Kidney Dysfunction In Patients Research Articles

Aberrant proximal tubule DNA methylation underlies phenotypic changes related to kidney dysfunction in patients with diabetes.

Epigenetic mechanisms are considered to contribute to diabetic nephropathy by maintaining memory of poor glycemic control during the early stages of diabetes. However, DNA methylation changes in the human kidney are poorly characterized, because of the lack of cell type-specific analysis. We examined DNA methylation in proximal tubules purified from diabetic nephropathy patients and identified differentially methylated CpG sites, given the critical role of proximal tubules in the kidney injury. Hypermethylation was observed at CpG sites annotated to genes responsible for proximal tubule functions, including gluconeogenesis, nicotinamide adenine dinucleotide synthesis, transporters of glucose, water, phosphate, and drugs, in diabetic kidneys, while genes involved in oxidative stress and the cytoskeleton exhibited demethylation. Methylation levels of CpG sites annotated to ACTN1, BCAR1, MYH9, UBE4B, AFMID, TRAF2, TXNIP, FOXO3, and HNF4A were correlated with the estimated glomerular filtration rate, while methylation of the CpG site in RUNX1 was associated with interstitial fibrosis and tubular atrophy. Hypermethylation of G6PC and HNF4A was accompanied by decreased expression in diabetic kidneys. Proximal tubule-specific hypomethylation of metabolic genes related to HNF4A observed in control kidneys was compromised in diabetic kidneys, suggesting a role for aberrant DNA methylation in the dedifferentiation process. Multiple genes with aberrant DNA methylation in diabetes overlapped genes with altered expressions in maladaptive proximal tubule cells, including transcription factors PPARA and RREB1. In conclusion, DNA methylation derangement in the proximal tubules of patients with diabetes may drive phenotypic changes, characterized by inflammatory and fibrotic features, along with impaired function in metabolism and transport.

The impact of mild and moderate COVID-19 infection on the progression of kidney dysfunction in patients with IgA nephropathy.

Previous research indicates that coronavirus disease 2019 (COVID-19) infection may have a role in triggering immunoglobulin A (IgA) nephropathy. However, limited research has explored the clinical implications of COVID-19 infection in individuals already diagnosed with IgA nephropathy. This study aimed to determine whether COVID-19 infection independently affects the subsequent trajectory of kidney function in IgA nephropathy patients. This was a single-center cohort study. The study included 199 patients diagnosed with IgA nephropathy. The COVID-19 infection status was determined using a combined method: a questionnaire and the Health Code application, both administered at the end of 2022 in northern China. Kidney function trajectory was assessed by the estimated glomerular filtration rate (eGFR), calculated based on serum creatinine levels measured during follow-up outpatient visits. The primary endpoint of interest was the eGFR trajectory. Out of the 199 participants, 75% (n=181) reported a confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, determined through antigen or polymerase chain reaction tests, accounting for 79% (n=143) of the infected patients. A significant majority (98%) experienced mild to moderate symptoms. Over a median follow-up period of 10.7months post-COVID-19 infection, notable clinical events included gross hematuria in 30 patients (16.6%), which normalized within an average of 3days. Additionally, a 2-fold increase in proteinuria or progression to the nephrotic range was observed in 10 individuals (5.5%). No cases of acute kidney injury were noted. COVID-19 exposure was associated with an absolute change in eGFR of 2.98mL/min/1.73m2 per month (95% confidence interval 0.46 to 5.50). However, in a fully adjusted model, the estimated changes in eGFR slope post-COVID-19 were -0.39mL/min/1.73m2 per month (95% confidence interval -0.83 to 0.06, P=.088) which included the possibility of no significant effect. Notably, a higher rate of kidney function decline was primarily observed in patients with a baseline eGFR <45mL/min/1.73m2 [-0.56mL/min/1.73m2 (-1.11 to -0.01), P=.048]. In the cohort, there were few instances of severe COVID-19 cases. The absence of long-term follow-up outcomes was observed. Overall, mild to moderate COVID-19 infection does not appear to significantly exacerbate the subsequent decline in kidney function among IgA nephropathy patients, particularly in those with preserved baseline kidney function.

