Abnormal Kidney Function Research Articles

Sidt2 is a key protein in the autophagy-lysosomal degradation pathway and is essential for the maintenance of kidney structure and filtration function

The regulation and homeostasis of autophagy are essential for maintaining organ morphology and function. As a lysosomal membrane protein, the effect of Sidt2 on kidney structure and renal autophagy is still unknown. In this study, we found that the kidneys of Sidt2−/− mice showed changes in basement membrane thickening, foot process fusion, and mitochondrial swelling, suggesting that the structure of the kidney was damaged. Increased urine protein at 24 h indicated that the kidney function was also damaged. At the same time, the absence of Sidt2 caused a decrease in the number of acidic lysosomes, a decrease in acid hydrolase activity and expression in the lysosome, and an increase of pH in the lysosome, suggesting that lysosomal function was impaired after Sidt2 deletion. The accumulation of autophagolysosomes, increased LC3-II and P62 protein levels, and decreased P62 mRNA levels indicated that the absence of the Sidt2 gene caused abnormal autophagy pathway flow. Chloroquine experiment, immunofluorescence autophagosome, and lysosome fusion assay, and Ad-mcherry-GFP-LC3B further indicated that, after Sidt2 deletion, the production of autophagosomes did not increase, but the fusion of autophagosomes and lysosomes and the degradation of autophagolysosomes were impaired. When incubating Sidt2−/− cells with the autophagy activator rapamycin, we found that it could activate autophagy, which manifested as an increase in autophagosomes, but it could not improve autophagolysosome degradation. Meanwhile, it further illustrated that the Sidt2 gene plays an important role in the smooth progress of autophagolysosome processes. In summary, the absence of the Sidt2 gene caused impaired lysosome function and a decreased number of acidic lysosomes, leading to formation and degradation disorders of the autophagolysosomes, which eventually manifested as abnormal kidney structure and function. Sidt2 is essential in maintaining the normal function of the lysosomes and the physiological stability of the kidneys.

289. Post COVID Syndrome Cohort Characterization

BackgroundPost COVID Syndrome (PCS) is significant morbidity following COVID-19. This study aims to identify biomarkers that predict PCS in a Gulf Coast cohort known for poor health outcomes.MethodsSince March 2020 the study Collection of Serum and Secretions for SARS CoV-2 Countermeasure Development (aka ClinSeqSer) has been enrolling subjects with confirmed acute COVID-19, with initial visit at 1 month and follow up every three months from symptom onset. At follow-up, subjects complete symptom questionnaire, physical examination, nasopharyngeal swab/saliva collection, blood draw. Subjects with >= one symptom new since COVID are PCS, remainder are Non-PCS experienced at initial one month visit and six months or longer. Univariate and bivariate analysis was carried out to study significant associations of currently available dataset (N=60).Figure 1. Post-COVID Symptoms Included if “new since covid”. For 60 subjects consented post-covid with completed questionnaire, results were analyzed. Most common symptoms reported were fatigue/tiredness or exhaustion (52%), muscle aches (38%), difficulty concentrating (33%) and headache (32%) as the most common symptoms during one month prior to their initial follow-up visit. The persistent symptoms experienced for six months or longer were fatigue/tiredness or exhaustion (25%), forgetfulness (22%), muscle aches (18%), and sleep difficulties (18%).ResultsCohort is 36 (60%) female, 24 (40%) male, age group of 49 (82%) 18-64 years, 11 (18%) 65+ years, 33 (55%) African American, 27 (45%) Caucasian. Median follow-up time after symptom onset: 290 days. Study cohort reported fatigue (52%), myalgias (38%), difficulty concentrating (33%), headache (32%) as most common symptoms during first month from initial symptom onset. Persistent symptoms ( >=6 months) are fatigue (25%), forgetfulness (22%), myalgias (18%), sleep difficulties (18%). Bivariate analysis shows that gender (female, P=0.04), past stroke/transient ischemic attack (P=0.04), deep venous thrombosis (P=0.02), abnormal kidney function (P=0.01) associate with PCS. Convalescent antibodies (ReSARS N IgG, S-RBD IgG) were measured and percentage inhibition of ACE2 spike interaction was recorded. Plasma inflammatory protein levels were measured using multiplex ELISA and Proximity Extension Assay technology during follow-up visit. Increased antibody ReSARS N IgG (2.91, 0.74-10.93; P=0.02) response and higher convalescent IL-10 (P=0.04) was associated with PCS. Percent inhibition of ACE2: spike interaction was not associated (P=0.79) with PCS. Nasal swab/saliva SARS-COV-2 sequencing has not identified a specific SARS-CoV-2 virus mutation predictive of PCS. Table 1. Demographic and Clinical Characteristics The bivariate analysis results showed that the gender (female, P=0.0354), history of stroke or transient ischemic attack (P=0.0382), chest pain from narrow heart vessels (P=0.0479), deep venous thrombosis (P=0.0241) and abnormal kidney function (P=0.0142) were associated with Post-COVID syndrome.Table 2. Antibodies and ACE2 spike inhibition. The convalescent antibodies, ReSARS N IgG and S-RBD IgG were measured in U/mL and percentage inhibition of ACE2 spike interaction was recorded during follow-up visit for PCS vs Non-PCS subjects. The increased antibody ReSARS N IgG (2.91, 0.74-10.93; P=0.0159) response was associated with Post-COVID syndrome. Percent inhibition of ACE2: spike interaction was not associated (P=0.7932) with PCS.Table 3. Plasma inflammatory protein levels. Plasma inflammatory protein levels were measured using multiplex ELISA (MSD) and Proximity Extension Assay technology (Olink) recorded during follow-up visit for PCS vs Non-PCS subjects, revealing IL-10 (P=0.0379) was associated with development of PCS.ConclusionThis study identifies initial clinical and biomarker predictors of PCS in a cohort that is 55% African American.Figure 2. Antibody ReSARS N IgG ReSARS N IgG measured in post-covid patients is significantly associated with post-COVID syndrome(P=0.0159). X axis: number of months from symptom onset to blood draw. Y axis: N IgG U/mL.Figure 3. Spike amino acid mutations Spike amino acid mutations detected in SARS-CoV-2 from acute-phase respiratory isolates. Nasal swab/saliva samples were collected from subjects with acute COVID-19 at time of enrollment into ClinSeqSer, stored at -80°C followed by RNA isolation and SARS-CoV-2 qRT-PCR. Samples with Ct value of ≤30 were then sequenced using NextSeq (Illumina). All sequences are deposited on GISAID and under BioProject (ID PRJNA681020). X axis: subject ID, with ID number increasing chronologically. Y axis: amino acid position of each mutation moving from N- to C-terminus.Disclosures Robert Garry, PhD, Zalgen Labs (Shareholder)

