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Fulltext The effect of regularly dosed paracetamol versus no paracetamol on renal function in Plasmodium knowlesi malaria (PACKNOW): study protocol for a randomised controlled trial

Cooper DJ, Plewes K, Grigg MJ, Rajahram GS, Piera KA, William T, et al.

Trials, 2018 Apr 24;19(1):250.
PMID: 29690924 DOI: 10.1186/s13063-018-2600-0

BACKGROUND: Plasmodium knowlesi is the most common cause of human malaria in Malaysia. Acute kidney injury (AKI) is a frequent complication. AKI of any cause can have long-term consequences, including increased risk of chronic kidney disease, adverse cardiovascular events and increased mortality. Additional management strategies are therefore needed to reduce the frequency and severity of AKI in malaria. In falciparum malaria, cell-free haemoglobin (CFHb)-mediated oxidative damage contributes to AKI. The inexpensive and widely available drug paracetamol inhibits CFHb-induced lipid peroxidation via reduction of ferryl haem to the less toxic Fe3+ state, and has been shown to reduce oxidative damage and improve renal function in patients with sepsis complicated by haemolysis as well as in falciparum malaria. This study aims to assess the ability of regularly dosed paracetamol to reduce the incidence and severity of AKI in knowlesi malaria by attenuating haemolysis-induced oxidative damage.
METHODS: PACKNOW is a two-arm, open-label randomised controlled trial of adjunctive paracetamol versus no paracetamol in patients aged ≥ 5 years with knowlesi malaria, conducted over a 2-year period at four hospital sites in Sabah, Malaysia. The primary endpoint of change in creatinine from enrolment to 72 h will be evaluated by analysis of covariance (ANCOVA) using enrolment creatinine as a covariate. Secondary endpoints include longitudinal changes in markers of oxidative stress (plasma F2-isoprostanes and isofurans) and markers of endothelial activation/Weibel-Palade body release (angiopoietin-2, von Willebrand Factor, P-selectin, osteoprotegerin) over 72 h, as well as blood and urine biomarkers of AKI. This study will be powered to detect a difference between the two treatment arms in a clinically relevant population including adults and children with knowlesi malaria of any severity.
DISCUSSION: Paracetamol is widely available and has an excellent safety profile; if a renoprotective effect is demonstrated, this trial will support the administration of regularly dosed paracetamol to all patients with knowlesi malaria. The secondary outcomes in this study will provide further insights into the pathophysiology of haemolysis-induced oxidative damage and acute kidney injury in knowlesi malaria and other haemolytic diseases.
TRIAL REGISTRATION: Clinicaltrials.gov, NCT03056391 . Registered on 12 October 2016.

Matched MeSH terms: Biomarkers/urine
Fulltext Analysis of Multiple Mycotoxins in the Qatari Population and Their Relation to Markers of Oxidative Stress

Al-Jaal B, Latiff A, Salama S, Hussain HM, Al-Thani NA, Al-Naimi N, et al.

Toxins (Basel), 2021 04 08;13(4).
PMID: 33917988 DOI: 10.3390/toxins13040267

Mycotoxins are naturally occurring food toxins worldwide that can cause serious health effects. The measurement of mycotoxin biomarkers in biological fluids is needed to assess individuals' exposure. The aim of this study was to investigate the incidence of mycotoxins in the Qatari population. Serum samples from 412 adults and urinary samples from 559 adults were analyzed for the presence of mycotoxin biomarkers. Multimycotoxin approaches have been applied, using liquid chromatography mass spectrometry methods. Samples were further analyzed for the oxidative stress markers and compared with regard to the incidence of mycotoxins. The presence of mycotoxins was identified in 37% of serum samples and in less than 20% of urine samples. It was found that 88% of positive of the samples were positive for only one mycotoxin, while 12% of positive samples had two or more mycotoxins. Trichothecenes and zearalenone metabolites were most commonly detected mycotoxins, followed by aflatoxins, roquefortine C and mycophenolic acid. The presence of mycotoxins was found to positively correlate with oxidative stress markers. The obtained results illustrate the importance of mycotoxin biomonitoring studies in humans and the need to elucidate the underlying mechanisms of mycotoxin-induced toxicity.

