Markers Of Chronic Kidney Disease Research Articles

Role of Serum Uromodulin in the Early Diagnosis of Chronic Kidney Disease

Abstract Background: The diagnosis of chronic kidney disease (CKD) is usually delayed, when significant functional renal impairment has already occurred. The diagnosis is complex and clinical and laboratory investigations play a crucial role. There are well-established markers of CKD – serum creatinine and cystatin C. However, the search for new reliable biomarkers that aid in the assessment of kidney function and predict the evolution of the disease is still in progress. Objective: To investigate the role of serum uromodulin (sUmod) as a marker for early diagnosis of renal impairment in patients with CKD. Materials and Methods: We investigated 70 patients, 28 male and 42 female, mean age 56.53 ± 11.753, with CKD in a prospective observational study. All patients were admitted to the Clinic of Nephrology at the “St. Ivan Rilski” University Hospital between April and November 2019. After obtaining written informed consent, laboratory blood and urine tests, abdominal ultrasound and sUmod investigations were performed in all patients. Results: Plasma uromodulin levels showed decrease with the increasing of the severity of renal impairment. sUmod displayed inverse correlation with serum creatinine (r = -0.467, p < 0.0001), cystatin C (r = -0.430, p < 0.0001) and urea (r = -0.495, p < 0.0001) and a positive correlation with eGFR (r = 0.628, p < 0.0001). Conclusion: The results of our study show that sUmod levels significantly correlate with all established laboratory parameters used for the evaluation of renal impairment. It can be used as a potential early biomarker for CKD diagnosis.

Association of mineral metabolism biomarkers with chronic kidney disease in Chinese adults

BackgroundWe aimed to examine the association of three mineral metabolism markers, including serum calcium, inorganic phosphorus, and intact parathyroid hormone with the risk of chronic kidney disease (CKD) at all stages.MethodsThis retrospective cohort study involved 3563 participants, including 3274 CKD patients and 289 healthy controls. CKD is diagnosed according to clinical guidelines from the 2012 KDIGO. Effect sizes are expressed odds ratio (OR) and 95 confidence interval (CI).ResultsAfter propensity score matching, per 0.5 mg/dL increment of inorganic phosphorus was significantly associated with 1.33-, 1.61-, and 2.85-fold increased risk of CKD at stages 1–2, 4, and 5, respectively. Regarding per 8 pg/mL increment of intact parathyroid hormone, significance was only noted for stage 5. In subsidiary analyses, the risk prediction of mineral metabolism markers under study was more evident in males and hypertensive subjects. A nomogram prediction model was constructed based on age, sex, and three mineral metabolism markers for CKD, with decent accuracy.ConclusionsOur findings indicate that serum calcium was associated with all-stage CKD risk, whereas the association for inorganic phosphorus and intact parathyroid hormone was significant at advanced stages.

The relationship between calcification inhibitor levels in chronic kidney disease and the development of atherosclerosis

Aim We aimed to investigate the factors affecting the development of atherosclerosis and the role of calcification inhibitors fetuin-A, matrix-Gla protein (MGP), osteoprotegerin (OPG) in atherosclerosis progress. Material and methods The study was planned to investigate the relationship of serum OPG, MGP and fetuin-A levels with the development of atherosclerosis in the stage 2–3–4–5 chronic kidney disease (CKD) patients who did not require dialysis treatment. Results 32 (17 female, 15 male) healthy individuals and 92 (49 females, 43 males) CKD patients were included. The mean carotid intima-media thickness (CIMT), C-reactive protein (CRP), fetuin-A, OPG and MGP of the two groups were compared statistically. In CKD patients, age, body mass index (BMI), CRP, triglyceride, urea, systolic blood pressure (SBP), fasting blood sugar have a positive linear relationship, fetuin-A, OPG, GFR have a negative linear relationship with CIMT. The mean CIMT, right CIMT, left CIMT, blood urea, CRP, urinary albumin excretion creatinine and age show a negative linear relationship with fetuin-A. Conclusion Fetuin-A levels begin to decline from the early stages of CKD and are significantly lower in patients with atherosclerosis as expressed with CIMT. This suggests that fetuin-A may be used as an early marker in CKD for increased cardiovascular risk. Early recognition of these risk factors is important and large-scale studies on vascular calcification inhibitors are needed.

