P0739PANEL OF SENSITIVE BIOMARKERS OF THE PRIMARY RESPONSE TO RENAL INJURY FOR AN EARLY DIAGNOSIS OF CHRONIC KIDNEY DISEASE

Abstract Background and Aims The identification of early kidney injury biomarkers is of utmost importance, since most widely used markers of kidney function vary only after several biological changes. Biomarkers allowing an earlier diagnosis of chronic kidney disease (CKD) would avoid delays in the treatment of patients. It is unlikely that a single marker is sufficient to detect the onset of CKD considering the multiple pathophysiological changes underlying primary renal response to renal injury. Several markers of inflammation, endothelial (dys)function, glomerular and tubulointerstitial injuries have been proposed and could be used combined as a panel of markers with different specificities, allowing an early detection of renal injury. Our aim was to study a panel of biomarkers proposed as early markers of renal injury, with different specificities, to evaluate and compare their sensitivities at different CKD stages. Method In this preliminary study, we enrolled 22 healthy individuals and 27 CKD patients separated into 3 groups, according to the CKD stage: 9 in stages 1 and 2; 9 in stage 3, and 9 in stages 4 and 5. None of the patients presented inflammatory, infectious or neoplastic diseases. Diagnosis and CKD stage assignment were performed according to KDIGO guidelines. We evaluated circulating levels of cystatin C (CystC), creatinine (Cr), beta trace protein (BTP) as markers of renal function; tissue inhibitor metalloproteinase 1 (TIMP-1), neutrophil gelatinase-associated lipocalin (NGAL) and transforming growth factor-β (TGF-β) as markers of interstitial tubulointerstitial injury; asymmetric dimethylarginine (ADMA) and tissue plasminogen activator (t-PA), as markers of endothelial (dys)function; pentraxin 3 (PTX3), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), as markers of inflammation; and, pro B-type natriuretic peptides (proBNP), as a marker of cardiac (dys)function. Results In early stages of CKD (1 and 2), we found significant changes in markers of renal function (BTP, but not Cr and CystC), of tubular interstitial injury (TIMP-1 and TGF-β), of inflammation (TNF-α), of endothelial (ADMA) and cardiac (proBNP) dysfunction (vs. controls). In stage 3, we found significant changes (vs. stages 1-2) in markers of renal function (Cr and CystC), inflammation (TNF-α, IL-6), endothelial dysfunction (t-PA) and tubulointerstitial injury (TIMP-1); in stages 4-5 (vs. stage 3), we found significant changes only in the classic marker, Cr, and a trend towards increased CystC. Moreover, we found that at stages 1-2 all patients showed higher levels of BTP and proBNP when compared to the median value in the control group; TIMP-1 and ADMA were increased in 7/9 patients; TNF-α was increased in 7/9 patients; and 7/9 patients had lower values of TGF-β compared to the median value of controls. For the classical markers, Cr and CystC, we found that 5/9 and 4/9 patients, respectively, had lower values than the median value of controls; however, only 2/9 patients showed abnormal creatinine values (vs. reference values). Conclusion Our data suggest that a panel including classic (Cr and CystC) and more sensitive blood markers of the primary response to renal injury (BTP, TIMP-1 or TGF-β, ADMA, TNF-α and proBNP) would allow an earlier diagnosis of CKD, avoiding a delay in diagnosis and management of CKD patients.

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MO472A PRELIMINARY STUDY OF POTENTIAL BIOMARKERS FOR EARLY DIAGNOSIS IN CHRONIC KIDNEY DISEASE

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab090.0034 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Irina Lousa ◽

Maria João Valente ◽

Susana Rocha ◽

Sofia D. Viana ◽

Inês Preguiça ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Renal Function ◽