Occult Kidney Dysfunction in Children With Transfusion-Dependent Thalassemia.

Background: Thalassemia is the commonest hemoglobinopathy in Southeast Asia. Kidney dysfunction is an underreported sequelae in children with thalassemia. We conducted a retrospective study to identify the prevalence of and predisposing factors for kidney dysfunction in children with transfusion-dependent thalassemia (TDT).Method: Abnormal kidney function was defined as children with a glomerular filtration rate (GFR) of <90 ml/min/1.73 m2 or a decline in GFR of >20 ml/min/1.73 m2 or presence of nephrotic range proteinuria within 3 years of commencing regular (every ≤6 weeks) red cell transfusion. Data analyzed were age at diagnosis of thalassemia, number of transfusion-years, iron chelation therapy, serum ferritin, and pre-transfusion hemoglobin levels.Results: Eighty-one children were studied. Mean age was 11.72 ± 5.275 years. Thirty out of 81 (37%) demonstrated abnormal kidney function. Evidence of glomerular hyperfiltration was seen in 29/81 patients (25.85%) at their last clinic visit. This fraction was doubled [48/81 (59.3%)] when the cohort was tracked back by 3 years from the last clinic encounter. Age at diagnosis (RR, 1.157; 95% CI, 1.014–1.319; p = 0.03) and duration of receiving transfusions (RR, 0.984; 95% CI, 0.974–0.994; p = 0.001) were associated with increased risk of developing abnormal kidney function.Conclusion: Abnormal kidney function in children with TDT may be overlooked by medical personnel without active screening measures. Children receiving regular red cell transfusions require systematic surveillance to enable early detection of kidney dysfunction and timely implementation of appropriate therapeutic interventions.

Risk of chronic kidney disease in patients with obstructive sleep apnea.

Chronic kidney disease (CKD) is a global health concern and a major risk factor for cardiovascular morbidity and mortality. Obstructive sleep apnea (OSA) may exacerbate this risk by contributing to the development of CKD. This study investigated the prevalence and patient awareness of the risk of CKD progression in individuals with OSA. Adults referred to five Canadian academic sleep centers for suspected OSA completed a questionnaire, a home sleep apnea test or in-lab polysomnography and provided blood and urine samples for measurement of estimated glomerular filtration rate (eGFR) and the albumin:creatinine ratio (ACR), respectively. The risk of CKD progression was estimated from a heat map incorporating both eGFR and ACR. 1295 adults (42% female, 54 ± 13 years) were categorized based on the oxygen desaturation index (4% desaturation): <15 (no/mild OSA, n = 552), 15-30 (moderate OSA, n = 322), and >30 (severe OSA, n = 421). After stratification, 13.6% of the no/mild OSA group, 28.9% of the moderate OSA group, and 30.9% of the severe OSA group had a moderate-to-very high risk of CKD progression (p < .001), which was defined as an eGFR <60 mL/min/1.73 m2, an ACR ≥3 mg/mmol, or both. Compared to those with no/mild OSA, the odds ratio for moderate-to-very high risk of CKD progression was 2.63 (95% CI: 1.79-3.85) for moderate OSA and 2.96 (2.04-4.30) for severe OSA after adjustment for CKD risk factors. Among patients at increased risk of CKD progression, 73% were unaware they had abnormal kidney function. Patients with moderate and severe OSA have an increased risk of CKD progression independent of other CKD risk factors; most patients are unaware of this increased risk.

