Biomarkers Of Chronic Kidney Disease Research Articles

Cardiac biomarkers in pediatric CKD—a prospective follow-up study

BackgroundThe N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitive cardiac-specific troponin T (hs-cTnT) are associated with abnormal cardiac structure and function and an increased risk of cardiovascular death in chronic kidney disease (CKD) patients. There is limited knowledge about these cardiac markers in pediatric CKD patients.MethodsLongitudinal levels of NT-proBNP and hs-cTnT were analyzed in 48 pediatric patients, 22 with CKD (GFR range 8.8–68 mL/min/1.73 m2) and 26 transplanted patients (CKD-T; GFR range 30–99 mL/min/1.73 m2). Follow-up was scheduled after 1 and 3 years. Longitudinal patterns and associations to kidney function, cardiovascular risk markers, and echocardiographic parameters were assessed.ResultsHigh NT-proBNP was present in 27% of CKD and 11% of CKD-T patients. Similarly 32% of CKD and 8% of CKD-T patients had elevated hs-cTnT levels. In longitudinal multivariate analyses, high log NT-proBNP was associated with low GFR (β = − 0.01, p = 0.01) and elevated left ventricular mass index (LVMI; β = 0.02, p = 0.05). The strong association to LVMI remained when using GFR-adjusted NT-proBNP in similar analysis. Patients with left ventricular hypertrophy (LVH) also had higher NT-proBNP (235 [146–301] ng/L) than patients without LVH (86 [11–477] ng/L), p = 0.02. High hs-cTnT over-time was also associated with low GFR (β = − 0.007, p = 0.01) and a low cc-TDI e´/a´, indicating a worse LV diastolic function (β = − 0.09, p = 0.05). This association did not persist for GFR-adjusted hs-cTnT.ConclusionsNT-proBNP and hs-cTnT are elevated in pediatric CKD and CKD-T patients. GFR-adjusted NT-proBNP was associated with longitudinal levels of elevated LVMI suggesting this might be a marker for early subclinical myocardial damage.Graphical abstractA higher resolution version of the Graphical abstract is available as Supplementary information.

RAGE and Serum Copeptin Act as a Potential Biomarker for Chronic Kidney Disease with and without Type 2 Diabetes Mellitus

RAGE and Serum Copeptin Act as a Potential Biomarker for Chronic Kidney Disease with and without Type 2 Diabetes Mellitus

Prognostic Signature of Chronic Kidney Disease in Advanced Age: Secondary Analysis from the InGAH Study with One-Year Follow-Up.

The negative impact of chronic kidney disease (CKD) on health status and quality of life in older patients has been well documented. However, data on frailty trajectories and long-term outcomes of older CKD patients undergoing structured Comprehensive Geriatric Assessment (CGA) with multidimensional frailty evaluation are sparse. Here, we analysed records from 375 CKD patients admitted to our university hospital (mean age 77.5 (SD 6.1) years, 36% female) who had undergone a CGA-based calculation of the frailty score with the multidimensional prognostic index (MPI) as well as follow-up evaluations at 3, 6 and 12 months after discharge. Based on the MPI score at admission, 21% of the patients were frail and 56% were prefrail. MPI values were significantly associated with KDIGO CKD stages (p = 0.003) and rehospitalisation after 6 months (p = 0.027) and mortality at 3, 6 and 12 months (p = 0.001), independent of chronological age. Kidney transplant recipients (KTR) showed a significantly lower frailty compared to patients with renal replacement therapy (RRT, p = 0.028). The association between frailty and mortality after 12 months appeared particularly strong for KTR (mean MPI 0.43 KTR vs. 0.52 RRT, p < 0.001) and for patients with hypoalbuminemia (p < 0.001). Interestingly, RRT was per se not significantly associated with mortality during follow up. However, compared to patients on RRT those with KTR had a significantly lower grade of care (p = 0.031) and lower rehospitalisation rates at 12 months (p = 0.010). The present analysis shows that the large majority of older CKD inpatients are prefrail or frail and that the risk for CKD-related adverse outcomes on the long term can be accurately stratified by CGA-based instruments. Further studies are needed to explore the prognostic and frailty-related signature of laboratory biomarkers in CKD.

