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  1. Bidin MZ, Shah AM, Stanslas J, Seong CLT
    Clin Chim Acta, 2019 Aug;495:239-250.
    PMID: 31009602 DOI: 10.1016/j.cca.2019.04.069
    INTRODUCTION: Chronic kidney disease (CKD) is a silent disease. Most CKD patients are unaware of their condition during the early stages of the disease which poses a challenge for healthcare professionals to institute treatment or start prevention. The trouble with the diagnosis of CKD is that in most parts of the world, it is still diagnosed based on measurements of serum creatinine and corresponding calculations of eGFR. There are controversies with the current staging system, especially in the methodology to diagnose and prognosticate CKD.

    OBJECTIVE: The aim of this review is to examine studies that focused on the different types of samples which may serve as a good and promising biomarker for early diagnosis of CKD or to detect rapidly declining renal function among CKD patient.

    METHOD: The review of international literature was made on paper and electronic databases Nature, PubMed, Springer Link and Science Direct. The Scopus index was used to verify the scientific relevance of the papers. Publications were selected based on the inclusion and exclusion criteria.

    RESULT: 63 publications were found to be compatible with the study objectives. Several biomarkers of interest with different sample types were taken for comparison.

    CONCLUSION: Biomarkers from urine samples yield more significant outcome as compare to biomarkers from blood samples. But, validation and confirmation with a different type of study designed on a larger population is needed. More comparison studies on different types of samples are needed to further illuminate which biomarker is the better tool for the diagnosis and prognosis of CKD.

    Matched MeSH terms: Renal Insufficiency, Chronic/blood*
  2. Almualm Y, Zaman Huri H
    Glob J Health Sci, 2015;7(4):96-109.
    PMID: 25946939 DOI: 10.5539/gjhs.v7n4p96
    Chronic Kidney Disease has become a public health problem, imposing heath, social and human cost on societies worldwide. Chronic Kidney Disease remains asymptomatic till late stage when intervention cannot stop the progression of the disease. Therefore, there is an urgent need to detect the disease early. Despite the high prevalence of Chronic Kidney Disease in Malaysia, screening is still lacking behind. This review discusses the strengths and limitations of current screening methods for Chronic Kidney Disease from a Malaysian point of view. Diabetic Kidney Disease was chosen as focal point as Diabetes is the leading cause of Chronic Kidney Disease in Malaysia. Screening for Chronic Kidney Disease in Malaysia includes a urine test for albuminuria and a blood test for serum creatinine. Recent literature indicates that albuminuria is not always present in Diabetic Kidney Disease patients and serum creatinine is only raised after substantial kidney damage has occurred.  Recently, cystatin C was proposed as a potential marker for kidney disease but this has not been studied thoroughly in Malaysia.  Glomerular Filtration Rate is the best method for measuring kidney function and is widely estimated using the Modification of Diet for Renal Disease equation. Another equation, the Chronic Kidney Disease Epidemiology Collaboration Creatinine equation was introduced in 2009. The new equation retained the precision and accuracy of the Modification of Diet for Renal Disease equation at GFR < 60ml/min/1.73m2, showed less bias and improved precision at GFR>60ml/min/1.73m2. In Asian countries, adding an ethnic coefficient to the equation enhanced its performance. In Malaysia, a multi-ethnic Asian population, the Chronic Kidney Disease Epidemiology Collaboration equation should be validated and the Glomerular Filtration Rate should be reported whenever serum creatinine is ordered. Reporting estimated Glomerular Filtration Rate will help diagnose patients who would have been otherwise missed if only albuminuria and serum creatinine are measured.
    Matched MeSH terms: Renal Insufficiency, Chronic/blood
  3. Lavinya AA, Lee CS, Hashim OH, Azwa I, Rajasuriar R, Lim SK, et al.
    Clin Biochem, 2019 Nov;73:90-97.
    PMID: 31401122 DOI: 10.1016/j.clinbiochem.2019.08.006
    BACKGROUND: Patients treated for human immunodeficiency virus (HIV) infection are prone to developing chronic kidney disease (CKD). Current methods used in assessing kidney function suffer inaccuracy in HIV-infected patients. This study aims to identify biomarkers that could complement existing methods of kidney assessment among HIV-infected subjects.