Kidney Disease ◽

Early Diagnosis ◽

Primary Response ◽

Therapeutic Interventions ◽

Cellular Damage ◽

Tubulointerstitial Injury ◽

Circulating Levels ◽

Potential Biomarkers

Abstract Background and Aims The conventionally used biomarkers for chronic kidney disease (CKD) diagnosis are not very sensitive for early diagnosis. Their values become clinically significant only when kidney damage is advanced, and a substantial filtration capacity has been lost. The reliance on these biomarkers may result in a long-time lapse in diagnosis, compromising the earlier use of successful therapeutic interventions to prevent CKD progression and reduce the risk of other common comorbidities. The study of earlier and more sensitive biomarkers for CKD diagnosis is an important medical need. Potentially new biomarkers reflecting different pathophysiological processes underlying CKD, such as changes in renal function, tubulointerstitial injury, inflammation and fibrosis, have been proposed. The use of a panel of biomarkers is likely to be synergetic in detecting CKD, since there are several different mechanisms by which CKD can initiate. Our aim was to identify markers of renal damage/dysfunction and evaluate their sensitivity for CKD detection, in patients at the earlier stages of the disease, stages 1 and 2. Method This study included 32 healthy controls and 29 CKD patients at stages 1 and 2, categorized according to the KDIGO guidelines, using the CKD-EPI equation based on serum creatinine to estimate the glomerular filtration rate (GFR). Causes of CKD in the studied patients were diabetes mellitus (n = 19), polycystic kidney disease (n = 1) and of unknown cause (n = 7) or other (n = 2). Circulating levels of creatinine and β-trace protein (BTP), as markers of renal function; interleukin 6 (IL-6), as a marker of inflammation; tissue inhibitor metalloproteinase 1 (TIMP 1), as a marker of tubulointerstitial injury; pro B-type natriuretic peptide (proBNP), as a marker of cardio-renal dysfunction; and cell-free DNA (cfDNA), as a marker of cellular damage, were evaluated. Results Compared to controls, we found significantly higher values of all studied markers in CKD patients (stage 1 and stage 2): BTP, TIMP-1, IL-6, pro-BNP, and cfDNA. In CKD patients, GFR was negatively correlated with circulating levels of pro-BNP (r = -0.610, P = 0.004, n = 20) and cfDNA (r = -0.408, P = 0.028, n = 29); and, microalbuminuria was positively correlated with circulating levels of BTP (r = 0.465, P = 0.013, n = 28). The biomarker cfDNA was positively correlated with TIMP-1 (r = 0.445, P = 0.16, n = 29) , a marker of tubulointerstitial injury, and with IL-6 (r = 0.670, P < 0.001, n = 29), a marker of inflammation. All patients presented at least two of the studied biomarkers with higher values than the median value presented by controls. Of all studied biomarkers, BTP was the one that was most altered in patients (86.2% presented higher values than the highest value presented by controls). Conclusion Our results suggest that the studied biomarkers are sensitive to the primary response to renal injury, being significantly elevated in the earlier stages of CKD, particularly BTP. Pro-BNP and cfDNA correlate well with disease severity assessed by GFR. The use of a panel comprising several biomarkers, related with different pathophysiological mechanisms underlying CKD initiation and progression, may increase the potential to detect patients at risk, when compared with the evaluation of each biomarker alone. Further validation for the use of these new potential biomarkers requires larger studies with standardized analytical methodologies. Acknowledgments: This work was supported by Applied Molecular Biosciences Unit (UCIBIO) and financed by FEDER COMPETE2020 funds UIDB/04378/2020 and UIDP/04539/2020 (CIBB); by POCI-01-0145-FEDER-007440; by FCT doctoral grant SFRH/BD/145939/2019; by funds from Portugal Regional Coordination and Development Commissions (Norte-01-0145-FEDER-000024).

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P0271SERUM VASCULAR ENDOTHELIAL GROWTH FACTOR-D LEVEL CORRELATES WITH RENAL FUNCTION AND ALBUMINURIA IN PATIENT WITH DIABETIC CHRONIC KIDNEY DISEASE

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p0271 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Hyeongwan Kim ◽

Jong Hwan Chong ◽

Woong Park ◽

Sung Kwang Park ◽

Won Kim

Keyword(s):

