Srinivas Subramanian

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.

‘Should we consider renaming ‘Mesoamerican Nephropathy’ as Nephropathy of Unknown Cause in Agricultural Labourers (NUCAL)?’

Mesoamerican nephropathy (MAN) refers to a kidney disease that primarily afflicts male labourers (usually in the agricultural sector) and has been mainly identified in regions of Central America. While the global prevalence and incidence is not known, in the regions where the condition has been recognised, the prevalence has been noted to be between 10% and 15%. Nearly 20 000 deaths have been attributed to this condition from El Salvador alone. The aetiology is unclear. It is thought to be contributed to by dehydration, malnutrition, fructose ingestion, electrolyte imbalance, pesticides, environmental toxins and heat injury. The role of genetics or other patient factors is unclear. Clusters of kidney disease with similar presentation have been identified in agricultural labourers in India, Egypt and Sri Lanka. The histopathology of this condition is characterised by interstitial fibrosis and tubular atrophy with glomerulosclerosis similar to that from Central America. The term MAN does not reflect the fact that this condition likely occurs beyond the confines of Central America. The term chronic kidney disease of unknown aetiology is very broad and includes kidney disease due to diverse aetiologies such as chronic glomerulonephritis, a kidney disease from a recognised condition that was not correctly diagnosed in the patient and so on. A better term may be Nephropathy of Unknown Cause in Agricultural Labourers (NUCAL). Even this term may be suboptimal as this does not say much about the pathogenesis of the condition. Once the aetiology of the condition is elucidated appropriate renaming may take place. Appropriate nomenclature is essential to the patients and science. By labelling this condition as NUCAL, the nephrology community will be recognising this as an occupational hazard for labourers in the agricultural sector. Second, it will be possible to track the cases from parts of the world outside of Central America to help understand the prevalence and incidence of this important condition. Third, by putting these cases from different continents in one basket, it will be possible to study if similar factors are in play in the aetiology and pathogenesis of this condition or if distinct factors play a role in different regions of the world and in different populations. Much needs to be done to serve these economically disadvantaged and vulnerable populations working in this vital economic sector. History has taught us that when we have an ‘occupational health’ approach to a medical condition, it raises the awareness of the disease, and leads to better protection of the workers in the form of preventive measures and appropriate compensation to those who are affected. The recognition of ‘Coal Workers Pneumoconiosis’ or ‘Black Lung’ is one example. There may be various barriers to recognition, treatment, registration of cases and conduct of research such as economics, politics and lack of political will, lack of awareness and education, action from special interest groups and different causes competing for limited resources. We need to act in a timely and effective manner to surmount these barriers. Appropriate nomenclature will help in fostering global awareness and international action.

A Score for Predicting Acute Kidney Injury After Coronary Artery Bypass Graft Surgery in an Asian Population.

OBJECTIVE To develop a scoring system to predict acute kidney injury in Asian patients after coronary artery bypass grafting. DESIGN A retrospective analysis of data collected in an institutional cardiac database. SETTING A tertiary academic hospital in a large metropolitan city. PARTICIPANTS The study comprised 954 patients with coronary artery disease. INTERVENTIONS All patients underwent coronary artery bypass surgery with cardiopulmonary bypass but did not undergo any other concomitant procedures. MEASUREMENTS AND MAIN RESULTS The main outcome measured was acute kidney injury as defined by the Acute Kidney Injury Network criteria. The following 6 clinical variables were independent predictors of kidney injury: age>60 years, diabetes requiring insulin, estimated glomerular filtration rate<60 mL/min/1.73 m(2), ejection fraction<40%, cardiopulmonary bypass time>140 minutes, and aortic cross-clamp time>100 minutes. These variables were used to develop the Singapore Acute Kidney Injury score. CONCLUSION The Singapore Acute Kidney Injury score is a simple way to predict, at the time of admission to the intensive care unit, an Asian patients risk of developing acute kidney injury after coronary artery bypass surgery.

Reliable quantification of the potential for equations based on spot urine samples to estimate population salt intake: protocol for a systematic review and meta-analysis.