Role of urinary neutrophil gelatinase-associated lipocalin in diabetic and nondiabetic patients with nephropathy

ObjectiveThe aim was to study the role of neutrophil gelatinase-associated lipocalin (NGAL) in diabetic nephropathy patients with type 2 diabetes.BackgroundDue to the high morbidity and mortality associated with diabetic nephropathy, it is important to establish a diagnosis and initiate therapy as soon as possible.Patients and methodsThis observational study was conducted on 88 subjects who were divided into four groups: Group 1 included 22 healthy individuals; group 2 included 22 type 2 diabetic patients with normoalbuminuria;, group 3 included 22 type 2 diabetic nephropathy patients; and group 4 included 22 nondiabetic patients with chronic kidney disease (CKD). All patients were admitted to the Internal Medicine Department at Menoufia University Hospital in the period from 20 December to 13 March 2019. Complete history, examination, and investigations urea, creatinine, fasting blood glucose, postprandial blood glucose, HbA1C, albumin/creatinine ratio, estimated glomerular filtration rate, and urinary NGAL were investigated for all subjects.ResultsUrea, creatinine and albumin/creatinine ratio were statistically significantly increased in diabetic nephropathy groups (145.30 ± 57.93), (3.95 ± 1.57), (201.27 ± 50.04) than in the diabetic group, while estimated glomerular filtration rate was significantly decreased among CKDs (23.64 ± 8.57) and diabetic nephropathy group (30.65 ± 14.34) than the diabetic (174.35 ± 86.13) and control groups (183.27 ± 44.17). Also, the level of NGAL was significantly increased in diabetic nephropathy groups (474.48 ± 308.22) and CKDs (367.37 ± 272.63) than diabetic groups (36.65 ± 28.30) and the control group (22.47 ± 21.16).ConclusionDiagnosis of diabetic nephropathy is based on the rise of creatinine and urea, and albumin/creatinine ratio with a decrease in estimated glomerular filtration rate. NGAL is a marker of CKD and any causes affecting the kidney. Cutoff point for NGAL was greater than 45 in patients with diabetes mellitus and greater than 30 in patients without diabetes, which were the best cutoff point for early detection of diabetic nephropathy.

Multisample Mass Spectrometry-Based Approach for Discovering Injury Markers in Chronic Kidney Disease

AbstractUrinary proteomics studies have primarily focused on identifying markers of chronic kidney disease (CKD) progression. Here, we aimed to determine urinary markers of CKD renal parenchymal injury through proteomics analysis in animal kidney tissues and cells and in the urine of patients with CKD. Label-free quantitative proteomics analysis based on liquid chromatography–tandem mass spectrometry was performed on urine samples obtained from 6 normal controls and 9, 11, and 10 patients with CKD stages 1, 3, and 5, respectively, and on kidney tissue samples from a rat CKD model by 5/6 nephrectomy. Tandem mass tag-based quantitative proteomics analysis was performed for glomerular endothelial cells (GECs) and proximal tubular epithelial cells (PTECs) before and after inducing 24-h hypoxia injury. Upon hierarchical clustering, out of 858 differentially expressed proteins (DEPs) in the urine of CKD patients, the levels of 416 decreased and 403 increased sequentially according to the disease stage, respectively. Among 2965 DEPs across 5/6 nephrectomized and sham-operated rat kidney tissues, 86 DEPs showed same expression patterns in the urine and kidney tissue. After cross-validation with two external animal proteome data sets, 38 DEPs were organized; only ten DEPs, including serotransferrin, gelsolin, poly ADP-ribose polymerase 1, neuroblast differentiation-associated protein AHNAK, microtubule-associated protein 4, galectin-1, protein S, thymosin beta-4, myristoylated alanine-rich C-kinase substrate, and vimentin, were finalized by screening human GECs and PTECs data. Among these ten potential candidates for universal CKD marker, validation analyses for protein S and galectin-1 were conducted. Galectin-1 was observed to have a significant inverse correlation with renal function as well as higher expression in glomerulus with chronic injury than protein S. This constitutes the first multisample proteomics study for identifying key renal-expressed proteins associated with CKD progression. The discovered proteins represent potential markers of chronic renal cell and tissue damage and candidate contributors to CKD pathophysiology.

Population-based comparison of chronic kidney disease prevalence and risk factors among adults living in the Punjab, Northern India and the USA (2013–2015)

ObjectivesIndia is witnessing a disturbing growth in non-communicable diseases (NCDs), including chronic kidney disease (CKD). Recently, a WHO STEPS survey was conducted in the state of Punjab, India to collect...

DNA methylation profiling identifies epigenetic differences between early versus late stages of diabetic chronic kidney disease.