Urinary miRNA Profiles in Chronic Kidney Injury-Benefits of Extracellular Vesicle Enrichment and miRNAs as Potential Biomarkers for Renal Fibrosis, Glomerular Injury, and Endothelial Dysfunction.

Micro-RNAs (miRNAs) are regulators of gene expression and play an important role in physiological homeostasis and disease. In biofluids, miRNAs can be found in protein complexes or in extracellular vesicles (EVs). Altered urinary miRNAs are reported as potential biomarkers for chronic kidney disease (CKD). In this context, we compared established urinary protein biomarkers for kidney injury with urinary miRNA profiles in obese ZSF1 and hypertensive renin transgenic rats. Additionally, the benefit of urinary EV enrichment was investigated in vivo and the potential association of urinary miRNAs with renal fibrosis in vitro. Kidney damage in both rat models was confirmed by histopathology, proteinuria, and increased levels of urinary protein biomarkers. In total, 290 miRNAs were elevated in obese ZSF1 rats compared with lean controls, whereas 38 miRNAs were altered in obese ZSF1 rats during 14-26 weeks of age. These 38 miRNAs correlated better with disease progression than established urinary protein biomarkers. MiRNAs increased in obese ZSF1 rats were associated with renal inflammation, fibrosis, and glomerular injury. Eight miRNAs were also changed in urinary EVs of renin transgenic rats, including one which might play a role in endothelial dysfunction. EV enrichment increased the number and detection level of several miRNAs implicated in renal fibrosis in vitro and in vivo. Our results show the benefit of EV enrichment for miRNA detection and the potential of total urine and urinary EV-associated miRNAs as biomarkers of altered kidney physiology, renal fibrosis and glomerular injury, and disease progression in hypertension and obesity-induced CKD.

Multiparametric quantitative renal MRI in children and young adults: comparison between healthy individuals and patients with chronic kidney disease

Multiparametric quantitative renal MRI may provide noninvasive radiologic biomarkers of chronic kidney disease (CKD) based on investigations in animal models and adults. We aimed to (1) obtain normative multiparametric quantitative MRI data from the kidneys of healthy children and young adults, (2) compare MRI measurements between healthy control participants and patients with CKD, and (3) determine if MRI measurements correlate with clinical and laboratory data as well as histology. This was a prospective, case-control study of 20 healthy controls and 12 CKD patients who underwent percutaneous renal biopsy ranging from 12 to 23years of age between October 2018 and March 2020. Kidney function was documented and pathology assessed for fibrosis/inflammation. Utilizing a field strength of 1.5T, we examined renal T1, T2, and T2* relaxation mapping, MR elastography (MRE), and diffusion-weighted imaging (DWI). A single analyst made all manual measurements for quantitative MRI pulse sequences. Independent measurements from cortex, medulla, and whole kidney were obtained by drawing regions of interest on single slices from the upper, mid, and lower kidney. A weighted average was calculated for each kidney; if two kidneys, the right and left were averaged. Continuous variables were compared with Mann-Whitney U test; bivariate relationships were assessed using Spearman rank-order correlation. Median estimated glomerular filtration rate (eGFR) was 112.3ml/min/1.73 m2 in controls (n = 20, 10 females) and 55.0ml/min/m2 in CKD patients (n = 12, 2 females) (p < 0.0001). Whole kidney (1333 vs. 1291ms; p = 0.018) and cortical (1212 vs 1137ms; p < 0.0001) T1 values were higher in CKD patients. Cortical T1 values correlated with eGFR (rho = -0.62; p = 0.0003) and cystatin C (rho = 0.58; p = 0.0007). Whole kidney (1.87 vs. 2.02 10-3 mm2/s; p = 0.007), cortical (1.89 vs. 2.04 10-3 mm2/s; p = 0.008), and medullary (1.87 vs. 1.98 10-3 mm2/s; p = 0.0095) DWI apparent diffusion coefficients (ADC) were lower in CKD patients. Whole kidney ADC correlated with eGFR (rho = 0.45; p = 0.012) and cystatin C (rho = -0.46; p = 0.009). Cortical histologic inflammation correlated with DWI ADC (rho = -0.71; p = 0.011). Renal T1 relaxation and DWI ADC measurements differ between pediatric healthy controls and CKD patients, correlate with laboratory markers of CKD, and may have histologic correlates.

