Markers Of Chronic Kidney Disease Research Articles

Dementia associated with chronic kidney disease is accompanied by increase in plasma amyloid beta and cardiovascular dysfunction.

In end-stage chronic kidney disease (CKD) the prevalence of cognitive impairment (CI) has been estimated at 30-60%. Cardiovascular diseases (CVD) including increased central arterial stiffness (CAS) accompany CKD development. CAS drives pulse pressure (PP) and pulsatile component index (PCI) increases and cerebral microvascular damage resulting in a reduction of blood supply to the brain hereby contributing to CI. Elevated PP and PCI are associated with higher mortality in CVD and CKD independently of BP. The aim of the study was to determine whether CKD potentiates CI development due to CAS and the resultant increase in the PCI, a major contributor to brain and renal microvasculature damage. Measurements of systolic and diastolic blood pressure (SBP, DBP), echocardiography (ECHO), plasma amyloid beta-40 (Aβ-40), BUN, creatinine, aspartate aminotransferase (AST), brain natriuretic peptide (BNP), and mini-mental status examination (MMSE) were performed in 25 patients with stage IV CKD and in 22 age- and sex-matched healthy controls (Table 1). PCI was calculated as a function of SBP and DBP. The data were analyzed by unpaired two-tailed t-test, Pearson correlation with P values adjusted for false discovery rate, and are presented as mean±SEM. CKD patients had higher SBP, PP, PCI, LV systolic and diastolic volume, lower LV ejection fraction, higher plasma BNP and AST (CVD markers), plasma Aβ-40 (Alzheimer's disease marker), BUN and creatinine (CKD markers) and lower score in MMSE vs. healthy control (Table 1). Cognitive test results positively correlated with LV stroke volume, negatively correlated with PCI, a measurement of pulsatility of BP, and negatively correlated with plasma ASP, a marker of CVD (Table 2). SBP and DBP did not correlate with cognitive parameters. Further investigation of the possible metabolic role of Aβ-40 in the development of CI in CKD patients, and whether plasma AST can be a marker of CI in CKD, will be assessed in the future studies. Higher PP, PCI and lower score in MMSE in CKD patients supports our hypothesis that cardiovascular remodeling in CKD is a key component of CI progression. Supported by the NIH Grant 1R15HL150721 (K.S.), and in part by NIH/NIA Intramural Research Program.

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.

Association of decreased glomerular filtration rate with renal hemodynamic disorders and inflammatory biomarkers in patients with medically-controlled hypertension of high cardiovascular risk

Aim. To assess markers of chronic kidney disease (CKD) in patients with medically-controlled hypertension (HTN) (<140/90 mm Hg), as well as to analyze potential association of decreased glomerular filtration rate (GFR) <60 ml/min/1,73 m2 with clinical data and therapy; to establish significant determinants of GFR decrease in this category of patients.Material and methods. The study included 70 patients with HTN and office blood pressure (BP) <140/90 mm Hg aged 64 (57; 68) years (men, 48,6%), of whom 40 patients were examined within the Russian multicenter CHRONOGRAPH program. Office BP was 130 (120; 140)/80 (72; 82) mm Hg. GFR and albuminuria were assessed. Twenty-four-hour BP monitoring and Doppler ultrasound of renal blood flow with estimation of resistance indices (RI) were performed. The content of highsensitivity C-reactive protein (hsCRP), interleukins (IL) 1β, 6, 10 and lipid transport function parameters was determined.Results. CKD markers were detected in 31,4% of patients (in 27,1% — a decrease in GFR <60 ml/min/1,73 m2; in 12,9% — pathological albuminuria). Patients with CKD markers were older, had higher office systolic BP and nocturnal pulse pressure, higher blood hsCRP and RI levels throughout the renal flow, and lower high-density lipoprotein cholesterol levels. In the presence of CKD markers, calcium channel blockers, aldosterone receptor antagonists and statins were used more often. The results of correlation analysis were used to determine the determinants of GFR decline. In the general group, GFR values had inverse correlations with age (Rs=-0,58, p<0,0001), segmental intrarenal artery RI (Rs= -0,4232, p=0,0005), blood hsCRP (Rs=-0,3998, p=0,0007), IL-1β (Rs=-0,3139, p=0,0086), office BP and some 24-hour BP parameters. In the presence of CKD markers, a direct association of GFR and IL-10 was determined (Rs=0,4293, p=0,046). In the absence of such markers, GFR had an inverse correlation with IL-1β content (Rs=-0,3110, p=0,0333). A multiple linear regression model included following independent determinants of GFR: age, blood hsCRP and RI in the segmental intrarenal arteries.Conclusion. Among patients with medically-controlled HTN of high cardiovascular risk, a high prevalence of CKD markers was revealed (31,4%). Compared with patients with preserved renal function, in the presence of CKD markers, there were higher levels of office systolic BP, nocturnal pulse pressure, blood hsCRP, and intrarenal artery RI. Associations were established between GFR and the levels of hsCRP, IL-1β and IL-10, which confirms the pathological role of inflammatory biomarkers in developing renal dysfunction in high-risk HTN. Age, elevated blood hsCRP levels, and intrarenal artery RI are independent determinants of decreased GFR in patients with medically-controlled HTN of high and very high cardiovascular risk. The data obtained shows the need for early prescription of combination antihypertensive therapy with nephro- and vasoprotective effects in this category of patients, as well as with an ability to depress the chronic subclinical inflammation.

