was diagnosed with idiopathic erythrocytosis.