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  1. Tan SH, Guan CA, Bujang MA, Lai WH, Voon PJ, Sim EUH
    Sci Rep, 2024 Jan 23;14(1):1997.
    PMID: 38263244 DOI: 10.1038/s41598-024-52421-9
    Gastrointestinal (GI) cancers account for a significant incidence and mortality rates of cancers globally. Utilization of a phenomic data approach allows researchers to reveal the mechanisms and molecular pathogenesis of these conditions. We aimed to investigate the association between the phenomic features and GI cancers in a large cohort study. We included 502,369 subjects aged 37-73 years in the UK Biobank recruited since 2006, followed until the date of the first cancer diagnosis, date of death, or the end of follow-up on December 31st, 2016, whichever occurred first. Socio-demographic factors, blood chemistry, anthropometric measurements and lifestyle factors of participants collected at baseline assessment were analysed. Unvariable and multivariable logistic regression were conducted to determine the significant risk factors for the outcomes of interest, based on the odds ratio (OR) and 95% confidence intervals (CI). The analysis included a total of 441,141 participants, of which 7952 (1.8%) were incident GI cancer cases and 433,189 were healthy controls. A marker, cystatin C was associated with total and each gastrointestinal cancer (adjusted OR 2.43; 95% CI 2.23-2.64). In this cohort, compared to Asians, the Whites appeared to have a higher risk of developing gastrointestinal cancers. Several other factors were associated with distinct GI cancers. Cystatin C and race appear to be important features in GI cancers, suggesting some overlap in the molecular pathogenesis of GI cancers. Given the small proportion of Asians within the UK Biobank, the association between race and GI cancers requires further confirmation.
    Matched MeSH terms: Cystatin C*
  2. Keshavarzi F
    Int J Clin Pharm, 2015 Oct;37(5):675-7.
    PMID: 26173939 DOI: 10.1007/s11096-015-0157-5
    Creatinine clearance estimation is widely used to evaluate the renal function of the patients in order to initiate or adjust the drugs dosage. However serum creatinine, as a muscle metabolism by-product, may not be a reliable parameter in underweight and/or non-ambulatory patients, such as geriatric, acquired immunodeficiency syndrome patients and bed-confined and cachexic cases. To avoid overestimation of the renal function in those patients, serum cystatin C can be considered as a sensitive and accurate alternative for serum creatinine.
    Matched MeSH terms: Cystatin C/blood*
  3. Mohd Tahir NA, Mohd Saffian S, Islahudin FH, Abdul Gafor AH, Makmor-Bakry M
    J Korean Med Sci, 2020 Sep 21;35(37):e306.
    PMID: 32959542 DOI: 10.3346/jkms.2020.35.e306
    BACKGROUND: The objective of this study was to compare the performance of cystatin C- and creatinine-based estimated glomerular filtration rate (eGFR) equations in predicting the clearance of vancomycin.

    METHODS: MEDLINE and Embase databases were searched from inception up to September 2019 to identify all studies that compared the predictive performance of cystatin C- and/or creatinine-based eGFR in predicting the clearance of vancomycin. The prediction errors (PEs) (the value of eGFR equations minus vancomycin clearance) were quantified for each equation and were pooled using a random-effects model. The root mean squared errors were also quantified to provide a metric for imprecision.

    RESULTS: This meta-analysis included evaluations of seven different cystatin C- and creatinine-based eGFR equations in total from 26 studies and 1,234 patients. The mean PE (MPE) for cystatin C-based eGFR was 4.378 mL min-1 (95% confidence interval [CI], -29.425, 38.181), while the creatinine-based eGFR provided an MPE of 27.617 mL min-1 (95% CI, 8.675, 46.560) in predicting clearance of vancomycin. This indicates the presence of unbiased results in vancomycin clearance prediction by the cystatin C-based eGFR equations. Meanwhile, creatinine-based eGFR equations demonstrated a statistically significant positive bias in vancomycin clearance prediction.

    CONCLUSION: Cystatin C-based eGFR equations are better than creatinine-based eGFR equations in predicting the clearance of vancomycin. This suggests that utilising cystatin C-based eGFR equations could result in better accuracy and precision to predict vancomycin pharmacokinetic parameters.

    Matched MeSH terms: Cystatin C/blood*
  4. Mohd Tahir NA, Mohd Saffian S, Islahudin FH, Abdul Gafor AH, Othman H, Abdul Manan H, et al.
    Nephron, 2020;144(4):204-212.
    PMID: 32050196 DOI: 10.1159/000505296
    BACKGROUND/AIMS: G73A polymorphism in the CST3 gene of cystatin C has been associated with Alzheimer's disease, age-related macular degeneration, and cardiovascular disease. However, studies investigating the influence of this genetic variability on serum cystatin C and cystatin-based renal function estimate are limited. Therefore, the aim of this study is to investigate the possible association of single-nucleotide polymorphism (rs1064039) of the CST3 gene on the serum cystatin C level and cystatin C-based estimated glomerular filtration rate (eGFR).

