Precision Medicine in Erythropoietin Deficiency and Treatment Resistance: A Novel Approach to Management of Anaemia in Chronic Kidney Disease.

The study of anaemia is a well-developed discipline where the concepts of precision medicine have, in part, been researched extensively. This review discusses the treatment of erythropoietin (EPO) deficiency anaemia and resistance in cases of chronic kidney disease (CKD). Traditionally, erythropoietin-stimulating agents (ESAs) and iron supplementation have been used to manage anaemia in cases of CKD. However, these treatments pose potential risks, including cardiovascular and thromboembolic events. Newer treatments have emerged to address these risks, such as slow-release and low-dosage intravenous iron, oral iron supplementation, and erythropoietin-iron combination therapy. Another novel approach is the use of hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs). This review highlights the need for precision medicine targeting the genetic components of EPO deficiency anaemia in CKD and discusses individual variability in genes such as the erythropoietin gene (EPO), the interleukin-ß gene (IL-ß), and the hypoxia-inducible factor gene (HIF). Pharmacogenetic testing aims to provide targeted therapies and interventions that are tailored to the specific characteristics of an individual, thus optimising treatment outcomes and minimising resistance and adverse effects. This article concludes by suggesting that receptor modification has the potential to revolutionise the treatment outcomes of patients with erythropoietin deficiency anaemia through the integration of the mentioned approach.

Knowledge of chronic kidney disease among undergraduate and postgraduate students in a public university in Klang Valley, Malaysia: A cross sectional study.

The prevalence of chronic kidney disease (CKD) risk factors such as diabetes mellitus, hypertension, and obesity among the young Malaysians are increasing. Understanding the factors associated with CKD knowledge could assists healthcare providers to design health education programmes. There are scarce local studies on CKD knowledge and its associated factors among university students. This subpopulation comprises of young people with diverse background and characteristics. This study was aimed to assess the CKD knowledge and its associated factors among university students. A cross-sectional study was conducted among Universiti Kebangsaan Malaysia students from July 2020 to August 2020. A convenience sampling method was applied. All students were invited to complete an online survey using Google Forms that were sent to their email. The survey consisted of questions related to their sociodemographic, socioeconomics, university programme enrolled, medical history, lifestyle characteristics and CKD knowledge. The data were analysed using SPSS Statistics 26.0. Multiple logistic regression analysis was performed to identify the final associated factors after controlling for confounders. A total of 3074 students participated and 32.6% of them had below average CKD knowledge. Students of male gender, enrolment in undergraduate programmes and non-health-related faculties/institutes were more likely to have below average CKD knowledge. Students who are Chinese, from high monthly household income family and with family history of CKD were less likely to have below average CKD knowledge. Almost one-third of the students had below average CKD knowledge. The six associated factors with CKD knowledge were non-modifiable. Of the six factors, three were associated with students being more likely to have below average CKD knowledge; another three were associated with students being less likely to have below average CKD knowledge. Future health education programmes to enhance CKD knowledge should be designed focusing on students who are more likely to have below average CKD knowledge.

Poor perception of chronic kidney diseases and its influencing factors among diabetics patients.

Purpose We aimed to determine predictors of chronic kidney disease (CKD) prevention among patients with diabetes. Method A cross-sectional study was conducted on 1000 selected respondents based on socio-demographic, socio-economic, general CKD perception knowledge, self-monitoring advocacy, preventive behavior, treatment compliance, and psychosocial factors. Using multiple logistic regression, variables and their association with impaired perception of CKD prevention were analyzed. Results Overall, 74% had poor perception regarding CKD prevention (68.7% of men and 31.3% of women). In multivariable analysis, those with weak illness identity fear were two times more likely to have poor perceptions (95% CI 1.563-3.196, p < 0.001). Respondents with weak medical practice (AOR = 2.33, 95% CI 1.609-2.381, p < 0.001) and weak cooperation (AOR = 1.563; 95% CI 1.099-2.224, p < 0.001) were more likely to have poor perceptions on CKD prevention. Concerning poor perception, significant predictors were self-employment, housewives, working in private jobs, weak knowledge on clear glycosuria, sleep problems, print media, digital media, illness identity fear, weak medical practice, and weak co-operation factors. Conclusion Media support is crucial for supporting and improving positive views regarding CKD knowledge. Interventions to reach people with limited awareness on CKD prevention, lower socioeconomic status, and poor social support may improve identification of patients with early-stage CKD. Particular care should be taken to recognize and provide necessary services regarding the early detection of CKD.