    METHODS: Plasma protein profiling was performed for HIV patients with CKD presented with negative/trace proteinuria (non-proteinuric) (n = 8) and their matched non-CKD controls, using two-dimensional gel electrophoresis (2DE); selected protein candidates were identified using mass spectrometry. Subsequently, altered plasma abundance of protein candidates were verified using Western blotting in HIV-infected subjects with non-proteinuric CKD (n = 8), proteinuric CKD (n = 5), and their matched non-CKD controls, as well as in HIV-uninfected subjects with impaired kidney function (n = 3) and their matched controls.

    RESULTS: Analysis of 2DE found significantly altered abundance of five protein candidates between HIV-infected patients with non-proteinuric CKD and without CKD: alpha-1-microglobulin (A1M), serum albumin (ALB), zinc-alpha-2-glycoprotein (AZGP1), haptoglobin (HP), and retinol binding protein (RBP4). Western blotting showed an increased abundance of A1M and HP in HIV-infected patients with non-proteinuric CKD compared to their non-CKD controls, whereas A1M, AZGP1, and RBP4 were significantly increased in HIV-infected patients with proteinuric CKD compared to their non-CKD controls. Such pattern was not found in HIV-uninfected subjects with impaired kidney function.

    CONCLUSION: The data suggests four proteins that may be used as biomarkers of CKD in HIV-infected patients. Further validation in a larger cohort of HIV-infected patients is necessary for assessing the clinical use of these proposed biomarkers for CKD.

    Matched MeSH terms: Renal Insufficiency, Chronic/blood*
  4. Khan I, Khan AH, Adnan AS, Sulaiman SAS, Hamzah ABA, Ahmed N, et al.
    Int Urol Nephrol, 2018 Jun;50(6):1113-1121.
    PMID: 29536424 DOI: 10.1007/s11255-018-1834-9
    PURPOSE: Creatinine is normally used to evaluate kidney function among elderly patients in clinical practice, which has been reported to be affected by socio-demographic factors like BMI and age. Cystatin C a newly introduced biomarker may be more efficient in identifying kidney function in obese and aged CKD patients. The aim of the current study was to assess the effect of BMI on endogenous biomarkers (cystatin C and creatinine) among elderly CKD patients in Malaysia, a first such study in the country.

    METHODS: The current study was conducted at the Hospital University Sains Malaysia, Kelantan. A total of 300 elderly Malay participants ≥ 65 years, with CKD, were taken in study. Demographic data, blood pressure, weight, and height were documented. Serum creatinine was assayed by Chemistry Analyzer Model Architect-C8000 (Jaffe Method), while serum cystatin C was examined by Human cystatin C ELISA kit (Sigma-Aldrich) using Thermo Scientific Varioskan Flash ELISA reader.

    RESULTS: The study participants were divided into three groups on the basis of age. There was a statistically significant difference at the p value chronic kidney disease patients. The study clearly evaluates the role of serum cystatin C as a good competitor of creatinine among the elderly CKD patients.

    Matched MeSH terms: Renal Insufficiency, Chronic/blood*
  5. Khor BH, Narayanan SS, Chinna K, Gafor AHA, Daud ZAM, Khosla P, et al.
    Nutrients, 2018 Sep 21;10(10).
    PMID: 30248953 DOI: 10.3390/nu10101353
    Blood fatty acids (FAs) are derived from endogenous and dietary routes. Metabolic abnormalities from kidney dysfunction, as well as cross-cultural dietary habits, may alter the FA profile of dialysis patients (DP), leading to detrimental clinical outcomes. Therefore, we aimed to (i) summarize FA status of DP from different countries, (ii) compare blood FA composition between healthy controls and DP, and (iii) evaluate FA profile and clinical endpoints in DP. Fifty-three articles from 1980 onwards, reporting FA profile in hemodialysis and peritoneal DP, were identified from PubMed, Embase, and the Cochrane library. Studies on pediatric, predialysis chronic kidney disease, acute kidney injury, and transplant patients were excluded. Moderate to high levels of n-3 polyunsaturated fatty acids (PUFA) were reported in Japan, Korea, Denmark, and Sweden. Compared to healthy adults, DP had lower proportions of n-3 and n-6 PUFA, but higher proportion of monounsaturated fatty acids. Two studies reported inverse associations between n-3 PUFAs and risks of sudden cardiac death, while one reported eicosapentaenoic acid + docosahexaenoic acid)/arachidonic acid ratio was inversely associated with cardiovascular events. The relationship between all-cause mortality and blood FA composition in DP remained inconclusive. The current evidence highlights a critical role for essential FA in nutritional management of DP.
    Matched MeSH terms: Renal Insufficiency, Chronic/blood*
  6. Chia YC, Lim HM, Ching SM
    J Am Heart Assoc, 2016 11 07;5(11).
    PMID: 27821404
    BACKGROUND: Visit-to-visit variability of systolic blood pressure (SBP) has been shown to contribute to cardiovascular events and all-cause mortality. However, little is known about its long-term effect on renal function. We aim to examine the relationship between visit-to-visit blood pressure variability (BPV) and decline in renal function in patients with hypertension and to determine the level of systolic BPV that is associated with significant renal function decline.