Matched MeSH terms: Biomarkers/urine
Fulltext Urinary type IV collagen levels in diabetes mellitus

Sthaneshwar P, Chan SP

Malays J Pathol, 2010 Jun;32(1):43-7.
PMID: 20614725 MyJurnal

Type IV collagen is the principal component of glomerular basement membrane and messangial matrix. Studies have shown increased levels of urinary type IV collagen (uIV) in diabetic patients compared to healthy controls. The concentration of uIV increases gradually as diabetic nephropathy progresses.
AIM AND METHOD: This study was carried out to determine whether urinary type IV collagen (uIV) can serve as an indicator of diabetic nephropathy. Using a sandwich enzyme immunoassay technique, uIV excretion was determined in 30 type 2 diabetic patients with normoalbuminuria and 20 patients with microalbuminuria.
RESULTS: uIV excretion was significantly increased in type 2 diabetics, in both normoalbuminuric and microalbuminuric patients, compared with healthy controls. The increase in urinary type IV collagen was well correlated with the amount of urinary albumin but not with HbA1C.
CONCLUSION: Our findings that uIV is higher in those with microalbuminuria and correlates with albuminuria, support uIV as an indicator of diabetic nephropathy. Whether the increased uIV excretion would predict the impending renal failure needs further confirmation.

Matched MeSH terms: Biomarkers/urine*
Fulltext Endothelial glycocalyx degradation and disease severity in Plasmodium vivax and Plasmodium knowlesi malaria

Barber BE, Grigg MJ, Piera KA, Chen Y, William T, Weinberg JB, et al.

Sci Rep, 2021 May 07;11(1):9741.
PMID: 33963210 DOI: 10.1038/s41598-021-88962-6

Degradation of the endothelial glycocalyx is associated with mortality in adult falciparum malaria. However, its role in the pathogenesis of non-falciparum malaria is unknown. In Malaysian patients with knowlesi (n = 200) and vivax (n = 61) malaria, and in healthy controls (n = 50), we measured glycocalyx breakdown products plasma syndecan-1 and urinary glycosaminoglycans, and evaluated correlations with biomarkers of disease severity. Urinary glycosaminoglycans were increased in patients with knowlesi and vivax malaria compared to healthy controls, and in knowlesi malaria were highest in those with severe disease. In knowlesi malaria, plasma syndecan-1 was also highest in those with severe disease, and correlated with markers of endothelial activation (angiopoietin-2, osteoprotegerin, ICAM-1), asymmetric dimethylarginine (ADMA) and impaired microvascular reactivity. Syndecan-1 also correlated with endothelial activation (ICAM-1, angiopoietin-2) and ADMA in vivax malaria. In knowlesi malaria increased syndecan-1 was associated with acute kidney injury, after controlling for age and parasitemia. In knowlesi malaria, the difference in median syndecan-1 between severe and non-severe disease was more marked in females than males. Endothelial glycocalyx degradation is increased in knowlesi and vivax malaria, and associated with disease severity and acute kidney injury in knowlesi malaria. Agents that inhibit glycocalyx breakdown may represent adjunctive therapeutics for severe non-falciparum malaria.

Matched MeSH terms: Biomarkers/urine
Twenty-four-hour urine constituents in stone formers: a study from the northeast part of Peninsular Malaysia