#1043 Metabolomics and proteomics study on kidney function post-liver transplantation

Abstract Background and Aims Hepatorenal syndrome (HRS) is a serious complication characterized by kidney dysfunction in patients with advanced liver disease. The pathophysiology of HRS is poorly understood and involves a combination of hemodynamic, circulatory, inflammatory, and hormonal factors. While some patients with HRS restore kidney function after liver transplantation (LT), others continue to have impaired kidney function. Understanding the mechanisms associated with persistent kidney dysfunction is essential for developing effective treatments and stratifying patients for combined liver-kidney transplantation versus LT only. Method We analyzed serum samples from 10 patients of the multicenter prospective study (INAID CTOT14). Five of them had no HRS and maintained an eGFR &amp;gt; 50 ml/min post-LT. One patient with HRS recovered kidney function post-LT. Four patients with HRS failed to regain kidney function at one- and two-months post-LT (eGFR &amp;lt; 30 ml/min). We categorized the five patients without HRS and one patient with recovered eGFR as Normal Kidney Function (NKF) group and the other four patients as Impaired Kidney Function (IKF) group. Serum samples were collected at one (visit 1) and two months (visit 2) post-LT and stored at −80°C until analysis. Both untargeted metabolomics and proteomics analysis were conducted using quantitative liquid chromatography tandem mass spectroscopy (LC-MS/MS) on Agilent® Q-TOF 6546. Data was analyzed by Agilent® Qualitative Workflow 10, Agilent® Profinder 10, MetaboAnalyst (V6.0), and Spectrum Mill MS software. Results A total of 150 metabolites were identified by LC-MS/MS based metabolomics. Principal component analysis (PCA) did not show significant differences between visit 1 and visit 2 samples (Fig. 1A). Therefore, visit 1 and visit 2 samples were analyzed together. With 12 samples in NKF and 8 samples in IKF group, the PCA score plot showed distinct clustering of the two groups (Fig. 1B). Volcano plot analysis was conducted to analyze metabolite differences between NKF and IKF. P-values were calculated using a Student's t-test, and differential metabolites were identified with a P-value cut-off of &amp;lt; .05 and a fold change &amp;gt; 2.0. The result revealed 37 downregulated and 13 upregulated metabolites when comparing NKF and IKF (Fig. 1C). Notably, creatinine was among the downregulated metabolites in the NKF group, validating the accuracy of our analysis. Untargeted proteomics analysis was also performed on all 20 samples. Using a P-value cut-off of .05 and a fold change &amp;gt;1.25, 43 proteins were found to be upregulated, and four proteins to be downregulated when comparing NKF to IKF. Fig. 2A lists the top 10 regulated proteins, with beta-2-microglobulin as the most significantly changed. Reactome® pathway analysis of these 47 proteins highlighted potential impacts on various biological pathways (Fig. 2B), providing potential valuable insights into the molecular alterations associated with kidney function post-LT. Conclusion Our comprehensive metabolomics and proteomics study characterized the molecular alterations associated with kidney function post-LT. The identified metabolites and proteins may provide valuable insights for understanding persistent kidney damage. Future research is warranted to confirm and correlate these findings with clinical outcomes, enhancing the applicability and significance of our results in the broader context of HRS and LT.

Impact of Chronic Kidney Disease on Major Adverse Cardiac Events in Patients with Acute Myocardial Infarction: A Retrospective Cohort Study

Background: Acute Myocardial Infarction (AMI) results in a reduction in patients’ life expectancy. Different risk factors affect the risk of Major Adverse Cardiac Events (MACE). Although the role of kidney dysfunction in patients with Chronic Kidney Disease (CKD) in cardiac events has been identified, many patients with AMI are unaware of their underlying kidney disease. This study aimed to compare the incidence of adverse cardiovascular events and identify predictors of major adverse cardiovascular events in the medium term among patients with and without renal dysfunction following AMI. Methods: This retrospective cohort study was conducted on 1039 patients who were hospitalized for Acute Myocardial Infarction (AMI) between 2018 and 2019. The patient cohort comprised 314 women (mean age: 69.8 ± 13.2 years) and 725 men (mean age: 60.5 ± 13.8 years). Patient data were obtained from the registry of patients with acute myocardial infarction and the participants were followed up for a minimum of one year following hospital discharge to assess the incidence of MACE. Results: The study found that patients with a Glomerular Filtration Rate (GFR) level below 60 had a significantly higher mortality rate than those with a GFR level of 60 or above (15.7% vs. 3.5%, p &lt; 0.0001). The multivariate analysis showed that Diabetes Mellitus (DM), GFR, and Non-ST Elevation Myocardial Infarction (NSTEMI) are significant risk factors for cardiovascular events. (p = 0.016, p = 0.015, p = 0.006 respectively), while variables such as sex, age, and Hypertension (HTN) were not significant risk factors. There was a negative correlation between GFR and death (0.241 - = r, p &lt; 0.0001) Conclusion: This study highlights the importance of detecting kidney disease during an AMI and managing risk factors for cardiovascular disease to improve health outcomes and reduce the risk of mortality.