Chronic Kidney Disease ◽

Vascular Endothelial Growth Factor ◽

Renal Function ◽

Kidney Disease ◽

Serum Levels ◽

Control Group ◽

Vascular Endothelial ◽

Stage 4 ◽

Ckd Stage ◽

Endothelial Growth Factor

Abstract Background and Aims Biomarkers associated with chronic kidney disease (CKD) may play a crucial role in patients with diabetic kidney diseases. Vascular endothelial growth factor (VEGF)-C and VEGF-D are lymphangiogenic growth factors. It has been well demonstrated that there is lympnagiogenesis in fibrotic kidney disease in human. Previously, we showed that renal VEGF-C and VEGF-D are involved in lymphangiogensis in renal fibrosis model. Recent studies have shown a relationship between sodium load and serum VEGF-C levels in hypertensive patients. Lymphatic endothelial proliferation has been detected in diabetic nephropathy. Thus, serum VEGF-C level has been introduced as a candidate marker of chronic kidney disease. However, until now, there have been few report about serum VEGF-D in patients with diabetic CKD. Thus, we evaluated the relationships between serum VEGF-D and renal function and albuminuria of diabetic CKD. Method We divided diabetic CKD patients into four groups: CKD stage 3, CKD stage 4, and CKD stage 5 (without dialysis). Total forty two Asian patients with diabetic CKD (14 patients with CKD stage 3, 14 patients with CKD stage 4 and 14 patients with CKD stage 5) and seven healthy controls without diabetes mellitus have been enrolled in this study. In this cross-sectional study, we performed comparative analysis with serum level of VEGF-D in patients with each group. We measured the levels of VEGF-D through the multiplexing using Luminex® technology. Results The serum levels of VEGF-D were higher in the CKD 3, CKD 4 and CKD 5 group compared with the control group (25.9±5.6 pg/ml in control group, 60.3±9.7in stage 3, 62.9±8.5 in stage 4, and 66.5±8.0 in stage 5). However, there was not a significant difference between CKD stage III or IV and CKD stage V in serum levels of VEGF-D. Serum VEGF-D level were negatively correlated with estimated glomerular filtration rate and positively correlated with serum creatinine. At GFR level ≥60 ml/min per 1.73 m2, serum VEGF-D were biomarkers in ROC analysis. There was a positive correlation between serum VEGF-D level and albuminuria in patient with diabetic CKD. We also found that serum VEGF-D level also correlated with urine protein-to-creatinine ratio in patient with diabetic CKD. Conclusion Serum VEGF-D is correlated with renal function in patients with diabetic CKD. VEGF levels in the serum correlate to the severity of proteinuria and albuminuria in diabetic CKD patients. Further large-scale studies are required to confirm these findings.

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MO474PCSK9 LEVELS AND MARKERS OF INFLAMMATION, OXIDATIVE STRESS AND ENDOTHELIAL DYSFUNCTION IN A POPULATION OF NON-DIALYSIS CHRONIC KIDNEY DISEASE PATIENTS: IS THERE AN ASSOCIATION?

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab090.0036 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Evangelia Ntounousi ◽

Konstantinos Tellis ◽

Paraskevi Pavlakou ◽

Anila Duni ◽

Vassilios Liakopoulos ◽

...

Keyword(s):