Hussein NS, Sadiq SM, Kamaliah MD, Norakmal AW, Gohar MN

Saudi J Kidney Dis Transpl, 2013 May;24(3):630-7.
PMID: 23640651

Urolithiasis is a common disease with increasing incidence and prevalence world-wide, probably more common in industrialized countries. The metabolic evaluation of 24-h urine collection has been considered as part of the management of urinary stone patients. The aim of this study was to evaluate the 24-h urine constituents in stone formers and its relation to demographic data in the northeast part of Peninsular Malaysia. One hundred and six patients were recruited in this study from two hospitals in the same geographical region; 96 patients fulfilled the inclusion criteria and an informed consent was obtained from all subjects. The 24-h urine was collected in sterile bottles with a preservative agent and calcium, oxalate, citrate, uric acid, magnesium and phosphate were tested using commercial kits on a Roche Hitachi 912 chemistry analyzer. The age (mean ± SD) of 96 patients was 56.45 ± 13.43 years and 82.3% of the patients were male while 17.7% were female. The 24-h urine abnormalities were hypercalciuria (14.5%), hyperoxaluria (61.4%), hypocitraturia (57.2%), hyperuricouria (19.7%), hypomagnesuria (59.3%) and hyperphosphaturia (12.5%). Hyperoxaluria (61.4%) was the most common abnormality detected during the analysis of 24-h urine constituents in contradiction to industrial countries, where hypercalciuria was the most common finding. The high frequencies of hypomagnesuria and hypocitraturia reflect the important role of magnesium and citrate in stone formation and their prophylactic role in the treatment of urinary stone disease in the given population.

Matched MeSH terms: Biomarkers/urine
Fulltext Rapid Detection of Sepsis using CESDA: the Caenorhabditis elegans Sepsis Detection Assay

Tee LF, Tan TL, Neoh HM, Jamal R

Rev Soc Bras Med Trop, 2019 Mar 14;52:e20180300.
PMID: 30892548 DOI: 10.1590/0037-8682-0300-2018

INTRODUCTION: The nematode Caenorhabditis elegans was used as a biological sensor to detect the urine of sepsis patients (CESDA assay).
METHODS: C. elegans was aliquoted onto the center of assay plates and allowed to migrate towards sepsis (T) or control (C) urine samples spotted on the same plate. The number of worms found in either (T) or (C) was scored at 10-minute intervals over a 60-minute period.
RESULTS: The worms were able to identify the urine (<48 hours) of sepsis patients rapidly within 20 minutes (AUROC=0.67, p=0.012) and infection within 40 minutes (AUROC=0.80, p=0.016).
CONCLUSIONS: CESDA could be further explored for sepsis diagnosis.

Matched MeSH terms: Biomarkers/urine*
Effect of Ipomoea aquatica ethanolic extract in streptozotocin (STZ) induced diabetic rats via1H NMR-based metabolomics approach

Abu Bakar Sajak A, Mediani A, Maulidiani, Mohd Dom NS, Machap C, Hamid M, et al.

Phytomedicine, 2017 Dec 01;36:201-209.
PMID: 29157816 DOI: 10.1016/j.phymed.2017.10.011

BACKGROUND: Ipomoea aquatica (locally known as "kangkung") has previously been reported to have hypoglycemic activities on glucose level in diabetes patients. However, the effect of I. aquatica ethanolic extract on the metabolites in the body has remained unknown.
PURPOSE: This study provides new insights on the changes of endogenous metabolites caused by I. aquatica ethanolic extract and improves the understanding on the therapeutic efficacy and mechanism of I. aquatica ethanolic extract.
METHODS: By using a combination of 1H nuclear magnetic resonance (NMR) with multivariate analysis (MVDA), the changes of metabolites due to I. aquatica ethanolic extract administration in obese diabetic-induced Sprague Dawley rats (OB+STZ+IA) were identified.
RESULTS: The results suggested 19 potential biomarkers with variable importance projections (VIP) above 0.5, which include creatine/creatinine, glucose, creatinine, citrate, carnitine, 2-oxoglutarate, succinate, hippurate, leucine, 1-methylnicotinamice (MNA), taurine, 3-hydroxybutyrate (3-HB), tryptophan, lysine, trigonelline, allantoin, formiate, acetoacetate (AcAc) and dimethylamine. From the changes in the metabolites, the affected pathways and aspects of metabolism were identified.
CONCLUSION: I. aquatica ethanolic extract increases metabolite levels such as creatinine/creatine, carnitine, MNA, trigonelline, leucine, lysine, 3-HB and decreases metabolite levels, including glucose and tricarboxylic acid (TCA) intermediates. This implies capabilities of I. aquatica ethanolic extract promoting glycolysis, gut microbiota and nicotinate/nicotinamide metabolism, improving the glomerular filtration rate (GFR) and reducing the β-oxidation rate. However, the administration of I. aquatica ethanolic extract has several drawbacks, such as unimproved changes in amino acid metabolism, especially in reducing branched chain amino acid (BCAA) synthesis pathways and lipid metabolism.