Adverse Drug Reactions of Antihypertensives and CYP3A5*3 Polymorphism Among Chronic Kidney Disease Patients.

Chronic kidney disease (CKD) patients may be more susceptible to adverse drug reactions (ADRs), given their complex medication regimen and altered physiological state driven by a decline in kidney function. This study aimed to describe the relationship between CYP3A5*3 polymorphism and the ADR of antihypertensive drugs in CKD patients. This retrospective, multi-center, observational cohort study was performed among adult CKD patients with a follow-up period of up to 3 years. ADRs were detected through medical records. CYP3A5*3 genotyping was performed using the direct sequencing method. From the 200 patients recruited in this study, 33 (16.5%) were found to have ADRs related to antihypertensive drugs, with 40 ADRs reported. The most frequent ADR recorded was hyperkalemia (n = 8, 20.0%), followed by bradycardia, hypotension, and dizziness, with 6 cases (15.0%) each. The most common suspected agents were angiotensin II receptor blockers (n = 11, 27.5%), followed by angiotensin-converting enzyme inhibitors (n = 9, 22.5%). The CYP3A5*3 polymorphism was not found to be associated with antihypertensive-related ADR across the genetic models tested, despite adjustment for other possible factors through multiple logistic regression (p > 0.05). After adjusting for possible confounding factors, the factors associated with antihypertensive-related ADR were anemia (adjusted odds ratio [aOR] 5.438, 95% confidence interval [CI]: 2.002, 14.288) and poor medication adherence (aOR 3.512, 95% CI: 1.470, 8.388). In conclusion, the CYP3A5*3 polymorphism was not found to be associated with ADRs related to antihypertensives in CKD patients, which requires further verification by larger studies.

Benchmarking Diet Quality to Assess Nutritional Risk in Hemodialysis Patients: Applying Adequacy and Moderation Metrics of the Hemodialysis-Healthy Eating Index.

OBJECTIVES: This study modified Healthy Eating Index (HEI) based on hemodialysis (HD)-specific nutritional guidelines and investigated associations between the diet quality (DQ) and nutritional risk in HD patients. METHODS: The HD-HEI tool adapted the Malaysian Dietary Guidelines 2010 framework according to HD-specific nutrition guidelines. This HD-HEI was applied to 3-day dietary records of 382 HD patients. Relationships between HD-HEI scores and nutritional parameters were tested by partial correlations. Binary logistic regression models adjusted with confounders were used to determine adjusted odds ratio (adjOR) with 95% confidence interval (CI) for nutritional risk based on HD-HEI scores categorization. RESULTS: The total HD-HEI score (51.3 ± 10.2) for this HD patient population was affected by ethnicity (Ptrend < .001) and sex (P = .003). No patient achieved "good" DQ (score: 81-100), while DQ of 54.5% patients were classified as "needs improvement" (score: 51-80) and remaining as "poor" (score: 0-51). Total HD-HEI scores were positively associated with dietary energy intake (DEI), dietary protein intake (DPI), dry weight, and handgrip strength, but inversely associated with Dietary Monotony Index (DMI) (all P < .05). Individually, scores for refined grain, total protein, and animal protein were positively associated with DEI (all P < .05), while total, animal, fish, and vegetable proteins indicated positive associations with DPI (all P < .05). Moderating metrics for convenience meals, saturated fats, sodium, and fluid negatively correlated toward DEI with similar trends for DPI excepting convenience meals and fluids. "Poor" DQ was associated with DMI ≥ 29.2 (adjOR 18.83, 95% CI 9.36-37.86, P < .001), Malnutrition Inflammation Score ≥ 5 (adjOR 1.78, 95% CI 1.01-3.15, P = .045), and protein energy wasting (adjOR 1.96, 95% CI 1.14-3.34, P = .031), but became nullified with covariate adjustments. "Poor" DQ was also associated with low lean tissue mass (<32.6 kg) in men (adjOR 2.38, 95% CI 1.01-5.58, P = .046) but not women. CONCLUSION: "Poor" DQ was associated with poor nutritional status in Malaysian HD patients, who should be targeted for nutritional counseling.

The effects of psychosocial and economic factors on the quality of life of patients with end-stage renal disease and their caregivers in Klang Valley, Malaysia: protocol for a mixed-methods study.