    METHODS AND RESULTS: This is a 15-year retrospective cohort study of 825 hypertensive patients. Blood pressure readings every 3 months were retrieved from the 15 years of clinic visits. We used SD and coefficient of variation as a measure of systolic BPV. Serum creatinine was captured and estimated glomerular filtration rate was calculated at baseline, 5, 10, and 15 years. The mean SD of SBP was 14.2±3.1 mm Hg and coefficient of variation of SBP was 10.2±2%. Mean for estimated glomerular filtration rate slope was -1.0±1.5 mL/min per 1.73 m2 per year. There was a significant relationship between BPV and slope of estimated glomerular filtration rate (SD: r=-0.16, P<0.001; coefficient of variation: r=-0.14, P<0.001, Pearson's correlation). BPV of SBP for each individual was significantly associated with slope of estimated glomerular filtration rate after adjustment for mean SBP and other confounders. The cutoff values estimated by the receiver operating characteristic curve for the onset of chronic kidney disease for SD of SBP was 13.5 mm Hg and coefficient of variation of SBP was 9.74%.

    CONCLUSIONS: Long-term visit-to-visit variability of SBP is an independent determinant of renal deterioration in patients with hypertension. Hence, every effort should be made to reduce BPV in order to slow down the decline of renal function.

    Matched MeSH terms: Renal Insufficiency, Chronic/blood*
  7. Teo BW, Koh YY, Toh QC, Li J, Sinha AK, Shuter B, et al.
    Singapore Med J, 2014 Dec;55(12):656-9.
    PMID: 25630321
    INTRODUCTION: Clinical practice guidelines recommend using creatinine-based equations to estimate glomerular filtration rates (GFRs). While these equations were formulated for Caucasian-American populations and have adjustment coefficients for African-American populations, they are not validated for other ethnicities. The Chronic Kidney Disease-Epidemiology Collaborative Group (CKD-EPI) recently developed a new equation that uses both creatinine and cystatin C. We aimed to assess the accuracy of this equation in estimating the GFRs of participants (healthy and with chronic kidney disease [CKD]) from a multiethnic Asian population.

    METHODS: Serum samples from the Asian Kidney Disease Study and the Singapore Kidney Function Study were used. GFR was measured using plasma clearance of 99mTc-DTPA. GFR was estimated using the CKD-EPI equations. The performance of GFR estimation equations were examined using median and interquartile range values, and the percentage difference from the measured GFR.

    RESULTS: The study comprised 335 participants (69.3% with CKD; 38.5% Chinese, 29.6% Malays, 23.6% Indians, 8.3% others), with a mean age of 53.5 ± 15.1 years. Mean standardised serum creatinine was 127 ± 86 μmol/L, while mean standardised serum cystatin C and mean measured GFR were 1.43 ± 0.74 mg/L and 67 ± 33 mL/min/1.73 m2, respectively. The creatinine-cystatin C CKD-EPI equation performed the best, with an estimated GFR of 67 ± 35 mL/min/1.73 m2.