Impact of Thyroid Status on Incident Kidney Dysfunction and Chronic Kidney Disease Progression in a Nationally Representative Cohort

ObjectiveTo examine the relationship between thyroid status and incident kidney dysfunction/chronic kidney disease (CKD) progression. Patients and MethodsWe examined incident thyroid status, ascertained by serum thyrotropin (TSH) levels measured from January 1, 2007, through December 31, 2018, among 4,152,830 patients from the Optum Labs Data Warehouse, containing deidentified retrospective administrative claims data from a large national health insurance plan and electronic health record data from a nationwide network of provider groups. Associations of thyroid status, categorized as hypothyroidism, euthyroidism, or hyperthyroidism (TSH levels >5.0, 0.5-5.0, and <0.5 mIU/L, respectively), with the composite end point of incident kidney dysfunction in patients without baseline kidney dysfunction and CKD progression in those with baseline CKD were examined using Cox models. ResultsPatients with hypothyroidism and hyperthyroidism had higher risk of incident kidney dysfunction/CKD progression in expanded case-mix analyses (reference: euthyroidism): adjusted hazard ratios (aHRs) (95% CIs) were 1.37 (1.34 to 1.40) and 1.42 (1.39 to 1.45), respectively. Incrementally higher TSH levels in the upper reference range and TSH ranges for subclinical, mild overt, and overt hypothyroidism (≥3.0-5.0, >5.0-10.0, >10.0-20.0, and >20.0 mIU/L, respectively) were associated with increasingly higher risk of the composite end point (reference: TSH level, 0.5 to <3.0 mIU/L): aHRs (95% CIs) were 1.10 (1.09 to 1.11), 1.37 (1.34 to 1.40), 1.70 (1.59 to 1.83), and 1.70 (1.50 to 1.93), respectively. Incrementally lower TSH levels in the subclinical (<0.5 mIU/L) and overt (<0.1 mIU/L) hyperthyroid ranges were also associated with the composite end point: aHRs (95% CIs) were 1.44 (1.41 to 1.47) and 1.48 (1.39 to 1.59), respectively. ConclusionIn a national cohort, TSH levels in the upper reference range or higher (≥3.0 mIU/L) and below the reference range (<0.5 mIU/L) were associated with incident kidney dysfunction/CKD progression.

Association between specific ultrasound features of joints and impaired kidney function among gout patients.

To investigate the relationship between the specific ultrasonic manifestations of lower limb joints and impaired kidney function in gouty arthritis. In this cross-sectional study, 408 patients with gouty arthritis were divided into two groups based on the status of renal function: normal group (n = 240) and renal impairment (n = 168) group. All patients underwent ultrasound examination of the bilateral knee, ankle, and first metatarsophalangeal joints to detect ultrasound features of double-contour sign (DC) and tophus. Multiple logistic regression analysis was conducted to assess the association between kidney dysfunction and ultrasound features. A number of potential clinical confounders were adjusted in the model. Univariable conditional logistic regression produces several significant risk factors of impaired kidney function which were the highest and current lever of serum urate acid, course of disease, frequency of attack, hyperlipidemia, hypertension, diabetes, coronary heart disease, presence of multiple tophus, and DC (P < 0.05). After correcting the course of disease and other risk factors, tophus was still an independent risk factor of impaired kidney function and the multivariable adjusted odds ratios (95% CI) was 1.789 (1.005-3.185, P = 0.05), however, the association was not significant in DC (OR = 1.098, 95% CI: 0.668-1.803, P = 0.71). The ultrasound feature of tophus was associated with kidney dysfunction in patients with gout, independent of clinical risk factors, which may be helpful in guiding clinical practice.

ДИСФУНКЦИЯ ПОЧЕК КАК ПРЕДИКТОР ПРОГРЕССИРОВАНИЯ АРТЕРИАЛЬНОЙ ГИПЕРТЕНЗИИ

A review of approaches to the treatment and early diagnosis of kidney dysfunction in patients with arterial hypertension is presented: the relevance of the problem, causes, pathogenetic mechanisms, clinical symptoms, diagnosis, new directions in treatment and prevention.