INTRODUCTION: The number of patients in Malaysia requiring dialysis is expected to rise substantially in the future due to the ageing population and increasing prevalence of diabetes mellitus and hypertension. Hence, more individuals will be expected to adopt the role of caregivers in the future. The upward trend of end-stage renal disease (ESRD) and caregiving for dialysis patients has detrimental consequences for both patients and caregivers in terms of their psychological well-being and quality of life. Despite the current circumstances, there are very few studies in Malaysia that have explored the psychosocial factors, specifically on the economic impact of the management of ESRD. METHODS AND ANALYSIS: This two-phase sequential explanatory mixed-methods design, incorporating a quantitative design (phase I) and a qualitative study (phase II), is to be conducted in 4 government hospitals and 10 other non-governmental organisations or private dialysis centres within Klang Valley, Malaysia. A cross-sectional survey (phase I) will include 236 patient-caregiver dyads, while focus group discussions (phase II) will include 30 participants. The participants for both phases will be recruited purposively. Descriptive statistics, independent sample t-tests and multiple regression analysis will be used for analyses in phase I, and thematic analysis will be used in phase II. ETHICS AND DISSEMINATION: Approval for the study has been obtained from the National Medical Research and Ethics Committee (MREC) (NMRR-21-1012-59714) and the Research Ethics Committee of Hospital Canselor Tuanku Muhriz UKM (UKM PPI/111/8/JEP-2021-078) and University of Malaya Medical Centre (MREC ID NO: 2 02 178-10346). Informed consent of the participants will be obtained beforehand, and no personal identifiers will be obtained from the participants to protect their anonymity. The findings will be published in peer-reviewed scientific journals and presented at national or international conferences with minimal anonymised data.

Clinical Characteristics of Patients with Coronavirus Disease 2019 (COVID-19) in a Teaching Hospital in Malaysia.

INTRODUCTION: Information on the clinical characteristics of local patients with confirmed COVID-19 is limited. This study aims to report the clinical characteristics of 147 patients admitted and receiving treatment at a teaching hospital. METHODOLOGY: Patients' socio-demographic and epidemiological data, clinical features, laboratory findings and clinical outcomes were extracted using a data sheet. RESULTS: The median patient age was 25 [interquartile range (IQR)] 20-44) years, and most of patients were male (68.7%) and of Malaysian nationality (88.4%). Almost half of the patients were from a case cluster related to a religious event (48.3%) and 12.9% had a history of overseas travel. A total of 33.3% of patients were not related to any case cluster, i.e. sporadic cases. Radiological investigation showed that 13.6% of the patients had chest X-ray changes and all laboratory parameters were within the normal ranges. Sixty-six patients (44.9%) experienced symptoms. The most common symptoms were rhinitis (66.7%), followed by fever (19.7%) and cough (15.2%). Age, gender, case cluster, comorbidity status, haemoglobin, albumin, total protein, bilirubin total and alkaline phosphatase level were associated with symptomatic status. CONCLUSIONS: In this single-centre study, COVID-19 infection led not only to case clusters, but also to sporadic infections, with patients being either symptomatic or asymptomatic. These sporadic cases and asymptomatic patients may hamper effective contact tracing, leading to rapid human-to-human transmission in our population. Future studies on the prevalence and clinical significance of asymptomatic and presymptomatic COVID-19 patients would pre-emptively address issues on further containment of the pandemic.

Effects of tocotrienols supplementation on markers of inflammation and oxidative stress: A systematic review and meta-analysis of randomized controlled trials.

Studies investigating the effects of tocotrienols on inflammation and oxidative stress have yielded inconsistent results. This systematic review and meta-analysis aimed to evaluate the effects of tocotrienols supplementation on inflammatory and oxidative stress biomarkers. We searched PubMed, Scopus, and Cochrane Central Register of Controlled Trials from inception until 13 July 2020 to identify randomized controlled trials supplementing tocotrienols and reporting circulating inflammatory or oxidative stress outcomes. Weighted mean difference (WMD) and corresponding 95% confidence interval (CI) were determined by pooling eligible studies. Nineteen studies were included for qualitative analysis, and 13 studies were included for the meta-analyses. A significant reduction in C-reactive protein levels (WMD: -0.52 mg/L, 95% CI: -0.73, -0.32, p < 0.001) following tocotrienols supplementation was observed, but this finding was attributed to a single study using δ-tocotrienols, not mixed tocotrienols. There were no effects on interleukin-6 (WMD: 0.03 pg/mL, 95% CI: -1.51, 1.58, p = 0.966), tumor necrosis factor-alpha (WMD: -0.28 pg/mL, 95% CI: -1.24, 0.68, p = 0.571), and malondialdehyde (WMD: -0.42 µmol/L, 95% CI: -1.05, 0.21, p = 0.189). A subgroup analysis suggested that tocotrienols at 400 mg/day might reduce malondialdehyde levels (WMD: -0.90 µmol/L, 95% CI: -1.20, -0.59, p < 0.001). Future well-designed studies are warranted to confirm the effects of tocotrienols on inflammatory and oxidative stress biomarkers, particularly on different types and dosages of supplementation. PROSPERO registration number: CRD42020198241.