Matched MeSH terms: Biomarkers/urine
Fulltext Urine Untargeted Metabolomic Profiling Is Associated with the Dietary Pattern of Successful Aging among Malaysian Elderly

Nik Mohd Fakhruddin NNI, Shahar S, Ismail IS, Ahmad Azam A, Rajab NF

Nutrients, 2020 Sep 23;12(10).
PMID: 32977370 DOI: 10.3390/nu12102900

Food intake biomarkers (FIBs) can reflect the intake of specific foods or dietary patterns (DP). DP for successful aging (SA) has been widely studied. However, the relationship between SA and DP characterized by FIBs still needs further exploration as the candidate markers are scarce. Thus, 1H-nuclear magnetic resonance (1H-NMR)-based urine metabolomics profiling was conducted to identify potential metabolites which can act as specific markers representing DP for SA. Urine sample of nine subjects from each three aging groups, SA, usual aging (UA), and mild cognitive impairment (MCI), were analyzed using the 1H-NMR metabolomic approach. Principal components analysis (PCA) and partial least-squares discriminant analysis (PLS-DA) were applied. The association between SA urinary metabolites and its DP was assessed using the Pearson's correlation analysis. The urine of SA subjects was characterized by the greater excretion of citrate, taurine, hypotaurine, serotonin, and melatonin as compared to UA and MCI. These urinary metabolites were associated with alteration in "taurine and hypotaurine metabolism" and "tryptophan metabolism" in SA elderly. Urinary serotonin (r = 0.48, p < 0.05) and melatonin (r = 0.47, p < 0.05) were associated with oat intake. These findings demonstrate that a metabolomic approach may be useful for correlating DP with SA urinary metabolites and for further understanding of SA development.

Matched MeSH terms: Biomarkers/urine*
Fulltext Association between Urinary Aflatoxin (AFM₁) and Dietary Intake among Adults in Hulu Langat District, Selangor, Malaysia

Sulaiman SH, Jamaluddin R, Sabran MR

Nutrients, 2018 Apr 07;10(4).
PMID: 29642443 DOI: 10.3390/nu10040460

Aflatoxin is a food contaminant and its exposure through the diet is frequent and ubiquitous. A long-term dietary aflatoxin exposure has been linked to the development of liver cancer in populations with high prevalence of aflatoxin contamination in foods. Therefore, this study was conducted to identify the association between urinary aflatoxin M₁ (AFM₁), a biomarker of aflatoxin exposure, with the dietary intake among adults in Hulu Langat district, Selangor, Malaysia. Certain food products have higher potential for aflatoxin contamination and these were listed in a Food Frequency Questionnaire, which was given to all study participants. This allowed us to record consumption rates for each food product listed. Concomitantly, urine samples were collected, from adults in selected areas in Hulu Langat district, for the measurement of AFM₁ levels using an ELISA kit. Of the 444 urine samples collected and tested, 199 were positive for AFM₁, with 37 of them exceeding the limit of detection (LOD) of 0.64 ng/mL. Cereal products showed the highest consumption level among all food groups, with an average intake of 512.54 g per day. Chi-square analysis showed that consumption of eggs (X² = 4.77, p = 0.03) and dairy products (X² = 19.36, p < 0.01) had significant associations with urinary AFM₁ but both food groups were having a phi and Cramer's V value that less than 0.3, which indicated that the association between these food groups' consumption and AFM₁ level in urine was weak.

Matched MeSH terms: Biomarkers/urine
Fulltext Relative Validity and Reproducibility of a Food Frequency Questionnaire for Assessing Dietary Intakes in a Multi-Ethnic Asian Population Using 24-h Dietary Recalls and Biomarkers

Whitton C, Ho JCY, Tay Z, Rebello SA, Lu Y, Ong CN, et al.

