Biomarkers Of Renal Dysfunction Research Articles

Comparative Evaluation of Complications in Untreated and Recurrent Urinary Tract Infections

Background: Urinary tract infections (UTIs) are common but can cause severe complications if untreated or recurrent, affecting renal function and antibiotic resistance. This study uniquely uses biomarkers such as CRP, NGAL, IL-6, and TNF-α to predict renal dysfunction and antibiotic resistance, highlighting their clinical significance. Objectives: To compare the complications of untreated and recurrent UTIs concerning renal function, systemic inflammation, oxidative stress, and antibiotic resistance using biomarker analysis. Methods: A comparative study was conducted on 500 adult patients (2022–2024) from two tertiary care hospitals. Patients were categorized into recurrent UTIs (≥3 episodes/year) and untreated UTIs (≥1 month without antibiotics). Biomarkers for renal dysfunction (creatinine, eGFR, NGAL), inflammation (CRP, IL-6, TNF-α, procalcitonin), and oxidative stress (MDA, KIM-1) were analyzed. Multivariate regression and statistical tests assessed predictors and significance. Results: Untreated UTIs were associated with significantly worse renal outcomes (creatinine: 2.1±0.4 mg/dL, eGFR: 54.2±6.1; p<0.001), higher inflammation (CRP: 35.7±5.9 mg/L; procalcitonin: 2.1±0.6 ng/mL; p<0.001), and elevated oxidative stress (MDA: 6.7±1.3 μmol/L). Recurrent UTIs had higher multidrug resistance rates (45% vs 28%, p=0.002). CRP, NGAL, and procalcitonin independently predicted renal dysfunction, while IL-6 and TNF-α were strong predictors of antibiotic resistance. Conclusions: Untreated UTIs pose severe risks for renal health and systemic inflammation, while recurrent UTIs increase antibiotic resistance. Biomarkers offer valuable predictive tools for early intervention, improving patient outcomes.

Assessment of novel biomarkers of renal dysfunction associated with lower urinary tract symptoms in men with benign prostatic hyperplasia

Introduction. The problem of diagnostics and treatment of patients with complex lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH) remains highly relevant. Clinical diagnostic methods do not always allow timely prediction of changes in renal, upper and lower urinary tract function with different types of treatment intervention. The search for potential biomarkers allowing minimally invasive assessment of the bladder and renal function condition seems to be a promising direction of scientific research.Objective. To identify potential urine and serum biomarkers allowing to assess renal function in patients with LUTS/BPH.Materials & methods. The study included 69 patients with LUTS/BPH and subsequently divided them into two groups. Group 1 included 48 patients with moderate LUTS who received combination therapy with alpha-1 adrenergic blockers (AABs) and 5-alpha reductase inhibitors (5ARIs). Group 2 included 21 patients with severe LUTS/BPH. Patients of group 2 underwent surgical treatment: transurethral resection of the prostate. In addition to standard research methods (IPSS, voiding diaries, laboratory, urodynamic and radiation techniques), to search for potential biomarkers in serum and urine, concentrations of: insulin-like growth factor binding protein-7 (IGFBP7), B-Cross Laps, Cystatin C, OPN, trefoil factor (TFF3), uromodulin, Clusterin, lactate dehydrogenase (LDH). The follow-up period for patients was 12 months.Results. The study noted that IGFBP7, Cystatin C, TFF3 in the blood serum, as well as LDH, Clusterin in the urine are associated with the severity of LUTS/BPH. Serum biomarker levels were initially higher in patients with severe LUTS compared to patients with moderate LUTS (group 1). The levels of these substrates decreased in patients of all groups during treatment (conservative therapy, surgical interventions for BPH). When assessing urinary biomarkers, the greatest decrease in Clusterin level by the end of follow-up was registered in group 1 patients, the least pronounced in group 2 patients. The initial value of LDH was twice higher in group 2 vs group 1 and progressively decreased after surgical treatment of bladder outlet obstruction.Conclusion. Biomarkers used to assess renal dysfunction in the development of LUTS/BPH are a promising area of scientific research. Panels of new markers will enable to predict renal dysfunction in patients with moderate-to-severe LUTS, which will improve the quality of medical care for this category of patients.

Association of renal biomarkers with fast progressor phenotype and related outcomes in anterior circulation large vessel occlusion stroke.