Oxidative Stress ◽

Chronic Kidney Disease ◽

Renal Function ◽

Lipid Metabolism ◽

Endothelial Dysfunction ◽

Kidney Disease ◽

Endothelial Damage ◽

Apo B ◽

Markers Of Inflammation ◽

Ckd Stage

Abstract Background and Aims Proprotein convertase subtilisin / kexin 9 (PCSK9) plays an important role in lipid metabolism while available literature regarding its involvement in the pathogenesis of atherosclerosis and in the expression of genes associated with apoptosis and inflammation is constantly increasing. Patients with chronic kidney disease (CKD) experience disproportionately increased cardiovascular morbidity and mortality due to dyslipidemia, accelerated atherosclerosis, inflammation, oxidative stress and other risk factors. In the present cross-sectional study, we investigated the possible association of serum PCSK9 levels with markers of inflammation, oxidative stress and endothelial damage in patients with CKD. Method Ninety-two patients with CKD stage II-ΙV (eGRF CKD-EPI 47.3 ±25.7ml/min/1,73m2, mean age 66 years, 51 men) were included. Plasma PCSK9 levels were correlated with comorbidities (arterial hypertension; diabetes mellitus, history of cardiovascular disease), renal function indices (eGFR, proteinuria – UPR/24h), lipid parameters (LDL-cholesterol, HDL-cholesterol, triglycerides, Lp (a), APO-A1, APO-B), as well as soluble biomarkers of inflammation, oxidative stress and endothelial damage (hs-CRP, fibrinogen, 8-epiPGF2a, ox-LDL, IL-6, TNF-α, sICAM-1, sVCAM-1). Results The mean plasma value of PCSK9 was 278.1ng/ml. PCSK9 levels showed direct correlation with serum triglycerides (p = 0.03), Lp(a) (p = 0.01), and sICAM-1 levels (p = 0.03). There was no significant correlation between PCSK9 levels and indices of renal function, other lipid profile parameters, inflammatory markers or co-morbidities. Multiple regression analysis showed a significant effect of the Lp(a) on PCSK9 levels, for each unit of higher Lp(a), an increase by 3.082 is expected (95% CI: 0.935 - 5.228, p=0.006). At the same time, patients receiving statins are expected to have on average 63.8ng/ml higher PCSK9 values compared to patients not receiving statins (95% CI: 14.6 - 113.5 p=0.012). Conclusion Plasma levels of PCSK9 in non-dialysis CKD patients are correlated with endothelial dysfunction and lipid metabolism parameters. Statin intake increases PCSK9 levels significantly in this patient population. PCSK9 levels are not correlated with the severity of kidney disease. Major prospective studies are necessary to investigate the role of PCSK9 in the atherosclerotic cardiovascular outcome in CKD

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P0203EARLY DETECTION OF BREAST ARTERIAL CALCIFICATION IN DIFFERENT STAGES OF CHRONIC KIDNEY DISEASE PATIENTS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p0203 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Basma Sultan ◽

Hamdy Omar ◽

Housseini Ahmed ◽

Mahmoud Elprince ◽

Osama Anter adly ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Lipid Profile ◽

Statistical Significance ◽

University Hospital ◽

Arterial Calcification ◽

Control Group ◽

Inpatient Ward ◽

Stage 4 ◽

Ckd Stage

Abstract Background and Aims Vascular calcification (VC) plays a major role in cardiovascular disease (CVD), which is one of the main causes of mortality in patients with chronic kidney disease (CKD). The study aims at early detection of breast arterial calcification (BAC) in different stages of CKD (stage 2, 3& 4) patients as an indicator of systemic VC. Method A case control study was conducted targeting CKD women, aged 18- 60 years old. The sample was divided into 3 groups; A,B,C (representing stage 2, 3 & 4 of CKD) from women who attended nephrology and Internal medicine clinics and admitted in inpatient ward in Suez Canal University Hospital. A 4th group (D) was formed as a control group and included women with normal kidney functions (each group (A, B, C, D) include 22 women). The selected participants were subjected to history taking, mammogram to detect BAC and biochemical assessment of lipid profile, Serum creatinine (Cr), Mg, P, Ca, PTH and FGF23. Results Our study detected presence of BAC in about 81.8% of hypertensive stage 4 CKD patients compared with 50% in stage 3 CKD, also in the majority of stage 4 CKD patients who had abnormal lipid profile parameters and electrolyte disturbance. Most of the variables had statistical significance regarding the presence of BAC. Conclusion Although it is difficult to determine the definite stage at which the risk of VC begins but in our study, it began late in stage 2 CKD, gradually increased prevalence through stage 3 and became significantly higher in stage 4. These results suggest that preventive strategies may need to begin as early as stage 2 CKD.

