Death and cardiovascular outcomes in end-stage renal failure patients on different modalities of dialysis

INTRODUCTION@#Cardiovascular morbidity and mortality in end-stage renal failure (ESRF) patients are high. We examined the incidence and predictors of death and acute myocardial infarction (AMI) in ESRF patients on different modalities of dialysis.@*METHOD@#Data were obtained from a population-based database (National Registry Disease Offices) in Singapore. The study cohort comprised all adult patients initiated on dialysis between 2007 and 2012 who were closely followed for the development of death and AMI until September 2014. Cox regression methods were used to identify predictors of death and AMI.@*RESULTS@#Of 5,309 patients, 4,449 were on haemodialysis and 860 on peritoneal dialysis (PD). Mean age of the cohort was 61 (±13) years (44% women), of Chinese (67%), Malay (25%) and Indian (7%) ethnicities. By September 2014, the incidence of all-cause death was 34%; close to a third of the patients died from a cardiovascular cause. Age >60 years and the presence of ischaemic heart disease, diabetes, stroke, peripheral vascular disease and PD were identified as independent predictors of all-cause death. PD patients had lower odds of survival compared to patients on haemodialysis (hazard ratio 1.51, 95% confidence interval 1.35-1.70, P<0.0001). Predictors of AMI in this cohort were older age (>60 years) and the presence of ischaemic heart disease, diabetes, stroke, peripheral vascular disease and current/ex-smokers. There were no significant differences in the incidence of AMI between patients on PD and haemodialysis.@*CONCLUSION@#The short-term incidence of death and AMI remains high in Singapore. Future studies should investigate the benefits of a tighter control of cardiovascular risk factors among ESRF patients on dialysis.

Age and diabetes mellitus associated with worse outcomes after percutaneous coronary intervention in a multi-ethnic Asian dialysis patient population

INTRODUCTION@#There is limited literature on clinical outcomes following percutaneous coronary intervention (PCI) in Asian dialysis patients. We evaluated the angiographic characteristics and clinical outcomes of dialysis patients treated with PCI in an Asian society.@*METHODS@#A retrospective analysis was performed of 274 dialysis patients who underwent PCI in a tertiary care institution from January 2007 to December 2012. Data on clinical and angiographic characteristics was collected. The primary endpoint was major adverse cardiac events (MACE), defined as a composite of cardiac death, acute myocardial infarction (AMI) and stroke at two years.@*RESULTS@#274 patients (65.0% male, median age 62.0 years) with 336 lesions (81.8% Type B2) were treated. 431 stents (35.0% drug-eluting stents) with a mean diameter of 2.96 mm and mean length of 21.30 mm were implanted. The MACE rate was 55.8% (n = 153) at two years, from death (36.5%) and AMI (35.0%). In multivariable analysis, age and diabetes mellitus were significant predictors of both mortality (odds ratio [OR] 1.09, 95% confidence interval [CI] 1.05-1.12, p < 0.001; OR 2.65, 95% CI 1.46-4.82, p = 0.001, respectively) and MACE (OR 1.06, 95% CI 1.03-1.08, p < 0.001; OR 1.84, 95% CI 1.07-3.15, p = 0.027, respectively). Left ventricular ejection fraction (LVEF) (OR 0.97, 95% CI 0.95-0.99, p = 0.006) was a significant predictor of mortality but not MACE.@*CONCLUSION@#Asian dialysis patients who underwent PCI had a two-year MACE rate of 55.8% due to death and AMI. Age, LVEF and diabetes mellitus were significant predictors of mortality at two years.