Renal dysfunction is a known predictor of long-term functional dependency after anterior circulation large vessel occlusion (ACLVO) stroke. However, the impact of renal dysfunction on early infarct growth rate (IGR) has not been previously demonstrated. The objective of this study was to define the association of creatinine-based renal biomarkers with fast or slow progressor phenotypes and related clinical outcomes in ACLVO stroke. This retrospective study examined patients with acute intracranial internal carotid artery or middle cerebral artery-M1 occlusions admitted between 2014 and 2019. Patients were included if they received baseline CT perfusion (CTP) or MRI on presentation within 24 h of estimated stroke onset. Infarct growth rate (IGR) was determined by ischemic core volume on CTP or MRI divided by time from stroke onset to imaging. IGR was used to stratify fast progressor (IGR ≥10 mL/h) and slow progressor (IGR < 10 mL/h) status. Renal dysfunction was assessed based on serum creatinine and estimated glomerular filtration rate (eGFR) on presenting laboratories. Logistic regression models, adjusted for significant covariates, identified independent associations between renal dysfunction biomarkers, progressor status, and clinical outcomes based on modified Rankin Scale (mRS) at 90 days. Among 230 patients with ACLVO, 29% were fast progressors, with median serum creatinine levels higher than slow progressors (1.1 vs. 0.9 mg/dL, p < 0.05) and lower median eGFR (66.2 vs. 69.0 mL/min/1.73m2, p < 0.05). Elevated creatinine (≥1.2 mg/dL) was independently associated with fast progressor status (adjusted OR 2.37, 95% CI 1.18-4.77), worse 90-day mRS (adjusted OR 1.88, 95% CI 1.01-3.51) and mortality (adjusted OR 2.57, 95% CI 1.14-5.79). Reduced eGFR (<60 mL/min/1.73m2) was independently associated with fast progressor status (adjusted OR 2.38, 95% CI 1.14-4.94), but not with 90-day mRS or mortality. Serum creatinine-based biomarkers of renal dysfunction were associated with fast progressor phenotype of ACLVO stroke, and worse clinical outcomes, which may help identify such patients earlier during emergency evaluation for expedited access to EVT. Future prospective studies are warranted to confirm and test implementation of these findings.

Urinary neutrophil gelatinase-associated lipocalin as early biomarker for renal disease in dogs with leishmaniosis

Canine leishmaniosis (CanL), caused by Leishmania sp., presents a wide array of symptoms; renal dysfunction is frequently observed in these dogs and is associated with a poor prognosis and increased mortality. The traditional biomarkers namely urea and creatinine can detect renal damage but only in advanced stages of the disease. However, it has been shown that the symmetric dimethylarginine assay (SDMA) or the protein/creatinine ratio (UPC) and are early biomarkers of renal dysfunction. Their elevation occurs earlier than that of creatinine, but other novel biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL) are currently under investigation. Our objective was to determine whether the urine NGAL-creatinine ratio (uNGAL/c) can provide very early diagnosis of kidney disease in CanL. In total, 68 dogs were included in the study: 15 healthy dogs and 53 dogs with CanL who were classified according to International Renal Interest Society (IRIS) classification: IRIS 1 (N= 34), IRIS 2 (N= 9) and IRIS 3/4 (N= 10). IRIS 1 was subdivided according to proteinuria in IRIS 1NP (13 dogs with UPC < 0.2), IRIS 1BL (8 dogs with UPC = 0.2–0.5) and IRIS 1 P (13 dogs with UPC > 0.5). Blood samples were collected for complete hematological and biochemistry analysis including plasma NGAL. Urinalysis included specific gravity, UPC, CysC and NGAL expressed as a ratio with creatinine. The mean concentrations of pCysC and SDMA in CanL, show a statistically significant increase from IRIS 1NP, not being statistically significant for pCysC in the IRIS 1BL group. The UPC show a statistically significant increase from IRIS 1NP. In all groups with CanL for uCysC/c and uNGAL/c was observed a statistically significant increase. The uNGAL/c in the group proteinuric animals, presents a positive correlation with all renal biomarkers studied. In the group of non-proteinuric animals, the uNGAL/c presents a positive correlation with SDMA and UPC. The uNGAL/c can be considered a reliable indicator of renal disease in dogs diagnosed with CanL who are non-azotemic and non-proteinuric.

RENAL DYSFUNCTION IN PRETERM INFANTS WITH PERINATAL PATHOLOGY: RISK FACTORS, SENSITIVITY AND SPECIFICITY OF LABORATORY MARKERS OF DAMAGE

RENAL DYSFUNCTION IN PRETERM INFANTS WITH PERINATAL PATHOLOGY: RISK FACTORS, SENSITIVITY AND SPECIFICITY OF LABORATORY MARKERS OF DAMAGE

Determination of Early Diagnostic Biomarkers of Renal Dysfunction After Cardiopulmonary Bypass: miR-21 and miR10a Mediated Postoperative Inflammation