Pulse Wave Velocity, Central Haemodynamic Parameters, and Markers of Kidney Function in Children

Objectives: Chronic kidney disease (CKD) is a well-established risk factor for cardiovascular diseases. Studies in adults have demonstrated the association between mildly decreased kidney function or even normal values of markers of kidney function to pulse wave velocity (PWV), a measure of arterial stiffness and a predictor of cardiovascular events. Our study aimed to evaluate associations between markers of CKD, PWV, and central haemodynamic parameters in children and adolescents at risk of subclinical kidney damage. Methods: 182 children and adolescents with hypertension, obesity, or hypercholesterolaemia (risk factors for subclinical kidney damage) were included in the study. The subjects were subdivided into 4 groups comprising children and adolescents with hypertension (group 1), obesity (group 2), hypercholesterolaemia (group 3), and a group with a combination of risk factors, such as obesity-related hypertension and metabolic syndrome (group 4). The study groups were compared to a group of healthy controls (group 5). PWV was measured by applanation tonometry (SphygmoCor, SCOR-Vx, Sydney, NSW, Australia) and laboratory parameters (serum creatinine, serum cystatin C, and microalbuminuria) were collected. Results: Pearson’s correlation coefficient demonstrated a statistically significant correlation between PWV and serum creatinine in group of all subjects (r = 0.220, p = 0.002). Further subdivision showed the correlation was significant in group 4 (r = 0.370, p = 0.002). In group 2 a correlation between PWV and cystatin C was found (r = −0.535, p = 0.009). In multiple regression analysis of all subjects with PWV as the dependent variable, age and diastolic blood pressure were statistically significant. Correlations between markers of kidney function and central haemodynamic parameters also showed significant correlations between serum creatinine and heart rate (HR) (r = −0.476, p < 0.001) as well as associated parameters (augmentation index, standardized at HR 75/min, ejection duration, and subendocardial viability ratio). Conclusions: Our study demonstrated a correlation between serum creatinine and PWV in children with combined risk factors for atherosclerosis and probable subclinical kidney damage. Further prospective research is needed to confirm the findings, and thus the preventive role of PWV determination in paediatric nephrology.