Translation of Pharmacodynamic Biomarkers of Antibiotic Efficacy in Specific Populations to Optimize Doses.

Antibiotic efficacy determination in clinical trials often relies on non-inferiority designs because they afford smaller study sample sizes. These efficacy studies tend to exclude patients within specific populations or include too few patients to discern potential differences in their clinical outcomes. As a result, dosing guidance in patients with abnormal liver and kidney function, age across the lifespan, and other specific populations relies on drug exposure-matching. The underlying assumption for exposure-matching is that the disease course and the response to the antibiotic are similar in patients with and without the specific condition. While this may not be the case, clinical efficacy studies are underpowered to ensure this is true. The current paper provides an integrative review of the current approach to dose selection in specific populations. We review existing clinical trial endpoints that could be measured on a more continuous rather than a discrete scale to better inform exposure–response relationships. The inclusion of newer systemic biomarkers of efficacy can help overcome the current limitations. We use a modeling and simulation exercise to illustrate how an efficacy biomarker can inform dose selection better. Studies that inform response-matching rather than exposure-matching only are needed to improve dose selection in specific populations.

Increasing urinary podocyte mRNA excretion and progressive podocyte loss in kidney contribute to the high risk of long-term renal disease caused by preterm birth

Podocyte abnormalities are common mechanism driving the progression of glomerular diseases, which account for most chronic kidney diseases (CKDs). However, the role of podocyte in the mechanism of high-risk long-term CKD caused by prematurity has not been well clarified. In present study, urine samples of 86 preterm infants and 32 full-term infants were collected, and podocyte-specific podocin mRNA levels in urine pellet were applied to indicate urinary podocyte mRNA excretion. In addition, in a preterm animal rat model, preterm rats were identified by delivery 2 days early. From the age of 3 weeks–12 months, urine samples were collected to examine podocyte mRNA excretion by measuring podocyte-specific podocin mRNA levels. Kidney samples at the age of 3 weeks, 2 months, and 12 months were collected from 8, 5 and 6 preterm rats and 9, 6 and 8 full-term rats, respectively, to examine podocyte density and podocyte area by measuring the podocyte specific nuclear marker WT-1 and the podocyte specific marker synaptopodin. As results, a more than threefold increase of urinary podocyte-specific podocin mRNA excretion rate was found in preterm infants compared with full-term infants. In addition, there was negative correlation between gestational age at birth and urinary podocin mRNA excretion. In preterm rats, a reduction in the total number of differentiated podocytes in glomeruli and an increased podocyte podocin mRNA excretion rate in urine were detected at the end of kidney differentiation. Moreover, long-term follow-up data in preterm rats showed there was an increased the risk of renal disease indicated by persistent podocyte mRNA loss, proteinuria, and enlarged glomeruli. In conclusion, increasing podocyte mRNA excretion in urine and podocyte loss in kidney led by prematurity drive the progression of long-term abnormal kidney function and could potentially explain the high risk of long-term CKD in preterm infants.

A Single Arm Clinical Trial to Assess the Combined Effectiveness of Anubhuta Kashaya and Kaishora Guggulu in the Management of Chronic Kidney Disease (CKD)

CKD encompasses a spectrum of pathophysiologic processes associated with abnormal kidney function and a progressive decline in the glomerular filtration rate (GFR). Elimination of Malas from the body is also an inductive of good health. There are totally three Malas explained by the Samhitas namely Purisha, Mutra &amp; Sweda. In Chronic Kidney Disease (CKD) where there is a less formation of Mutra, the Karma of Mutra is removing Kleda (waste products) from the body. So, the Kleda which resides in the body causes Pratiloma gati of Vata leading to different variety of diseases which involves Dusti of Rakta. Therefore, use of Mutrala &amp; Raktashodhaka Dravyas may be helpful in the subjects of CKD. There is no availability of direct description of CKD in Ayurvedic science, except Vrukka roga Adhikara of Bhaishajya Ratnavali. So, we studied the disease with Ayurvedic concepts on the basis of general signs and symptoms.&#x0D; Here 28 subjects diagnosed with Chronic Kidney Disease (CKD) fulfilling the inclusion criteria were selected incidentally for study. For each subject of CKD Amapachana and Koshtashodhana was done with Hareetakyadi churna, Anubhuta Kashaya and Kaishora Guggulu are administered as Shamanoushadhi. With this intervention, we are able to give mild to moderate improvement in subjective and objective parameters. During the study improvement of subjective parameters are well appreciated than the objective parameters. The objective of the study is to establish the combined effectiveness of Anubhuta Kashaya and Kaishora guggulu in the management of Chronic Kidney Disease.&#x0D;