Objective: Acute renal failure (ARF) prevalence is high among patients who undergo cardiopulmonary bypass (CPB), and this condition can only be diagnosed via serum creatinine level (sCr) conventionally within 48 hours. Therefore, we need early novel diagnosis biomarkers to start preventive treatment of ARF. For that reason, we aimed to analyze if plasma miR-21 derived from heart, correlates with kidney- enriched miR-10a during inflammatory IL-6, IL-1β, and TNF-α response in terms of acute renal failure 30 minutes after CPB.&#x0D; Methods: Patients (n=46, Female:8 and Male:38), aged 61.08±9.41, who underwent CPB surgery were included. Blood samples were collected during the pre – and post-CPB (30 minutes after CPB). Demographic data of all cases were collected. Quantification of expression levels of miR-21 and miR-10a was done via quantitative PCR (qPCR). Determination of plasma concentration of relevant cytokines, IL-6, IL-1β, and TNF-α was done via ELISA.&#x0D; Results: The circulating level of miR-21 during post-CPB period (-11.78±6.98) was significantly higher (p≤0.05) than pre-CPB period (-6.55±7.11), but there was no significant change (p&gt;0.05) in the circulating level of miR-10a between pre – (-12.22±3.55) and post-CPB (-11.60±3.36) periods. When we compared the mean ΔΔCt values of miR-21 and miR-10a, downregulation was observed in the expression level of miR-10a (0.62±3.77) whilst the expression level of miR-21 (-5.22±7.25) was upregulated (p≤0.05). The levels of plasma concentration of IL-6 (2.74±2.50 ng/l) and TNF-α (83.63±9.33 ng/l) were increased during post-CPB period (both were ***p

Investigation of symmetric dimethylarginine as a serologic marker for kidney function in striped skunks (Mephitis mephitis).

Kidney disease is prevalent among veterinary species, including zoo animals; however, investigations into this condition in striped skunks (Mephitis mephitis) are scarce. Diagnostic tools for kidney diseases in this species also remain limited. This study aimed to assess the utility of symmetric dimethylarginine as a biomarker for kidney disease in captive striped skunks in Korea. This retrospective study analysed 11 striped skunks housed at the Everland Zoo between 2017 and 2021. Blood samples were collected during health checks. Kidney function was assessed through blood analysis and diagnostic ultrasound, with necropsies conducted on deceased animals. Symmetric dimethylarginine levels were measured in 27 plasma samples collected from 11 skunks. Over the study period, seven skunks were diagnosed with kidney disease. Analysis of 27 blood samples revealed a concurrent increase in SDMA levels with concentrations of blood urea nitrogen and blood creatinine. In 3 of the 7 skunks with kidney disease, symmetric dimethylarginine exceeded 14 µg/dL prior to the elevation of blood urea nitrogen and blood creatinine above the upper reference limit. To our knowledge, this is the first study investigating symmetric dimethylarginine in captive striped skunks in Korea. Our findings suggest that symmetric dimethylarginine may serve as an early and consistent biomarker for renal dysfunction in striped skunks. Further studies with larger clinical sample size from striped skunks are needed to validate the clinical utility of blood symmetric dimethylarginine concentration.

Hepatorenal Syndrome-Novel Insights into Diagnostics and Treatment.

Hepatorenal syndrome (HRS) is a disorder associated with cirrhosis and renal impairment, with portal hypertension as its major underlying cause. Moreover, HRS is the third most common cause of acute kidney injury, thus creating a major public health concern. This review summarizes the available information on the pathophysiological implications of HRS. We discuss pathogenesis associated with HRS. Mechanisms such as dysfunction of the circulatory system, bacterial infection, inflammation, impaired renal autoregulation, circulatory, and others, which have been identified as critical pathways for development of HRS, have become easier to diagnose in recent years. Additionally, relatively recently, renal dysfunction biomarkers have been found indicating renal injury, which are involved in the pathophysiology of HRS. This review also summarizes the available information on the management of HRS, focusing on vasoconstrictive drugs, renal replacement therapy, and liver transplant together with currently being investigated novel therapies. Analyzing new discoveries for the underlying causes of this condition assists the general research to improve understanding of the mechanism of pathophysiology and thus prevention of HRS.