Effects of CYP3A5 Polymorphism on Rapid Progression of Chronic Kidney Disease: A Prospective, Multicentre Study.

Personalised medicine is potentially useful to delay the progression of chronic kidney disease (CKD). The aim of this study was to determine the effects of CYP3A5 polymorphism in rapid CKD progression. This multicentre, observational, prospective cohort study was performed among adult CKD patients (≥18 years) with estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2, who had ≥4 outpatient, non-emergency eGFR values during the three-year study period. The blood samples collected were analysed for CYP3A5*3 polymorphism. Rapid CKD progression was defined as eGFR decline of >5 mL/min/1.73 m2/year. Multiple logistic regression was then performed to identify the factors associated with rapid CKD progression. A total of 124 subjects consented to participate. The distribution of the genotypes adhered to the Hardy-Weinberg equilibrium (X2 = 0.237, p = 0.626). After adjusting for potential confounding factors via multiple logistic regression, the factors associated with rapid CKD progression were CYP3A5*3/*3 polymorphism (adjusted Odds Ratio [aOR] 4.190, 95% confidence interval [CI]: 1.268, 13.852), adjustments to antihypertensives, young age, dyslipidaemia, smoking and use of traditional/complementary medicine. CKD patients should be monitored closely for possible factors associated with rapid CKD progression to optimise clinical outcomes. The CYP3A5*3/*3 genotype could potentially be screened among CKD patients to offer more individualised management among these patients.

Evaluation of the Pharmacokinetics and Exposure-Response Relationship of Dapagliflozin in Patients without Diabetes and with Chronic Kidney Disease.

BACKGROUND AND OBJECTIVE: Dapagliflozin, a sodium-glucose co-transporter inhibitor, was originally developed as an oral glucose-lowering drug for the treatment of type 2 diabetes mellitus. Emerging data suggest that cardiovascular and kidney benefits extend to patients without diabetes. Limited pharmacological data are, however, available in patients without diabetes. We aimed to characterise the pharmacokinetic profile of dapagliflozin in patients with chronic kidney disease without type 2 diabetes. METHODS: Plasma samples were collected in a randomised, placebo-controlled, double-blind, cross-over trial (DIAMOND, NCT03190694, n = 53) that assessed the effects of 10 mg of dapagliflozin in patients with a glomerular filtration rate ≥ 25 mL/min/1.73 m2 and proteinuria > 500 mg/day. Mixed-effects models were used to develop a pharmacokinetic model and to evaluate the association between plasma exposure and response. RESULTS: Plasma concentrations (n = 430 observations) from 48 patients (mean age 50.8 years, mean glomerular filtration rate 57.9 mL/min/1.73 m2, median proteinuria 1115 mg/24 h) were best described using a two-compartment model with first-order elimination. Apparent clearance and volume of distribution were 11.7 (95% confidence interval 10.7-12.7) L/h and 44.9 (95% confidence interval 39.0-50.9) L, respectively. Median dapagliflozin plasma exposure was 740.9 ng h/mL (2.5th-97.5th percentiles: 434.0-1615.3). Plasma exposure increased with decreasing kidney function. Every 100-ng h/mL increment in dapagliflozin plasma exposure was associated with a decrease in the urinary albumin:creatinine ratio (ß = - 2.8%, p = 0.01), glomerular filtration rate (ß = - 0.5 mL/min/1.73 m2, p < 0.01) and systolic blood pressure (ß = - 0.4 mmHg, p = 0.03). CONCLUSIONS: The dapagliflozin plasma concentration-time profile in patients with non-diabetic kidney disease appears similar to the profile of patients with diabetic kidney disease described in the literature. Furthermore, the plasma exposure was associated with changes in risk markers for kidney disease.