We investigated a cross-sectional epigenome-wide association study of patients with early and late diabetes-associated chronic kidney disease (CKD) to identify possible epigenetic differences between the two groups as well as changes in methylation across all stages of diabetic CKD. We also evaluated the potential of using a panel of identified 5'-C-phosphate-G-3' (CpG) sites from this cohort to predict the progression of diabetic CKD. This cross-sectional study recruited 119 adults. DNA was extracted from blood using the Qiagen QIAampDNA Mini Spin Kit. Genome-wide methylation analysis was performed using Illumina Infinium MethylationEPIC BeadChips (HM850K). Intensity data files were processed and analysed using the minfi and MissMethyl packages for R. We examined the degree of methylation of CpG sites in early versus late diabetic CKD patients for CpG sites with an unadjusted P-value <0.01 and an absolute change in methylation of 5% (n = 239 CpG sites). Hierarchical clustering of the 239 CpG sites largely separated the two groups. A heat map for all 239 CpG sites demonstrated distinct methylation patterns in the early versus late groups, with CpG sites showing evidence of progressive change. Based on our differentially methylated region (DMR) analysis of the 239 CpG sites, we highlighted two DMRs, namely the cysteine-rich secretory protein 2 (CRISP2) and piwi-like RNA-mediated gene silencing 1(PIWIL1) genes. The best predictability for the two groups involved a receiver operating characteristics curve of eight CpG sites alone and achieved an area under the curve of 0.976. We have identified distinct DNA methylation patterns between early and late diabetic CKD patients as well as demonstrated novel findings of potential progressive methylation changes across all stages (1-5) of diabetic CKD at specific CpG sites. We have also identified associated genes CRISP2 and PIWIL1, which may have the potential to act as stage-specific diabetes-associated CKD markers, and showed that the use of a panel of eight identified CpG sites alone helps to increase the predictability for the two groups.

Early pediatric chronic kidney disease is associated with brain volumetric gray matter abnormalities.

Background:The impact of pediatric chronic kidney disease (pCKD) on the brain remains poorly defined. The objective of this study was to compare brain morphometry between children with early stage pCKD and typically developing peers using structural magnetic resonance imaging (MRI).Methods:The sample age range was 6–16 years. A total of 18 children with a diagnosis of pCKD (CKD stages 1–3) due to congenital anomalies of the kidney and urinary tract and 24 typically developing peers were included. Volumetric data from MRI and neurocognitive testing were compared using linear models including pCKD status, age, maternal education level, and socioeconomic status.Results:Cerebellar gray matter volume was significantly smaller in pCKD, t(38)=−2.71, p = 0.01. In contrast, cerebral gray matter volume was increased in pCKD, t(38)=2.08, p = 0.04. Reduced cerebellum gray matter volume was associated with disease severity, operationalized as estimated glomerular filtration rate (eGFR), t(14)=2.21, p = 0.04 and predicted lower verbal fluency scores in the pCKD sample. Enlarged cerebral gray matter in the pCKD sample predicted lower scores on mathematics assessment.Conclusion:This study provides preliminary evidence for a morphometric underpinning to the cognitive deficits observed in pCKD.

Under-Recognition of Neonatal Acute Kidney Injury and Lack of Follow-Up.

Acute kidney injury (AKI) incidence is 30% in neonatal intensive care units (NICU). AKI is associated with increased mortality and risk of chronic kidney disease (CKD) in children. To assess follow-up and early CKD, we retrospectively reviewed outcomes of Cincinnati Children's Hospital Medical Center (CCHMC) cohort of neonates from the AWAKEN trial (2014). Data from 81 CCHMC patients were extracted from the AWAKEN dataset. KDIGO (Kidney Disease: Improving Global Outcomes) criteria for serum creatinine (SCr) and urine output (UOP) <1 mL/kg/h, reported per 24 hours on postnatal days 2 to 7, were used to define AKI. Charts were reviewed until May 2019 for death, nephrology consult, AKI diagnosis on discharge summary, follow-up, and early CKD at >6 months of age (defined as: estimated glomerular filtration rate < 90 mL/min/1.73 m2, hyperfiltration, proteinuria, hypertension, or abnormal ultrasound). Patients were considered to have renal follow-up if they had ≥1 follow-up visit containing: SCr, urinalysis, or blood pressure measurement. Seventy-seven patients had sufficient data to ascertain AKI diagnosis. In total 47 of 77 (61%) were AKI+ by SCr or UOP criteria (20 stage 1, 14 stage 2, 13 stage 3). Four died during their admission and five were removed from CKD analyses due to urologic anomalies. AKI-UOP alone outnumbered AKI-SCr (45 AKI+ vs 5 AKI+ for all stages). 33% of patients had <2 SCr measured while inpatient. Only 3 of 47 AKI+ patients had a nephrology consult (all stage 3 by SCr) and 2 of 47 had AKI included in discharge summary. 67% of AKI+ patients had follow-up. In total 10 of 43 (23%) AKI+ versus 12 of 25 (48%) AKI- patients had ≥1 marker of early CKD assessed after 6 months. Based on SCr, 3 of 7 (43%) AKI+ had hyperfiltration versus 0 of 7 (0%) AKI- (p = 0.19). AKI is vastly under-recognized in the NICU, especially if based on SCr alone. This leads to insufficient follow-up to ascertain renal sequelae in this high-risk population. · AKI is under-recognized in high-risk neonates.. · There is a lack of adequate follow-up.. · Identification of AKI by SCr alone is insufficient..