THU339 Neutrophil Gelatinase-associated Lipocalin And B2-microglobulin May Reflect Early Diabetic Nephropathy In Asymptomatic Patients With Type 1 Diabetes

Abstract Disclosure: N. Papadopoulou: None. M. Arkoumani: None. I. Papassotiriou: None. A. Mantzou: None. G.P. Chrousos: None. N. Tentolouris: None. C. Kanaka-Gantenbein: None. Type 1 diabetes (T1D) is a frequent autoimmune disease in childhood, adolescence and young adulthood and may cause microvascular complications. Several studies have shown that increased serum or urine Neutrophil Gelatinase-Associated Lipocalin (NGAL) and beta 2 microglobulin (b2-microglobulin) are associated with microvascular complications like nephropathy. Hypothesis and Underlying Question the Research Addresses: We assessed the role of serum and urine NGAL and b2-microglobulin, biomarkers of renal dysfunction, in unravelling early renal dysfunction in T1D. Overview of Experimental Design and Methodology: Two patient groups who took part in two-centers’ prospective cohorts were studied. Sixty-one patients with T1D, aged 5-17 years from the Diabetes Center of Aghia Sophia Children’s Hospital, University of Athens, Greece, and 34 patients with T1D aged 18-44 years from the Diabetes Center, 1st Propaedeutic Department Laiko of the Laikon University Hospital of Athens, Greece were recruited. Sixty age- and sex-matched apparently healthy controls were also included in the study . Along with standard blood and urine chemistry, serum and urine NGAL concentrations and serum b2-microglobulin were determined by means of immunoenzymatic techniques. Estimated glomerular filtration rate (eGFR) was calculated with CKD EPI. Both physical and laboratory examinations were obtained in 2 time-points, at baseline and 12 months later. Main Results: In both young and adult groups with T1D, urine NGAL correlated positively with microalbuminuria (r=0.33, p=0.003) and decreased eGFR (r= -0.37, p=0.0008) irrespectively of gender or age. Decreased values of eGFR were correlated with increased values of b2-microglobulin (r= -0.30, p=0.002). Interpretation of Results and Conclusions: Urine NGAL as well as serum b2-microglobulin levels, proposed biomarkers of renal dysfunction, correlated with indices of early diabetic nephropathy, characterized by both microalbuminuria and decreased eGFR in patients with T1D, showing similar results in a broad patients’ age range. Thus, this marker may unmask early reversible renal dysfunction before overt nephropathy appears. However, prior to its clinical application, this biomarker must undergo thorough validation in several cohorts. Presentation: Thursday, June 15, 2023

DIAGNOSTIC AND PROGNOSTIC VALUE OF Β2-MICROGLOBULIN IN THE DEVELOPMENT OF CARDIORENAL SYNDROME IN PATIENTS WITH TYPE 2 DIABETES MELLITUS AND ARTERIAL HYPERTENSION

Arterial hypertension is the largest pandemic in the history of mankind, which defines the structure of cardiovascular morbidity and mortality. Currently, the correlation between hypertension and various pathological conditions and diseases has been proven, which largely determines its progression and contributes to the development of cardiovascular and renal complications. These diseases include type 2 diabetes mellitus, which is spreading globally as a pandemic. The history of arterial hypertension in combination with type 2 diabetes mellitus is often accompanied by the development of cardiorenal syndrome, so it is crucial to diagnose renal dysfunction and prevent cardiovascular complications in such patients. One of these biomarkers is β2-microglobulin (β2-M), which depends on the glomerular filtration rate and tubular reabsorption.&#x0D; Materials and methods. 90 patients with AH (men/women – 48/42) and 20 control subjects were examined. During a thorough examination and follow-up of patients, they were classified into 3 groups: patients with AH – group 1 – 31 people; group 2 – AH in combination with T2DM – 31 people; group 3 – patients with AH, T2DM, and obesity – 28 people. Body weight and height were measured in all patients, and BMI = body weight/height2 (m2) was calculated. The β2-microglobulin levels in the patients' serum, cardiotrophin-1, catestatin, leptin, cystatin C, neutrophil gelatinase-associated lipocalin, and N-terminal pro-brain natriuretic peptide, 25-OH total vitamin D, serum insulin levels, glycosylated hemoglobin, lipid metabolism, and systolic and diastolic blood pressure were measured. Statistical data analysis was performed using Statistica, 12 (Stat Soft Inc, USA) and Microsoft Office Excel 2013. The data are presented as mean (M) and standard deviation (δ). Differences between groups of mean values were evaluated using the Student's t-test.&#x0D; Results and conclusions. The level of β2-M in the observed groups of patients differed significantly from that of healthy individuals. An increase in β2-M concentration allowed us to confirm the presence of tubular renal dysfunction, which was not diagnosed by conventional methods. All examined patients were divided into 2 groups depending on the β2-M level. Our data prove the role of β2-microglobulin as an independent biomarker of renal dysfunction, as well as the development of early cardiovascular complications. The data obtained from the mathematical models between creatinine and β2-microglobulin, urea and β2-microglobulin levels show a highly significant correlation between β2-microglobulin and renal function and demonstrate that β2-microglobulin is an independent factor in the prediction of renal dysfunction in patients with hypertension and concomitant type 2 diabetes mellitus. β2-microglobulin is a biomarker that should be used in the diagnosis and prognosis of early manifestations of cardiorenal syndrome.