Nutrients, 2017 Sep 25;9(10).
PMID: 28946670 DOI: 10.3390/nu9101059

The assessment of diets in multi-ethnic cosmopolitan settings is challenging. A semi-quantitative 163-item food frequency questionnaire (FFQ) was developed for the adult Singapore population, and this study aimed to assess its reproducibility and relative validity against 24-h dietary recalls (24 h DR) and biomarkers. The FFQ was administered twice within a six-month interval in 161 adults (59 Chinese, 46 Malay, and 56 Indian). Fasting plasma, overnight urine, and 24 h DR were collected after one month and five months. Intra-class correlation coefficients between the two FFQ were above 0.70 for most foods and nutrients. The median correlation coefficient between energy-adjusted deattenuated FFQ and 24 h DR nutrient intakes was 0.40 for FFQ1 and 0.39 for FFQ2, highest for calcium and iron, and lowest for energy and carbohydrates. Significant associations were observed between urinary isoflavones and soy protein intake (r = 0.46), serum carotenoids and fruit and vegetable intake (r = 0.34), plasma eicosapentaenoic acid and docosahexaenoic acid (EPA + DHA) and fish/seafood intake (r = 0.36), and plasma odd chain saturated fatty acids (SFA) and dairy fat intake (r = 0.25). Associations between plasma EPA + DHA and fish/seafood intake were consistent across ethnic groups (r = 0.28-0.49), while differences were observed for other associations. FFQ assessment of dietary intakes in modern cosmopolitan populations remains feasible for the purpose of ranking individuals' dietary exposures in epidemiological studies.

Matched MeSH terms: Biomarkers/urine
Fulltext A population-based study measuring the prevalence of chronic kidney disease among adults in West Malaysia

Hooi LS, Ong LM, Ahmad G, Bavanandan S, Ahmad NA, Naidu BM, et al.

Kidney Int, 2013 Nov;84(5):1034-40.
PMID: 23760287 DOI: 10.1038/ki.2013.220

In this population-based study, we determine the prevalence of chronic kidney disease in West Malaysia in order to have accurate information for health-care planning. A sample of 876 individuals, representative of 15,147 respondents from the National Health and Morbidity Survey 2011, of the noninstitutionalized adult population (over 18 years old) in West Malaysia was studied. We measured the estimated glomerular filtration rate (eGFR) (CKD-EPI equation); albuminuria and stages of chronic kidney disease were derived from calibrated serum creatinine, age, gender and early morning urine albumin creatinine ratio. The prevalence of chronic kidney disease in this group was 9.07%. An estimated 4.16% had stage 1 chronic kidney disease (eGFR >90 ml/min per 1.73 m(2) and persistent albuminuria), 2.05% had stage 2 (eGFR 60-89 ml/min per 1.73 m(2) and persistent albuminuria), 2.26% had stage 3 (eGFR 30-59 ml/min per 1.73 m(2)), 0.24% had stage 4 (eGFR 15-29 ml/min per 1.73 m(2)), and 0.36% had stage 5 chronic kidney disease (eGFR <15 ml/min per 1.73 m(2)). Only 4% of respondents with chronic kidney disease were aware of their diagnosis. Risk factors included increased age, diabetes, and hypertension. Thus, chronic kidney disease in West Malaysia is common and, therefore, warrants early detection and treatment in order to potentially improve outcome.
Study name: National Health and Morbidity Survey (NHMS-2011)

Matched MeSH terms: Biomarkers/urine
1H NMR based pharmacometabolomics analysis of urine identifies metabolic phenotype of clopidogrel high on treatment platelets reactivity in coronary artery disease patients

Amin AM, Sheau Chin L, Teh CH, Mostafa H, Mohamed Noor DA, Sk Abdul Kader MA, et al.