Medium‐grade proteinuria is a risk factor for incident markers of chronic kidney disease

Medium-grade proteinuria (100-500mg/g creatinine) is common among people living with HIV/AIDS (PLWHA) but is often undetected or ignored. This prospective, observational cohort study examined medium-grade proteinuria as a risk factor for markers of chronic kidney disease (CKD). Quantitative urine samples were collected from 241 PLWHA without known renal disease at baseline between January 2009 and February 2011 and at follow-up 240weeks later. Multivariate analysis was performed to assess medium-grade proteinuria as a risk factor for incident markers of CKD (estimated glomerular filtration rate <60mL/min/1.73m2 , albuminuria, phosphaturia). Incident markers of CKD were identified in 33 patients (14%), of whom 24 (74%) had medium-grade proteinuria at baseline. Of these, 22 even had proteinuria of <200mg/g creatinine. Multivariate analysis showed an adjusted relative risk (aRR) of 2.4 for patients with baseline medium-grade proteinuria to develop signs of CKD. Age was identified as an additional independent predictor. By testing for interaction, tenofovir disoproxil fumarate (TDF)-independent proteinuria was strongly associated with incident CKD markers (aRR = 12.1). Medium-grade proteinuria of 100-500mg/g creatinine is both frequent in PLWHA and a significant risk factor for developing markers of CKD, especially in the absence of TDF. Relevant risk seems to be associated with proteinuria levels as low as 100-200mg/g creatinine. Current guidelines recommend specific action for proteinuria exceeding 135-200mg/g but still will miss a relevant number of PLWHA potentially at risk for CKD. An even lower cut-off to trigger nephrological work-up and potentially renoprotective interventions appears to be indicated.

P0195THE RELATIONSHIP BETWEEN CALCIFICATION INHIBITOR LEVELS IN CHRONIC KIDNEY DISEASE AND THE DEVELOPMENT OF ATHEROSCLEROSIS