MRI-phenotype of kidney structural changes in patients with resistant hypertension: correlations with functional markers

The aim: to determine the phenotype of kidney damage characteristic of resistant arterial hypertension by MRI, including the volume of renal parenchyma, and its association with biomarkers of renal dysfunction.Patients and methods. The main group included 35 patients with resistant arterial hypertension (RAH), average age 57.6±8.4 years. The comparison group consisted of 20 men and women without cardiovascular pathology, comparable in gender and age. To determine the qualitative and quantitative changes in the kidneys, MRI was performed (1.5 Tesla, Titan vantage, Toshiba). Kidney volumes (TKV, TCV) were calculated using the ellipsoid formula. Kidney volumes indexed for height, BMI and body surface area were calculated. Renal dysfunction was assessed by the level of serum creatinine and cystatin C, as well as by the value of eGFR (CKD-EPI).Results. The MR phenotype of kidney changes in resistant hypertension is described – renal cortex surface roughness, renal cortex thinning, decreased kidney sizes, and rounded kidney shape. The relationship of the renal parenchyma volume indexed for height with the level of cystatin C (r=-0.36), creatinine (r=-0.48) and eGFR (r=0.49) was revealed.Conclusion. The hypertensive renal MRI-phenotype includes a decreased in kidney size, thinning of the renal cortex, renal cortex surface roughness and rounded shape of the kidneys. The total volume of the renal cortex indexed for height has a close relationship with serum biomarkers of renal dysfunction, and is recommended for use as a non-invasive marker reflecting the state of the kidneys in resistant arterial hypertension.

Plasma Neurofilament Light Chains as Blood-Based Biomarkers for Early Diagnosis of Canine Cognitive Dysfunction Syndrome.

The number of elderly dogs is increasing significantly worldwide, and many elderly dogs develop canine cognitive dysfunction syndrome (CCDS). CCDS is the canine analog of Alzheimer's disease (AD) in humans. It is very important to develop techniques for detecting CDDS in dogs. Thus, we used the detection of neurofilament light chains (NfL) in plasma as a blood-based biomarker for the early diagnosis of canine Alzheimer's disease using immunomagnetic reduction (IMR) technology by immobilizing NfL antibodies on magnetic nanoparticles. According to the 50-point CCDS rating scale, we divided 36 dogs into 15 with CCDS and 21 without the disease. The results of our IMR assay showed that the plasma NfL levels of dogs with CCDS were significantly increased compared to normal dogs (p < 0.01). By plasma biochemical analysis, we further confirmed that the liver and renal dysfunction biomarkers of dogs with CCDS were significantly elevated compared to normal dogs (p < 0.01-0.05). On the basis of our preliminary study, we propose that IMR technology could be an ideal biosensor for detecting plasma NfL for the early diagnosis of CCDS.

Relationships between growth indicators, liver and kidney function markers, and blood concentrations of essential and potentially toxic elements in environmentally exposed young children

Environmental exposure to multiple metals and metalloids is widespread, leading to a global concern relating to the adverse health effects of mixed-metals exposure, especially in young children living around industrial areas. This study aimed to quantify the concentrations of essential and potentially toxic elements in blood and to examine the potential associations between multiple elements exposures, growth determinants, and liver and kidney function biomarkers in children living in several industrial areas in Dhaka, Bangladesh. The blood distribution of 20 trace elements As, Ag, Bi, Br, Cd, Co, Cr, Cu, I, Mn, Hg, Mo, Ni, Pb, Se, Sb, Tl, V, U, and Zn, growth determinants such as body mass index and body fats, blood pressure, liver and kidney injury biomarkers including serum alanine aminotransferase and alkaline phosphatase activities, serum calcium, and creatinine levels, blood urea nitrogen, and hemoglobin concentrations, and glomerular filtration rate were measured in 141 children, aged six to 16 years. Among these elements, blood concentrations of Ag, U, V, Cr, Cd, Sb, and Bi were measured below LOQs and excluded from subsequent statistical analysis. This comprehensive study revealed that blood concentrations of these elements in children, living in industrial areas, exceeded critical reference values to varying extents; elevated exposure to As, Pb, Br, Cu, and Se was found in children living in multiple industrial areas. A significant positive association between elevated blood Tl concentration and obesity (β = 0.300, p = 0.007) and an inverse relationship between lower As concentration and underweight (β = −0.351, p < 0.001) compared to healthy weight children indicate that chronic exposure to Tl and As may influence the metabolic burden and physical growth in children. Concentration-dependent positive associations were observed between the blood concentrations of Cu, Se, and Br and hepatic- and renal dysfunction biomarkers, an inverse association with blood Mo and I level, however, indicates an increased risk of Cu, Se, and Br-induced liver and kidney toxicity. Further in-depth studies are warranted to elucidate the underlying mechanisms of the observed associations. Regular biomonitoring of elemental exposures is also indispensable to regulate pollution in consideration of the long-term health effects of mixed-elements exposure in children.

