Qi Chun Toh

Glomerular filtration rates in healthy Asians without kidney disease.

The Chronic Kidney Disease Collaboration – Epidemiology (CKD‐EPI) glomerular filtration rates (GFR) estimation equation is believed to estimate GFR more accurately in healthy people but this has not been validated in Asians. We studied the distribution of GFR in a multi‐ethnic Asian population without CKD, and compared the performance of measures of GFR estimation, including the CKD‐EPI equation, Cockroft‐Gault equation, and 24‐hour urine creatinine clearances.

Spot Urine Tests in Predicting 24-Hour Urine Sodium Excretion in Asian Patients

OBJECTIVE The control of hypertension is often suboptimal, and it is frequently due to excessive sodium intake. Monitoring sodium intake is cumbersome and involves 24-hour collection of urine. We hypothesize that a spot urine test can accurately predict 24-hour urine sodium excretion in an Asian population. DESIGN This is a prospective, observational study. We used stored urine specimens (n = 333) from the Asian Kidney Disease Study and Singapore Kidney Function Study Phase I. We measured spot urine tests and correlated these variables to the previously measured 24-hour urine sodium measurements. RESULTS Age, gender, ethnicity, diastolic blood pressure, height, weight, body mass index, serum creatinine, spot urine sodium, spot urine chloride, and spot urine osmolality were associated with 24-hour urine sodium excretion. The final model for predicting 24-hour urine sodium less than 100 mmol included age, gender, ethnicity, weight, and spot urine sodium. CONCLUSION Spot urine sodium can help monitor a patients sodium intake when used in the derived 5-variable equation.

Spot urine estimations are equivalent to 24-hour urine assessments of urine protein excretion for predicting clinical outcomes.

Background. The use of spot urine protein to creatinine ratios in estimating 24 hr urine protein excretion rates for diagnosing and managing chronic kidney disease (CKD) predated the standardization of creatinine assays. The comparative predictive performance of spot urine ratios and 24 hr urine collections (of albumin or protein) for the clinical outcomes of CKD progression, end-stage renal disease (ESRD), and mortality in Asians is unclear. We compared 4 methods of assessing urine protein excretion in a multiethnic population of CKD patients. Methods. Patients with CKD (n = 232) provided 24 hr urine collections followed by spot urine samples the next morning. We created multiple linear regression models to assess the factors associated with GFR decline (median follow-up: 37 months, IQR 26–41) and constructed Cox proportional-hazards models for predicting the combined outcome of ESRD and death. Results. The linear regression models showed that 24 hr urine protein excretion was most predictive of GFR decline but all other methods were similar. For the combined outcomes of ESRD and death, the proportional hazards models had similar predictive performance. Conclusions. We showed that all methods of assessments were comparable for clinical end-points, and any method can be used in clinical practice or research.

Serum Leptin and Age-Related Macular Degeneration

PURPOSE Leptin, a 167-amino acid protein secreted by adipocytes, has been shown to reduce beta-amyloid deposition and intracellular lipid concentration in animal models, two key pathogenic mechanisms underlying aging. We examined the association between serum leptin levels and AMD. METHODS We conducted a population-based case-control study including Chinese and Indian adults aged 40 to 80 years who participated in the Singapore Epidemiology of Eye Diseases Study (2007-2011). Age-related macular degeneration was assessed from retinal photographs graded using a modified Wisconsin Age-Related Maculopathy Grading System (n = 426; early = 389, late = 37). Controls (n = 927) without AMD were frequency matched for age, sex, and ethnicity. Serum leptin levels were measured using direct sandwich ELISA. RESULTS Participants with AMD had lower levels of leptin compared with those without (mean [SD] = 10.0 [11.5] ng/mL versus 12.9 [16.4] ng/mL; P = 0.001). Mean levels of leptin among those with late, early, and without AMD were 8.8, 10.1, and 12.9 ng/mL (P trend = 0.005). In multivariable models adjusting for potential confounders, including smoking, body mass index, blood pressure, and high-density lipoprotein cholesterol, increasing quartiles of leptin were associated with lower odds of AMD, odds ratio (95% confidence interval) of AMD was 0.56 (0.34-0.92) comparing highest to lowest quartile of serum leptin. In subgroup analyses, the inverse association between leptin and AMD was significant in women, Indian ethnicity, and ex-smokers. CONCLUSIONS Higher serum leptin levels were inversely associated with AMD. These findings, if confirmed in prospective studies, may provide insights into new pathogenic pathways and possibly therapeutic targets in AMD.