Comparison of two different toxin-induced kidney fibrosis models in terms of inflammatory responses

Chronic kidney disease (CKD) is characterized by persistent abnormalities in kidney function, accompanied by structural changes. Interstitial fibrosis, characterized by the accumulation of extracellular matrix (ECM) proteins, is frequently detected during CKD development. Given the multiple underlying causes of CKD, numerous animal models have been developed to advance our understanding of human nephropathy. Herein, we compared two reliable toxin-induced mouse kidney fibrosis models in terms of fibrosis and inflammation. Administration of folic acid (250 mg/kg, intraperitoneal injection) or an adenine diet (0.25 % for three weeks) afforded similar effects on kidney function, as detected by increased serum nitrogen levels. In addition, the kidneys exhibited a similar extent of tubule dilation and kidney damage. The degree of fibrosis was compared using various biological methods. Although both models developed a significant fibrotic phenotype, the adenine diet-fed model showed a marginally higher increase in fibrosis than the folic acid model, as reflected by increased kidney ECM gene and protein levels. We further compared inflammatory responses in the kidneys. Interestingly, pro-inflammatory responses, including cytokine expression and immune cell infiltration, were significantly increased in adenine diet-fed kidneys. Furthermore, collagen expression was identified in the macrophage-infiltrated region, implying the importance of inflammation in fibrogenesis. Collectively, we observed that the adenine diet-fed kidney fibrosis model presented a higher inflammatory response with increased fibrosis when compared with the folic acid-induced kidney fibrosis model, indicating the importance of the inflammatory response in fibrosis development.

Diabetes associated risk for mortality increases with time among first stroke survivors - Findings from the Israeli National Stroke Registry.

Diabetes is a major risk factor for ischemic stroke and may affect post-stroke survival. Previous large scale studies of long-term post-stroke survival are limited and most of them excluded older patients from the study population. To compare the risk factors and sociodemographic characteristics between first ischemic stroke cases with and without diabetes and to assess the mortality risk associated with diabetes. Using population-based National Stroke Registry in Israel, all patients hospitalized for a first event of ischemic stroke between the years 2014-2018 were followed for all-cause mortality. Chi-square analysis was used to compare the differences in risk factors, sociodemographic profile and cumulative mortality between patients with and without diabetes. Cox proportional hazards models were used to estimate the hazard ratio for mortality in selected timeframes. Among 41,639 patients with a first event of ischemic stroke, 44.5% were previously diagnosed with diabetes. Diabetic patients were more likely to be males, members of the Arab ethnic group, with lower socioeconomic status and a higher prevalence of cardiovascular comorbidities, anemia, leukocytosis and abnormal kidney function. Diabetes was associated with a higher mortality risk in the first year and long term, but not in the first month following stroke. Diabetes-associated mortality risk interacted with time and age, was higher in younger age and increased with time. Our findings suggest that diabetes is associated with a higher prevalence of comorbidities among patients with first ischemic stroke and with a higher risk for mortality in the mid and long term, which is more profound in younger age.

MA12.02 Factors Associated with Severe COVID-19 Infections in Lung Cancer Patients

Lung cancer patients are at increased risk of developing complications from COVID-19 disease. Real-world data may better identify lung cancer patients who are at an increased risk of developing complications while maximizing the benefit of anti-cancer therapy. We conducted a retrospective cohort study using the VA COVID-19 Shared Data Resource (CSDR), VA Cancer Registry, and VA Corporate Data Warehouse (CDW), which centralizes electronic health data for patients seen at VA facilities nationwide. We included patients with a diagnosis of lung cancer between October 1, 2015 and December 1, 2020, and a diagnosis of COVID-19 between February 2, 2020 and December 1, 2020. Serious SARS-CoV-2 infection was defined as the occurrence of any of the following within 2 weeks after diagnosis: (a) hospitalization, (b) ICU admission, (c) utilization of respiratory support (mechanical ventilation or intubation). Data abstracted included: age at COVID-19 diagnosis, gender, race, ethnicity, urban status, date of diagnosis of lung cancer, histology, stage, cancer treatment, individual comorbidities and most recent laboratory results prior to COVID-19 diagnosis. Patients were stratified into 3 groups: mild/moderate COVID-19 infection, serious, but non-fatal infection, fatal infection. Differences in categorical variables, were assessed using χ2 test, while Kruskal-Wallis rank sum test was used for continuous variables. Multivariable logistic regression models were fit relative to the outcomes of interest, i.e., serious SARS-CoV-2 infection and death from SARS-CoV-2 infection. We identified 352 lung cancer patients with COVID-19. Of these, 54 (15.3%) had severe disease and 34 others (9.7%) died. Patients who had fatal or severe infection were older than those with mild/moderate infection (median age: 74.1 and 73.8 yrs vs. 72.1 yrs; p=0.01). Patients who suffered a fatal or severe infection were also more likely than patients with mild/moderate infection to exhibit elevated creatinine levels (50.0% and 31.5%, vs. 20.5%, p = 0.003) and low hemoglobin levels (67.6% and 51.9%, vs. 39.0%, p = 0.003). In addition, 70.6% of patients who died within two weeks of SARS-CoV-2 infection suffered from diabetes, compared to 40.2% of patients with mild/moderate infection.On multivariable logistic regression, variables associated with increased odds of severe infection or death were: age (OR: 1.07; 95% CI 1.03-1.12; p=0.002), stage IV (6.06; 1.19-30.84; 0.03), elevated creatinine (2.29; 1.2-4.39; 0.01), anemia (2.02, 1.07-3.83; 0.03). Type of cancer treatment, recent surgery or radiation, chronic obstructive pulmonary disease, hypertension, diabetes, acute myocardial infection were not associated with an increased risk of severe/fatal infection. Factors associated with fatal infection included checkpoint inhibitor therapy (OR: 7.06; 95% CI, 1.21-41.11; p=0.03), diabetes (3.53; 1.9-11.46; 0.04) and abnormal creatinine level (4.48; 1.52-13.15; 0.006). Almost 25% of lung cancer patients with COVID-19 infection developed complications or died. Increasing age, stage IV disease, abnormal kidney function and low hemoglobin level were associated with a severe/fatal SARS-CoV-2 infection, while checkpoint inhibitor therapy, diabetes and abnormal creatinine levels were associated with increased mortality from COVID-19 disease.