#4154 CIRCULATING BETA-TRACE PROTEIN VERSUS CREATININE AS MARKERS OF EARLY KIDNEY (DYS)FUNCTION IN THE NX-INDUCED RAT MODEL OF CHRONIC KIDNEY DISEASE

Abstract Background and Aims Beta trace protein (BTP) is a low molecular weight protein that has been proposed as an earlier biomarker of decreased glomerular filtration rate (GFR) and renal damage, than the traditional biomarkers, particularly in the creatinine blind range. Early biomarkers of renal (dys)function are needed to allow, in due time, the detection and treatment, to prevent worsening of the disease. To the authors’ knowledge, neither urine nor serum BTP has been assessed in animals with kidney disease. In the present study, we aimed to concomitantly evaluate BTP and creatinine circulating levels, to compare their value as early biomarkers of renal dysfunction, by performing the studies in rat models of mild and moderate chronic renal failure (CRF) induced by nephrectomy. Method Male Wistar rats, 12 weeks old, were randomly divided in three groups: Sham (n = 8, subjected to surgical process without kidney mass reduction), Mild CRF (n = 8, subjected to 1/2 nephrectomy), and Moderate CRF (n = 7, subjected to 5/6 nephrectomy). After five weeks, rats were sacrificed, blood and kidneys were collected. We analysed the circulating levels of BTP and creatinine and studied the association of BTP concentration with the glomerular and tubulointerstitial lesions, and with the traditional biomarkers of renal (dys)function, eGFR and creatinine. Results The serum levels of BTP were correlated with serum levels of creatinine (r = 0.575, p = 0.004) and also with eGFR (r = -0.453, p = 0.030); additionally, we found positive correlations with the total score of mild and advanced tubular lesions (r = 0.610, p = 0.02 and r = 0.517, p = 0.011, respectively), observed in kidney sections. The circulating levels of BTP increased with disease severity; Mild CRF showed a higher value of BTP than Sham group, although without statistical significance that was reached in Moderate CRF group, as observed for serum creatinine. The combined use of BTP and creatinine did not improve the discriminatory power in early disease detection. Though, the combination showed stronger correlations with the total score of tubular lesions (r = 0.849, p &amp;lt; 0.001 for mild tubular lesions and r = 0.774, p &amp;lt; 0.01 for advanced tubular lesions). Conclusion In rat models of mild and moderate CRF induced by nephrectomy, serum BTP levels increased with kidney function worsening, and correlated with disease severity, assessed by GFR and the degree of histopathological alterations. However, the earlier diagnostic value of BTP does not outperform serum creatinine in this model.

Diabetes with kidney injury may change the abundance and cargo of urinary extracellular vesicles.

Urinary extracellular vesicles (uEVs) are derived from epithelia facing the renal tubule lumen in the kidney and urogenital tract; they may carry protein biomarkers of renal dysfunction and structural injury. However, there are scarce studies focusing on uEVs in diabetes with kidney injury. A community-based epidemiological survey was performed, and the participants were randomly selected for our study. uEVs were enriched by dehydrated dialysis method, quantified by Coomassie Bradford protein assay, and adjusted by urinary creatinine (UCr). Then, they identified by transmission electron microscopy (TEM), nanoparticle track analysis (NTA), and western blot of tumor susceptibility gene 101. Decent uEVs with a homogeneous distribution were finally obtained, presenting a membrane-encapsulated structure like cup-shaped or roundish under TEM, having active Brownian motion, and presenting the main peak between 55 and 110 nm under NTA. The Bradford protein assay showed that the protein concentrations of uEVs were 0.02 ± 0.02, 0.04 ± 0.05, 0.05 ± 0.04, 0.07 ± 0.08, and 0.11 ± 0.15 μg/mg UCr, respectively, in normal controls and in prediabetes, diabetes with normal proteinuria, diabetes with microalbuminuria, and diabetes with macroproteinuria groups after adjusting the protein concentration with UCr by calculating the vesicles-to-creatinine ratio. The protein concentration of uEVs in diabetes with kidney injury increased significantly than the normal controls before and after adjusting the UCr. Therefore, diabetes with kidney injury may change the abundance and cargo of uEVs, which may be involved in the physiological and pathological changes of diabetes.

A Cross-Sectional Study of p66Shc Gene Expression in Liquid Biopsy of Diabetic Patients. Is it Possible to Predict the Onset of Renal Disease?