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P0949EFFECT OF DIETARY PHOSPHORUS RESTRICTION ON FIBROBLAST GROWTH FACTOR,KLOTHO AND BODY COMPOSITION IN CHRONIC KIDNEY DISEASE PATIENTS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p0949 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Trisha Sachan ◽

Anita Saxena ◽

Amit Gupta

Keyword(s):

Chronic Kidney Disease ◽

Body Composition ◽

Renal Function ◽

Kidney Disease ◽

Urinary Protein ◽

Dietary Phosphorus ◽

Ckd Stage ◽

Significant Difference ◽

The Mean ◽

Fgf 23

Abstract Background and Aims Changes in dietary phosphorus regulate serum FGF-23, parathyroid hormone, 1,25(OH)(2)D and Klotho concentrations . Cardiovascular disease (CVD) is the principal killer of patients with chronic kidney disease and hyperphosphetemia is a potent risk factor it. Of many causative factors for CVD in CKD, dietary interventions involving restriction of dietary phosphorous intake can help reduce onset of CVD at early stages of CKD with other corrective measures. Muscle wasting is a consequence of uremic syndrome which alters body composition. The aim of the study was to study effect of dietary phosphorous restriction on FGF-23, iPTH, Klotho, 1,25(OH)(2)D and body composition in chronic kidney disease patients. Method This is a longitudinal study with 12 months intervention, approved by Ethics Committee of the institute. A total 132 subjects were recruited (66 healthy controls, 66 CKD patient. of 66 patients 33 were in CKD stage 1 and 33 in stage 2. GFR was calculated with the help of MDRD formula. Biochemical parameters of subjects were evaluated at baseline, 6 and 12 months along with the anthropometric measurements (body weight, height, mid upper arm circumference (MUAC), and skin folds). Three days dietary recall was taken to evaluate energy, protein and phosphorous intake. CKD patients whose dietary phosphorous intake was more than 1000 mg/day, were given intense dietary counseling and prescribed dietary modifications by restricting dietary phosphorous between 800-1000 mg/day. Results The mean age of controls and patients was 37.01±9.62 and 38.27±12.06 and eGFR of 136.94±11.77 and 83.69±17.37 respectively. One way ANOVA showed significant difference among controls and the study groups in hemoglobin (p<0.001), s albumin (p<0.001), FGF-23 (p<0.001), klotho (p<0.001), urinary protein (p<0.001) and Nephron Index (p<0.001).The mean energy intake (p = 0.001) and dietary phosphorous intake (p<0.001) of the CKD patients decreased significantly with the decline in the renal function along with the anthropometric measures i.e. BMI (p = 0.041),WHR (p = 0.015) and all four skin folds (p<0.001). On applying Pearson’s correlation, eGFR correlated negatively with urinary protein (-0.739, 0.000), FGF-23 (-0.679, 0.000) and serum phosphorous (-0.697, 0.000) and positively with klotho (0.872, 0.000). FGF-23 correlated negatively with klotho (-0.742, 0.000). Dietary phosphorous was found to be positively correlated with urinary protein (0.496, 0.000), serum phosphorous (0.680, 0.000) and FGF-23 (0.573, 0.000) and negatively with Klotho (-0.602, 0.000). Nephron index revealed a positive correlation with eGFR (0.529, 0.000). Urinary protein correlated negatively with klotho (-0.810, 0.000). A multiple linear regression was run to predict eGFR from anthropometric variables such as BMI, WHR, MUAC, skin folds thickness and handgrip strength. All anthropometric variables predicted decline in eGFR (p<0.05, R2 =0.223). At 6 and 12 months; repeated ANOVAs analysis showed a statistically significant difference in serum creatinine (p=0.000), serum phosphorous (p=0.000), FGF-23(p=0.000) and klotho (p=0.000). Conclusion Elevated levels of FGF-23 and decreased Klotho levels, with the moderate decline in renal function improved with the restricted phosphorous diet at 6 and 12 months emphasizing the importance of phosphorus restriction at an early stage.

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Risk of Stroke, Bleeding, and Death in Patients with Nonvalvular Atrial Fibrillation and Chronic Kidney Disease

Cardiology ◽

10.1159/000504877 ◽

2020 ◽

Vol 145 (3) ◽

pp. 178-186

Author(s):

Yoav Arnson ◽

Moshe Hoshen ◽

Adi Berliner-Sendrey ◽

Orna Reges ◽

Ran Balicer ◽

...