Abstract Background and Aims Atherosclerosis and its associated cardiovascular diseases starting from the early stages of chronic kidney disease (CKD) are the most important cause of increased morbi-mortality in the CKD process. In studies performed in patients with end-stage renal disease (ESRD), it is observed that the calcification occured in the vascular structures was an important component of the atero-arteriolosclerosis process. The number of studies investigating the relationship between vascular calcification and the development of atherosclerosis and increased morbi-mortality in the process of CKD are quite small and limited to patients undergoing hemodialysis (HD) treatment for ESRD. We aimed to investigate the factors affecting the development of atherosclerosis and the role of calcification inhibitors fetuin-A, matrix-Gla protein (MGP), osteoprotegerin (OPG) in atherosclerosis progress. Method Our study was planned to investigate the relationship of serum OPG, MGP and fetuin-A levels with the development of atherosclerosis in the stage 2-3-4-5 chronic kidney patients who did not require dialysis treatment. Thirty-two (17 female, 15 male) healthy individuals and 92 (49 females, 43 males) CKD cases were included. The healthy control group did not have a history of regular use of medication for any reason, known acute or chronic disease. Chronic kidney disease group, with no acute disease, no history of known malignancy and cerebrovascular disease. The patients' GFR was also calculated with CKD-EPI Formula. The mean carotid artery intima media thickness was calculated by dividing the sum of right and left carotid artery intima media thickness. Statistical analysis was performed with IBM SPSS Statistics 20.0.0. Results The laboratory data of the healthy control group, stage 2 CKD group, stage 3 CKD group, stage 4 CKD group and stage 5 CKD groups were statistically compared with the healthy control group, between themselves and the whole CKD group, the results were given in Table-1. Chronic kidney disease group divided into two groups; carotid artery intima media thickness less than 0.750 millimeters (without subclinical atherosclerosis) and those above 0.750 millimeters (with subclinical atherosclerosis). The mean C-IMT, CRP, FETUIN-A, OPG and MGP of the two groups were compared statistically and the results are shown in Table-2. In chronic kidney patients, age (r = 0.493, p &amp;lt;0.001), BMI (r = 0.337, p = 0.001), CRP (r = 0.301, p = 0.004), TG (r = 0.245, p = 0.019 ), urea (r = 0.228, p = 0.029), SBP (r = 0.212, p = 0.043), fasting blood sugar (r = 0.212, p = 0.043) have positive linear relationship, fetuin-A (r = -0.409, P = 0.001), OPG (r = -0.235, p = 0.024), GFR (r = -0.209, p = 0.046) have a negative linear relationship with CIMT. The multiple relationships between CIMT and other variables are given in Table-3. The mean CIMT (r =-0.417, p = 0.001), right CIMT (r = -0.412, p = 0.001), left CIMT (r = -0.410, p = 0.001), urea (r = -353, p = 0.007), CRP (r = -0.322, p = 0.014), UPE (r = -0.301, p = 0.022), creatinine (r = -0.277, p = 0.035), age (r = -0.262, p = 0.047) show a negative linear relationship with Fetuin-A. Multiple relationships between fetuin-A and other variables are given in Table-4. Conclusion Our study shows that; In particular, fetuin-A levels, which is a vascular calcification inhibitor, begin to decline from the early stages of CKD and is significantly lower in patients with atherosclerosis. This suggests that fetuin-A may be used as an early marker in CKD with increased cardiovascular mortality. On the other hand, contradictions related to the levels of OPG and MGP in CKD and its role in the development of atherosclerosis continue. The results in our study also support this situation. Reducing mortality and morbidity in CKD primarily depends on reducing the risk of cardiovascular events. Pre-recognition of these risks is important, so large-scale studies on vascular calcification inhibitors are needed.

Distinct Responses of Gut Microbiota to Jian-Pi-Yi-Shen Decoction Are Associated With Improved Clinical Outcomes in 5/6 Nephrectomized Rats.

Gut dysbiosis contributes to the development and progression of chronic kidney disease (CKD) and its complications. However, the effect of drugs on the gut microbiota of CKD patients and its influence on treatment outcomes remains to be explored. Here, we assessed whether the response of gut microbiota to the traditional Chinese medicine Jian-Pi-Yi-Shen (JPYS) decoction differed from that to piperazine ferulate (PF), a kidney-targeted drug, by 16S rDNA sequencing, and whether the difference could be linked with drug-specific clinical outcomes. We showed that both JPYS and PF improved renal function, but only JPYS was able to restore the blood reticulocyte counting and serum calcium level in CKD rats. We also found that weighted UniFrac beta-diversity of the gut microbiome of the JPYS treated rats was significantly different from that of PF. Microbiome markers of drug-specific response were identified and subjected to correlation network analysis, together with clinical parameters and KEGG pathways. Among the microbiome markers of CKD, Corynebacterium was found to form a network hub that was closely correlated with the JPYS responder Enterococcus, suggesting a potential indirect impact of JPYS on Corynebacterium via interspecies interactions. We also identified two network hubs of the PF responder Blautia and the JPYS-only marker Coprococcus, which were connected with many genera and clinical parameters. They might serve as keystone taxa driving the response of gut microbiota to the drugs and influence host outcomes. Moreover, the JPYS-only marker Clostridium_XIVb was found to be connected to many pathways that are associated with CKD progression and might account for the improved outcomes in the JPYS treated rats. At last, the identified keystone markers of drug response were validated by qPCR for their differential abundance between CKD and the two drugs. Taken together, our study revealed that the responses of gut microbiota to JPYS were distinct from that to PF, and pinpointed drug-specific keystone microbiome markers closely correlated to clinical parameters, which could serve as candidate microbiome targets for further studies on their roles in medicating the drug efficacy of TCM in CKD.