Renal biomarkers in cats: A review of the current status in chronic kidney disease.

Serum creatinine concentration, the classical biomarker of chronic kidney disease (CKD) in cats, has important limitations that decrease its value as a biomarker of early CKD. Recently, serum symmetric dimethylarginine concentration was introduced as a novel glomerular filtration rate biomarker for the early detection of CKD in cats. However, data on its specificity are still limited. The limitations of conventional biomarkers and the desire for early therapeutic intervention in cats with CKD to improve outcomes have prompted the discovery and validation of novel renal biomarkers to detect glomerular or tubular dysfunction. Changes in the serum or urinary concentrations of these biomarkers may indicate early kidney damage or predict the progression of kidney before changes in conventional biomarkers are detectable. This review summarizes current knowledge on renal biomarkers in CKD in cats, a field that has progressed substantially over the last 5 years.

Advances in proteomic profiling of pediatric kidney diseases.

Chronic kidney disease(CKD) can progress to kidney failure and require dialysis or transplantation, while early diagnosis can alter the course of disease and lead to better outcomes in both pediatric and adult patients. Significant CKD comorbidities include the manifestation of cardiovascular disease, heart failure, coronary disease, and hypertension. The pathogenesis of chronic kidney diseases can present as subtle and especially difficult to distinguish between different glomerular pathologies. Early detection of adult and pediatric CKD and detailed mechanistic understanding of the kidney damage can be helpful in delaying or curtailing disease progression via precise intervention toward diagnosis and prognosis. Clinically, serum creatinine and albumin levels can be indicative of CKD, but often are a lagging indicator only significantly affected once kidney function has severely diminished. The evolution of proteomics and mass spectrometry technologies has begun to provide a powerful research tool in defining these mechanisms and identifying novel biomarkers of CKD. Many of the same challenges and advances in proteomics apply to adult and pediatric patient populations. Additionally, proteomic analysis of adult CKD patients can be transferred directly toward advancing our knowledge of pediatric CKD as well. In this review, we highlight applications of proteomics that have yielded such biomarkers as PLA2R, SEMA3B, and other markers of membranous nephropathy as well as KIM-1, MCP-1, and NGAL in lupus nephritis among other potential diagnostic and prognostic markers. The potential for improving the clinical toolkit toward better treatment of pediatric kidney diseases is significantly aided by current and future development of proteomic applications.

Plasma Haptoglobin and Group-specific Component Phenotypic Variants Increase the Risk of Chronic Kidney Disease

ABSTRACT The researchers studied the correlation of Haptoglobin (HP) and Group-specific Component (GC) plasma protein biomarkers in chronic kidney disease (CKD) patients and non-CKD controls using discontinuous-polyacrylamide gel electrophoresis. The results showed a significant difference between the CKD and control clusters of 2-2 variants for HP (p=0.0036) and GC (p= 0.0033). The current research indicates 2-2 phenotype is an independent risk determinant for CKD, while risk analysis reports odds value &gt;1 for both protein polymorphisms signifying an effective risk towards CKD. The multifactor dimensional reduction analysis also detailed HP and GC markers have a strengthening and stronger association and are causative for CKD development. Collectively, the findings signify a potential risk of plasma HP and GC polymorphisms being susceptible to CKD and their key role in the deterioration of kidney functions.

MicroRNAs as Potential Biomarkers for the Diagnosis of Chronic Kidney Disease: A Systematic Review and Meta-Analysis.