Keyword(s):

Atrial Fibrillation ◽

Chronic Kidney Disease ◽

Renal Function ◽

Kidney Disease ◽

Impaired Renal Function ◽

Bleeding Risk ◽

Intracranial Bleeding ◽

Increased Risk ◽

Ckd Stage ◽

Stroke Death

Introduction: Atrial fibrillation (AF) and chronic kidney disease (CKD) are both associated with increased risk of stroke, and CKD carries a higher bleeding risk. Oral anticoagulation (OAC) treatment is used to reduce the risk of stroke in patients with nonvalvular AF (NVAF); however, the risk versus benefit of OAC for advanced CKD is continuously debated. We aim to assess the management and outcomes of NVAF patients with impaired renal function within a population-based cohort. Methods: We conducted a retrospective observational cohort study using ICD-9 healthcare coding. Patients with incident NVAF between 2004 and 2015 were identified stratified by CKD stage. We compared treatment strategies and estimated risks of stroke, death, or any major bleeding based on CKD stages and OAC treatment. Results: We identified 85,116 patients with incident NVAF. Patients with impaired renal function were older and had more comorbidities. OAC was most common among stage 2 CKD patients (49%) and least in stages 4–5 CKD patients (27.6%). Higher CKD stages were associated with worse outcomes. Stroke rates increased from 1.04 events per 100 person-years (PY) in stage 1 CKD to 3.72 in stages 4–5 CKD. Mortality increased from 3.42 to 32.95 events/100 PY, and bleeding rates increased from 0.89 to 4.91 events/100 PY. OAC was associated with reduced stroke and intracranial bleeding risk regardless of CKD stage, and with a reduced mortality risk in stages 1–3 CKD. Conclusion: Among NVAF patients, advanced renal failure is associated with higher risk of stroke, death, and bleeding. OAC was associated with reduced stroke and intracranial bleeding risk, and with improved survival in stages 1–3 CKD.

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Nicorandil, a Katp channel opener, alleviates chronic renal injury by targeting podocytes and macrophages

AJP Renal Physiology ◽

10.1152/ajprenal.00158.2012 ◽

2012 ◽

Vol 303 (3) ◽

pp. F339-F349 ◽

Cited By ~ 19

Author(s):

Yoshifuru Tamura ◽

Katsuyuki Tanabe ◽

Wataru Kitagawa ◽

Shunya Uchida ◽

George F. Schreiner ◽

...

Keyword(s):

Oxidative Stress ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Xanthine Oxidase ◽

Renal Injury ◽

Vascular System ◽

K Channel ◽

Sulfonylurea Receptor ◽

Glomerular Injury ◽

Tubulointerstitial Injury

Nicorandil exhibits a protective effect in the vascular system, which is thought to be due to vasodilatation from opening ATP-dependent potassium channels and donation of nitric oxide. Recently, nicorandil was shown to be renoprotective in models of acute kidney injury and glomerulonephritis. However, the specific mechanisms of renoprotection are unclear. We evaluated the effect of nicorandil on the rat remnant kidney model of chronic kidney disease. Blood pressure was unchanged by a 10-wk course of nicorandil, while albuminuria was significantly reduced. Glomerular injury and tubulointerstitial injury were also ameliorated by nicorandil. Oxidative stress, as noted by renal nitrotyrosine level and urine 8-hydroxy-2′-deoxyguanosine, were elevated in this model and was significantly reduced by nicorandil treatment. Treatment was associated with maintenance of the mitochondrial antioxidant, manganese SOD, in podocytes and with suppression of xanthine oxidase expression in infiltrating macrophages. Interestingly, these two cell types express sulfonylurea receptor 2 (SUR2), a binding site of nicorandil in the ATP-dependent K channel. Consistently, we found that stimulating SUR2 with nicorandil prevented angiotensin II-mediated upregulation of xanthine oxidase in the cultured macrophage, while xanthine oxidase expression was rather induced by blocking SUR2 with glibenclamide. In conclusion, nicorandil reduces albuminuria and ameliorates renal injury by blocking oxidative stress in chronic kidney disease.