Validity of Ultrasound Imaging in Measuring Quadriceps Muscle Thickness and Cross-Sectional Area in Patients Receiving Maintenance Hemodialysis.

BACKGROUND: Muscle wasting, prevalent in maintenance hemodialysis (HD) patients diagnosed with protein-energy wasting, represents an assessment challenge in the outpatient HD setting. Quadriceps muscle thickness (QMT) and cross-sectional area (CSA) assessment by ultrasound (US) is a potential surrogate measure for muscle wasting. We aimed to determine the validity of US to measure QMT and CSA against the gold standard-computed tomography (CT). METHODS: Twenty-six patients on HD underwent US and CT scans on the same day, postdialysis session. QMT for rectus femoris (RF) and vastus intermedius (VI) muscles was taken at the midpoint (MID) and two-thirds (2/3) of both thighs and CSA of the RF muscle (RFCSA ), respectively. Correlation between US and CT measurements was determined by intraclass correlation coefficient (ICC) and Bland-Altman plot. RESULTS: ICC (95% CI) computed between US and CT was 0.94 (0.87-0.97), 0.97 (0.93-0.99), 0.94 (0.87-0.97), 0.94 (0.86-0.97), and 0.92 (0.83-0.97) for RFMID, VIMID, RF2/3, VI2/3 , and RFCSA , respectively (all P < 0.001). Bland-Altman analysis indicated no bias in agreement between both methods. CONCLUSION: The US imaging offers a valid and quick bedside assessment approach to assess muscle wasting in HD patients.

Muscle Status Response to Oral Nutritional Supplementation in Hemodialysis Patients With Protein Energy Wasting: A Multi-Center Randomized, Open Label-Controlled Trial.

Background: Muscle wasting, observed in patients with end-stage kidney disease and protein energy wasting (PEW), is associated with increased mortality for those on hemodialysis (HD). Oral nutritional supplementation (ONS) and nutrition counseling (NC) are treatment options for PEW but research targeting muscle status, as an outcome metric, is limited. Aim: We compared the effects of combined treatment (ONS + NC) vs. NC alone on muscle status and nutritional parameters in HD patients with PEW. Methods: This multi-center randomized, open label-controlled trial, registered under ClinicalTrials.gov (Identifier no. NCT04789031), recruited 56 HD patients identified with PEW using the International Society of Renal Nutrition and Metabolism criteria. Patients were randomly allocated to intervention (ONS + NC, n = 29) and control (NC, n = 27) groups. The ONS + NC received commercial renal-specific ONS providing 475 kcal and 21.7 g of protein daily for 6 months. Both groups also received standard NC during the study period. Differences in quadriceps muscle status assessed using ultrasound (US) imaging, arm muscle area and circumference, bio-impedance spectroscopy (BIS), and handgrip strength (HGS) methods were analyzed using the generalized linear model for repeated measures. Results: Muscle indices as per US metrics indicated significance (p < 0.001) for group × time interaction only in the ONS + NC group, with increases by 8.3 and 7.7% for quadriceps muscle thickness and 4.5% for cross-sectional area (all p < 0.05). This effect was not observed for arm muscle area and circumference, BIS metrics and HGS in both the groups. ONS + NC compared to NC demonstrated increased dry weight (p = 0.039), mid-thigh girth (p = 0.004), serum prealbumin (p = 0.005), normalized protein catabolic rate (p = 0.025), and dietary intakes (p < 0.001), along with lower malnutrition-inflammation score (MIS) (p = 0.041). At the end of the study, lesser patients in the ONS + NC group were diagnosed with PEW (24.1%, p = 0.008) as they had achieved dietary adequacy with ONS provision. Conclusion: Combination of ONS with NC was effective in treating PEW and contributed to a gain in the muscle status as assessed by the US, suggesting that the treatment for PEW requires nutritional optimization via ONS.

COVID-19 in Malaysia: exposure assessment and prevention practices among healthcare workers at a teaching hospital.