For Chronic Kidney Disease (CKD), the study of microRNA as a biomarker has become an exciting area, so we carried out a meta-analysis to investigate the potential diagnostic values of miRNAs in CKD. We searched Pubmed, Cochrane Library, Embase, and Web of science databases to identify relevant publications published from the establishment of the database to April 30, 2021. We included a total of 26 articles containing 56 studies. There were 4,098 patients with CKD and 2,450 patients without CKD. We found that the overall sensitivity and specificity of miRNAs in CKD diagnosis were 0.86 (95% CI: 0.83–0.89) and 0.79 (95% CI: 0.75–0.83), respectively. In addition, we plotted the summary receiver operator characteristic (SROC) curve to assess diagnostic accuracy, with the area under the curve (AUC) of 0.90 (95% CI: 0.87–0.92). Subgroup analysis showed that sensitivity, specificity, and AUC of miRNAs in plasma and serum were 0.84, 0.78, 0.88; and 0.79, 0.76, 0.83, respectively, while miRNAs in urine were 0.89 for sensitivity, 0.82 for specificity, and 0.92 for AUC. Moreover, we found that the panel of microRNAs (miRNAs) could improve the pooled sensitivity (0.88, 0.81, and 0.91 for sensitivity, specificity, and AUC, respectively). We believe that miRNAs have great potential to become an effective diagnostic biomarker for CKD. Panels of miRNA have higher accuracy than single miRNAs. Additionally, miRNAs in both blood and urine have significant accuracy in the diagnosis of CKD; nevertheless, urine is superior.

Urinary Retinol-Binding Protein 4 is Associated With Renal Function and Rapid Renal Function Decline in Kidney Transplant Recipients

Urinary retinol-binding protein 4 (RBP4) has been known as a biomarker of chronic kidney disease. In this study, we evaluated the association of urinary RBP4 with renal function and progression of renal function in kidney transplant recipients (KTRs). A total 50 KTRs were included in this study. Proteomic analysis with liquid chromatography-mass spectrometry and tandem mass spectrometry was performed to discover potential urinary biomarkers. Several urinary proteins including RBP4 were identified and then validated by enzyme-linked immunosorbent assay. Rapid renal function decline was defined as estimated glomerular filtration rate (eGFR) decline of >3 mL/min/1.73 m2/year or initiation of dialysis, and 19 (38%) were included in rapid renal function decline group. Urinary RBP4/creatinine was inversely correlated with allograft function (r=-0.54, P < .001 with eGFR, and r=0.49, P < .001 with serum creatinine, respectively). Urinary RBP4/creatinine was higher in rapid renal function decline group than in stable renal function group (184.9 ± 156.7 vs 83.1 ± 99.9, P=.017). Log-transformed urinary RBP4/creatinine was significantly associated with rapid renal function decline in univariate logistic regression analysis (Odds ratio [OR] 7.59, confidence interval [CI] 2.04-36.70, P=.005). In multivariate logistic regression adjusted with recipient age and sex, donor age, number of HLA mismatch, and acute rejection episode, urinary RBP4/creatinine remained a significant factor for rapid renal function decline (OR 9.43, CI 1.99-65.65, P=.010). Receiver operating characteristic analysis showed that the area under the curve of urinary RBP4/creatinine was 0.747 (CI 0.608-0.886, P < .001) for rapid renal function decline. Urinary RBP4 levels are associated with renal function and might be used to predict rapid renal function decline in KTRs.

Identification of biomarkers of chronic kidney disease among kidney-derived proteins

BackgroundChronic kidney disease (CKD) has few objective symptoms, and it is difficult to make an early diagnosis by using existing methods. Therefore, new biomarkers enabling diagnosis of renal dysfunction at an early stage need to be developed. Here, we searched for new biomarkers of CKD by focusing on kidney-derived proteins that could sensitively reflect that organ’s disease state.MethodsTo identify candidate marker proteins, we performed a proteomics analysis on renal influx and efflux blood collected from the same individual.ResultsProteomics analysis revealed 662 proteins in influx blood and 809 in efflux. From these identified proteins, we selected complement C1q as a candidate; the plasma C1q level was significantly elevated in the renal efflux of donors. Moreover, the plasma concentration of C1q in a mouse model of diabetic nephropathy was significantly increased, in association with increases in blood glucose concentration and urinary protein content. Importantly, we demonstrated that the tendency of C1q to increase in the plasma of CKD patients was correlated with a decrease in their estimated glomerular filtration rate.ConclusionOverall, our results indicate that our approach of focusing on kidney-derived proteins is useful for identifying new CKD biomarkers and that C1q has potential as a biomarker of renal function.

The Association of Toxoplasma gondii IgG Antibody and Chronic Kidney Disease Biomarkers.