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Study of serum homocysteine level in patients with chronic kidney disease and its association with renal function and serum albumin

International Journal of Research in Medical Sciences ◽

10.18203/2320-6012.ijrms20202265 ◽

2020 ◽

Vol 8 (6) ◽

pp. 2195

Author(s):

Vandana Yadav ◽

Vivek Prakash ◽

Bushra Fiza ◽

Maheep Sinha

Keyword(s):

Chronic Kidney Disease ◽

Renal Function ◽

Kidney Disease ◽

Serum Creatinine ◽

Serum Albumin ◽

Control Group ◽

Serum Homocysteine ◽

The Mean ◽

Gandhi Medical College ◽

And Control

Background: Chronic kidney disease (CKD) includes irreversible destruction of nephrons leading to progressive decline in glomerular filtration rate. A preferential defect in Homocysteine disposal could hypothetically occur in CKD and subsequently lead to hyperhomocysteinemia. Understanding the status of Homocysteine and other parameters in CKD is useful in the management of the disease. Objective of the study is to estimate serum Homocysteine in CKD patients and its association with renal function and serum albumin in patients with CKD.Methods: The study design involves hospital based observational comparative study. The study was conducted in Department of Biochemistry in association with Department of Nephrology of Mahatma Gandhi Medical College and Hospital, Jaipur between May 2017 to June 2018. 100 diagnosed patients of CKD, visiting the Outpatient Department of Nephrology were enrolled as cases for the study. Patients having cardiovascular disease, Chronic liver disease, Age more than 60 years and pregnant females were excluded from study. The control group consists of 100 age and sex matched healthy individuals.Results: The mean serum creatinine levels of case and control group were 7.50±3.74 mg% and 0.83±0.22 mg% respectively. The mean of serum homocysteine levels of subject group was 27.35±12.52 µmol/L while the mean serum homocysteine levels of control group was 11.06±3.52 µmol/L. The serum homocysteine levels were significantly higher in the CKD patient group. The serum level of albumin in CKD patients and control group were 2.86±0.86 g/dl and 4.10±0.58 g/dl respectively. A positive correlation was found between serum creatinine and serum homocysteine levels. A negative correlation between serum homocysteine and serum albumin was found.Conclusions: Findings of the present study exhibit that serum homocysteine levels are elevated in CKD in comparison to healthy controls and it is positively correlated with serum creatinine level.

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ACTI ON OF N- ACETYLCYSTEI NE ON ASYMMETRI C DIMETHYLARGININE AND ALBUMINURIA IN STAGE 1-4 NONDIABETIC CHRONIC KIDNEY DISEASE PATIENTS

Indonesian Journal of Tropical and Infectious Disease ◽

10.20473/ijtid.v1i3.2198 ◽

2010 ◽

Vol 1 (3) ◽

pp. 146

Author(s):

MOCHAMMAD THAHA ◽

Widodo Widodo ◽

Moh. Yogiantoro ◽

WENNY PUTRI NILAMSARI ◽

MOCHAMAD YUSUF ◽

...

Keyword(s):