Comparison of CKD-EPI Cystatin C and Creatinine Glomerular Filtration Rate Estimation Equations in Asian Indians

Background. Chronic kidney disease (CKD) is identified in the general population using estimated glomerular filtration rates (eGFR) calculated from a serum creatinine-based equation, the chronic kidney disease-epidemiology collaboration (CKD-EPI) equation. Using serum cystatin C in combination may improve eGFR accuracy. We evaluated the new CKD-EPI equations incorporating cystatin C in a population of Asian Indians in classifying CKD across body mass index, diabetes, and hypertension status. Methods. We retrieved standardized serum creatinine and serum cystatin C data from a cohort of 2877 Asian Indians aged 40–80 years from the Singapore Indian Eye Study and calculated eGFR (in mL/min/1.73 m2) with the new CKD-EPI equations and serum creatinine only equation. Results. The creatinine only equation mean eGFR (88 ± 17) was similar to using spline Log cystatin C (88 ± 22). The lowest mean eGFR (81 ± 21) was obtained with the spline Log cystatin C—age, sex, and weight equation. The creatinine only equation had the fewest participants (7.1%) with eGFR <60 and spline Log cystatin C—age, sex, and weight equation had the most (16.1%). Conclusions. Using serum cystatin C resulted in widely varying eGFR which significantly affected the classification of chronic kidney disease.

Serum high-sensitivity troponin concentrations in a multi-ethnic Asian population of stable chronic kidney disease patients

*Corresponding author: Boon Wee Teo, MB, BCh, FASN, Assistant Professor, Yong Loo Lin School of Medicine, Department of Medicine, National University of Singapore, 1E Kent Ridge Road, Level 10 NUHS Tower Block, Singapore 119228, Singapore, Phone: +65 6772 2544, Fax: +65 6779 4112, E-mail: mdctbw@nus.edu.sg. http://orcid.org/0000-0002-4911-8507 Titus Lau and Horng Ruey Chua: Department of Medicine, National University Health System, Singapore Qi Chun Toh, Weng Kin Wong, Sabrina Haroon and Srinivas Subramanian: Yong Loo Lin School of Medicine, Department of Medicine, National University of Singapore Sharon Saw: Department of Laboratory Medicine, National University Hospital, Singapore Sunil Sethi: Yong Loo Lin School of Medicine, Department of Pathology, National University of Singapore Letter to the Editor

Assessment of Muscle Mass and Its Association with Protein Intake in a Multi-Ethnic Asian Population: Relevance in Chronic Kidney Disease

BACKGROUND Clinical practice guidelines recommend objective nutritional assessments in managing chronic kidney disease (CKD) patients but were developed while referencing to a North-American population. Specific recommendations for assessing muscle mass were suggested (mid-arm circumference, MAC; corrected mid-arm muscle area, cAMA; mid-arm muscle circumference, MAMC). This study aimed to assess correlation and association of these assessments with dietary protein intake in a multi-ethnic Asian population of healthy and CKD patients. METHODS We analyzed 24-hour urine collections of selected participants to estimate total protein intake (TPI; g/day). Ideal body weight (IDW; kg) was calculated and muscle assessments conducted. Analyses involved correlation and linear regression, taking significance at p<0.05. RESULTS There were 232 stable CKD patients and 103 healthy participants comprising of 51.0% male, 38.5% Chinese, 29.6% Malay, 23.6% Indian, and 8.4% others. The mean TPI was 58.9 ± 18.4 g/day in healthy participants and 53.6 ± 19.4 g/day in CKD patients. When normalized to ideal body weight, TPI-IDW (g/kg/day) was similar in healthy and CKD participants. Overall, TPI was associated with MAC (r=0.372, p<0.001), cAMA (r=0.337, p<0.001), and MAMC (r=0.351, p<0.001). TPI-IDW was also associated with MAC (r=0.304, p<0.001), cAMA (r=0.202, p<0.001), and MAMC (r=0.200, p<0.001) but not for TPI normalized to actual body weight. When examined separately, TPI was associated with MAC, cAMA, and MAMC in both CKD and healthy participants, but was associated with TPI-IDW only in CKD patients. CONCLUSION Total protein intake was associated with muscle assessments in all participants. TPI normalized to IDW should only be used in CKD patients.

Comparison of Different Measures of Fat Mass and Their Association with Serum Cystatin C Levels

Introduction. Cystatin C (CysC) is a glomerular filtration rate (GFR) marker affected by GFR and obesity. Because percentage body fat (%BF) distribution is affected by ethnicity, different measures of %BF may improve CysC prediction. This study aims to create multivariate models that predict serum CysC and determine which %BF metric gives the best prediction. Methods. Serum CysC was measured by nephelometric assay. We estimated %BF by considering weight, body mass index, waist-hip ratio, triceps skin fold, bioimpedance, and Deurenberg and Yap %BF equations. A base multivariate model for CysC was created with a %BF metric added in turn. The best model is considered by comparing values, , Akaike information criterion (AIC), and Bayesian information criterion (BIC). Results. There were 335 participants. Mean serum CysC and creatinine were 1.27 mg/L and 1.44 mg/dL, respectively. Variables for the base model were age, gender, ethnicity, creatinine, serum urea, c-reactive protein, log GFR, and serum albumin. %BF had a positive correlation with CysC. The best model for predicting CysC included bioimpedance-derived %BF ( ), with the highest (0.917) and the lowest AIC and BIC (−371, −323). Conclusion. Obesity is associated with CysC, and the best predictive model for CysC includes bioimpedance-derived %BF.