Background: Toxoplasma gondii (T. gondii) is a parasite that infects more than 40 million Americans and causes toxoplasmosis. Most cases of toxoplasmosis are asymptomatic; however, T. gondii is capable of invading organs like the kidney, causing chronic infections and cell destruction. Methods: This study focused on evaluating the association between T. gondii exposure and chronic kidney disease (CKD) using data from the 2009–2010 National Health and Nutrition Examination Survey (NHANES). T. gondii exposure was assessed using Toxoplasma gondii IgG antibody status, and the status of CKD was assessed using the CKD biomarkers. The evaluation of risk rate and population prevalence was performed. In addition, multivariable regression models were used to further investigate this association after adjusting for sociodemographic, anthropometric, behavioral, and clinical covariates commonly associated with kidney dysfunction. Results: The positive T. gondii IgG antibody participants had significantly higher levels of CKD biomarkers, including second albumin-to-creatinine ratio (p = 0.0376), second albuminuria (p = 0.0005), and persistent albuminuria (p < 0.0001) compared to the negative participants. Furthermore, there were statistical associations between T. gondii exposure and the status of CKD (negative vs. positive) (p = 0.0001), and between T. gondii exposure and the CKD stage (negative, stage 1, …, stage 5) (p = 0.0004). Without adjusting for age, the positive T. gondii participants had a significantly higher risk (27% higher) of having CKD than the negative participants (RRcrude = 1.27, 95% CI: 1.09–1.49). The age-adjusted prevalence of CKD was higher among Toxoplasma-positive participants compared to the Toxoplasma-negative participants (10.45 vs. 8.99). T. gondii infection was significantly associated with CKD (OR = 1.40, 95% CI = 1.06–1.84, p = 0.00447) after adjusting for age, gender, race/ethnicity, and BMI. Age was positively associated with CKD (OR = 8.89, 95% CI = 6.31–12.51, p < 0.0001) with the participants 45+ years old being 8.89 times more likely to have CKD than those who are <45 years old, after adjusting for T. gondii infection, gender, race/ethnicity, and BMI. Moreover, positive T. gondii increased the odds of CKD progression (OR = 1.41, 95% CI = 1.07–1.86, p = 0.0424). Conclusions: Positive T. gondii IgG antibody is associated with CKD and the progression of CKD stages. This association is more apparent among older people. Further investigations are needed to examine these findings in different geographical locations and among differentially exposed populations.

Association of Serum Beta-Trace Protein Levels in Patients with Chronic Kidney Disease: A Case-control Study

Introduction: Chronic Kidney Disease (CKD) is common disorder showing decreased Glomerular Filtration Rate (GFR) value (&lt;60 mL/min/1.73 m2 ). Because of limitations of creatinine as a biomarker of GFR, new alternative biomarkers are being investigated, such as Beta-Trace Protein (BTP) is low molecular weight proteins that are filtered by the glomeruli. Serum BTP have been shown to be more helpful for estimating GFR. Aim: To assess the role of Beta-Trace Protein (BTP) as a potential biomarker of Chronic Kidney Disease (CKD) in comparison to serum urea, serum creatinine, fasting blood sugar and Creatinine Clearance Rate (CCR). Materials and Methods: This case-control study was conducted at Government Medical College, Rajouri, Jammu and Kashmir, India, from February 2021 to December 2021. Total 50 known patients of kidney diseases and 50 healthy individuals above the age of 18 years were enrolled in the study. Blood samples were collected from all individuals and serum BTP, serum urea level, serum creatinine level, fasting blood sugar were measured. Correlation of BTP with serum urea level, serum creatinine level, Fasting Blood Glucose (FBG) level, and CCR was calculated by Pearson Correlation test. Results: In present study, 50 patients in case groups (33 male and 17 females) and 50 healthy controls (25 males and 25 females) were included. Among controls, the mean age of patients was 52.12±5.66 years and among cases 55.94±10.51 years. BTP level was increased two times (from 32.06±11.25 µg/ml to 66.36±27.80 µg/ml) in CKD patients than controls individuals. BTP level was positively correlated with serum urea level, serum creatinine level, and FBG level while negatively correlated with CCR. Conclusion: BTP may be a useful and reliable serum marker for identifying the magnitude of renal dysfunction in patients with CKD and may have its place beside serum creatinine as an alternative endogenous GFR marker.

Advances in the Progression and Prognosis Biomarkers of Chronic Kidney Disease.