Prevalence of hepatitis C virus infection and the IL28B genotype polymorphism among blood donors and high-risk populations

INTRODUCTION@#To study the prevalence of hepatitis C virus (HCV) infection in blood donor (BD), haemodialysis (HD) and intravenous drug user (IVDU) populations in Singapore and assess the IL28B polymorphism if HCV positive.@*METHODS@#The BD population were healthy volunteers, the HD population were patients who were on haemodialysis for at least six months of follow-up between January 2009 and December 2014. IVDU population was from inmates at halfway houses who consented.@*RESULTS@#Between 2011 and 2014, of 161,658 individuals who underwent screening prior to blood donation, 95 (0.059%) were positive for HCV. Of the 42 sera available, common genotypes (GTs) were GT-3 (47.6%) and GT-1 (31.0%). Of 1,575 HD patients, 2.2% were anti-HCV positive. The HCV GT distribution was HCV GT-1 (32.4%), HCV GT-3 (20.5%) and GT-6 (8.8%). 83 halfway house inmates were screened. Of the 47 IVDUs, 36.2% were anti-HCV positive with predominant GT-3 (%). IL28B polymorphism was noted to be CC predominantly 85.3%.@*CONCLUSION@#Prevalence of HCV infection has decreased in both the BD and HD populations. However, it remains high in the IVDU population. GT-1 remains the most common in the HD population; however, GT-3 infection is now more common among the BD population in Singapore. IL28B - CC is the predominant variant among the HCV-infected individuals in Singapore.

Percutaneous Endovascular Treatment to Salvage Non-Maturing Arteriovenous Fistulas in a Multiethnic Asian Population

<p><b>INTRODUCTION</b>An arteriovenous fistula (AVF) is the preferred method for haemodialysis in patients with end-stage renal failure. Previous studies have shown value in attempting percutaneous transluminal angioplasty (PTA) to salvage AVFs that fail to mature, but they are relatively small in size and mainly reported in Western populations. We reviewed our data of PTA in non-maturing AVFs to establish whether this technique is translatable to our local multiethnic population.</p><p><b>MATERIALS AND METHODS</b>We retrospectively reviewed the medical records and procedural images of 105 patients who had PTA for non-maturing AVFs performed at our department from January 2008 to January 2011. Technical success was defined as ≤30% residual stenosis after angioplasty. Clinical success was defined as at least 1 successful haemodialysis session within 4 weeks after PTA.</p><p><b>RESULTS</b>All 105 patients underwent angioplasty for at least 1 haemodynamically significant stenosis. Six (5.7%) had additional embolisation of accessory veins. Technical success was achieved in 95.2% of cases. The clinical success rate was 76.2%. Primary patency rates at 3, 6 and 12 months were 83%, 45% and 28%, respectively. Secondary patency rates at 3, 6 and 12 months were 90%, 79% and 70%, respectively. The minor complication rate was 18.1%. No major complications were encountered. An average of 1.7 interventions per access-year was required to maintain AVF patency. Patients with a preoperative vein size >2.0 mm and age <55 years were more likely to achieve clinical success, although not statistically significant.</p><p><b>CONCLUSION</b>PTA is a viable option to help salvage non-maturing AVFs in a multiethnic Asian population.</p>

Percutaneous transluminal angioplasty of transplant renal artery stenosis

<p><b>INTRODUCTION</b>This study aimed to assess the outcome of percutaneous transluminal angioplasty (PTA) as the primary treatment for transplant renal artery stenosis (TxRAS).</p><p><b>MATERIALS AND METHODS</b>A retrospective review of PTA of TxRAS from April 1999 to December 2008 was performed. Twenty-seven patients (17 males (M):10 females (F)) with the mean age of 49.5 years underwent PTA of TxRAS in the review period. Indications for PTA were suboptimal control of hypertension (n=12), impaired renal function (n=6) and both suboptimal control of hypertension and impaired renal function (n=9). All patients had doppler ultrasound scans prior to their PTA. In addition, 5 of these patients had computed tomography angiography (CTA) and another 7 had magnetic resonance angiography (MRA) evaluation. Mean follow-up period was 57.0 months (range, 7 to 108 months).</p><p><b>RESULTS</b>The stenotic lesions were located proximal to the anastomosis (n=2), at the anastomosis (n=15), and distal to the anastomosis (n=14). Technical success rate was 96.3%. One case was complicated by extensive dissection during PTA, resulting in subsequent graft failure. The overall clinical success rate was 76.9%. Seven out of 26 patients had restenoses (26.9% of cases). These were detected at a mean of 14.3 months post angioplasty (range, 5 to 38 months). All 7 patients underwent a second PTA successfully. Three of these patients required more than 1 repeat PTA.</p><p><b>CONCLUSION</b>PTA is safe and effective in the management of symptomatic TxRAS and should be the primary treatment of choice. Close surveillance for restenosis is required and when diagnosed, re-angioplasty can be performed.</p>