Особливості порушень ліпідного спектра та компонентів системи згортання крові у дітей із коморбідними станами при ювенільному ідіопатичному артриті

Актуальність. У дітей і підлітків із ювенільним ідіопатичним артритом (ЮІА) прискореному розвитку атеросклерозу та формуванню коморбідної патології сприяє висока імунозапальна активність хвороби. Зазвичай формування атеросклерозу відбувається паралельно з порушеннями системи згортання крові, тобто виникають явища атеротромбозу. Через це вважалось за необхідне визначити особливості ліпідного спектра крові та системи гемостазу в дітей з ЮІА та коморбідною патологією. Матеріали та методи. Обстежено 97 дітей (5–18 років) хворих на ЮІА. Пацієнти були розподілені на дві групи. Першу групу становили 38 дітей (39,2 %) без ознак коморбідної патології, у другу групу (з ознаками коморбідної патології) увійшло 59 дітей (60,8 %). Вивчали ліпідний спектр крові та коагулограму. Статистична обробка проводилась за допомогою пакета статистичних програм Statgrafics 16.0. Результати. У дітей з ЮІА та проявами коморбідної патології встановлено ознаки гіперкоагуляції, особливо виражені при порушенні ліпідного спектра крові. Під час дослідження параметрів ліпідного спектра крові у хворих із високими показниками фібриногену встановлено підвищення рівня ліпопротеїнів низької щільності (р &lt; 0,02), тригліцеридів (р &lt; 0,02) та коефіцієнта атерогенності (р &lt; 0,03). При аналізі функції нирок встановлено, що в групі з коморбідною патологією у 21,4 % дітей показники швидкості клубочкової фільтрації знаходились або в межах дуже низьких значень, або в межах гіперфільтрації. Показники протеїнурії у дітей групи з коморбідністю мали більш високі значення і потребували особливої уваги. Аналіз ліпідного спектра крові в групі хворих з ознаками порушень функції нирок свідчить, що у цих хворих ще більше зростає рівень атерогенних фракцій ліпідів. За результатами аналізу системи згортання в цій групі виявлено лише підвищення протромбінового індексу (р &lt; 0,05). Отже, в дітей з ЮІА формування коморбідної патології відбувається на тлі активності процесу, супроводжується формуванням атерогенних дисліпідемій і підвищенням тромбогенного потенціалу системи згортання крові. Зростання концентрації циркулюючих імунних комплексів і залучення нирки до патологічного процесу підвищує ступінь патологічних змін ліпідного спектра крові та системи гемостазу. Висновки. Встановлено, що прогностично не сприятливими ознаками формування коморбідної патології у хворих на ЮІА є: збереження активності патологічного процесу з підвищенням концентрації циркулюючих імунних комплексів, наявність протеїнурії, підвищення рівня загального холестерину, коефіцієнта атерогенності та фібриногену.