    METHODS: Study subjects include patients with various levels of renal function recruited from the nephrology clinic and wards of a tertiary hospital. The blood samples collected were analyzed for serum cystatin C and creatinine levels by particle-enhanced turbidimetric immunoassay and kinetic alkaline picrate method, respectively. DNA was extracted using a commercially available kit. -Polymerase chain reaction results were confirmed by direct DNA Sanger sequencing.

    RESULTS: The genotype percentage (G/G = 73%, G/A = 24.1%, and A/A = 2.9%) adhere to the Hardy-Weinberg equilibrium. The dominant allele found in our population was CST3 73G allele (85%). The regression lines' slope of serum cystatin C against creatinine and cystatin C-based eGFR against creatinine-based eGFR, between G and A allele groups, showed a statistically significant difference (z-score = 3.457, p < 0.001 and z-score = 2.158, p = 0.015, respectively). Patients with A allele had a lower serum cystatin C level when the values were extrapolated at a fixed serum creatinine value, suggesting the influence of genetic factor.

    CONCLUSION: Presence of CST3 gene G73A polymorphism affects serum cystatin C levels.

    Matched MeSH terms: Cystatin C/blood*; Cystatin C/genetics
  5. Azrina Md Ralib, Iqbalmunawwir Ab Rashid, Nur Aisyah Ishak, Suhaila Nanyan, Nur Fariza Ramly, Mohd Basri Mat Nor
    MyJurnal
    Plasma Cystatin C (CysC) is as an early functional marker for acute kidney
    injury. Estimates of glomerular filtration rate using CysC (eGFRCysC) has been used in
    some clinical setting. We evaluated the utility of CysC and eGFRCysC in diagnosing acute
    kidney injury (AKI) and predicting death in critically ill patients with sepsis. (Copied from article).
    Matched MeSH terms: Cystatin C
  6. Marwyne MN, Loo CY, Halim AG, Norella K, Sulaiman T, Zaleha MI
    Med J Malaysia, 2011 Oct;66(4):313-7.
    PMID: 22299549 MyJurnal
    Obesity and overweight are strong independent risk factors for chronic kidney disease (CKD). Using serum creatinine-based estimated glomerular filtration rate (eGFR) equations in these subjects may be inaccurate. On the other hand, cystatin C-based eGFR equations may overestimate CKD prevalence as recent findings suggest an association of cystatin C with obesity. The objective of this study was to assess the accuracy of a cystatin C-based eGFR equation compared to two creatinine -based eGFR equations in overweight and obese subjects.
    Matched MeSH terms: Cystatin C/blood*
  7. 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: Cystatin C/blood
  8. 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 cystatin C levels were observed on the basis of patient's age and BMI.