    CONCLUSION: The new creatinine-cystatin C equation estimated GFR with little bias, and had increased precision and accuracy in our multiethnic Asian population. This two-biomarker equation may increase the accuracy of population studies on CKD, without the need to consider ethnicity.
    Matched MeSH terms: Renal Insufficiency, Chronic/blood*
  8. Saheb Sharif-Askari F, Syed Sulaiman SA, Saheb Sharif-Askari N, Al Sayed Hussain A, Railey MJ
    PLoS One, 2014;9(9):e106517.
    PMID: 25181525 DOI: 10.1371/journal.pone.0106517
    Anticoagulation therapy is usually required in patients with chronic kidney disease (CKD) for treatment or prevention of thromboembolic diseases. However, this benefit could easily be offset by the risk of bleeding.
    Matched MeSH terms: Renal Insufficiency, Chronic/blood
  9. Abu Seman N, Witasp A, Wan Mohamud WN, Anderstam B, Brismar K, Stenvinkel P, et al.
    J Diabetes Res, 2013;2013:298019.
    PMID: 24350299 DOI: 10.1155/2013/298019
    Recent reports have demonstrated that elevated plasma long pentraxin 3 (PTX3) levels are associated with cardiovascular and chronic kidney diseases. In the current study, we investigated the plasma PTX3 levels in 296 Malay subjects including the subjects with normal glucose tolerance (NGT) and type 2 diabetes (T2DM) patients with or without DN by using an enzyme-linked immune-sorbent assay. Results showed that in males, plasma PTX3 levels in T2DM patients without DN were lower than that in the subjects with NGT (2.78 versus 3.98 ng/mL; P = 0.021). Plasma PTX3 levels in T2DM patients with DN were decreased compared to the patients without DN (1.63 versus 2.78 ng/mL; P = 0.013). In females, however, no significant alteration of plasma PTX3 levels among NGT subjects and T2DM patients with and without DN was detected. Furthermore, an inverse correlation between PTX3 and body mass index was found in male subjects with NGT (P = 0.012; r = -0.390), but not in male T2DM patients, neither in all females. The current study provided the first evidence that decreased plasma PTX3 levels are associated with T2DM and DN in Malay men and also suggested that PTX3 may have different effects in DN and chronic kidney diseases.
    Matched MeSH terms: Renal Insufficiency, Chronic/blood
  10. Ng YM, Lim SK, Kang PS, Kadir KA, Tai MS
    BMC Nephrol, 2016 10 18;17(1):151.
    PMID: 27756244
    BACKGROUND: Epidemiological studies have shown an inverse relationship between vitamin D levels and cardiovascular diseases. However, this does not infer a causal relationship between the two. Chronic kidney disease (CKD) patients have a high prevalence of vitamin D deficiency and carotid atherosclerosis. Therefore, in this study we have aimed to determine the association between serum 25-hydroxyvitamin D levels and carotid atherosclerosis in the CKD population.

    METHODS: 100 CKD stage 3-4 patients were included in the study. Direct chemiluminesent immunoassay was used to determine the level of serum 25-hydroxyvitamin D. All subjects underwent a carotid ultrasound to measure common carotid artery intima-media thickness (CCA-IMT) and to assess the presence of carotid plaques or significant stenosis (≥50 %). Vitamin D deficiency was defined as serum 25-hydroxyvitamin D 

    Matched MeSH terms: Renal Insufficiency, Chronic/blood*
  11. Toussaint ND, Pedagogos E, Lioufas NM, Elder GJ, Pascoe EM, Badve SV, et al.
    J Am Soc Nephrol, 2020 11;31(11):2653-2666.
    PMID: 32917784 DOI: 10.1681/ASN.2020040411
    BACKGROUND: Hyperphosphatemia is associated with increased fibroblast growth factor 23 (FGF23), arterial calcification, and cardiovascular mortality. Effects of phosphate-lowering medication on vascular calcification and arterial stiffness in CKD remain uncertain.

    METHODS: To assess the effects of non-calcium-based phosphate binders on intermediate cardiovascular markers, we conducted a multicenter, double-blind trial, randomizing 278 participants with stage 3b or 4 CKD and serum phosphate >1.00 mmol/L (3.10 mg/dl) to 500 mg lanthanum carbonate or matched placebo thrice daily for 96 weeks. We analyzed the primary outcome, carotid-femoral pulse wave velocity, using a linear mixed effects model for repeated measures. Secondary outcomes included abdominal aortic calcification and serum and urine markers of mineral metabolism.

    RESULTS: A total of 138 participants received lanthanum and 140 received placebo (mean age 63.1 years; 69% male, 64% White). Mean eGFR was 26.6 ml/min per 1.73 m2; 45% of participants had diabetes and 32% had cardiovascular disease. Mean serum phosphate was 1.25 mmol/L (3.87 mg/dl), mean pulse wave velocity was 10.8 m/s, and 81.3% had abdominal aortic calcification at baseline. At 96 weeks, pulse wave velocity did not differ significantly between groups, nor did abdominal aortic calcification, serum phosphate, parathyroid hormone, FGF23, and 24-hour urinary phosphate. Serious adverse events occurred in 63 (46%) participants prescribed lanthanum and 66 (47%) prescribed placebo. Although recruitment to target was not achieved, additional analysis suggested this was unlikely to have significantly affected the principle findings.