Association between abnormal renal function and sleep among male coal workers in Xingtai City

Objective To explore the relationship between sleep duration, insomnia, shift work and kidney function among male coal workers in Xingtai City, and to provide a theoretical basis for the prevention and treatment of kidney diseases in male coal workers. Methods A cross-sectional study was uesd. Relevant information was collected through questionnaires and blood biochemical analysis. Mutiple Logistic regression model was used to explore the relationship between abnormal renal function and sleep, night shift work. Results The prevalence of abnormal renal function among male workers in coal enterprises was 5.3%. The proportion of individuals with night shift work, sleep duration ≤5 h and insomnia were 63.2%, 4.0%, and 10.0% respectively. After adjusting for age, sleep duration, shift work and and insomnia, the results of multivariate Logistic regression analysis model showed that the relationship between shift work (OR=1.557, 95% CI: 1.078-2.250, P=0.018), sleep duration ≤ 5 h (OR=1.886, 95% CI: 1.005-3.540, P=0.048), group with sleep problems (OR=1.810, 95% CI: 1.286-2.546, P=0.001) and abnormal renal function was attenuated. The relationship between insomnia and abnormal renal function was not statistically significant (P=0.279). According to the stratified analysis of the shift work, after adjusting the related abnormal renal function among shift workers (Ptrend=0.001). Conclusions Sleep and shift work independently associate with abnormal renal function in male coal workers. The risk of abnormal kidney function increases with the severity of sleep problems.

Environmental exposure to lead, mercury, and cadmium is not associated with abnormal kidney function in Korean adolescents.

We aimed to elucidate the relationship between environmental exposure to lead (Pb), mercury (Hg), and cadmium (Cd) which were measured in blood and the kidney function of adolescents. Cross-sectional study was conducted using data from the Korea National Health and Nutrition Examination Survey from 2010 to 2017. Statistical procedures were performed to analyze the Korean population of adolescents aged 12-17years. Regression analysis was performed, and covariates included age, sex, body mass index, smoking status, and other heavy metal levels. The median blood levels of Pb, Hg, and Cd were 1.165μg/dL, 1.805μg/L, and 0.304μg/L, respectively. Adolescents with Pb levels in the highest quartile (> 1.454μg/dL) had a 3.35mL/min/1.73 m2-lower estimated glomerular filtration rate using creatinine (eGFRcr) (95% confidence interval (CI), -6.03 to -0.68mL/min/1.73 m2) compared to those in the lowest quartile (< 0.856μg/dL) in the unadjusted model. However, there was no association between the blood Pb level and eGFRcr in the adjusted model. Levels of Hg and Cd were not associated with eGFRcr in either model. High blood levels of all three heavy metals were not associated with the risk of hypertension. There was no association between increased blood levels of Pb, Hg, and Cd; eGFRcr; and increased risk of hypertension in Korean adolescents who were exposed to relatively low levels of heavy metals.

Complications after native kidney biopsy: definitive data.

To assess the risk of complications associated with native kidney biopsies. This review will highlight recent advances on the risk factors for major bleeding and risk management in patients with native kidney biopsy. Recent studies provided new important data regarding the individualization of the risk of bleeding after kidney biopsy. A new bleeding risk score was proposed as a risk stratification tool, useful for shared decision making and procedure choice. The risk of complications is low (<1%) in most patients but varies widely. Risk factors include Charlson index, frailty index, female gender, dyslipidemia, anemia, thrombocytopenia, cancer, abnormal kidney function, glomerular disease, autoimmune disease, vasculitis, hematologic disease, and thrombotic microangiopathy. A new bleeding score can help physicians and patients to assess the risk of bleeding enabling informed consent, and decide to perform it or not, and to prefer transjugular vs percutaneous route.

English

BACKGROUND Chronic kidney disease (CKD) includes a spectrum of different pathophysiology processes associated with abnormal kidney function, and a progressive decline in GFR. Progression of CKD is associated with having a number of complications, including thyroid dysfunction, dyslipidaemia, and cardiovascular diseases. METHODS The present study was conducted among 60 CKD patients (cases) and 60 healthy controls to compare their thyroid and lipid profile, who attended the Department of Medicine in SGRDIMSR, Sri Amritsar from January 2019 to December 2020.These 60 CKD patients were grouped as group A. Group A was further divided into various stages as per KIDGO staging according to GFR. 60 healthy individuals were taken as controls and were kept as Group B. Demographic features (age and sex) and medical history of diabetes mellitus, hypertension were noted and blood samples (5mL) were analysed for blood urea, serum creatinine, free triiodothyronine (T3), free thyroxine (T4), thyroid stimulating hormone (TSH), total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), very low density lipoprotein (VLDL) and triglycerides. RESULTS Thyroid dysfunction was observed in patients of CKD, the most common being overt hypothyroidism (56.6 %) followed by subclinical hypothyroidism (16.6 %), low T3 (15 %), and hyperthyroidism (1.6 %). Hypercholesterolemia, low HDL, elevated LDL, VLDL and triglyceride levels were observed in 74.9 %, 85.0 %, 38.3 %, 41.6 % and 76.6 % patients, respectively. Patients with CKD with 5 had significantly higher risk of having thyroid dysfunction and dyslipidaemia as compared to patients with stage 3 and 4. CONCLUSIONS Thyroid dysfunction and dyslipidaemia were common in patients with CKD. Prevalence of hypothyroidism, dyslipidaemia increases with progression of CKD. Hence early detection of thyroid dysfunction and dyslipidaemia is imperative to improve mortality and morbidity of CKD patients. KEYWORDS Chronic Kidney Disease, Dyslipidaemia, Thyroid Dysfunction

The impact of periodontal disease and dental cleaning procedures on serum and urine kidney biomarkers in dogs and cats.