Association between intraoperative starch use and postoperative kidney dysfunction in patients undergoing major gastro-intestinal surgery: A propensity score-matched analysis.

The impact of intraoperative starch-based fluid therapy on postoperative kidney dysfunction in patients undergoing major abdominal surgery is uncertain. Low molecular weight starch is expected to cause less postoperative kidney dysfunction. This retrospective study evaluated the impact of intraoperative 6% hydroxyethyl starch on postoperative renal dysfunction. The primary outcome of this study was postoperative acute kidney injury as per KDIGO definition within 72 hours of surgery. This study analysed data from 461 patients with a median (interquartile range) age of 45 (33-58) years, and 48.2% of all patients were female. The proportion (95% confidence interval) of patients who developed acute kidney injury was 0.18 (0.14-0.21); 62.9% of patients had acute kidney injury stage I, 32% had acute kidney injury stage II, and the rest were acute kidney injury stage III. In the propensity score-matched sample, the average treatment effect of intraoperative colloid use on postoperative serum creatinine at day 3 (p = 0.32), duration of postoperative intensive care unit stay (p = 0.97), duration of hospital stay (p = 0.37), postoperative worst international normalised ratio (p = 0.92), and postoperative transfusion requirement (p = 0.40) were not statistically significant. Intraoperative use of low molecular weight hydroxyethyl starch use was not associated with postoperative kidney dysfunction and coagulopathy in adult patients undergoing major open abdominal surgery.

Predictors and significance of kidney dysfunction in patients with chronic graft-versus-host disease.

Kidney complications have been studied in allogeneic hematopoietic stem cell transplant patients but not specifically among chronic graft-versus-host disease (cGVHD) patients. Participants (n = 365) enrolled in the cross-sectional cGVHD natural history study (NCT00092235) were assessed for kidney dysfunction and overall survival. Kidney dysfunction was analyzed for associations in univariate and multivariable analyses. Kidney dysfunction (eGFR < 60) was found in 64 patients, and 29 patients had moderate-severe kidney dysfunction (eGFR < 45). Patients with kidney dysfunction were more likely treated with cyclosporine at evaluation or to have received it for GVHD prophylaxis, or prior treatment of GVHD. Patients with kidney dysfunction were less severely affected by cGVHD of skin, mouth, and joints/fascia. In multivariable modeling, history of cyclosporine use (OR = 2.19, 95% CI 1.13-4.25), angiotensin receptor blocker use (OR = 5.57, 95% CI 1.49-20.84), proteinuria (OR = 2.39, 95% CI 1.19-4.79), lower CRP (OR = 0.95, 95% CI 0.91-0.99), lower C3 (OR = 0.98, 95% CI 0.97-0.99), and lower hemoglobin (OR = 0.70, 95% CI 0.58-0.84) were jointly associated with kidney dysfunction. Overall survival was lower in those with moderate-severe kidney dysfunction (p = 0.015), demonstrating the importance of addressing kidney dysfunction in this population. The association of kidney dysfunction with less severe cGVHD suggests an etiology unrelated to cGVHD but potentially a consequence of drug-related toxicities.

Association between fatty liver index and risk of end-stage renal disease stratified by kidney function in patients with type 2 diabetes: A nationwide population-based study

ObjectiveThe effects of nonalcoholic fatty liver disease on the risk of end-stage renal disease (ESRD) remain unclear. We investigated the association between the fatty liver index (FLI) and risk of ESRD in patients with type 2 diabetes. MethodsThis population‐based observational cohort study enrolled patients with diabetes who underwent health screening between 2009 and 2012 and utilized data from the Korean National Health Insurance Services. The FLI functioned as a surrogate marker for the presence of hepatic steatosis. Chronic kidney disease (CKD) was defined as an estimated glomerular filtration rate < 60 ml/min/1.73 m² calculated using the Modification of Diet in Renal Disease equation. We performed Cox proportional hazards regression. ResultsIncident ESRD developed in 19,476 of 1,900,598 patients with type 2 diabetes during a median follow-up of 7.2 years. After adjusting for conventional risk factors, patients with high FLI scores had a higher risk for ESRD: FLI, 30–59 [hazard ratio (HR) = 1.124; 95% confidence interval (CI), 1.083–1.166]; FLI ≥ 60 [HR = 1.278; 95% CI, 1.217–1.343] compared with those with FLI < 30. The association between a high FLI score (≥ 60) and incident ESRD was more prominent in women than in men (male, FLI ≥60: HR, 1.106; 95% CI = 1.041–1.176 and female, FLI ≥ 60: HR, 1.835; 95% CI = 1.689–1.995). The association between a high FLI score (≥ 60) and the risk of ESRD differed according to baseline kidney function. High FLI scores increased the risk of ESRD (HR = 1.268; 95% CI, 1.198–1.342) in patients with CKD at baseline. ConclusionHigh FLI scores are associated with a greater risk of ESRD in patients with type 2 diabetes with CKD at baseline. Close monitoring and appropriate management of hepatic steatosis may aid in preventing the progression of kidney dysfunction in patients with type 2 diabetes and CKD.