Chronic kidney disease (CKD) is one of the increasingly serious public health concerns worldwide; the global burden of CKD is increasingly due to high morbidity and mortality. At present, there are three key problems in the clinical treatment and management of CKD. First, the current diagnostic indicators, such as proteinuria and serum creatinine, are greatly interfered by the physiological conditions of patients, and the changes in the indicator level are not synchronized with renal damage. Second, the established diagnosis of suspected CKD still depends on biopsy, which is not suitable for contraindication patients, is also traumatic, and is not sensitive to early progression. Finally, the prognosis of CKD is affected by many factors; hence, it is ineviatble to develop effective biomarkers to predict CKD prognosis and improve the prognosis through early intervention. Accurate progression monitoring and prognosis improvement of CKD are extremely significant for improving the clinical treatment and management of CKD and reducing the social burden. Therefore, biomarkers reported in recent years, which could play important roles in accurate progression monitoring and prognosis improvement of CKD, were concluded and highlighted in this review article that aims to provide a reference for both the construction of CKD precision therapy system and the pharmaceutical research and development.

Metabolite Genome-Wide Association Study for Indoleamine 2,3-Dioxygenase Activity Associated with Chronic Kidney Disease.

Chronic kidney disease (CKD) causes progressive damage to kidney function with increased inflammation. This process contributes to complex amino acid changes. Indoleamine 2,3-dioxygenase (IDO) has been proposed as a new biomarker of CKD in previous studies. In our research, we performed a metabolite genome-wide association study (mGWAS) to identify common and rare variants associated with IDO activity in a Korean population. In addition, single-nucleotide polymorphisms (SNPs) selected through mGWAS were further analyzed for associations with the estimated glomerular filtration rate (eGFR) and CKD. A total of seven rare variants achieved the genome-wide significance threshold (p < 1 × 10−8). Among them, four genes (TNFRSF19, LOC105377444, LOC101928535, and FSTL5) associated with IDO activity showed statistically significant associations with eGFR and CKD. Most of these rare variants appeared specifically in an Asian geographic region. Furthermore, 15 common variants associated with IDO activity were detected in this study and five novel genes (RSU1, PDGFD, SNX25, LOC107984031, and UBASH3B) associated with CKD and eGFR were identified. This study discovered several loci for IDO activity via mGWAS and provided insight into the underlying mechanisms of CKD through association analysis with CKD. To the best of our knowledge, this is the first study to suggest a genetic link between IDO activity and CKD through comparative and integrated analysis.

Associations of Plasma Biomarkers of Inflammation, Fibrosis, and Kidney Tubular Injury With Progression of Diabetic Kidney Disease: A Cohort Study

Most circulating biomarkers of chronic kidney disease (CKD) progression focus on factors reflecting glomerular filtration. Few biomarkers capture nonglomerular pathways of kidney injury or damage, which may be particularly informative in populations at high risk for CKD progression such as individuals with diabetes. Cohort study. 594 participants (mean age, 70 years; 53% women) of the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study who had diabetes and an estimated glomerular filtration rate (eGFR)<60mL/min/1.73m2 at baseline. Plasma biomarkers of inflammation/fibrosis (TNFR1 and TNFR2, suPAR, MCP-1, YKL-40) and tubular injury (KIM-1) measured at the baseline visit. Incident kidney failure with replacement therapy (KFRT). Cox proportional hazards regression and least absolute shrinkage and selection operator regression adjusted for established risk factors for kidney function decline, baseline eGFR, and urinary albumin-creatinine ratio (UACR). A total of 98 KFRT events were observed over a mean of 6.2±3.5 (standard deviation) years of follow-up. Plasma biomarkers were modestly associated with baseline eGFR (correlation coefficients ranging from-0.08 to-0.65) and UACR (0.14 to 0.56). In individual biomarker models adjusted for eGFR, UACR, and established risk factors, hazard ratios for incident KFRT per 2-fold higher biomarker concentrations were 1.52 (95% CI, 1.25-1.84) for plasma KIM-1, 1.54 (95% CI, 1.08-2.21) for TNFR1, 1.91 (95% CI, 1.16-3.14) for TNFR2, and 1.39 (95% CI, 1.05-1.84) for YKL-40. In least absolute shrinkage and selection operator regression models accounting for biomarkers in parallel, plasma KIM-1 and TNFR1 remained associated with incident KFRT. Single biomarker measurement, lack of follow-up eGFR assessments. Individual plasma markers of inflammation/fibrosis (TNFR1, TNFR2, YKL-40) and tubular injury (KIM-1) were associated with risk of incident KFRT in adults with diabetes and an eGFR<60mL/min/1.73m2 after adjustment for established risk factors.