Background Methods based on spot urine samples (a single sample at one time-point) have been identified as a possible alternative approach to 24-hour urine samples for determining mean population salt intake. Objective The aim of this study is to identify a reliable method for estimating mean population salt intake from spot urine samples. This will be done by comparing the performance of existing equations against one other and against estimates derived from 24-hour urine samples. The effects of factors such as ethnicity, sex, age, body mass index, antihypertensive drug use, health status, and timing of spot urine collection will be explored. The capacity of spot urine samples to measure change in salt intake over time will also be determined. Finally, we aim to develop a novel equation (or equations) that performs better than existing equations to estimate mean population salt intake. Methods A systematic review and meta-analysis of individual participant data will be conducted. A search has been conducted to identify human studies that report salt (or sodium) excretion based upon 24-hour urine samples and spot urine samples. There were no restrictions on language, study sample size, or characteristics of the study population. MEDLINE via OvidSP (1946-present), Premedline via OvidSP, EMBASE, Global Health via OvidSP (1910-present), and the Cochrane Library were searched, and two reviewers identified eligible studies. The authors of these studies will be invited to contribute data according to a standard format. Individual participant records will be compiled and a series of analyses will be completed to: (1) compare existing equations for estimating 24-hour salt intake from spot urine samples with 24-hour urine samples, and assess the degree of bias according to key demographic and clinical characteristics; (2) assess the reliability of using spot urine samples to measure population changes in salt intake overtime; and (3) develop a novel equation that performs better than existing equations to estimate mean population salt intake. Results The search strategy identified 538 records; 100 records were obtained for review in full text and 73 have been confirmed as eligible. In addition, 68 abstracts were identified, some of which may contain data eligible for inclusion. Individual participant data will be requested from the authors of eligible studies. Conclusions Many equations for estimating salt intake from spot urine samples have been developed and validated, although most have been studied in very specific settings. This meta-analysis of individual participant data will enable a much broader understanding of the capacity for spot urine samples to estimate population salt intake.

Description of an Urgent-Start Peritoneal Dialysis Program in Singapore

500 A vast majority of patients with end-stage renal disease (ESRD) starts dialysis sub-optimally in an unplanned manner (1). These patients either present late or have an acute or unexpected deterioration of renal function resulting in the urgent need for dialysis. Consequently, 60 – 70% of patients who progress to ESRD do not have a functioning access at the time of dialysis initiation. Hemodialysis (HD) through a central venous catheter (CVC) is the default dialysis modality for such patients (1). In spite of the fact that starting HD with a CVC is independently associated with increased mortality, high rates of bacteremia, and increased hospitalization rates (2,3), peritoneal dialysis (PD) is rarely considered a practical option for urgent initiation of dialysis. Inability to create rapid PD access, lack of standards and protocols, worries about catheter leakages, relative ease of CVC insertion, and physicians’ preferences are the usual stumbling blocks. A majority of such patients subsequently stays on HD, as PD is rarely presented as an option once HD therapy is established, even to the patients who would otherwise have been considered excellent candidates for PD. As a result, the number of patients on PD remains unacceptably low worldwide (4). In Singapore, the percentage of ESRD patients on PD has steadily declined, from over 20% in 2002 to less than 15% in 2014 (5). Regardless of the method of PD catheter insertion (surgical, peritoneoscopic, or percutaneous), a waiting period of 2 to 4 weeks is usually recommended before dialysis initiation. This break-in period is considered vital to minimize the risk of catheter-related complications, especially the pericatheter or incisional leaks. Dialysate leakage has been reported in 15% to 37% of PD patients and is most common within 2 weeks of PD catheter insertion with conventional PD initiation (6,7). Urgent-start PD, defined as the initiation of dialysis using a modified prescription within 2 weeks of PD catheter insertion, is increasingly viewed as a practical and suitable option for ESRD patients who need to start dialysis urgently (6,7,8). Initiation of PD, even in late-presenting patients, can result in a reduced number of subsequent procedures, better preservation of residual renal function, better quality of life, and reduced overall cost of dialysis (9,10). Recent studies have shown that PD is a safe and efficient alternative to HD in acute unplanned dialysis settings. There is no significant difference in patient survival between the 2 modalities. The incidence of dialysis-related complications, especially bacteremia, is much lower in PD than in HD patients (11). Others have shown comparable outcomes and complication rates between urgentand elective-start PD (12). However, urgent-start PD has its unique logistical requirements. A successful urgent-start PD program requires the establishment of specific infrastructure, protocols, and clinical pathways involving multiple healthcare professionals and support staff. In this article, we describe our experience of developing an urgent-start PD program in a Singapore center. We believe that our urgent-start PD program can serve as a framework to develop similar services in other centers in our region. Before July 2015, all our incident PD patients were planned. All PD catheters were placed by urologists, predominantly using the laparoscopic method. Peritoneal dialysis training was typically started 2 to 4 weeks after catheter insertion. All patients needing urgent initiation of dialysis received HD through a CVC. An urgent-start PD program was initiated in July 2015 involving a lead urgent-start PD nephrologist, an interventional nephrologist certified to place percutaneous PD catheters under fluoroscopic guidance, a lead urgent-start PD nurse and a PD coordinator. In the planning phase, a comprehensive outline of the program was developed. The logistical, operational, and staffing requirements were identified. The essential elements included an adequate outpatient space and beds to provide low-volume PD exchanges; a mechanism to ensure rapid PD catheter insertions; a suitable number of PD nurses to supervise low-volume PD exchanges in both inpatient and outpatient settings; a dedicated outpatient clinic for rapid assessments and follow-up of patients; and a PD coordinator to streamline the pathway. Details of specific equipment and supplies required such as PD catheters, transfer sets, PD solutions, and PD catheter insertion set were specified. Nursing support was secured by providing education about urgent-start PD and involving them in the design of protocols and policies to assist in the management of urgent-start PD patients. Medical social worker support was ensured for fast-tracked financial assistance for patients entering the program on short notice. Detailed workflows, protocols, and urgent-start PD prescriptions were developed. A comprehensive framework for patient monitoring and followup was established to ensure patient safety (supplementary online material). A business case was then presented to the hospital’s senior management. The potential benefits to the patients and the institution were highlighted, including the possible reduction in the use of CVC and related blood stream infections, reduced hospitalizations, decreased length of stay, increased patient choice and satisfaction, increased PD uptake, and reduced dialysis cost to the patients and institution. An interventional nephrology program for percutaneous insertion of PD catheters under fluoroscopic guidance was developed to ensure rapid and timely placement of PD Supplemental material available at www.pdiconnect.com DESCRIPTION OF AN URGENT-START PERITONEAL DIALYSIS PROGRAM IN SINGAPORE