The objective of this study was to evaluate the benefits and inherent risks of dental cleaning procedures, based on serum and urine biomarkers for kidney function and tissue damage, in dogs and cats. Thirty-one asymptomatic, mostly older dogs (14 neutered male and 17 ovariohysterectomized female dogs of various breeds between 3 and 14 years old) and cats (19 neutered male and 12 ovariohysterectomized female domestic short hair cats between 2 and 16 years old) diagnosed with periodontal disease on physical exam, and recommended by their veterinarian to have dental cleaning under general anesthesia were evaluated in a prospective study. Serum and urine samples were collected from dogs and cats 1 week before, 6 hours after, and again 1 week after the dental cleaning procedure. Samples were analyzed for biomarkers of kidney function [serum creatinine (Cr), symmetric dimethylarginine (SDMA), and blood urea nitrogen (BUN), and urine for specific gravity (USG) and protein:creatinine (UPC) ratio]. A panel of biomarkers for renal tissue damage was also assessed [serum β-aminoisobutyric acid (BAIB), and urine cystatin B and clusterin]. Samples collected one week before dental cleaning procedures showed that increased age and severity of dental disease were linked to abnormal kidney function biomarker values (age: elevated SDMA and Cr concentrations and isosthenuric USG values; disease severity: elevated UPC ratios) as well as elevated urine cystatin B and clusterin concentrations. Directly after the dental cleaning procedure, an increased number of cats with elevated SDMA concentrations was observed (specifically in cats with longer duration of dental procedures). Extended duration of dental procedures (≥60 min) was linked to increased urine cystatin B and clusterin concentrations, whereas shorter duration procedures was linked to decreased urine cystatin B and clusterin. Higher SDMA concentrations persisted in cats one week after the dental cleaning procedures and were linked to elevated UPC ratios one week before cleaning procedures. In conclusion, the results of this study indicate a link between severity of dental disease, renal tissue injury, and impaired renal function. Longer duration dental procedures in cats may carry inherent risks of kidney injury and impaired renal function.

Study of clinical profile of chronic kidney disease in non-diabetic patients

Background: Chronic kidney disease (CKD) encompasses a spectrum of different pathophysiological processes associated with abnormal kidney function and a progressive decline in glomerular filtration rate. Cardiovascular disease is one of the major cause of morbidity and mortality in patients at every stage of CKD. Diabetes mellitus and hypertension together being major cause for CKD. Hypertension is a common cause for CKD and an independent risk factor for cardiovascular disease. This study mainly focused on the causes of CKD other than diabetes mellitus. An early detection and appropriate intervention of these patients will possibly help prevent progression of renal disease.Methods:We assessed 55 non diabetic CKD patients who presented to the OPD/IPD in Victoria hospital, Bowring and Lady Curzon hospital and other hospitals affiliated to Bangalore medical college and research institute during period June 2018 to December 2019. A detailed history and clinical examination was performed and patients were subjected to necessary investigations.Results: The commonest etiology for CKD was found to be hypertensive nephropathy followed by glomerulonephritis. Common symptoms were generalized weakness, lower limb swelling. Commonest signs are pallor, pedal edema and hypertension.Conclusions:CKD is a major health problem. Diabetic nephropathy is the commonest cause for CKD followed by hypertensive nephropathy and glomerulonephritis. Anaemia, pedal oedema, oliguria and generalised weakness were the major presenting clinical signs and symptoms in CKD. This condition when detected in early stages and managed can slow down the progression of CKDs and delay the need of renal replacement therapy.

Robotics-assisted epicardial left atrial appendage clip exclusion.

ObjectivesWe demonstrate the feasibility and safety of robotics-assisted left atrial appendage clip exclusion in clinical practice.MethodsAnalysis of a single center robotics-assisted left atrial appendage clip exclusion experience using an epicardial linear clip device in patients with atrial fibrillation with high-risk of thromboembolic stroke and intolerance to oral anticoagulants.ResultsDuring the period from December 2017 to September 2020, we performed 42 robotics-assisted left atrial appendage clip exclusions in response to increased risk of bleeding in patients with atrial fibrillation and intolerance to oral anticoagulants. The average congestive heart failure, hypertension, age, diabetes, stroke, and vascular disease score was 5.2 ± 1.6 and hypertension, abnormal liver or kidney function, stroke, bleeding, labile international normalized ratio, elderly, drugs (aspirin, other antiplatelets, or anticoagulants) score was 4.5 ± 0.9. No patients died intraoperatively or within 30 days, or due to conversion to thoracotomy, intraoperative complications, or failure to apply the clip satisfactorily. The procedure was successfully completed despite pericardial adhesions in 2 patients with prior coronary bypass grafts and 3 with postpericarditis scars. Intraoperative transesophageal echocardiography was performed in 38 out of 42 patients; satisfactory exclusion with left atrial appendage stump <5 mm was confirmed in all. Average length of stay was 3.4 ± 3 days with 12 out of 42 patients discharged within 24 hours. Oral anticoagulants were discontinued in 41 out of 42 patients and no cases of 30-day stroke, myocardial ischemia, or new arrhythmias were observed. One case of hemothorax required thoracoscopy a day later. There was no reported thromboembolic stroke or transient ischemic attack at 12 months. One case of late lacunar stroke was due to in situ small intracranial vessel thrombosis without left atrial appendage thrombus on imaging.ConclusionsRobotics-assisted left atrial appendage clip exclusion is a safe and feasible minimally invasive method for left atrial appendage management in patients with atrial fibrillation with intolerance to oral anticoagulants and increased risk of thromboembolic stroke.

