Disease Progression ; Humans ; Nephrology ; Renal Dialysis ; Renal Insufficiency, Chronic ; complications ; diagnosis ; physiopathology ; therapy

Aged ; Child ; Geriatrics ; Humans ; Pediatrics

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.
Disease Progression ; Evidence-Based Medicine ; history ; Genetic Predisposition to Disease ; Genomics ; history ; Glomerulonephritis, IGA ; genetics ; history ; History, 20th Century ; History, 21st Century ; Humans ; Polymorphism, Genetic ; Singapore

INTRODUCTIONRenal transplantation is the treatment of choice for children with end-stage renal failure (ESRF). The paediatric renal transplant programme in Singapore was initiated in 1989. This study aimed to examine our outcomes over the 19-year period from 1989 to 2007.

MATERIALS AND METHODSA total of 38 renal transplants were performed at our centre. Another 4 patients with overseas transplants who returned within 3 weeks post-transplant were included. The proportion of living donor (LD) transplants was 61.9%. Structural abnormalities and glomerulopathies were the most common aetiologies comprising 33% each. Median age at transplant was 13.9 years and median waiting time was 2.2 years. LD transplant recipients were younger and had a shorter waiting time than deceased donor (DD) recipients.

RESULTSOverall patient survival rates were 95%, 92%, 86% and 86% at 1, 5, 10 and 15 years, respectively. There were 4 deaths, of which 3 were due to infections. Graft survival rates at 1, 5, 10 and 15 years for LD and DD transplants were 100%, 89.5%, 67.3%, 67.3% and 80.8%, 56.5%, 42.2%, 28.3% respectively, and were significantly higher in LD transplants. The main cause of graft loss was rejection following non-adherence. Multivariate analysis showed male gender, late acute rejections and acute tubular necrosis as predictors of graft failure. There was a high incidence of early bacterial infections (42.9%) and cytomegalovirus disease (16.7%).

CONCLUSIONOur graft survival rates for LD transplants were comparable to North American rates, although our DD transplant rates were slightly worse, probably a reflection of the prevailing transplant policies.

Adolescent ; Child ; Child, Preschool ; Female ; Graft Survival ; Humans ; Kidney Failure, Chronic ; surgery ; Kidney Transplantation ; utilization ; Living Donors ; supply & distribution ; Male ; Multivariate Analysis ; Outcome Assessment (Health Care) ; trends ; Postoperative Complications ; epidemiology ; Singapore ; epidemiology ; Survival Analysis ; Young Adult

INTRODUCTIONThis 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.

MATERIALS AND METHODSThe 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.

RESULTSIn 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%.

DISCUSSIONThe 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.

CONCLUSIONThe prevalence of urinary abnormalities in Singapore has remained the same, now and three decades ago.

Adult ; Aged ; Aged, 80 and over ; Female ; Hematuria ; epidemiology ; pathology ; Humans ; Male ; Middle Aged ; Prevalence ; Proteinuria ; epidemiology ; pathology ; Renal Insufficiency, Chronic ; epidemiology ; pathology ; Risk Assessment ; Singapore ; epidemiology ; Urinalysis ; Urinary Tract Infections ; epidemiology ; Young Adult

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.
Angiotensin Receptor Antagonists ; administration & dosage ; Disease Progression ; Dose-Response Relationship, Drug ; Genomics ; methods ; Glomerulonephritis, IGA ; drug therapy ; genetics ; pathology ; Haplotypes ; Humans ; Molecular Sequence Data ; Polymorphism, Single Nucleotide

COVID-19 ; Child ; Humans ; Kidney Failure, Chronic ; Kidney Transplantation ; Liver ; Liver Transplantation ; Living Donors ; SARS-CoV-2

Kidneys of paediatric deceased donors were previously considered suboptimal for older recipients. An 18-month-old deceased donor was made available via Singapore's Medical (Therapy, Education and Research) Act. To the best of our knowledge, she is the youngest local donor. We herein report a case of successful kidney transplantation, using the en bloc technique, to a 15-year-old girl with renal failure secondary to bilateral cystic dysplastic kidney.
Adolescent ; Age Factors ; Female ; Humans ; Infant ; Kidney Diseases, Cystic ; surgery ; Kidney Transplantation ; methods ; Renal Insufficiency ; surgery ; Tissue Donors ; Tissue and Organ Procurement ; methods

The aim of this Biologic Advisory Group (BAG) Malaysia consensus guideline is to provide clinicians managing cutaneous diseases with biologics relevant parameters to consider prior to initiating or stopping or continuing any biologic treatment in the current landscape of the COVID-19 pandemic. Besides reviewing the medical literatures on COVID-19 and evidences related to other human coronavirus or influenza, expert opinions and clinical experiences are shared and debated in formulation of this biologic consensus guideline.