J Pharm Biomed Anal, 2017 Nov 30;146:135-146.
PMID: 28873361 DOI: 10.1016/j.jpba.2017.08.018

Clopidogrel high on treatment platelets reactivity (HTPR) has burdened achieving optimum therapeutic outcome. Although there are known genetic and non-genetic factors associated with clopidogrel HTPR, which explain in part clopidogrel HTPR, yet, great portion remains unknown, often hindering personalizing antiplatelet therapy. Nuclear magnetic resonance (1H NMR) pharmacometabolomics analysis is useful technique to phenotype drug response. We investigated using 1H NMR analysis to phenotype clopidogrel HTPR in urine. Urine samples were collected from 71 coronary artery disease (CAD) patients who were planned for interventional angiographic procedure prior to taking 600mg clopidogrel loading dose (LD) and 6h post LD. Patients' platelets function testing was assessed with the VerifyNow® P2Y12 assay at 6h after LD. Urine samples were analysed using 1H NMR. Multivariate statistical analysis was used to identify metabolites associated with clopidogrel HTPR. In pre-dose samples, 16 metabolites were associated with clopidogrel HTPR. However, 18 metabolites were associated with clopidogrel HTPR in post-dose samples. The pathway analysis of the identified biomarkers reflected that multifactorial conditions are associated with clopidogrel HTPR. It also revealed the implicated role of gut microbiota in clopidogrel HTPR. Pharmacometabolomics not only discovered novel biomarkers of clopidogrel HTPR but also revealed implicated pathways and conditions.

Matched MeSH terms: Biomarkers/urine
Adenylosuccinate lyase deficiency in a Malaysian patient, with novel adenylosuccinate lyase gene mutations

Chen BC, McGown IN, Thong MK, Pitt J, Yunus ZM, Khoo TB, et al.

J Inherit Metab Dis, 2010 Dec;33 Suppl 3:S159-62.
PMID: 20177786 DOI: 10.1007/s10545-010-9056-z

Most cases of adenylosuccinate lyase (ADSL OMIM 103050) deficiency reported to date are confined to the various European ethnic groups. We report on the first Malaysian case of ADSL deficiency, which appears also to be the first reported Asian case. The case was diagnosed among a cohort of 450 patients with clinical features of psychomotor retardation, global developmental delay, seizures, microcephaly and/or autistic behaviour. The patient presented with frequent convulsions and severe myoclonic jerk within the first few days of life and severe psychomotor retardation. The high performance liquid chromatography (HPLC) profile of the urine revealed the characteristic biochemical markers of succinyladenosine (S-Ado) and succinyl-aminoimidazole carboximide riboside (SAICAr). The urinary S-Ado/SAICAr ratio was found to be 1.02 (type I ADSL deficiency). The patient was compound heterozygous for two novel mutations, c.445C > G (p.R149G) and c.774_778insG (p.A260GfsX24).

Matched MeSH terms: Biomarkers/urine
Preclinical toxicological evaluations of the sclerotium of Lignosus rhinocerus (Cooke), the Tiger Milk mushroom

Lee SS, Enchang FK, Tan NH, Fung SY, Pailoor J

J Ethnopharmacol, 2013 May 2;147(1):157-63.
PMID: 23458920 DOI: 10.1016/j.jep.2013.02.027

Lignosus rhinocerus (Tiger Milk mushroom) is distributed in South China, Thailand, Malaysia, Indonesia, Philippines and Papua New Guinea. In Malaysia, it is the most popular medicinal mushroom used by the indigenous communities to relieve fever, cough, asthma, cancer, food poisoning and as a general tonic. In China, this mushroom is an expensive traditional medicine used to treat liver cancer, chronic hepatitis and gastric ulcers. The sclerotium of the mushroom is the part with medicinal value. This rare mushroom has recently been successfully cultivated making it possible to be fully exploited for its medicinal and functional benefits. The present study was carried out to evaluate the chronic toxicity of the sclerotial powder of Lignosus rhinocerus cultivar (termed TM02), its anti-fertility and teratogenic effects as well as genotoxicity.

Matched MeSH terms: Biomarkers/urine
Fulltext An Investigation into the Antiobesity Effects of Morinda citrifolia L. Leaf Extract in High Fat Diet Induced Obese Rats Using a (1)H NMR Metabolomics Approach

Gooda Sahib Jambocus N, Saari N, Ismail A, Khatib A, Mahomoodally MF, Abdul Hamid A