A common disease masked by complex clinical manifestations: A case report of hypothyroidism

Background: Hypothyroidism is a common disease in elderly people. Although hypothyroidism can theoretically have clinical implications related to nearly all major organs, it is often excluded from diagnostic algorithms for elderly patients with multi-system disease because its symptoms are non-specific. Case summary: A 61-year-old woman presented with dizziness, fatigue, facial swelling, dry cracked skin, and myalgia. She had a 2-year history of impairment of multiple organs and multiple adverse drug events. Blood tests showed abnormal liver and kidney function, an elevated creatine kinase concentration, and hyperlipidaemia. During the last 2 years, she had experienced multiple severe adverse drug events, including eosinophilia and systemic symptoms caused by carbamazepine, acute kidney impairment related to ceftriaxone and cefdinir, exfoliative dermatitis caused by ceftazidime, and intolerance to statins. After visiting several large hospitals, she was finally diagnosed in our clinic with hypothyroidism. At the time of diagnosis, she was extremely ill and unable to walk independently. After taking levothyroxine, all of her symptoms and signs completely resolved. Conclusion: Hypothyroidism might be overlooked in elderly patients, especially those with complex and severe clinical conditions. Keywords: Aged; adverse drug events; multiple organ dysfunction; hypothyroidism.

Comparative Effectiveness of Machine Learning Approaches for Predicting Gastrointestinal Bleeds in Patients Receiving Antithrombotic Treatment

Anticipating the risk of gastrointestinal bleeding (GIB) when initiating antithrombotic treatment (oral antiplatelets or anticoagulants) is limited by existing risk prediction models. Machine learning algorithms may result in superior predictive models to aid in clinical decision-making. To compare the performance of 3 machine learning approaches with the commonly used HAS-BLED (hypertension, abnormal kidney and liver function, stroke, bleeding, labile international normalized ratio, older age, and drug or alcohol use) risk score in predicting antithrombotic-related GIB. This retrospective cross-sectional study used data from the OptumLabs Data Warehouse, which contains medical and pharmacy claims on privately insured patients and Medicare Advantage enrollees in the US. The study cohort included patients 18 years or older with a history of atrial fibrillation, ischemic heart disease, or venous thromboembolism who were prescribed oral anticoagulant and/or thienopyridine antiplatelet agents between January 1, 2016, and December 31, 2019. A cohort of patients prescribed oral anticoagulant and thienopyridine antiplatelet agents was divided into development and validation cohorts based on date of index prescription. The development cohort was used to train 3 machine learning models to predict GIB at 6 and 12 months: regularized Cox proportional hazards regression (RegCox), random survival forests (RSF), and extreme gradient boosting (XGBoost). The performance of the models for predicting GIB in the validation cohort, evaluated using the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, positive predictive value, and prediction density plots. Relative importance scores were used to identify the variables that were most influential in the top-performing machine learning model. In the entire study cohort of 306 463 patients, 166 177 (54.2%) were male, 193 648 (63.2%) were White, the mean (SD) age was 69.0 (12.6) years, and 12 322 (4.0%) had experienced a GIB. In the validation data set, the HAS-BLED model had an AUC of 0.60 for predicting GIB at 6 months and 0.59 at 12 months. The RegCox model performed the best in the validation set, with an AUC of 0.67 at 6 months and 0.66 at 12 months. XGBoost was similar, with AUCs of 0.67 at 6 months and 0.66 at 12 months, whereas for RSF, AUCs were 0.62 at 6 months and 0.60 at 12 months. The variables with the highest importance scores in the RegCox model were prior GI bleed (importance score, 0.72); atrial fibrillation, ischemic heart disease, and venous thromboembolism combined (importance score, 0.38); and use of gastroprotective agents (importance score, 0.32). In this cross-sectional study, the machine learning models examined showed similar performance in identifying patients at high risk for GIB after being prescribed antithrombotic agents. Two models (RegCox and XGBoost) performed modestly better than the HAS-BLED score. A prospective evaluation of the RegCox model compared with HAS-BLED may provide a better understanding of the clinical impact of improved performance.