INTRODUCTION: During the second wave of the coronavirus disease 19 (COVID-19) pandemic, Malaysia reported several COVID-19 clusters related to healthcare workers. Thus, addressing and understanding the risk of exposure in healthcare workers is important to prevent future infection and reduce secondary COVID-19 transmission within the healthcare settings. In this study, we aim to assess exposure and prevention practices against COVID-19 among healthcare workers at the Hospital Canselor Tuanku Muhriz, a university teaching hospital based in Kuala Lumpur, Malaysia. METHODOLOGY: A total of 571 healthcare workers at COVID-19 and non-COVID-19 wards as well as the emergency department and laboratory staff at COVID-19 testing labs were recruited. The presence of novel human coronavirus (SARS-CoV-2) and IgM/IgG antibodies were confirmed in all healthcare workers. The healthcare workers responded to an online Google Forms questionnaire that evaluates demographic information and comorbidities, exposure and adherence to infection prevention and control measures against COVID-19. Descriptive analysis was performed using Statistical Package for the Social Sciences 24.0. RESULTS: Three healthcare workers (0.5%) tested positive for SARS-CoV-2, while the remaining 568 (99.5%) were negative. All were negative for IgM and IgG antibodies during recruitment (day 1) and follow-up (day 15). More than 90% of the healthcare workers followed infection prevention and control practices recommendations regardless of whether they have been exposed to occupational risk for COVID-19. CONCLUSIONS: The healthcare workers' high level of adherence to infection prevention practices at this hospital helped reduce and minimize their occupational exposure to COVID-19.

The chronic kidney disease perception scale (CKDPS): development and construct validation.

BACKGROUND: Chronic kidney disease has become a major health problem around the world. It displays no symptoms until the later stages. Therefore, its early detection is crucial, and a suitable intervention is necessary to halt its development. The aim of this study was to develop and validate a recently formulated Chronic Kidney Disease Perception Scale (CKDPS) for diabetic patients based on Social Psychology, and their perceptions based on the Health Belief Model (HBM). METHODS: The newly developed CKDPS instrument was tested on 300 patients with diabetes mellitus in a cross-sectional study. The number of domains, model-fit index, construct validity, and internal consistency of this instrument were determined using exploratory (EFA) and confirmatory factor analysis (CFA). RESULTS: The EFA yielded nine domains: illness identity, timeline motivation, medical practice and co-operation for Social Psychology, and perceived benefit, perceived barriers, perceived susceptibility, perceived severity, and perceived cue to action for HBM. Four items with low factor loading were removed. CFA yielded the following fit indices for Social Psychology: the goodness of fit index (GFI) = 0.889, comparative fit index (CFI) = 0.934, root mean square error of approximation (RMSEA) = 0.053, normed chi-square (NC) = 1.831; and the following for HBM: GFI = 0.834, CFI = 0.957, RMSEA = 0.053, NC = 1.830. Values of Cronbach's α ranged between 0.760 and 0.909. CONCLUSIONS: The CKDPS includes 61 questions across nine domains, divided under two categories of Social Psychology and HBM. It is also a valid and reliable tool for measuring diabetic patients' perception of CKD prevention that can be used in larger studies.

Clinical and genetic markers of erythropoietin deficiency anemia in chronic kidney disease (predialysis) patients.

Aim: To determine the clinical and genetic markers associated with erythropoietin deficiency anemia in predialysis individuals. Materials & methods: Patients were categorized into cases and control group. Demographic characteristics and clinical parameters were obtained from medical record review and serum EPO and ferritin were obtained with ELISA. HIF-1α (rs2057482), IL-1ß (rs1143627) and EPO (rs1617640) gene polymorphism were genotyped. Results: Female gender, glomerular filtration rate, treatment with hematinics, anticoagulant and diuretic were strong predictors of EPO-deficient anemia in predialysis chronic kidney disease patients. Genetic polymorphism in the HIF-1α recessive model was associated with non-EPO-deficiency, followed by EPO recessive allele associated with low-serum erythropoietin and IL-1ß recessive model with low hemoglobin level. Conclusion: EPO-deficiency anemia can be diagnosed more conveniently in the presence of biomarkers.

A Meta-Analysis on the Performance of Cystatin C- versus Creatinine-based eGFR Equations in Predicting Vancomycin Clearance.

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.

Protein-Energy Wasting Assessment and Clinical Outcomes in Patients with Acute Kidney Injury: A Systematic Review with Meta-Analysis.