Effects of a High-Protein Diet on Kidney Injury under Conditions of Non-CKD or CKD in Mice.

Considering the prevalence of obesity and global aging, the consumption of a high-protein diet (HPD) may be advantageous. However, an HPD aggravates kidney dysfunction in patients with chronic kidney disease (CKD). Moreover, the effects of an HPD on kidney function in healthy individuals are controversial. In this study, we employed a remnant kidney mouse model as a CKD model and aimed to evaluate the effects of an HPD on kidney injury under conditions of non-CKD and CKD. Mice were divided into four groups: a sham surgery (sham) + normal diet (ND) group, a sham + HPD group, a 5/6 nephrectomy (Nx) + ND group and a 5/6 Nx + HPD group. Blood pressure, kidney function and kidney tissue injury were compared after 12 weeks of diet loading among the four groups. The 5/6 Nx groups displayed blood pressure elevation, kidney function decline, glomerular injury and tubular injury compared with the sham groups. Furthermore, an HPD exacerbated glomerular injury only in the 5/6 Nx group; however, an HPD did not cause kidney injury in the sham group. Clinical application of these results suggests that patients with CKD should follow a protein-restricted diet to prevent the exacerbation of kidney injury, while healthy individuals can maintain an HPD without worrying about the adverse effects.

Perirenal Fat and Kidney Function Deterioration in Patients With Acute Decompensated Heart Failure.

The thick perirenal fat pad can induce high intracapsular pressure and cause compression of the renal vasculature and resultant congestive nephropathy. The current study investigated the association of perirenal fat thickness with kidney dysfunction in patients with acute decompensated heart failure (ADHF). Data from 266 patients hospitalized with ADHF were analyzed. Patients were divided into two groups according to the glomerular filtration rate (GFR) at admission (preserved kidney function [GFR ≥60 mL/min/1.73 m2] and reduced kidney function [GFR <60 mL/min/1.73 m2] groups). Right and left posterior perirenal fat thicknesses were measured using computed tomography, and their average values were calculated. Associated factors with reduced kidney function was assessed by logistic regression model, presenting with odds ratio (OR) and confidence interval (CI). Increasing age (OR, 1.08; 95% CI, 1.04-1.12; p<0.001), diabetes mellitus (OR, 2.46; 95% CI, 1.18-5.12; p<0.017), increased log N-terminal pro-B-type natriuretic peptide (NT-proBNP) (OR, 1.82; 95% CI, 1.32-2.52; p<0.001), and increased average perirenal fat thickness (OR, 1.11; 95% CI, 1.06-1.16; p<0.001) were independently associated with reduced kidney function. In the subgroup analyses, patients over 70 years old, the ratio of mitral-to-mitral annular velocity >15, elevated log NT-proBNP had a significantly higher association with increased perirenal fat thickness with reduced kidney function. Thick perirenal fat pads were independently associated with kidney function deterioration in patients hospitalized with ADHF.

Enhanced SHP-1 Expression in Podocyturia Is Associated with Kidney Dysfunction in Patients with Diabetes

Diabetic kidney disease (DKD) remains the leading cause of end stage kidney disease worldwide. Despite significant advances in kidney care, there is a need to improve noninvasive techniques to predict the progression of kidney disease better for patients with diabetes. After injury, podocytes are shed in urine and may be used as a biologic tool. We previously reported that SHP-1 is upregulated in the kidney of diabetic mice, leading to podocyte dysfunction and loss. Our objective was to evaluate the expression levels of SHP-1 in urinary podocytes and kidney tissues of patients with diabetes. In this prospective study, patients with and without diabetes were recruited for the quantification of SHP-1 in kidney tissues, urinary podocytes, and peripheral blood monocytes. Immunochemistry and mass spectrometry techniques were applied for kidney tissues. Urinary podocytes were counted, and expression of SHP-1 and podocyte markers were measured by quantitative PCR. A total of 66 participants (diabetic n=48, nondiabetic n=18) were included in the analyses. Diabetes was associated with increased SHP-1 expression in kidney tissues (P=0.03). Nephrin and podocin mRNA was not significantly increased in urinary podocytes from patients with diabetes compared with those without diabetes, whereas levels of SHP-1 mRNA expression significantly correlated with HbA1c and estimated glomerular filtration rate (eGFR). Additionally, follow-up (up to 2 years post recruitment) evaluation indicated that SHP-1 mRNA expression continued to increase with eGFR decline. Levels of SHP-1 in urinary podocytes may serve as an additional marker of glomerular disease progression in this population.