Elevated Plasma Soluble Urokinase-Type Plasminogen Activator Receptor (suPAR) in Sickle Cell Disease - a Marker of Chronic Kidney Disease

Background: Sickle cell nephropathy (SCN) is one of the most common complications of SCD, leading in most cases to chronic kidney disease (CKD) and end-stage renal disease (ESRD). Despite the high prevalence of CKD in sickle cell disease (SCD) patients, there remains a poor understanding of the pathophysiological mechanism of SCN and a lack of biomarkers for early detection of SCD-associated CKD. Soluble urokinase-type plasminogen activator receptor (suPAR) is an emerging biomarker of CKD. suPAR is a member of the fibrinolytic system, which is dysregulated in SCD patients.Objective: To evaluate suPAR as a biomarker of SCD-associated nephropathy and identify plasma proteases responsible for its increase in SCD.Methods: The study was approved by Howard University review board (IRB) and all subjects provided written inform consent prior to the sample collection. Whole blood and urine samples were collected from 77 SCD patients and 10 healthy individuals, and plasma was isolated. Levels of creatinine and cystatin C in plasma and albumin and creatinine in urine were measured by ELISA. eGFR was calculated using CKD-EPI creatinine-cystatin equation, and CKD stages were assigned. Plasma suPAR was measured by ELISA and was correlated with CKD stages. The activities of candidates uPAR proteases: Neutrophile elastase (NE), urokinase-type plasminogen activator (uPA) and plasmin in plasma samples from SCD patients were measured and compared to healthy participants.Results:The average age of SCD patients was 42.5 years (range 18-67 years). Most patients had HbSS genotype (67.5%),19.5% of patients were HbSC (hemoglobin C sickle cell compound heterozygous), and 13% had HbS β-thalassemia. More than half (53.2 %) were females.We observed an increased level of plasma suPAR (>3ng/ml) in more than 60% of SCA patients without renal disease, representing a risk factor for CKD progression. Plasma suPAR levels further increased in the patients with CKD and positively correlated with stages of CKD (r=0.419, R2=0.1696). Analysis of plasma proteases that cleaved uPAR producing soluble peptides (suPAR) demonstrated increased urokinase-type plasminogen activator (uPA) activity without significant changes in neutrophile elastase.Conclusion:This study validated plasma suPAR as a potential marker of CKD in SCD patients and identified plasma uPA as a uPAR protease that may increase circulating suPAR in SCD. Future longitudinal analysis of suPAR levels in patients with SCA is needed.Acknowledgments:We thank Drs. Namita Kumari and Xiaomei Niu for their help in samples identification. This work was supported by NIH Research Grants 1R01HL125005-06A1, 5U54MD007597, 1P30AI117970-06,1UM1AI26617, and 1SC1HL150685. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Paraoxonase 1 (PON1) L55M and Q192R polymorphisms are not associated with chronic kidney disease in Thai individuals with type 2 diabetes.

Decreased paraoxonase 1 (PON1) activity and PON1 polymorphisms have been found to be associated with chronic kidney disease (CKD) in type 2 diabetes mellitus (T2DM). This study aimed to investigate the association of the PON1 L55M and Q192R polymorphisms with CKD in T2DM, as well as their relationship with PON1 activity. A total of 166 T2DM patients, including 83 CKD patients and 83 non-CKD patients, were recruited. Biochemical parameters and paraoxonase (PONase) and arylesterase (AREase) activities were measured. The PON1 L55M and Q192R polymorphisms were analysed by a polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method. Data were analysed using the chi-square test, Student's t-test and logistic regression analysis. Total cholesterol, TGs, LDL-C and Cr were significantly higher in CKD patients than in non-CKD patients. In contrast, the estimated glomerular filtration rate (eGFR) and AREase activity were significantly lower in CKD patients than in non-CKD patients (P<.05). The genotype and allele frequencies of the PON1 L55M and Q192R polymorphisms were not significantly different between CKD and non-CKD patients. Multivariate logistic regression analysis showed no association between the PON1 L55M and Q192R polymorphisms and CKD in T2DM. In addition, among all patients, patients with the PON1 LM genotype had significantly lower PONase activity than those with the LL genotype (P<.05). Among all patients, CKD patients and non-CKD patients, those with the PON1 RR genotype had significantly higher PONase activity but lower AREase activity than patients with the QR and QQ genotypes (P<.05). PON1 activity was influenced by the PON1 L55M and Q192R polymorphisms. However, the PON1 L55M and Q192R polymorphisms may not be considered genetic biomarkers for CKD in T2DM.