A Plant-Centered Diet and Markers of Early Chronic Kidney Disease during Young to Middle Adulthood: Findings from the Coronary Artery Risk Development in Young Adults (CARDIA) Cohort

BackgroundFew studies have evaluated whether plant-centered diets prevent progression of early stage chronic kidney disease (CKD). ObjectivesWe examined the association between plant-centered diet quality and early CKD markers. MethodsWe prospectively examined 2869 black and white men and women in the Coronary Artery Risk Development in Young Adults Study free of diagnosed kidney failure in 2005–2006 [examination year 20 (Y20); mean age: 45.3 ± 3.6 y]. CKD marker changes from Y20 to 2015–2016 (Y30) were considered, including estimated glomerular filtration rate (eGFR; serum creatinine), urinary albumin-to-creatinine ratio (ACR), and both. Diet was assessed through interviewer-administered diet histories at Y0, Y7, and Y20, and plant-centered diet quality was quantified with the A Priori Diet Quality Score (APDQS). Linear regression models were used to examine the association of APDQS and subsequent 10-y changes in CKD markers. ResultsAfter adjustment for sociodemographic, behavioral, and diet factors, we found that higher APDQS was related to less adverse changes in CKD markers in the subsequent 10-y period. Compared with the lowest APDQS quintile, the highest quintile was associated with an attenuated increase in lnACR (−0.25 mg/g; 95% CI: −0.37, −0.13 mg/g; P-trend < 0.001), whereas the highest quintile was associated with an attenuated decrease in eGFR (4.45 mL·min−1·1.73 m−2; 95% CI: 2.46, 6.43 mL·min−1·1.73 m−2). There was a 0.50 lower increase in combined CKD markers [ln(ACR) z score – eGFR z score] when comparing the extreme quintiles. Associations remained similar after further adjustment for hypertension, diabetes, and obesity as potential mediating factors. The attenuated worsening CKD marker changes associated with higher APDQS strengthened across increasing initial CKD category; those with the best diet and microalbuminuria in Y10–Y20 returned to high normal albuminuria (all P-interaction < 0.001). ConclusionsIndividuals who consumed plant-centered, high-quality diets were less likely to experience deterioration of kidney function through midlife, especially among participants with initial stage characterized as mild CKD.

Sex-related Changes in Circadian Rhythm of Inflammatory and Oxidative Stress Markers in CKD.

Introduction. Circadian system is deeply involved in renal function. The circadian timing system may be disrupted in chronic kidney disease (CKD) patients. Gender differences in CKD have been reported. This research aimed to investigate the gender differences in the circadian rhythm of inflammatory and oxidant markers of CKD. Methods. Male, intact female, and ovariectomized (OVX) female rats (twenty-four in each group) were randomly assigned to control and CKD groups. The rats were further divided into day (12:00 p.m.) and night (12:00 a.m.) subgroups. Evaluations of each sample were carried out a day after the last day of adenine administration. Results. Final results revealed that the circadian rhythm of plasma melatonin , kidney malondialdehyde (MDA), and transforming growth factor- β (TGF-β) levels in CKD group were the same as the control group. Melatonin and total antioxidant capacity (TAC) levels significantly decreased in the CKD group compared with the control group in day and night subgroups, whereas MDA and TGF-β levels increased. Male group in comparison with the intact female group significantly showed less melatonin and TAC but higher MDA and TGF-β levels which could be due to CKD. Conclusion. Findings of this study represent gender differences in circadian rhythm amplitude of inflammation, melatonin, and oxidative stress in CKD animals, probably in favor of female sex steroids. These findings emphasize on the importance of gender differences in CKD progression; therefore, considerable attention must be paid to gender in the treatment of CKD.Introduction. Circadian system is deeply involved in renal function. The circadian timing system may be disrupted in chronic kidney disease (CKD) patients. Gender differences in CKD have been reported. This research aimed to investigate the gender differences in the circadian rhythm of inflammatory and oxidant markers of CKD. Methods. Male, intact female, and ovariectomized (OVX) female rats (twenty-four in each group) were randomly assigned to control and CKD groups. The rats were further divided into day (12:00 p.m.) and night (12:00 a.m.) subgroups. Evaluations of each sample were carried out a day after the last day of adenine administration. Results. Final results revealed that the circadian rhythm of plasma melatonin , kidney malondialdehyde (MDA), and transforming growth factor- β (TGF-β) levels in CKD group were the same as the control group. Melatonin and total antioxidant capacity (TAC) levels significantly decreased in the CKD group compared with the control group in day and night subgroups, whereas MDA and TGF-β levels increased. Male group in comparison with the intact female group significantly showed less melatonin and TAC but higher MDA and TGF-β levels which could be due to CKD. Conclusion. Findings of this study represent gender differences in circadian rhythm amplitude of inflammation, melatonin, and oxidative stress in CKD animals, probably in favor of female sex steroids. These findings emphasize on the importance of gender differences in CKD progression; therefore, considerable attention must be paid to gender in the treatment of CKD. DOI: 10.52547/ijkd.6242