COVID-19 and hepatorenal syndrome.

Coronavirus disease 2019 (COVID-19) is a highly infectious disease which emerged into a global pandemic. Although it primarily causes respiratory symptoms for affected patients, COVID-19 was shown to have multi-organ manifestations. Elevated liver enzymes appear to be commonly observed during the course of COVID-19, and there have been numerous reports of liver injury secondary to COVID-19 infection. It has been established that patients with pre-existing chronic liver disease (CLD) are more likely to have poorer outcomes following COVID-19 infection compared to those without CLD. Co-morbidities such as diabetes, hypertension, obesity, cardiovascular and chronic kidney disease frequently co-exist in individuals living with CLD, and a substantial population may also live with some degree of frailty. The mechanisms of how COVID-19 induces liver injury have been postulated. Hepatorenal syndrome (HRS) is the occurrence of kidney dysfunction in patients with severe CLD/fulminant liver failure in the absence of another identifiable cause, and is usually a marker of severe decompensated liver disease. Select reports of HRS following acute COVID-19 infection have been presented, although the risk factors and pathophysiological mechanisms leading to HRS in COVID-19 infection or following COVID-19 treatment remain largely unestablished due to the relative lack and novelty of published data. Evidence discussing the management of HRS in high-dependency care and intensive care contexts is only emerging. In this article, we provide an overview on the speculative pathophysiological mechanisms of COVID-19 induced HRS and propose strategies for clinical diagnosis and management to optimize outcomes in this scenario.

The association of angiotensin-converting enzyme inhibitors and angiotensin 2 receptor blockers with renal protection in patients with SARS-CoV-2

Abstract Background Kidney dysfunction is a prevalent disease that leads to many complications over time, such as hypertension, heart disease, and death. ACEI/ARBs are known to be renoprotective. However, few studies describe the association between ACEI/ARB use and kidney dysfunction in patients with SARS-CoV-2 infection. Purpose To explore the association between patients with SARS-CoV-2 and kidney dysfunction in patients taking an ACEI/ARB. We hypothesize a negative association between patients with SARS-CoV-2 taking an ACEI/ARB and kidney dysfunction. Methods A retrospective query between March 2020 and April 2021 was performed in patients 18 years and older who tested positive for SARS-CoV-2 using a polymerase chain reaction test. Patients were divided into two groups: kidney dysfunction and no kidney dysfunction. Kidney dysfunction was defined as any diagnosis of chronic kidney disease or acute kidney injury. Primary outcomes were all-cause mortality and hospitalization rate. Secondary outcomes included myocardial infarction (MI), hypotension, intubation, vasopressor use, ventricular tachycardia, and ventricular fibrillation. We used multivariate logistic regression to adjust for baseline characteristics. Results We identified 996 patients with kidney dysfunction and 22,106 without kidney dysfunction who tested positive for SARS-CoV-2. The incidence was 258 (25.9%) for ACEI/ARB use in patients with kidney dysfunction. Adjusted odds ratio (OR) for patients with kidney dysfunction was 5.705 (95% Confidence Interval [CI]: 4.554–7.146; p&amp;lt;0.001) for hospitalization, 0.895 (95% CI: 0.707–1.135; p&amp;lt;0.361) for patients taking ACEI/ARB, and 0.529 (95% CI: 0.333–0.838; &amp;lt;0.007) for mortality in patients with kidney dysfunction who took ACEI/ARB. All secondary outcomes had significantly greater adjusted OR (p&amp;lt;0.001), except for MI (p&amp;lt;0.339), ventricular tachycardia (p&amp;lt;0.697), and ventricular fibrillation (p&amp;lt;0.060). Conclusion To date, the benefits of ACEI/ARB in SARS-CoV-2 patients have been controversial. While ACEI/ARB is known to have renoprotective properties, we did not find a significant association between ACEI/ARB and kidney dysfunction in patients with SARS-CoV-2. However, we found the use of ACEI/ARB in patients with kidney dysfunction to be associated with lower mortality. Therefore, clinicians should continue using this medication for its mortality benefits in patients with kidney dysfunction and its cardioprotective effects. Funding Acknowledgement Type of funding sources: None.