    CONCLUSION: Cystatin C is not related to BMI and age among elderly 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: Cystatin C/blood*
  9. 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: Cystatin C/blood*
  10. Ralib AM, Pickering JW, Shaw GM, Than MP, George PM, Endre ZH
    Crit Care, 2014;18(6):601.
    PMID: 25366893 DOI: 10.1186/s13054-014-0601-2
    INTRODUCTION: Acute Kidney Injury (AKI) biomarker utility depends on sample timing after the onset of renal injury. We compared biomarker performance on arrival in the emergency department (ED) with subsequent performance in the intensive care unit (ICU).
    METHODS: Urinary and plasma Neutrophil Gelatinase-Associated Lipocalin (NGAL), and urinary Cystatin C (CysC), alkaline phosphatase, γ-Glutamyl Transpeptidase (GGT), α- and π-Glutathione S-Transferase (GST), and albumin were measured on ED presentation, and at 0, 4, 8, and 16 hours, and days 2, 4 and 7 in the ICU in patients after cardiac arrest, sustained or profound hypotension or ruptured abdominal aortic aneurysm. AKI was defined as plasma creatinine increase ≥ 26.5 μmol/l within 48 hours or ≥ 50% within 7 days.
    RESULTS: n total, 45 of 77 patients developed AKI. Most AKI patients had elevated urinary NGAL, and plasma NGAL and CysC in the period 6 to 24 hours post presentation. Biomarker performance in the ICU was similar or better than when measured earlier in the ED. Plasma NGAL diagnosed AKI at all sampling times, urinary NGAL, plasma and urinary CysC up to 48 hours, GGT 4 to 12 hours, and π-GST 8 to 12 hours post insult. Thirty-one patients died or required dialysis. Peak 24-hour urinary NGAL and albumin independently predicted 30-day mortality and dialysis; odds ratios 2.87 (1.32 to 6.26), and 2.72 (1.14 to 6.48), respectively. Urinary NGAL improved risk prediction by 11% (IDI event of 0.06 (0.002 to 0.19) and IDI non-event of 0.04 (0.002 to 0.12)).
    CONCLUSION: Early measurement in the ED has utility, but not better AKI diagnostic performance than later ICU measurement. Plasma NGAL diagnosed AKI at all time points. Urinary NGAL best predicted mortality or dialysis compared to other biomarkers.
    TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ACTRN12610001012066. Registered 12 February 2010.
    Matched MeSH terms: Cystatin C/urine*
  11. Chitra P, Bakthavatsalam B, Palvannan T
    Biomed Pharmacother, 2014 Sep;68(7):881-5.
    PMID: 25194446 DOI: 10.1016/j.biopha.2014.07.017
    Rheumatoid arthritis in HIV patients undergoing HAART is associated with increased risk of side effect. Elevation of uric acid (UA) is important in tissue damage, deposition of crystal in joints leads to the development of rheumatoid arthritis in the HAART complaint group. This study was carried out to investigate the relationship of uric acid, RA factor, ANA, ESR, cystatin C, urea and creatinine in the HAART complaint group. Moreover; the ratio of uric acid/cystatin C, uric acid/urea and uric acid/creatinine were also studied. To analyze the progression of HIV, the immunological parameters were correlated with uric acid. Our result showed a statistically high significant increase in uric acid, RA factor, ANA, ESR, cystatin C, urea and creatinine in the HAART complaint group when compared to HAART non-complaint group, early stage and control. The ratio of uric acid/cystatin C, uric acid/urea, uric acid/creatinine were significantly increased in the HAART complaint group. Statistically significant positive correlation was observed between uric acid and cystatin C, urea, creatinine, absolute CD4 and CD8 count. The increased level of uric acid, RA factor, ANA, ESR, cystatin C and increased ratio of uric acid/cystatin C in the HAART complaint group might conclude the mechanism underlying the increased risk for rheumatoid arthritis in the HAART complaint group which may relate to the combined effects of low-grade inflammation and renal dysfunction.

    Study done in India
    Matched MeSH terms: Cystatin C/metabolism
  12. Jayasekara JMKB, Dissanayake DM, Shihana F, Sivakanesan R, Silva RN, Gunawickrama SHNP
    Malays J Med Sci, 2018 Nov;25(6):67-75.
    PMID: 30914880 DOI: 10.21315/mjms2018.25.6.7
    Background: Chronic kidney disease of uncertain aetiology (CKDu) is one of the major health concerns among agricultural communities in Sri Lanka. Individuals involved in severe agricultural works for their livelihood are highly vulnerable for this disease and patients have been detected with persisting proteinuria at community-level screening. The current study was designed to evaluate the diagnosis of two functional markers of kidney damage using individuals with persisting proteinuria as the baseline.

    Methods: One hundred and fifty hard-working agricultural farmers from high-prevalence area for CKDu (Madawachchiya) were screened three times for proteinuria; 66 proteinuric and 21 non-proteinuric were identified as the baseline classification. Selected individuals were analysed further for creatinine, protein and cystatin C in urine and creatinine, cystatin C in serum. Urine protein-to-creatinine ratio (UP/UC) was calculated.

    Results: Based on creatinine and cystatin C cut-off levels in serum, individuals were classified as high or normal. Diagnosis of two functional markers (creatinine and cystatin C) were evaluated using receiver operating characteristic (ROC) curve and in terms of sensitivity and specificity using UP/UC as the baseline. Creatinine and cystatin C-based eGFR (estimated Glomerular filtration rate) levels were calculated, and Pearson's correlation coefficient was determined between different eGFR measurements using UP/UC. Mean (SD) UP/UC ratio, serum creatinine, and serum cystatin C levels of the proteinuric subjects were 129.0 (18.4) mg/mmol, 1.35 (0.39) mg/dL, 1.69 (0.58) mg/L. For non-proteniuric individuals, the results were found to be 14.4 (2.28), 1.22 (0.40) mg/dL, 0.82 (0.25) mg/L. The ROC analysis showed excellent accuracy in using cystatin C for identifying proteinuric patients than creatinine area under the curve (AUC): 0.9675, P < 0.001). Cut-off points were identified as 1.015 mg/dL for serum creatinine and 0.930mg/L for cystatin C. Furthermore, cystatin C based Hoek formula showed the better correlation (0.635, P < 0.001) with UP/UC compared with creatinine based modification of diet in renal disease (MDRD) formula.

    Conclusion: The study showed elevated serum cystatin C in patients with persisting proteinuria compared with non-responding serum creatinine. Moreover, cystatin C-based eGFR equations were more accurate to determine the kidney function than serum creatinine in proteinuric patients who are vulnerable for CKDu in high-prevalence areas.

    Matched MeSH terms: Cystatin C
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