Intravesical Bacillus Calmette-Guerin and its complications: 12 years of learning experience in a single local institution.

INTRODUCTION: Intravesical Bacillus Calmette-Guerin (BCG) therapy is the standard adjuvant treatment for non-muscle-invasive bladder carcinoma (NMIBC) with carcinoma in situ, in addition to tumour resection. We aimed to study BCG complications that preclude adequate treatment of NMIBC in an Asian population. METHODS: This retrospective study was conducted using a large, prospectively maintained bladder cancer database. 336 patients received intravesical BCG therapy for bladder cancer in our institution between 2004 and 2016, with an average follow-up duration of 63 months. RESULTS: The study included 258 (76.8%) male and 78 (23.2%) female patients. The median age of the patients at diagnosis of bladder cancer was 69 (range 17-94) years, and the median number of BCG instillations was 6 (range 1-27). 52 (15.5%) patients received maintenance therapy. The most common complications included urinary tract infection with/without sepsis (n = 18, 5.4%), haematuria (n = 9, 2.7%) and acute urinary retention (n = 4, 1.2%). 93.3% of the patients with complications presented early, within one month of completion of therapy. 22 out of 30 complications were Clavien-Dindo grade ≤ 2. 10 (33.3%) patients were admitted to hospital because of BCG-related adverse effects. The most common reasons for termination were urosepsis (2/30, 6.7%) and acute urinary retention (2/30, 6.7%). Patients aged ≥ 80 years at diagnosis were at higher risk of developing BCG-related complications (19.0% vs. 7.5%, p = 0.01). CONCLUSION: This retrospective cohort and subgroup study showed that intravesical BCG therapy is well tolerated and has a low incidence of complications even in the elderly and patients with multiple comorbidities.

Dietary Protein Intake in a Multi-ethnic Asian Population of Healthy Participants and Chronic Kidney Disease Patients.

INTRODUCTION: Clinical practice guidelines recommend different levels of dietary protein intake in predialysis chronic kidney disease (CKD) patients. It is unknown how effectively these recommendations perform in a multi-ethnic Asian population, with varied cultural beliefs and diets. We assess the profi le of protein intake in a multi-ethnic Asian population, comparing healthy participants and CKD patients. MATERIALS AND METHODS: We analysed the 24-hour urine collections of the Asian Kidney Disease Study (AKDS) and the Singapore Kidney Function Study (SKFS) to estimate total protein intake (TPI; g/day). We calculated ideal body weight (IDW; kg): 22.99 × height2 (m). Standard statistical tests were applied where appropriate, and linear regression was used to assess associations of continuous variables with protein intake. RESULTS: There were 232 CKD patients and 103 healthy participants with 35.5% diabetics. The mean TPI in healthy participants was 58.89 ± 18.42 and the mean TPI in CKD patients was 53.64 ± 19.39. By US National Kidney Foundation (NKF) guidelines, 29/232 (12.5%) of CKD patients with measured glomerular filtration rate (GFR) <25 (in mL/min/1.73 m2) had a TPI-IDW of <0.6 g/kg/day. By Caring for Australasians with Renal Impairment (CARI) guidelines, 76.3% (177/232) of CKD patients had TPI-IDW >0.75g/kg/ day. By American Dietetic Association (ADA) guidelines, 34.7% (44/127) of CKD patients with GFR <50 had TPI-IDW between 0.6 to 0.8 g/kg/day. Only 1/6 non-diabetic CKD patients with GFR <20 had a protein intake of between 0.3 to 0.5 g/kg/day. A total of 21.9% (25/114) of diabetic CKD patients had protein intake between 0.8 to 0.9 g/kg/day. CONCLUSION: On average, the protein intake of most CKD patients exceeds the recommendations of guidelines. Diabetic CKD patients should aim to have higher protein intakes.

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.

Normalisation of urinary biomarkers to creatinine for clinical practice and research--when and why.

Acute kidney injury (AKI) and chronic kidney disease (CKD) are major health problems. Urinary biomarkers have both diagnostic and prognostic utility in AKI and CKD. However, how biomarker excretion rates should be reported, especially whether they should be normalised to urinary creatinine concentration (uCr), is controversial. Some studies suggest that normalisation to uCr may be inappropriate at times, as urinary creatinine excretion rate may vary greatly, depending on the situation. Notably, recent studies suggest that while normalisation of values to UCr may be valid for the evaluation of CKD and prediction of AKI sequelae and occurrences, it could be inappropriate for the diagnosis of AKI, or in the presence of certain acute kidney disease states.

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.

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 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 m(2)) 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.

Glomerular filtration rates in healthy Asians without kidney disease.

AIM: 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. MATERIALS AND METHODS: A total of 103 healthy volunteers without a history of kidney disease, hypertension, or diabetes underwent GFR measurement using 3-sample plasma clearance of (99m) Tc-DTPA. Cockroft-Gault estimated GFR and 24-hour urine creatinine clearances were normalized to body surface area. RESULTS: The mean measured GFR was 101 ± 15.8 mL/min per 1.73 m(2) and was lowest in Indians (93 ± 12.3 mL/min per 1.73 m(2); P < 0.001). The CKD-EPI equation appears to be more accurate for healthy participants. Estimated GFR correlated with measured GFR (r = 0.57, P < 0.001), and the mean difference is 3.72 ± 14.43 mL/min per 1.73 m(2) (P < 0.001). However, estimating GFR using self-directed 24-hour urine creatinine clearances is poorer than using the CKD-EPI equation. CONCLUSIONS: GFR estimation using self-directed 24-hour urine collection for creatinine clearance is less accurate than using the CKD-EPI equation. A larger study is required to clarify GFR in healthy Asians, and the association of health outcomes of Asian kidney donors with lower GFR thresholds.

Dietary sodium intake in a multiethnic Asian population of healthy participants and chronic kidney disease patients.

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.

Performance of the CKD-EPI creatinine-cystatin C glomerular filtration rate estimation equations in a multiethnic Asian population.

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.

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 patient's sodium intake when used in the derived 5-variable equation.

Identification of cellular membrane proteins interacting with hepatitis B surface antigen using yeast split-ubiquitin system.

Hepatitis B surface antigen (HBsAg) is the major component of the envelope of hepatitis B virus (HBV). As a resident membrane protein in the endoplasmic reticulum, it plays a key role in the viral morphogenesis. Little is known about cellular proteins that interact with HBsAg and thereby contributing to HBV morphogenesis. Using the yeast split-ubiquitin system, a number of cellular membrane proteins have been isolated in this study. These include a resident protein of endoplasmic reticulum (thioredoxin-related transmembrane protein 2), an adaptor protein involved in clathrin-mediated endocytosis and HIV-mediated downregulation of CD4, and a co-receptor of coxsakie B virus. The significance of our findings is suggested by the identification of cellular membrane proteins interacting with other virus proteins. Further functional analysis of these HBsAg- interacting cellular membrane proteins should shed new insights on their role in HBV morphogenesis.