Peritoneal Dialysis as the Dialysis Initial Modality of Choice for Renal Replacement Therapy Initiation: Moving from "why" to "why Not"

costs associated with ambulance and para-transit to and back from the HD centers can be significant. PD wins over HD in the arena of convenience to the patients. PD is done in the comfort of the patient’s home and allows them a limited degree of flexibility. HD requires the patients to stick to a rigid schedule in most instances. It requires commuting to the dialysis center and back except in those who are on home HD. Preservation of RRF should be an important goal for every nephrologist. The presence of RRF is associated with lesser mortality, lesser need for hospitalizations and can help in clearance of “middle molecules” that are not well cleared by conventional HD. PD correlates with better preservation of RRF. This may, in part, explain the mortality advantage that PD patients enjoy especially in the early years after initiation of PD [6] . Despite the above evidence, the prevalent practice remains that when a hospitalized patient requires timely initiation of RRT, HD is the preferred modality. This is despite the evidence that PD can be initiated in a timely and effective manner. Patients who are initiated on PD urgently tend to stay on PD long term. When HD is initiated urgently, this is done so through a tunneled or a nontunneled dialysis catheter. The use of dialysis catheter comes with additional risks of catheter-related blood We nephrologists have been trained to offer peritoneal dialysis (PD) as a comparable option for renal replacement therapy (RRT) on par with hemodialysis (HD). This is understandable in the era of “expert opinions” and “customer is king” culture where a shopper can go to a grocer and choose from any of the multitude of options available for something like fat-free milk. The authors are however perturbed by the unfair treatment that PD gets despite evidence that suggests that it is comparable in outcomes [1] but superior in costs [2] , convenience, preservation of residual renal function (RRF) [3] and delivering a better quality of life [4] . In our opinion, PD should be offered as the default option to the patient requiring RRT and HD considered in patients who have either contraindications to PD or in patients who feel that PD is not right for them. End-stage renal disease affects the socioeconomically disadvantaged sections of the society disproportionately in the developed world. Dialysis costs impose a financial strain in a large proportion of these patients [5] . In addition to costs to the individual, dialysis also imposes a significant burden on the economies of countries. In different contexts where costs have been studied, PD was found to be cost effective when compared with HD [2] . For those with higher dependency and limited mobility, the Received: March 20, 2017 Accepted: April 2, 2017 Published online: April 28, 2017

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

Should antiviral monotherapy with nucleotide analogs be the primary treatment option for focal segmental glomerulosclerosis-related nephrotic syndrome in chronic hepatitis B infection?