Assessment of Kidney Dysfunction in Patients with Chronic Heart Failure

BACKGROUND: Heart failure and kidney disease share common pathophysiological pathways which can lead to mutual dysfunction, known as cardiorenal syndrome. The formation of cardiorenal syndrome in patients with chronic heart failure (CHF) is a natural manifestation of a functionally interconnected process at the organ level. Renal dysfunction is a common and independent factor in the progression of the disease, a high incidence of cardiovascular events, and death in the population. AIM: The aim of the study of the relationship between kidney dysfunction and the clinical course of the disease, quality of life, and indicators of the left ventricular systolic function in patients with CHF. MATERIALS AND METHODS: The study involved 150 patients with CHF I–III functional class according to the New York Heart Association. Exercise tolerance (6 min walk test) was assessed, the clinical condition was assessed using the clinical assessment scale, and the quality of life of patients with CHF (QoL) was assessed according to the Minnesota QOL questionnaire. An assessment of the functional state of the kidneys was carried out: The level of serum creatinine was determined; glomerular filtration rate (GFR) was calculated using the calculation formulas CKD-EPI. The assessment of renal blood flow was carried out using the ultrasound apparatus “SONOACEX6” (Korea). The structural and functional state of the myocardium and the process of left ventricle (LV) remodeling were assessed using the “MEDISON ACCUVIX V20” echocardiograph (Korea), using a 3.25 MHz transducer in standard echocardiographic positions, by the transthoracic method in accordance with the recommendations of the American Association of Echocardiography. RESULTS: The results of the study of physical performance according to 6 min walk test in patients of Group I with CHF GFR &gt;60 ml/min/1.73 m2 were 363.59 ± 7.6 m, respectively. The decrease in the distance traveled according to the 6 min walk test data in Group II of patients with eGFR ≤60 ml/min/1.73 m2, exercise tolerance was more pronounced than in patients of Group I and this figure was 248.7 ± 11.0 m, which was 46.2% lower than the results of Group I of the study (p &lt; 0.001). Analysis of the parameters of clinical manifestations according to the data of the clinical assessment scale showed that in patients of Group I, the total score was 5.5 ± 0.13 points. In CHF patients with renal dysfunction, changes were also noted at the level of the lobar and segmental renal arteries, characterized by a significant increase in pulsatility index and resistance index, there was a decrease in speed indicators during diastole, systole, and the average blood flow velocity. Further analysis of the parameters of LV systolic function ejection fraction (EF), as well as fractional shortening of the LV in systole (Fs%), showed that in Group II, these indicators had significant differences with Group I. There was a significant difference in EF by 10.5% and 25.4% and Fs% by 11.2% (p &lt; 0.001). CONCLUSION: In CHF patients with impaired renal function, changes in renal blood flow were characterized by a significant increase in pulsatile and resistive indices, a decrease in the rate of renal blood flow at the level of the lobar and segmental renal arteries.

Plasma apoM Levels and Progression to Kidney Dysfunction in Patients With Type 1 Diabetes.

Apolipoprotein M (apoM), primarily carried by HDL, has been associated with several conditions, including cardiovascular disease and diabetic nephropathy. This study proposes to examine whether plasma apoM levels are associated with the development of diabetic kidney disease, assessed as progression to macroalbuminuria (MA) and chronic kidney disease (CKD). Plasma apoM was measured using an enzyme immunoassay in 386 subjects from the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) cohort at DCCT entry and closeout and the concentrations used to determine the association with risk of progression to kidney dysfunction from the time of measurement through 18 years of EDIC follow-up. apoM levels, at DCCT baseline, were higher in patients who developed CKD than in those who retained normal renal function. At DCCT closeout, participants who progressed to MA, CKD, or both MA and CKD also had significantly higher apoM levels than those who remained normal, and increased levels of apoM were associated with increased risk of progression to both MA (risk ratio [RR] 1.30 [95% CI 1.01, 1.66]) and CKD (RR 1.69 [95% CI 1.18, 2.44]). Our results strongly suggest that alterations in apoM and therefore in the composition and function of HDL in type 1 diabetes are present early in the disease process and are associated with the development of nephropathy.