Cancer among end-stage renal disease patients on dialysis

<p><b>INTRODUCTION</b>The aim of this study is to investigate the risk of cancer among end-stage renal disease (ESRD) patients on dialysis in Singapore.</p><p><b>MATERIALS AND METHODS</b>The study looks at a retrospective cohort of 5505 ESRD patients who had received dialysis between 1998 and 2007. The cancer risk of these patients would be compared against the risk of the general population.</p><p><b>RESULTS</b>During a median follow-up time of 3.9 years, 267 (4.9%) dialysis patients developed cancer. The risk of cancer (excluding non-melanoma skin cancer) is 1.66 times higher in dialysis patients than the general population, and is highest at age less than 35 years old and at first year after dialysis. Cancer risk was found to be significantly higher among Chinese dialysis patients, followed by Malays, compared to the general population. The 3 sites with highest elevated cancer risks among dialysis patients compared to the general population are kidney, tongue and multiple myeloma.</p><p><b>CONCLUSION</b>The finding of elevated cancer risk among younger dialysis patients is similar to other international studies. High cancer risks among specific cancer sites were also consistent with other studies. In view of the lack of screening procedures for these cancers and shortened expected survival of ESRD patients, cancer screening of ESRD patients should be individualised and based on a reasonable life expectancy and transplant candidacy, keeping in mind the competing risk of cardiovascular mortality.</p>

Genomics and disease progression in IgA nephritis

Apart from clinical, histological and biochemical indices, genomics are now being employed to unravel the pathogenetic mechanisms in the disease progression of IgA nephritis (IgAN). The results of angiotensin converting enzyme (ACE) gene polymorphism have been controversial. Those patients with the DD genotype seem to have a poorer prognosis. However, with high dose angiotensin receptor blocker (ARB) therapy, the ACE gene polymorphism status of a patient may no longer be a matter for concern as those with the DD genotype would also respond favourably to high dose ARB therapy. Association studies with gene sequencing and haplotypes have suggested that multiple genes are involved in the pathogenesis of IgAN. Some workers have reported a synergistic effect in the combined analysis of AGT-M235T and ACE I/D polymorphism. With the use of deoxyribo nucleic acid (DNA) microarray, tens of thousands of gene expressions genome-wide can be examined together simultaneously. A locus of familial IgAN has been described with strong evidence of linkage to IgAN1 on chromosome 6q22-23. Two other loci were reported at 4q26-31 and 17q12-22. DNA microarray techniques could also help in the identification of specific pathogenic genes that are up- or down-regulated and this may allow genome wide analyses of these genes and their role in the pathogenesis and progression of IgAN. Recently, using genome-wide association studies (GWAS) more loci for disease susceptibility for IgAN have been identified at 17p13, 8p23, 22q12, 1q32 and 6p21.