Nutritional assessment is essential to identify patients with acute kidney injury (AKI) who are protein-energy wasting (PEW) and at risk of poor clinical outcomes. This systematic review aimed to investigate the relationship of nutritional assessments for PEW with clinical outcomes in patients with AKI. A systematic search was performed in PubMed, Scopus, and Cochrane Library databases using search terms related to PEW, nutrition assessment, and AKI to identify prospective cohort studies that involved AKI adult patients with at least one nutritional assessment performed and reported relevant clinical outcomes, such as mortality, length of stay, and renal outcomes associated with the nutritional parameters. Seventeen studies reporting eight nutritional parameters for PEW assessment were identified and mortality was the main clinical outcome reported. A meta-analysis showed that PEW assessed using subjective global assessment (SGA) was associated with greater mortality risk (RR: 1.99, 95% CI: 1.36-2.91). Individual nutrition parameters, such as serum chemistry, body mass, muscle mass, and dietary intakes, were not consistently associated with mortality. In conclusion, SGA is a valid tool for PEW assessment in patients with AKI, while other nutrition parameters in isolation had limited validity for PEW assessment.

Effects of the SGLT2 inhibitor dapagliflozin on proteinuria in non-diabetic patients with chronic kidney disease (DIAMOND): a randomised, double-blind, crossover trial.

BACKGROUND: SGLT2 inhibition decreases albuminuria and reduces the risk of kidney disease progression in patients with type 2 diabetes. These benefits are unlikely to be mediated by improvements in glycaemic control alone. Therefore, we aimed to examine the kidney effects of the SGLT2 inhibitor dapagliflozin in patients with proteinuric kidney disease without diabetes. METHODS: DIAMOND was a randomised, double-blind, placebo-controlled crossover trial done at six hospitals in Canada, Malaysia, and the Netherlands. Eligible participants were adult patients (aged 18-75 years) with chronic kidney disease, without a diagnosis of diabetes, with a 24-h urinary protein excretion greater than 500 mg and less than or equal to 3500 mg and an estimated glomerular filtration rate (eGFR) of at least 25 mL/min per 1·73 m2, and who were on stable renin-angiotensin system blockade. Participants were randomly assigned (1:1) to receive placebo and then dapagliflozin 10 mg per day or vice versa. Each treatment period lasted 6 weeks with a 6-week washout period in between. Participants, investigators, and study personnel were masked to assignment throughout the trial and analysis. The primary outcome was percentage change from baseline in 24-h proteinuria during dapagliflozin treatment relative to placebo. Secondary outcomes were changes in measured GFR (mGFR; via iohexol clearance), bodyweight, blood pressure, and concentrations of neurohormonal biomarkers. Analyses were done in accordance with the intention-to-treat principle. This study is registered with ClinicalTrials.gov, NCT03190694. FINDINGS: Between Nov 22, 2017, and April 5, 2019, 58 patients were screened, of whom 53 (mean age 51 years [SD 13]; 32% women) were randomly assigned (27 received dapagliflozin then placebo and 26 received placebo then dapagliflozin). One patient discontinued during the first treatment period. All patients were included in the analysis. Mean baseline mGFR was 58·3 mL/min per 1·73 m2 (SD 23), median proteinuria was 1110 mg per 24 h (IQR 730-1560), and mean HbA1c was 5·6% (SD 0·4). The difference in mean proteinuria change from baseline between dapagliflozin and placebo was 0·9% (95% CI -16·6 to 22·1; p=0·93). Compared with placebo, mGFR was changed with dapagliflozin treatment by -6·6 mL/min per 1·73 m2 (-9·0 to -4·2; p<0·0001) at week 6. This reduction was fully reversible within 6 weeks after dapagliflozin discontinuation. Compared with placebo, bodyweight was reduced by 1·5 kg (0·03-3·0; p=0·046) with dapagliflozin; changes in systolic and diastolic blood pressure and concentrations of neurohormonal biomarkers did not differ significantly between dapagliflozin and placebo treatment. The numbers of patients who had one or more adverse events during dapagliflozin treatment (17 [32%] of 53) and during placebo treatment (13 [25%] of 52) were similar. No hypoglycaemic events were reported and no deaths occurred. INTERPRETATION: 6-week treatment with dapagliflozin did not affect proteinuria in patients with chronic kidney disease without diabetes, but did induce an acute and reversible decline in mGFR and a reduction in bodyweight. Long-term clinical trials are underway to determine whether SGLT2 inhibitors can safely reduce the rate of major clinical kidney outcomes in patients with chronic kidney disease with and without diabetes. FUNDING: AstraZeneca.