Recovery of serum metallothionein level after hemodialysis in patients with end stage renal failure

Metallothioneins (MTs) are intracellular metal-protein which not alone have inactivated heavy metals but also have traced elements while improving the antioxidant status. Serum levels of some heavy metals and trace elements showed toxic levels in the end-stage renal failure. This study is aimed to determine the serum level of metallothionein in patients with chronic kidney disease (CKD) and to show the effects of hemodialysis on its level. This cross-sectional study included 125 patients with CKD managed with regular hemodialysis. Estimated glomerular filtration rate (eGFR) was calculated by using the Cockroft and Gault equation adjusted to the body surface area (ml/min/m2), and 4 variable modified diet in renal disease (4-v MDRD) equation (ml/min/1.73m2). The mean ± SD of serum metallothionein was significantly less than the corresponding level of healthy subjects (1113.4±289.5 pg/ml versus 1536.0±341.4 pg/ml). Hemodialysis improves the serum level of metallothionein to attain 1437.6±406.1 pg/ml. There is a non-significant correlation between serum metallothionein with the eGFR and hemodialysis did not produce a significant effect on the correlation between serum metallothionein with eGFR. We conclude that serum metallothionein level is a useful prognostic marker for CKD and hemodialysis plays a role in the recovery of serum metallothionein level.

Markers and risk factors for chronic kidney disease in sub-Saharan Africans: baseline levels and 12-month trajectories in newly referred patients in Cameroon

BackgroundLittle is known about the changes in disease makers and risk factors in patients with chronic kidney disease (CKD) under nephrological care in Africa. This study aimed to evaluate the baseline level of markers of CKD and their 12-month time-trend in newly referred patients in a tertiary hospital in Cameroon.MethodsThis was a retrospective cohort study including 420 patients referred for CKD between 2006 and 2012 to the nephrology unit of the Douala General Hospital in the littoral region of Cameroon. Their disease and risk profile was assessed at baseline and every 3 months for 1 year. Estimated glomerular filtration rate (eGFR) was based on MDRD and Schwartz equations. CKD was diagnosed in the presence of eGFR< 60 ml/min/1.73 m2 and/or proteinuria> 1+ and/or abnormal renal ultrasound persisting for ≥3 months. Data analysis used mixed linear regressions.ResultsOf the 420 patients included, 66.9% were men and mean age was 53.8 (15.1) years. At referral, 37.5% of the participants were at CKD Stage 3, 30.8% at stage 4 and 26.8% at stage 5. There was 168 (40%) diabetic and 319 (75.9%) hypertensive patients. After some improvement during the first 3 months, eGFR steadily decreased during the first year of follow-up, and this pattern was robust to adjustment for many confounders. Systolic and diastolic blood pressure levels significantly fluctuated during the first twelve months of follow-up. Changes in the levels of other risk factors and markers of disease severity over time were either borderline or non-significant.ConclusionPatients with CKD in African settings are referred to the nephrologist at advanced stages. This likely translates into a less beneficial effects of specialised care on the course of the disease.

Early responsiveness to continuous erythropoietin receptor activator predicts renal prognosis and is determined by a novel antioxidative marker in non-dialysis chronic kidney disease: a prospective, observational, single-center study.

Responsiveness to erythropoietin-stimulating agents (ESAs) is important for anemia management in chronic kidney disease (CKD). We assessed the effects of a continuous erythropoietin receptor activator (CERA) on renoprotection beyond anemia management and the correlation between the responsiveness to ESAs and oxidative stress markers in CKD. This single-center, prospective, observational study was conducted over 24months. We administered CERA to 35 non-dialysis patients with hemoglobin (Hb) < 11g/dL and examined the results of the serum diacron-reactive oxygen metabolite (dROMs) test for oxidative stress markers and biological antioxidant potential (BAP) test for antioxidant markers. We then examined the renoprotective effects of CERA and the responsiveness to CERA. Eighteen patients experienced renal events (doubling of serum creatinine levels, decreased estimated glomerular filtration rate to < 6.0mL/min/1.73 m2, or initiation of renal replacement therapy), seventeen of which survived. Kaplan-Meier analysis showed that responsiveness to CERA during the initial 3-month treatment period was a good predictor of renal events. Moreover, a high response to CERA during the 3months independently suppressed renal events (hazard ratio, 0.344). High BAP levels at baseline were significantly associated with high responsiveness to CERA during the initial 3-month treatment period. Responsiveness to CERA during the first 3months was an important indicator of CKD progression. Moreover, BAP test results determined responsiveness to CERA. This is the first report to show how antioxidant levels can be a potential marker of CERA's ability to control anemia in CKD patients.