Background: Diabetic nephropathy (DN) is a disorder affecting glomerular function that, histologically, is due to the presence of glomerulosclerosis accompanied with endothelial dysfunction of the afferent and efferent renal arterioles. Insulin resistance in diabetic patients is known to be one of the causes of endothelial dysfunction because it increases oxidative stress, and one of the main genes regulating the production pathways of reactive oxygen species is p66Shc. The aim of this study was to evaluate the p66Shc gene expression as a precocious biomarker of renal dysfunction in diabetic patients, using liquids samples of urine sediment and peripheral blood. Methods: 29 diabetic patients and 37 healthy donors were recruited from the Centro Universitário FMABC outpatient clinic. The RT-gPCR technique was applied to evaluate p66Shc gene expression in urine and peripheral blood samples from diabetic patients, which were compared with healthy donors. Results: There was no significant expression of p66Shc gene in samples from diabetic patients compared with healthy donors. However, p66Shc expression in the blood samples of diabetics (0.02417±0.078652-ΔCT, n=29) was 3.6 times higher than in healthy participants (0.00689±0.01758, n=37) while in the urine samples, it was 1.48 times higher in diabetics group (0.02761±0.05412-ΔCT) than in CTL group (0.0186±0.02199). Conclusion: There was no significant p66Shc gene expression in peripheral blood and urine samples of diabetic patients without kidney injury compared with healthy donors, although there is a tendency for this gene to participate in the oxidative imbalance present in diabetes.

Association of Adiponectin With biochemical parameters in patients with chronic kidney diseases on Hemodialysis process in Erbil city

Adiponectin (Adipo.) is a hormone produced by adipocytes that circulate in the blood. Serum Adipo. concentrations are elevated in several chronic kidney disease (CKD) conditions and are a predictor of end-stage renal disease. The association between Adipo. levels and the progression of the disease are not well established. This study aimed to determine if there was a relationship between serum Adipo. levels and inflammatory, metabolic, and CKD progression in Erbil. In a case-control study of 200 participants, 100 with CKDs were on hemodialysis (HD) in Erbil teaching hospital. To collect the necessary information from participants, a study questionnaire was used. Adipo. hormone levels and other metabolic parameters were measured. Total Cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), very-low-density lipoprotein (VLDL), fasting blood sugar, C-reactive protein (CRP), glycosylated hemoglobin (HbA1c), creatinine, albumin, and urea were all measured in the blood. 90.0% of the cases were at stage 5 of CKD, the Serum Adipo. levels were higher when compared with a healthy control group (13.26 ±0.96 µg/ml vs 2.17±0.75 µg/ml). In conclusion, our study found A high level of Adipo. in CKD patients can predict inflammation and malnutrition and is considered a biomarker for renal dysfunction.

Kidney injury molecule-1 and cystatin C as early biomarkers for renal dysfunction in Iraqi type 2 diabetes mellitus patients

Diabetic kidney disease (DKD) is caused by a variety of processes. As a result, one biomarker is insufficient to represent the complete process. This study Evaluate the diagnostic value of serum kidney injury molecule-1(KIM-1) and cystatin C (CysC) as early biochemical markers of DKD and predictive their sensitivities and specificities as biomarkers of nephropathy in Iraqi type 2 diabetic (T2DM) patients. This cross-sectional study include 161 T2DM patients from Diabetes and Endocrinology Center at Merjan medical city in Babylon. Patients divided according to urinary albumin creatinine ratio(ACR) (Group1:ACR≤30mg/g,Group2:ACR&gt;30mg/g). Random spot urine and fasting blood samples were taken from each patient and urinary ACR, blood glycated hemoglobin(HbA1c), and serum glucose, creatinine(SCr), lipid profile, CysC, KIM-1 were assayed, and the estimated glomerular filtration rat (eGFR) was calculated. When compared to the normoalbuminuric group, the DKD group had significantly greater prevalence of retinopathy, and significantly elevated HbA1c and total cholesterol values. Also had significantly greater serum levels of KIM-1 and CysC, and there is a significant (P-value&lt; 0.01) positive correlation between them. In contrast, GFR was significantly higher in normoalbuminuric group and was significantly negatively correlated with both CysC and KIM-1. Multiple linear regression analysis, found that there were a significant positive association between CysC, KIM-1 and ACR. ROC analysis reveal that eGFR had the highest area under the curve(AUC=0.717), while SCr had the lowest AUC(0.556). In conclusion, Serum KIM-1 and CysC levels consider as early biomarker for DKD along with eGFR that consider the best diagnostic indicator of DKD, Additionally, there is a strong correlation between serum CysC and KIM-1 as well as other renal measures that indicate deteriorating kidney function.