MO106: Circulating Neutrophil Count is Associated with Severity of Chronic Kidney Disease

Abstract BACKGROUND AND AIMS Neutrophils (Ns) play a key role in inflammation and tissue injury, in particular in acute renal failure, by releasing a complex of cytotoxic products such as reactive oxygen intermediates, enzymes and microbicidal polypeptides. These effects are prevented or mitigated by Ns depletion [1, 2]. Here we investigated the relationships between Ns count and the severity of kidney dysfunction in patients with chronic kidney disease (CKD). METHOD In this cross-sectional study we evaluated the association between circulating Ns absolute number, CKD stage and measured glomerular filtration rate (mGFR) in 393 patients with renal disease from different causes. CKD stage was established on the basis of mGFR and K/DOQI guidelines [3]. The relationships of Ns count and other considered covariates with mGFR were evaluated by uni- and multi-variable linear regression models (Table 1). Variables considered in univariable models are listed in Table 1. Variables included in multivariable models were identified with forward selection. Circulating Ns were measured by Coulter LH 780 Hematology Analyzer (Beckman Coulter, Milan, Italy). The GFR was measured by the iohexol plasma clearance technique, a gold standard for direct GFR measurement [4]. P &amp;lt; .05 was considered as statistically significant. RESULTS The mean ± SD age and mGFR of the patients were 54.64 ± 13.75 years and 62.75 ± 22.52 mL/min/1.73 m2 (range: 15.53–131.79 mL/min/1.73 m2), respectively. Most patients had a kidney function in stage 2 and 3a (Figure 1A). The absolute number of Ns averaged 4.32 ± 1.77 × 103µL−1. Ns counts increased progressively in parallel with increasing CKD stage (P &amp;lt; .005, Figure 1A) and were negatively correlated with mGFR (P &amp;lt; .001, Figure 1B). At multivariable analysis, mGFR was associated negatively with Ns count and positively with basophils (Bs) count (Table 1). CONCLUSION In patients with CKD higher numbers of Ns and lower numbers of Bs, even within the normal range, were independently associated with more severe renal insufficiency. A major limitation of the study is the cross-sectional design that does not allow to establish a causal relationship between Ns count and severity of kidney dysfunction. These data provide the basis for studies to investigate mechanisms explaining these associations.

Decreased preoperative urinary uromodulin as a predictor of acute kidney injury and perioperative kidney dysfunction in patients undergoing cardiac surgery: A prospective cohort study

BackgroundAcute kidney injury (AKI) is a major complication following cardiac surgery that substantially increases mortality. We explored the clinical utility of urinary uromodulin (uUMOD), a marker of renal tubular reserve, for preoperative identification of patients at risk for AKI and perioperative kidney dysfunction. MethodsThis prospective observational study included patients who underwent cardiac surgery between December 2019 and January 2021. AKI was defined according to the Kidney Disease Improving Global Outcomes criteria; perioperative kidney dysfunction was accessed using a longitudinal estimated glomerular filtration rate. ResultsA total of 409 participants were enrolled. Patients with uUMOD ≤ 20.7 µg/mL were associated with a higher risk for AKI (odds ratio, 3.24; 95% confidence interval: 1.87–5.63, P < 0.001), independent of baseline kidney function. The uUMOD exhibits adequate discrimination for predicting AKI, with an area under the receiver operating characteristic curve of 0.713 (95% confidence interval: 0.652–0.773), and has well-fitted calibration (Hosmer-Lemeshow goodness-of-fit test, P = 0.163). The trajectory analysis revealed that decreased uUMOD levels were linked to a higher risk of patients being assigned to a worse perioperative kidney function cluster. ConclusionsDecreased preoperative uUMOD is independently associated with an increased risk of AKI and perioperative kidney dysfunction after cardiac surgery.

POS-212 RENAL AA AMYLOIDOSIS: A RETROSPECTIVE CLINICOPATHOLOGIC STUDY WITH EMPHASIS ON PROGNOSIS CONDUCTED IN 74 FRENCH PATIENTS DIAGNOSED BETWEEN 2010 AND 2021

AA amyloidosis is a protein folding disease characterized by extracellular deposition of amyloid A fibrils derived from the serum amyloid A inflammation protein, causing kidney dysfunction in patients with chronic inflammatory conditions. Several histological studies found a link between the topography or abundance of amyloid deposits and clinical presentation or renal prognosis. However, most of these studies are now outdated, present a non-exhaustive clinical collection and may no longer represent the current epidemiology, especially in France.