SUN-137 PREVALENCE OF CHRONIC KIDNEY DISEASE MARKERS IN SAUDI ARABIA: POPULATION BASED PILOT STUDY

Chronic Kidney Disease (CKD) affects about 10% of the world’s adult population and is expected to grow by 6% annually between 2018 and 2025. As the patient population increases, the healthcare system needs to adapt to respond to rising costs globally. No official statistics on total number of CKD in Saudi Arabia. The aim of this study was to determine the prevalence and some of determinant factors of CKD among relatives of dialysis patients in Saudi Arabia. Diaverum screening project is targeting first line relatives of all patients in our dialysis clinics. The present cross sectional community based study was conducted in our dialysis center in Taif from the western region of Saudi Arabia. Demographic and clinical data were collected. Estimated glomerular filtration rate (eGFR) < 60 mL/min//1.73 m2, proteinuria, and hematuria were defined as markers of CKD. GFR was evaluated by using serum creatinine level and the modified CKD epidemiology collaboration equation. Total number of dialysis patients was 190. Total number of screened were 250 first degree relatives over 3 months period. Out of 250 participants, 116 (46%) were males and 135 (54%) were females. The median age group is from 25 to 44 years. Total overweight and obesity are 67.5 %, overweight is more prevalent among men where females were more obese. Undiagnosed diabetes mellitus in 4% (9 out of 217) of non-diabetic screened relatives. History of DM in 34 out of 251 (13.5%) with average BMI of 31.2%. The prevalence of CKD markers: eGFR < 60 mL/min//1.73 m2, hematuria and proteinuria was observed in 4.4%, 13.6% and 29.6%, respectively. The overall prevalence of CKD stages 3 to 5 was 4.4%. Stages 1, 2, 3, 4, and 5 of CKD were found in 57.8%, 37.8%, 4%, 0.4%, and 0% of the participants, respectively. This is the first study in Saudi Arabia, we determined the prevalence of markers and risk factors for CKD among the first-degree relatives of dialysis patients of the Diaverum AB screening program in Saudi Arabia. This is a pilot case of data analysis will be completed later in all Diaverum AB clinics.

Kidney function and glucose metabolism in overweight and obese cats

Background In people, obesity and prediabetes mellitus might predispose to chronic kidney disease (CKD). Aims To assess the association of overweight [Body condition score (BCS) >5] and glucose metabolism alterations, with established or potential markers of CKD. In addition, fructosamine and fasted blood glucose were compared as predictors of early abnormal glucose metabolism. Methods 54 clinically healthy cats were included in a cross-sectional study comprising 25 neutered males and 29 (28 neutered) females aged 7.2 (5.5–9.4) years. Two potential markers of CKD, namely urinary free active transforming growth factor-β1-creatinine ratio and urinary retinol binding protein-creatinine ratio were measured along with other parameters to assess CKD. A receiver operating curve was used to identify the best sensitivity and specificity of fructosamine to identify cats with fasting glucose >6.5 mmol/L. Results No association was found between BCS and markers of CKD. Fructosamine was greater in cats with fasting glucose >6.5 mmol/L compared to those with fasting glucose ≤6.5 mmol/L. A fructosamine concentration ≥250 µmol/L was able to detect cats with hyperglycemia with a sensitivity of 77% and a specificity of 65%. Furthermore, fructosamine was more strongly correlated with fasting glucose than albumin-corrected fructosamine (r = 0.43, p = 0.002 vs r = 0.32, p = 0.026). Cats with higher fructosamine had lower serum symmetric dimethylarginine concentrations. Conclusion The present study does not suggest an effect of obesity on renal function in domestic cats. Clinical relevance Fructosamine might be of value for the diagnosis of prediabetes mellitus in cats.

An update on chronic kidney disease in Aboriginal Australians.