Urinary neutrophil gelatinase‐associated lipocalin: A novel biomarker for predicting chronic kidney disease in patients with nonalcoholic fatty liver disease

AbstractAimsNonalcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD) are common diseases worldwide. Reports of a high prevalence of CKD in NAFLD patients have been documented. Urinary neutrophil gelatinase‐associated lipocalin (NGAL) is a reliable biomarker for renal dysfunction, and it is recommended for early detection of acute kidney injury (AKI) in cirrhotic patients. Currently, there is no evidence for using urine NGAL to predict CKD in NAFLD patients. We aim to determine the proportion of CKD and identify the predictive value of NGAL and other factors associated with CKD in these patients.MethodsA single‐center, cross‐sectional study was conducted between July 2018 and December 2019 in consecutive NAFLD patients diagnosed by transient elastography (TE) or liver biopsy at a tertiary care university hospital in Bangkok, Thailand. Advanced liver fibrosis is defined as fibrosis stages 3–4. The definition of CKD is estimated glomerular filtration rate (eGFR) &lt;60 ml⋅min−1⋅1.73 m−2 based on the Kidney Disease Improving Global Outcomes (KDIGO) guideline 2012. Urine NGAL level was measured by enzyme linked immunosorbent assay technique.ResultsA total of 101 NAFLD patients were included with a mean age of 54 ± 16 years. Among these patients, 14 (13.9%), 13 (12.9%), and 32 (31.7%) had fibrosis stages 2, 3, and 4, respectively. Nine percent (9 of 101) of patients with NAFLD with a mean eGFR of 42.66 ± 17.42 ml⋅min−1⋅1.73 m−2. The statistically significant factors associated with CKD were a higher level of urine NGAL (55.1 [25.15–150.60] vs. 15.1 [9.67–25.15] ng/ml; p = 0.006), a higher level of TE (17.3 [6.85–46.20] vs. 7.7 [5.6–11.7] kPa; p = 0.038), and a presence of advanced fibrosis (77.8% vs. 40.7%; p = 0.041), compared to those without CKD. Urine NGAL was the only significant factor associated with CKD in NAFLD patients. The cutoff level of urine NGAL at 36.75 ng/ml showed odds ratio of 21.27 (95% CI: 3.97–113.82; p &lt; 0.001) and 1.02 (95% CI: 1.00–1.04; p = 0.024) by univariate and multivariate analyses, respectively. The selected urine NGAL cutoff demonstrated a sensitivity and specificity of 77.8% and 85.9% for predicting CKD, respectively.ConclusionsThe proportion of CKD in NAFLD patients was 9% and the presence of advanced fibrosis was a significant risk factor associated with CKD. Additionally, urine NGAL was significantly associated with CKD in NAFLD patients using a cutoff level of 36.75 ng/ml for predicting CKD with acceptable sensitivity and specificity. A larger prospective cohort study is needed to validate our findings.

Evaluation of symmetric dimethylarginine in cats with acute kidney injury and chronic kidney disease.

BackgroundSerum symmetric dimethylarginine (SDMA) concentrations are considered a biomarker for renal dysfunction in dogs and humans with acute kidney injury (AKI). No studies have assessed SDMA in cats with AKI.Hypothesis/ObjectivesSDMA correctly identifies cats with azotemic AKI.AnimalsFifteen control cats, 22 with novel AKI, 13 with acute on chronic‐AKI (AoC) and 19 with chronic kidney disease (CKD).MethodsRetrospective study. Cats with azotemia (serum creatinine concentrations >1.7 mg/dL) were defined as having AKI or CKD based on history, clinical signs, clinicopathological findings and diagnostic imaging, and classified using the International Renal Interest Society (IRIS) grading/staging systems. Serum SDMA concentrations were compared between groups with nonparametric methods, and correlations assessed using Spearman's correlation coefficient. Data are presented as median [range].ResultsSDMA concentrations were 11 (8‐21) μg/dL, 36 (9‐170)μg/dL, 33 (22‐75) μg/dL and 25 (12‐69) μg/dL in control, novel AKI, AoC and CKD cats. SDMA concentrations were significantly higher in cats with novel AKI (P < .001), AoC (P < .001) and CKD (P < .01) compared to controls. SDMA concentrations were significantly higher in cats with more advanced AKI (IRIS grade IV‐V) compared to less severe AKI (IRIS grade II). Serum creatinine and SDMA concentrations had a significant correlation in cats with novel AKI (r s = 0.826, n = 22; P < .001) and a significant correlation when all cats across all 4 groups were considered together (r s = 0.837, n = 69; P < .001).Conclusions and Clinical ImportanceSerum SDMA concentrations are elevated in cats with established AKI (novel and AoC) and CKD, providing evidence for use of SDMA as a biomarker for AKI in cats.