Prevalence and Significance of Pyuria in Chronic Kidney Disease Patients in Saudi Arabia.

Chronic kidney disease (CKD) is considered a major health problem, which poses a burden for health care systems worldwide. It has been estimated that 10% of the population worldwide have CKD; however, most of the cases are undiagnosed. If left untreated, CKD could lead to kidney failure, which highlights the importance of early diagnosis and treatment. Pyuria has been reported in CKD patients, and could be the result of several comorbidities, such as diabetes, or urinary tract infections (UTIs). A few studies have shown that pyuria is associated with the late stages of CKD. However, there are limited data on the prevalence of non-UTI (sterile) and UTI–pyuria in different CKD patient populations, and its association with the decline in kidney function and progression of CKD. In this retrospective study, we report the prevalence of pyuria (sterile and UTI) in 754 CKD patients of King Fahd Specialist Hospital, Buraydah, Saudi Arabia. Our data showed that 164/754 CKD patients (21.8%) had pyuria, whereas 590 patients (78.2%) presented with no pyuria. There was a significantly higher percentage of late-stage (stage 4) CKD patients in the pyuric group compared to the non-pyuric group (36.6% vs. 11.9%). In line with the previous data, proteinuria was detected in a significantly higher percentage of pyuric patients, in addition to significantly higher levels of serum creatinine and urea, compared to non-pyuric patients. Furthermore, 13.4% of the pyuric CKD patients had UTI, whereas 86.6% presented with sterile pyuria. E. coli was indicated as the causative agent in 45.5% of UTI patients. Our patient data analysis showed that a significantly higher percentage of UTI–pyuric CKD patients, than sterile pyuric patients (63.6% vs. 19.7%), had higher numbers of urinary white blood cells (>50/HPF, WBCs). The data also showed that a higher percentage of UTI–pyuric patients were late-stage CKD patients, compared to sterile pyuric patients (50% vs. 34.5%). Our findings indicate that a high level of pyuria could be considered as a marker for late-stage CKD, and that UTI is an important risk factor for the decline in kidney function and the progression to late-stage CKD. We believe that further studies are needed to correlate pyuria to kidney function, which could be helpful in monitoring the progression of CKD. Moreover, the management of comorbidities, such as diabetes and UTIs, which are risk factors for CKD and associated pyuria, could help to control the progression of CKD to the late stages.

Risk Factors, Symptoms, Biomarkers, and Stages of Chronic Kidney Disease

Whereas the symptoms of chronic kidney disease (CKD) in diabetes are few, there are many risk factors and biomarkers that can be used to identify individuals at high risk for development of this complication, and many of these are targets for intervention to prevent or delay the disease. This article describes the risk factors and other markers of CKD and the various stages of the disease.

Hypertension due to loss of water

In the current issue of Acta Physiologica, two papers are published investigating the development of arterial hypertension under conditions of pathological loss of free water in two disease models. Kovaric et al 1 studied rats with chronic renal failure, shedding excessive free water via their remnant kidney due to a hypostenuric concentrating defect. Wild et al. 2 investigated a transgenic mouse model for psoriasis, losing free water via the psoriatic skin lesions. In both cases the animals displayed hypertension, cutaneous vasoconstriction, and metabolic adaptations towards enhanced production of urea and organic osmolytes typical for a phylogenetically ancient water conservation response termed aestivation 3 . The international consortia of investigators spearheaded by Titze, Karbach, and Kitada therefore conclude that in both cases the hypertension was due to cutaneous vasoconstriction in an attempt to limit epidermal water loss. Because in either case the hypertension was associated with loss of water, and thus with hypo- rather than hypervolemia, the authors argue, that this concept of pathogenesis of hypertension is antipodal to the classic view that relies on hypervolemia due to sodium retention.