National Health Survey on the prevalence of urinary abnormalities in the population: then and now (1975 to 2012)

<p><b>INTRODUCTION</b>This paper presents the results of a community survey on urinary abnormalities which covered 1/80th of the population of Singapore in 1975. These findings were compared with the data from the Singapore National Service Registrants in 1974 as well as data from a recent survey in Singapore and that of other Asian and Western countries.</p><p><b>MATERIALS AND METHODS</b>The study covered 18,000 persons aged 15 years and above, representing a sampling fraction of 1/80th of the population. A total of 16,808 respondents attended the field examination centres, of whom 16,497 had their urine sample tested representing 92.7% of the sample population.</p><p><b>RESULTS</b>In the dipstick urine testing at the field examination centres, 769 subjects (4.6%) were found to have urinary abnormalities. Two hundred and eighty-two (36.7%) of these 769 subjects were found to have urinary abnormalities based on urine microscopy constituting a prevalence of 1.71%. The prevalence of proteinuria was 0.63% and for both haematuria and proteinuria was 0.73%. The prevalence for hypertension was 0.43% and renal insufficiency was 0.1%.</p><p><b>DISCUSSION</b>The consensus is that routine screening for chronic kidney disease (CKD) in the general population is not cost effective as the yield is too low. Whilst, most studies showed that screening of the general population was not cost effective, it has been suggested that screening for targeted groups of subjects could help to identify certain risk groups who may benefit from early intervention to prevent or retard the progression of CKD.</p><p><b>CONCLUSION</b>The prevalence of urinary abnormalities in Singapore has remained the same, now and three decades ago.</p>

3rd College of Physicians' lecture--translational research: From bench to bedside and from bedside to bench; incorporating a clinical research journey in IgA nephritis (1976 to 2006)

Translational research (TR) can be defined as research where a discovery made in the laboratory (bench) can be applied in the diagnosis, treatment or prevention of a disease. Examples of medical discoveries contributing to translational medicine (TM) include the isolation of insulin by Banting (Nobel Laureate, 1923), the discovery of penicillin by Alexander Fleming (Nobel Laureate, 1945) and recently the discovery of the role of bacterium Helicobacter pylori in the causation of gastritis and peptic ulcer by Marshall and Warren (Nobel Laureates, 2005). Clinical research (CR) would be a more appropriate term for the bulk of research work undertaken by doctors. CR embraces both clinical based and laboratory-based research. The terminology "bedside to bench" applies more to CR as opposed to "bench to bedside" in the case of TR. But regardless of who does it, as long as the discovery can be translated to the bedside and results in improvement in patient care it can be considered a contribution to TM. Our work spans a 30-year period, involving laboratory-based research, clinical trials and genomics of IgA nephritis (Nx). This is a series of work to elucidate the pathogensis and therapy of IgANx. Plasma beta-thromboglobulin (BTG) an in-vivo index of platelet aggregation and anti-thrombin III increase due to a constant thrombogenecity resulting from platelet degranulation formed the basis for anti-platelet and low-dose warfarin therapy. A study of the natural history of IgANx revealed 2 courses, a slowly progressive course with end-stage renal failure (ESRF) at 7.7 years and a more rapid course at 3.3 years. Triple therapy (cyclophosphamide, persantin and low-dose warfarin) delayed progression to ESRF by about 8 years and for some patients up to 20 years. Documentation of abnormal suppressor T cell function provided the basis for immune therapy. Four patterns of proteinuria were present in IgANx and it is the quality and not so much the quantity of proteinuria which determined the prognosis. Low molecular weight proteinuria was a bad prognostic marker. A controlled therapeutic trial using ACEI/ATRA showed that therapy decreases proteinuria, improves renal function and converts non-selective to selective proteinuria. Subsequent work confirmed that it was the ATRA, not the ACEI which contributed to improved renal function. Individual anti proteinuria response to ATRA varies depending on ACE gene polymorphism. We found that the II genotype of the ACE gene was renoprotective and patients with this genotype had significantly reduced incidence of ESRF compared to those with the DD genotype. Patients responsive to ATRA therapy can retard progression to ESRF by up to 32 years. Mild renal failure can be reversed with possible regression of glomerulosclerosis because of glomerular remodelling by ATRA.