Renal involvement is the most common extrahepatic manifestation of chronic hepatitis B virus (HBV) infection. While membranous nephropathy is the most frequent, the association with focal segmental glomerulosclerosis (FSGS) is not as strong, and only a few cases have been described in the literature. In particular, the tip variant FSGS is extremely rare and to our knowledge has not previously been described in association with chronic HBV infection. The management of such cases can be challenging. Immunosuppression may lead to enhanced viral replication and flare-up of the hepatic disease. Antiviral treatment has been reported to induce remission in hepatitis B-associated glomerulonephritis in a few cases. However, their use is primarily restricted to the treatment of associated liver disease, and the current guidelines do not provide specific recommendations on HBV-mediated kidney disease in the absence of hepatic involvement. We describe a case of nephrotic syndrome due to secondary tip variant FSGS in a patient with chronic HBV infection who went into complete remission with antiviral therapy alone and present an argument for the use of oral antiviral agents as the primary treatment option for FSGS-related nephrotic syndrome in chronic HBV-infected patients without progressive liver disease.

A Case To Swap Hemodialysis Catheters For Peritoneal Dialysis Catheters in Late-Presenting End-Stage Renal Disease

Editor: Up to 70% of end-stage renal disease (ESRD) patients start dialysis in an unplanned manner without a definitive functioning dialysis access. Hemodialysis (HD) through a central venous catheter (CVC) is the default initial dialysis modality for a majority of such patients (1). This is despite the fact that starting HD through a CVC is independently associated with adverse outcomes and reduced survival. A recent extensive Canadian observational study involving nearly 50,000 incident dialysis patients showed that patients starting HD via a CVC had 80% higher mortality at 1 year as compared with those who began HD through a functioning atriovenous fistula (AVF) or an atriovenous graft (AVG). Survival on peritoneal dialysis (PD) was similar to HD via AVF/AVG in this group of patients. These relationships persisted over a follow-up period of 5 years (2). Furthermore, patients starting HD via a CVC are also more likely to have subsequent dialysis access-related complications, higher incidences of bloodstream infections, a higher number of emergency room visits, and more frequent hospital admissions as compared with PD and HD via AVF/AVG (3). Central venous catheter use can also hamper the maturation of AVF/ AVG and lead to complications such as central venous stenosis, which can often lead to failure of AVF/AVG and make further vascular access creation somewhat tricky. Despite the apparent advantages, PD has not traditionally been considered a viable option for late-presenting ESRD patients. It is usually believed that PD cannot be initiated until at least 2 weeks after the insertion of a PD catheter. Worries about potential complications such as catheter leaks, inability to establish a timely PD access, relative ease to insert HD catheters, and lack of experience in the urgent initiation of PD have been some of the common reasons for not offering PD to late-presenting ESRD patients (1). However, in the last few years, some physicians have tried to clarify these misconceptions. A few reports, including the one by the authors, describing protocols to initiate PD immediately after the insertion of a PD catheter, using modified prescriptions, have been published in the literature (1,4). Our experience and that of others have shown that urgent-start PD is a viable and effective option for latepresenting ESRD patients and can be a safe alternative to HD via CVC. Urgent-start PD has been shown to be as efficient as conventional-start PD, with comparable shortand long-term outcomes. In particular, urgent-start PD is not associated with increased hospitalizations, a higher number of mechanical complications, and greater mortality or technique failure rates than conventional-start PD (1,4). Studies have also shown that urgent PD is comparable to urgent HD regarding effectiveness and efficiency. More importantly, urgent-start PD has been shown to have a significantly lower rate of dialysis-related complications, substantially less probability of bloodstream infections, lesser need for subsequent procedures, and fewer catheter reinsertions as compared with urgent HD via CVC (5,6). Moreover, urgent-start PD is more economical than urgentstart HD via a CVC. Liu et al. reported that the estimated cost of urgent-start PD in the United States over the first 90 days was