The correlation between fibroblast growth factor-23 and ESRD patients with hearing impairment.

BackgroundEnd-stage renal disease (ESRD) patients often experience hearing impairment, resulting in a high rate of disability and a decline in their quality of life. Fibroblast growth factor-23 (FGF23) is a diagnostic biomarker for chronic kidney disease (CKD) and a pathogenic contributor to CKD progression. However, the correlation between FGF23 level and CKD patients with hearing impairment remains elusive. This study aimed to investigate the relationship between the FGF23 and ESRD accompanied with hearing impairment.MethodsA total of 144 ESRD patients, who were admitted to the First Affiliated Hospital of Kunming Medical University from November to December 2020, were enrolled in this study. Firstly, 144 ESRD patients underwent pure-tone audiometry (PTA). Secondly, it was attempted to randomly select 20 ESRD patients with normal hearing, and 20 ESRD patients with hearing impairment (match ratio, 1:1). Age- and gender-matched healthy people (n = 20) were also recruited as controls group. The expression levels of FGF23 was detected by enzyme-linked immunosorbent assay (ELISA).ResultsThe results of pure-tone audiometry showed that the prevalence of hearing impairment in ESRD patients was 80.5%. Male ESRD patients were more likely to develop hearing impairment compared to female patients. The incidence rate of hearing impairment at a high frequency was significantly higher than that at a low frequency (P < 0.01). The serum levels of FGF23, phosphorus, and parathyroid hormone (PTH) in ESRD patients with hearing impairment significantly increased compared with those with normal hearing and healthy controls.ConclusionESRD patients had a higher risk of hearing loss, especially high-frequency hearing impairment. As FGF23 level increased, the risk of hearing loss was also elevated. The hearing impairment in ESRD patients was associated with the degree of kidney injury, and serum FGF23 level.

Measurement of Inflammation-Related Biomarkers in Different Chronic Kidney Diseases in Humans: Role of Aging and Gender?

INTRODUCTION: Chronic kidney disease (CKD) is a worldwide health problem which becomes a substantial emerging cause of morbidity. The inflammation can be resulted via different mechanisms in different kidney diseases including the imbalance of proinflammatory/anti-inflammatory biomarkers levels. This study aimed to measure the level of physiological bioactive substances as inflammation-related biomarkers in different CKD and to investigate whether gender or aging is critical in these measurements. MATERIALS AND METHODS: 84 persons (19 healthy, 29 chronic glomerulonephritis, 26 diabetic nephropathy, 6 benign nephrosclerosis, 4 lupus nephritis) were enrolled in this study. The inflammation progression degree in CKD was estimated by measuring the plasma level of neutrophil gelatinase-associated lipocalin (NGAL), monocyte chemoattractant protein 1 (MCP1), and clusterin (CLU) using ELISA. Serum total protein, urea and creatinine were measured using an automatic analyzer. RESULTS: Plasma level of urea and creatinine was increased while total protein level was decreased in all the patients compared to control participants. The level of NGAL, MCP1 and CLU was significantly increased in all the kidney diseases compared to controls. In addition, there were no differences in the level of inflammation-related markers between women and men. Moreover, the levels of inflammatory markers were increased in the kidney diseases regardless of the age difference. CONCLUSIONS: This study showed that the physiological bioactive substances NGAL, MCP1 and CLU can be increased in renal pathologies and considered as good indicators of progression of inflammation in chronic kidney diseases, with no role of gender and age in their increment plasma levels.