Effect of Dapagliflozin on Cardiovascular Outcomes According to Baseline Kidney Function and Albuminuria Status in Patients With Type 2 Diabetes

Sodium-glucose cotransporter 2 inhibitors, such as dapagliflozin, promote renal glucose excretion and reduce cardiovascular (CV) deaths and hospitalizations for heart failure (HHF) among patients with type 2 diabetes. The relative CV efficacy and safety of dapagliflozin according to baseline kidney function and albuminuria status are unknown. To assess the CV efficacy and safety of dapagliflozin according to baseline estimated glomerular filtration rate (eGFR) and urinary albumin to creatinine ratio (UACR). This secondary analysis of the randomized clinical trial Dapagliflozin Effect on Cardiovascular Events-Thrombolysis in Myocardial Infarction 58 compared dapagliflozin vs placebo in 17 160 patients with type 2 diabetes and a baseline creatinine clearance of 60 mL/min or higher. Patients were categorized according to prespecified subgroups of baseline eGFR (<60 vs ≥60 mL/min/1.73 m2), urinary albumin to creatinine ratio (UACR; <30 vs ≥30 mg/g), and of chronic kidney disease (CKD) markers using these subgroups (0, 1, or 2). The study was conducted from May 2013 to September 2018. Dapagliflozin vs placebo. The dual primary end points were major adverse cardiovascular events (myocardial infarction, stroke, and CV death) and the composite of CV death or HHF. At baseline, 1265 patients (7.4%) had an eGFR below 60 mL/min/1.73 m2, and 5199 patients (30.9%) had albuminuria. Among patients having data for both eGFR and UACR, 10 958 patients (65.1%) had an eGFR equal to or higher than 60 mL/min/1.73 m2 and an UACR below 30 mg/g (mean [SD] age, 63.7 [6.7] years; 40.1% women), 5336 patients (31.7%) had either an eGFR below 60 mL/min/1.73 m2 or albuminuria (mean [SD] age, 64.1 [7.1] years; 32.6% women), and 548 patients (3.3%) had both (mean [SD] age, 66.8 [6.9] years; 30.5% women). In the placebo group, patients with more CKD markers had higher event rates at 4 years as assessed using the Kaplan-Meier approach for the composite of CV death or HHF (3.9% for 0 markers, 8.3% for 1 marker, and 17.4% for 2 markers) and major adverse cardiovascular events (7.5% for 0 markers, 11.6% for 1 marker, and 18.9% for 2 markers). Estimates for relative risk reductions for the composite of CV death or HHF and for major adverse cardiovascular events were generally consistent across subgroups (both P > .24 for interaction), although greater absolute risk reductions were observed with more markers of CKD. The absolute risk difference for the composite of CV death or HHF was greater for patients with more markers of CKD (0 markers, -0.5%; 1 marker, -1.0%; and 2 markers, -8.3%; P = .02 for interaction). The numbers of amputations, cases of diabetic ketoacidosis, fractures, and major hypoglycemic events were balanced or numerically lower with dapagliflozin compared with placebo for patients with an eGFR below 60 mL/min/1.73 m2 and an UACR of 30 mg/g or higher. The effect of dapagliflozin on the relative risk for CV events was consistent across eGFR and UACR groups, with the greatest absolute benefit for the composite of CV death or HHF observed among patients with both reduced eGFR and albuminuria. ClinicalTrials.gov Identifier: NCT01730534.

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 &lt; 0.0001), cystatin C (r = -0.430, p &lt; 0.0001) and urea (r = -0.495, p &lt; 0.0001) and a positive correlation with eGFR (r = 0.628, p &lt; 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.