We provide a brief update on some aspects of chronic kidney disease (CKD) in Indigenous Australians, with CKD referring to all stages of pre-terminal kidney disease, as well as to end-stage kidney failure (ESKF), whether or not a person receives renal replacement therapy (RRT). Recently recorded rates of ESKF and RRT were 6- and 8-fold those recoded for non-Indigenous Australians with age adjustment, while non-dialysis CKD hospitalizations and CKD-attributed deaths were 8-fold and 3-fold higher. The median age of Indigenous people who developed ESKF was ~30 years less than for non-Indigenous people, and 84% of them received RTT, while only half of non-Indigenous people with ESKF did so. However, the nationwide average Indigenous incidence rate of RRT appears to have stabilized. The 2012 Australian Health Survey showed elevated levels of CKD markers in Indigenous people at the community level. For all CKD parameters, rates among Indigenous people were strikingly correlated with increasing remoteness of residence and socioeconomic disadvantage, and there was a female predominance in remote areas. The burden of renal disease in Australian Indigenous people is seriously understated by Global Burden of Disease Mortality methodology, because it employs underlying cause of death only, and because deaths of people on RRT are frequently attributed to non-renal causes. These data give a much-expanded view of CKD in Aboriginal people. Methodologic approaches must be remedied for a full appreciation of the burden, costs, and outcomes of the disease, to direct appropriate policy development.

Assessment of Albuminuria, Estimated-Glomerular Filtration Rate And Uric Acid As Markers For Chronic Kidney Disease among Family Members of Sudanese Renal Failure Patients On Hemodialysis

Background: Chronic kidney disease (CKD) is a global public health problem that increased rapidly throughout the world, and it was recommended that it should be discovered earlier especially among high risk population.&#x0D; Objective: To assess albuminuria, estimated glomerular filtration rate (eGFR) and uric acid as markers for CKD among first degree relatives (FDRs) of hemodialysis patients.&#x0D; Materials and methods: This is an analytical, case control study conducted at Khartoum state during May 2015 to May 2018, targeting 135 FDRs of end stage renal disease (ESRD) Sudanese patients on hemodialysis and other 161 healthy individuals serving as control group. Their plasma was prepared and analyzed for creatinine, uric acid, calcium, phosphate, and alkaline phosphatase. Also spot random urine sample was collected and analyzed for creatinine and micro albumin, from which albumin to creatinine ratio (ACR) was calculated. The plasma parameters were analyzed by Mendray BS 200 auto analyzer, while urine parameters were analyzed by using Cobas auto analyzer.&#x0D; Results: The mean levels of ACR and urine micro albumin were significantly increased while the mean levels of e-GFR and urine creatinine were significantly reduced in FDRs when compared to control group (The means ± SD were: 10 ± 4.4, 123.1 ± 68.2, 93.1 ± 25.6 and153.3 ± 115.3 versus 0.92±0.10, 14.9±2.05, 99.4±22.5 and 190.3±108.8, the p values were: 0.024, 0.001, 0.027 and 0.005 respectively). But there were no significant differences between means levels of calcium, phosphorus, uric acid and alkaline phosphatase when compared in FDRs versus control group. The correlation analysis showed significant positive correlation of serum uric acid with serum creatinine(r= 0.587, P value = 0.000).&#x0D; Conclusion: Albuminuria which was detected by ACR was significantly increased among FDRs of hemodialysis patients, while the eGFR was reduced, hence they are prone to develop CKD.

Clinical Significance Of Linc00342 Expression In The Peripheral Blood Lymphocytes Of Patients With Chronic Kidney Disease.

ObjectiveTo investigate the expression of Linc00342 in peripheral blood lymphocytes in patients with chronic kidney disease (CKD) and healthy people and to identify Linc00342 as a biomarker of chronic kidney disease.MethodsPeripheral blood samples were collected from 30 patients with chronic kidney disease and 10 healthy volunteers at the First Affiliated Hospital of Bengbu Medical College, China. According to CKD classification, the patients were divided into three CKD groups (the CKD1/2 group, CKD3/4 group and CKD5 group) and a healthy volunteer group (the H group). The relative expression of Linc00342 in lymphocytes was detected by RT-PCR, while the IL-6 and IL-10 levels in the serum were detected by ELISA. In addition, the general data of the patients and healthy volunteers were recorded. Finally, SPSS software was used for statistical analysis.ResultsThe expression level of Linc00342 in the peripheral blood lymphocytes of the four groups increased significantly as the CKD grade increased, and there were statistically significant differences (p < 0.01). There was a positive linear correlation between the expression of Linc00342 in peripheral blood lymphocytes and the eGFR (p < 0.05), which was expressed by the linear model equation: Y = 2.532 + 0.012X. Among the inflammatory factors for the early diagnosis of CKD, the area under the ROC curve for the expression of Linc00342 in peripheral blood lymphocyte was 0.953, the standard error was 0.034 and the 95% confidence interval was 0.000–1.000.ConclusionThe expression level of Linc00342 in peripheral blood lymphocytes can reflect the severity of CKD, and Linc00342 is possibly used as a molecular marker of CKD.