    CONCLUSIONS: In patients with stage 3b/4 CKD, treatment with lanthanum over 96 weeks did not affect arterial stiffness or aortic calcification compared with placebo. These findings do not support the role of intestinal phosphate binders to reduce cardiovascular risk in patients with CKD who have normophosphatemia.

    CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Australian Clinical Trials Registry, ACTRN12610000650099.

    Matched MeSH terms: Renal Insufficiency, Chronic/blood*
  12. Lim LL, Ng YM, Kang PS, Lim SK
    J Diabetes Investig, 2018 Mar;9(2):375-382.
    PMID: 28519964 DOI: 10.1111/jdi.12696
    AIMS/INTRODUCTION: Vitamin D is suggested to influence glucose homeostasis. An inverse relationship between serum 25-hydroxyvitamin D (25[OH]D) and glycemic control in non-chronic kidney disease (CKD) patients with type 2 diabetes was reported. We aimed to examine this association among type 2 diabetes patients with CKD.

    MATERIALS AND METHODS: A total of 100 type 2 diabetes participants with stage 3-4 CKD were recruited. Blood for glycated hemoglobin (HbA1c ), serum 25(OH)D, renal and lipid profiles were drawn at enrollment. Correlation and regression analyses were carried out to assess the relationship of serum 25(OH)D, HbA1c and other metabolic traits.

    RESULTS: A total of 30, 42, and 28% of participants were in CKD stage 3a, 3b and 4, respectively. The proportions of participants based on ethnicity were 51% Malay, 24% Chinese and 25% Indian. The mean (±SD) age and body mass index were 60.5 ± 9.0 years and 28.3 ± 5.9 kg/m2 , whereas mean HbA1c and serum 25(OH)D were 7.9 ± 1.6% and 37.1 ± 22.2 nmol/L. HbA1c was negatively correlated with serum 25(OH)D (rs = -0.314, P = 0.002), but positively correlated with body mass index (rs = 0.272, P = 0.006) and serum low-density lipoprotein cholesterol (P = 0.006). There was a significant negative correlation between serum 25(OH)D and total daily dose of insulin prescribed (rs = -0.257, P = 0.042). Regression analyses showed that every 10-nmol/L decline in serum 25(OH)D was associated with a 0.2% increase in HbA1c .

    CONCLUSIONS: Lower serum 25(OH)D was associated with poorer glycemic control and higher insulin use among multi-ethnic Asians with type 2 diabetes and stage 3-4 CKD.

    Matched MeSH terms: Renal Insufficiency, Chronic/blood*
  13. Joshi K, Boettiger D, Kerr S, Nishijima T, Van Nguyen K, Ly PS, et al.
    Pharmacoepidemiol Drug Saf, 2018 Nov;27(11):1209-1216.
    PMID: 30246898 DOI: 10.1002/pds.4657
    PURPOSE: Renal disease is common among people living with human immunodeficiency virus (HIV). However, there is limited information on the incidence and risk factors associated with renal dysfunction among this population in Asia.

    METHODS: We used data from the TREAT Asia HIV Observational Database. Patients were included if they started antiretroviral therapy during or after 2003, had a serum creatinine measurement at antiretroviral therapy initiation (baseline), and had at least 2 follow-up creatinine measurements taken ≥3 months apart. Patients with a baseline estimated glomerular filtration rate (eGFR) ≤60 mL/min/1.73 m2 were excluded. Chronic kidney disease was defined as 2 consecutive eGFR values ≤60 mL/min/1.73 m2 taken ≥3 months apart. Generalized estimating equations were used to identify factors associated with eGFR change. Competing risk regression adjusted for study site, age and sex, and cumulative incidence plots were used to evaluate factors associated with chronic kidney disease (CKD).

    RESULTS: Of 2547 patients eligible for this analysis, tenofovir was being used by 703 (27.6%) at baseline. Tenofovir use, high baseline eGFR, advanced HIV disease stage, and low nadir CD4 were associated with a decrease in eGFR during follow-up. Chronic kidney disease occurred at a rate of 3.4 per 1000 patient/years. Factors associated with CKD were tenofovir use, old age, low baseline eGFR, low nadir CD4, and protease inhibitor use.

    CONCLUSIONS: There is an urgent need to enhance renal monitoring and management capacity among at-risk groups in Asia and improve access to less nephrotoxic antiretrovirals.

    Matched MeSH terms: Renal Insufficiency, Chronic/blood
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