J Diabetes Res, 2016;2016:2391592.
PMID: 26798649 DOI: 10.1155/2016/2391592

The prevalence of obesity is increasing worldwide, with high fat diet (HFD) as one of the main contributing factors. Obesity increases the predisposition to other diseases such as diabetes through various metabolic pathways. Limited availability of antiobesity drugs and the popularity of complementary medicine have encouraged research in finding phytochemical strategies to this multifaceted disease. HFD induced obese Sprague-Dawley rats were treated with an extract of Morinda citrifolia L. leaves (MLE 60). After 9 weeks of treatment, positive effects were observed on adiposity, fecal fat content, plasma lipids, and insulin and leptin levels. The inducement of obesity and treatment with MLE 60 on metabolic alterations were then further elucidated using a (1)H NMR based metabolomics approach. Discriminating metabolites involved were products of various metabolic pathways, including glucose metabolism and TCA cycle (lactate, 2-oxoglutarate, citrate, succinate, pyruvate, and acetate), amino acid metabolism (alanine, 2-hydroxybutyrate), choline metabolism (betaine), creatinine metabolism (creatinine), and gut microbiome metabolism (hippurate, phenylacetylglycine, dimethylamine, and trigonelline). Treatment with MLE 60 resulted in significant improvement in the metabolic perturbations caused obesity as demonstrated by the proximity of the treated group to the normal group in the OPLS-DA score plot and the change in trajectory movement of the diseased group towards the healthy group upon treatment.

Matched MeSH terms: Biomarkers/urine
Serum and urine interleukin-17A levels as biomarkers of disease activity in systemic lupus erythematosus

Nordin F, Shaharir SS, Abdul Wahab A, Mustafar R, Abdul Gafor AH, Mohamed Said MS, et al.

Int J Rheum Dis, 2019 Aug;22(8):1419-1426.
PMID: 31179646 DOI: 10.1111/1756-185X.13615

OBJECTIVES: This study examined the correlations of both serum and urine interleukin-17A (IL-17A) levels with disease activity in systemic lupus erythematosus (SLE). This study was also aimed at determining their sensitivity and specificity as biomarkers of disease activity in SLE.
METHODS: A cross-sectional study was performed involving SLE patients (n = 120 patients) from Universiti Kebangsaan Malaysia Medical Centre (UKMMC). Serum and urinary IL-17A levels were determined by immunoassay while disease activity was assessed using Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) and British Isles Lupus Assessment Group's 2004 index (BILAG 2004) scores. The correlations between serum and urinary IL-17A levels with total SLEDAI-2K and BILAG 2004 scores were determined using bivariate correlation analyses. Receiver operating characteristic curves were calculated to determine their sensitivity and specificity as disease activity biomarkers.
RESULTS: Both serum and urinary IL-17A levels correlated with total scores of BILAG 2004, BILAG renal, BILAG mucocutaneous, and SLEDAI-2K (P

Matched MeSH terms: Biomarkers/urine
Apparent bioavailability of isoflavones in urinary excretions of postmenopausal Malay women consuming tempeh compared with milk

Haron H, Ismail A, Shahar S, Azlan A, Peng LS

Int J Food Sci Nutr, 2011 Sep;62(6):642-50.
PMID: 21574819 DOI: 10.3109/09637486.2011.570742

Quantitation of isoflavones in humans is important to establish the benefits of these compounds to the populations. Urinary isoflavones are frequently used as a biomarker of isoflavone bioavailability from food or supplement since urine contains 100-fold higher concentrations of isoflavones. The objective of the present study was to determine and compare the urinary excretions of daidzein (DA), genistein (GE) and equol (EQ) in postmenopausal Malay women following the consumption of tempeh and milk in a calcium absorption study and to test the hypothesis that the excretion of isoflavones following consumption of tempeh maybe higher compared with milk. The amounts of DA (47.06 ± 4.18 μmol/h), GE (33.27 ± 3.71 μmol/h) and EQ (24.35 ± 4.34 μmol/h) excreted in urine following tempeh consumption were significantly higher (P < 0.05) compared with those in milk (3.51 ± 0.62 μmol/h DA, 2.79 ± 0.35 μmol/h GE and 0 μmol/h EQ). Almost all studied postmenopausal Malay women were able to excrete EQ following consumption of 240 g tempeh but only one subject can be classified as an equol producer. We concluded that most postmenopausal Malay women excreted DA, GE and EQ in their urine following tempeh consumption and the amount of the excreted isoflavones were higher compared with those in milk. However, further studies are needed to determine whether longer periods of time are required to capture EQ producers.