Oxidative Stress ◽

Chronic Kidney Disease ◽

Treatment Group ◽

Kidney Disease ◽

Day Treatment ◽

Oral Treatment ◽

Control Group ◽

Adma Level ◽

Ckd Stage ◽

Stage 1

Background: Uremic patients are in a pro-oxidant state and show an increased level of asymmetric dimethylarginine (ADMA), which is due to increased PRMT1 activity and reduced dimethylarginine dimethylaminohydrolase (DDAH) as degradation enzymes. Reactive oxidant species may play an important role in increasing the action of PRMT1 and in inhibiting the action of DDAH. Albuminuria and ADMA are closely correlated with progression of cardiovascular disease in chronic kidney disease (CKD) patients as well as indicators for decreasing renal function. Although ACEIs and/or ARBs reduced albuminuria in CKD patients, the results are still conflicting. Several factors in these patients may play important roles in the mechanism of albuminuria such as oxidative stress. The antioxidant N-acetylcysteine may prove to have beneficial therapeutic effect, because it can reduce oxidative stress as shown by evidence in humans, and subsequently increase ADMA. The objective of the present study is to explore the contribution of the antioxidant N-acetylcysteine (NAC) to the decrease of ADMA and albuminuria in non-diabetic CKD patients. Material and Methods: Patients with non-DM CKD stage 1–4 with albuminuria were randomized to receive ACEI and/or ARB alone (control group) or with antioxidant NAC 600 mg orally twice a day (treatment group). Observations were performed for 3 months to measure ADMA and albuminuria before and after-treatment. 80 patients in total 40 in the control group and 40 in the treatment group were used. Results: After oral treatment with NAC, the plasma level of ADMA in the treatment group increased from 0.604 µmol/l to 0.689 µmol/l, whereas ADMA level in the control group exhibited a higher increase from 0.561 µmol/l to 0.743 µmol/l. The increases in these groups were significantly different (p < 0.02). Moreover, the level of albuminuria was reduced from 148.12 µg/mg • cr to 132.7 µg/mg • cr in the treatment group, and from 75.25 µg/mg • cr to 71.85 µg/mg • cr in the control group. The difference was significant (p < 0.001). Conclusion: The anti-oxidant N-acetylcysteine can be used as adjuvant therapy to inhibit the progression of CKD in patients by decreasing the ADMA level and albuminuria.

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Investigation on Urinary and Serum Alpha Klotho in Dogs with Chronic Kidney Disease

10.21203/rs.3.rs-16759/v1 ◽

2020 ◽

Author(s):

Hong jae Yi ◽

Jong bok Lee ◽

Kyu pil Lee ◽

Kun ho Song ◽

Kyoung won Seo

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Fibroblast Growth Factor 23 ◽

Stepwise Multiple Regression ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Phosphorus Concentration ◽

Creatinine Ratio ◽

Ckd Stage ◽

Clinical Consequences

Abstract Background: As a co-receptor for fibroblast growth factor 23, klotho plays a pivotal role in phos-phate metabolism. The kidney is known to be not only the main source of soluble alpha-klotho but also functions as the principal regulator maintaining its concentration. Previous studies in human par-ticipants showed that the concentration of soluble alpha-klotho in serum and urine decreased in chronic kidney disease (CKD) patients. However, no previous study has assessed soluble alpha-klotho levels in dogs. This study aimed to measure serum and urinary alpha-klotho levels in CKD dogs and identify their associations with International Renal Interest Society (IRIS) CKD stages and other parameters known to be associated with CKD.Methods: Serum and urinary alpha klotho concentrations were measured by a commercially avail-able canine-specific sandwich enzyme-linked immunosorbent assay kit and compared between groups by a nonparametric Kruskal–Wallis test. Spearman’s correlation coefficient was used to eval-uate the relationships between variables. A stepwise multiple regression analysis was performed to estimate the effects of independent predictors on klotho concentrations.Results: The urine klotho-to-creatinine ratio (UrKl/Cr) was significantly lower in stage 3 dogs than the control group and was significantly lower in dogs with stage 3 and 4 CKD than in those with stage 1 and 2 disease. UrKl/Cr was negatively correlated with serum symmetric dimethylarginine (sSDMA), blood urea nitrogen (BUN), creatinine, and phosphorus concentration. Serum alpha-klotho concentration in dogs with stages 2 and 3 CKD were significantly lower than those in the control group. There was no significant correlation between serum alpha-klotho and BUN, creatinine, and phosphorus concentrations. No statistically significant differences were observed in UrKl/Cr and se-rum alpha-klotho concentration between groups based on sex, age, urine protein-to-creatinine ratio (UPC), or blood pressure.Conclusions: UrKl/Cr decreased in dogs with advanced CKD, and it was negatively correlated with sSDMA, BUN, creatinine, and phosphorus concentrations. Thus, klotho may play a role in the path-ogenesis of CKD and its clinical consequences, including CKD-mineral bone disorder, in dogs. Alt-hough serum klotho concentration was negatively correlated with sSDMA levels, it was not appar-ently related to IRIS CKD stage or other parameters known to be associated with CKD.

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