Matched MeSH terms: Biomarkers/urine
Fulltext Chronic kidney disease screening methods and its implication for Malaysia: an in depth review

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: Biomarkers/urine
Chronic kidney disease, cardiovascular disease and mortality: A prospective cohort study in a multi-ethnic Asian population

Lim CC, Teo BW, Ong PG, Cheung CY, Lim SC, Chow KY, et al.

Eur J Prev Cardiol, 2015 Aug;22(8):1018-26.
PMID: 24857889 DOI: 10.1177/2047487314536873

BACKGROUND: Few studies have examined the impact of chronic kidney disease (CKD) on adverse cardiovascular outcomes and deaths in Asian populations. We evaluated the associations of CKD with cardiovascular disease (CVD) and all-cause mortality in a multi-ethnic Asian population.
DESIGN: Prospective cohort study of 7098 individuals who participated in two independent population-based studies involving Malay adults (n = 3148) and a multi-ethnic cohort of Chinese, Malay and Indian adults (n = 3950).
METHODS: CKD was assessed from CKD-EPI estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR). Incident CVD (myocardial infarction, stroke and CVD mortality) and all-cause mortality were identified by linkage with national disease/death registries.
RESULTS: Over a median follow-up of 4.3 years, 4.6% developed CVD and 6.1% died. Risks of both CVD and all-cause mortality increased with decreasing eGFR and increasing albuminuria (all p-trend <0.05). Adjusted hazard ratios (HR (95% confidence interval)) of CVD and all-cause mortality were: 1.54 (1.05-2.27) and 2.21 (1.67-2.92) comparing eGFR <45 vs ≥60; 2.81 (1.49-5.29) and 2.34 (1.28-4.28) comparing UACR ≥300 vs <30. The association between eGFR <60 and all-cause mortality was stronger among those with diabetes (p-interaction = 0.02). PAR of incident CVD was greater among those with UACR ≥300 (12.9%) and that of all-cause mortality greater among those with eGFR <45 (16.5%).
CONCLUSIONS: In multi-ethnic Asian adults, lower eGFR and higher albuminuria were independently associated with incident CVD and all-cause mortality. These findings extend previously reported similar associations in Western populations to Asians and emphasize the need for early detection of CKD and intervention to prevent adverse outcomes.

Matched MeSH terms: Biomarkers/urine
Hyperexcretion of homocitrulline in a Malaysian patient with lysinuric protein intolerance

Habib A, Md Yunus Z, Azize NA, Ch'ng GS, Ong WP, Chen BC, et al.

Eur J Pediatr, 2013 Sep;172(9):1277-81.
PMID: 23358709 DOI: 10.1007/s00431-013-1947-1

Lysinuric protein intolerance (LPI; MIM 222700) is an inherited aminoaciduria with an autosomal recessive mode of inheritance. Biochemically, affected patients present with increased excretion of the cationic amino acids: lysine, arginine, and ornithine. We report the first case of LPI diagnosed in Malaysia presented with excessive excretion of homocitrulline. The patient was a 4-year-old male who presented with delayed milestones, recurrent diarrhea, and severe failure to thrive. He developed hyperammonemic coma following a forced protein-rich diet. Plasma amino acid analysis showed increased glutamine, alanine, and citrulline but decreased lysine, arginine and ornithine. Urine amino acids showed a marked excretion of lysine and ornithine together with a large peak of unknown metabolite which was subsequently identified as homocitrulline by tandem mass spectrometry. Molecular analysis confirmed a previously unreported homozygous mutation at exon 1 (235 G > A, p.Gly79Arg) in the SLC7A7 gene. This report demonstrates a novel mutation in the SLC7A7 gene in this rare inborn error of diamino acid metabolism. It also highlights the importance of early and efficient treatment of infections and dehydration in these patients.
CONCLUSION: The diagnosis of LPI is usually not suspected by clinical findings alone, and specific laboratory investigations and molecular analysis are important to get a definitive diagnosis.

Matched MeSH terms: Biomarkers/urine

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