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K T Woo

Publications and source records attributed to K T Woo.

At least 37 records · Page 2Linked to original sources

Proteinuria and angiotensin converting enzyme (ACE) gene polymorphism.

INTRODUCTION: Although proteinuria is traditionally regarded as the result of glomerular damage, recent evidence suggests that proteinuria can directly cause renal damage through lysosomal injury, growth factor induced tubular fibrosis and transcriptase genes which trigger vasoactive and inflammatory renal damage. The renin angiotensin system which releases angiotensin, a most powerful vasoconstrictor and mediator of mesangial cell proliferation and matrix expansion, has been associated with progressive renal injury. This paper reviews the role of angiotensin converting enzyme (ACE) gene polymorphisms in the genesis of progressive renal failure, as well as their role in the response of proteinuria to ACE inhibitor (ACEI) or angiotensin receptor antagonist (ATRA) therapy. METHODOLOGY: The deletion/insertion polymorphism of the ACE gene has 3 genotypes DD, ID and II. Reported studies on the association of ACE gene polymorphisms with patients with IgA nephritis and progressive renal failure, including their response to ACEI or ATRA therapy, were reviewed. RESULTS: Individuals with the DD genotypes have a higher risk of declining renal function with progressive IgA nephritis and more rapid deterioration to renal failure. Therapy with ACEI and or ATRA may be beneficial in patients with IgA nephritis with renal impairment and non-selective proteinuria as such patients may respond to therapy with improvement in protein selectivity, decrease in proteinuria and improvement in renal function. CONCLUSION: ACE genotypes appear to predict antiproteinuric response to ACEI therapy. ACEI/ATRA therapy probably modifies pore size distribution by reducing the radius of large non-selective pores, causing the shunt pathway to become less pronounced resulting in less leakage of protein into the urine.

Angiotensin-Converting Enzyme Inhibitors↗

Rhabdomyolysis and acute renal failure complicating detergent ingestion.

Rhabdomyolysis should be considered in the aetiology of all patients with unexplained acute renal failure (ARF). Early recognition provides the opportunity to initiate therapy aimed at preventing or limiting nephrotoxicity from the released heme pigment, myoglobin. We report an adult patient who developed ARF following the ingestion of a large amount of household detergent which, as far as we are aware, has not been previously described. The report illustrates the importance of measuring muscle enzyme levels and urinary myoglobin to confirm the possibility of rhabdomyolysis in any unusual presentation of ARF.

Acute Kidney Injury↗

The changing pattern of glomerulonephritis in Singapore over the past two decades.

This study reviews the pattern of glomerulonephritis (GN) in Singapore over the past 2 decades. In the earlier decade the pattern was typical of most Asian countries with mesangial proliferative GN (Mes GN) (56%) as the most common form of primary GN including the nephrotic syndrome (40%). In the 2nd decade the pattern undergoes a change. Though Mes GN is the commonest primary GN (42%), the commonest form of nephrotic syndrome is now minimal change disease (30%) with Mes GN decreasing to 25% among all primary nephrotic syndromes. Both minimal change and focal global sclerosis account for 50% of steroid/cyclophosphamide responsive GN today. Membranous GN though still uncommon, has increased from 3% (1st decade) to 6% (2nd decade) (p < 0.01). IgA nephritis is still the commonest primary GN occurring in Singapore (42% of all primary GN in the 1st decade and 45% in the 2nd decade). The present pattern of GN in Singapore, though, still predominantly Asian with the preponderance of mesangial proliferative GN with a relatively low incidence of membranous GN contrasts with the pattern in the West where membranous GN is the commonest form of primary GN. Even the incidence of FSGS has not increased as in the West where there is a rising incidence. The underlying basis for most GN in Singapore as in other Asian countries and elsewhere is antigen-driven: infective antigen as well as food or other allergens.

Adolescent↗

Conducting clinical trials in Singapore.

All clinical trials in Singapore will now have to conform to the Medicines (Clinical Trials) Amended Regulations 1998 and the Singapore Good Clinical Practice (GCP) Guidelines 1998. The Medical Clinical Research Committee (MCRC) has been established to oversee the conduct of clinical drug trials in Singapore and together with the legislations in place, these will ensure that clinical trials conducted in Singapore are properly controlled and the well-being of trial subjects are safe guarded. All clinical drug trials require a Clinical Trial Certificate from the MCRC before the trial can proceed. The hospital ethics committee (EC) vets the application for a trial certificate before it is sent to MCRC. The drug company sponsoring the trial has to indemnify the trial investigators and the hospital for negligence arising from the trial. The MCRC, apart from ensuring the safety of trial subjects, has to provide continuing review of the clinical trial and monitors adverse events in the course of the trial. The EC will conduct continuing review of clinical trials. When a non-drug clinical trial is carried out, the EC will ensure that the proposed protocol addresses ethical concerns and meets regulatory requirements for such trials. There is great potential for pharmaceutical Research & Development (R&D) in Singapore. We must develop our skills and infrastructure in clinical trials to enable Singapore to be a regional hub for R&D of drugs in Asia.

Adverse Drug Reaction Reporting Systems↗

Current therapeutic strategies in glomerulonephritis.

Over the past 20 years the therapy of glomerulonephritis (GN) has evolved. Today apart from steroids and cyclophosphamide, newer agents like cyclopsorine A and tracrolimus (FK 506) have been reported to achieve remission (partial or complete) in patients with nephrotic syndrome due to various GN which have failed to respond to steroids and cyclophosphamide. For those patients who do not respond to any of the primary therapeutic agents, there are now other therapies available like angiotensin II converting enzyme inhibitors, angiotensin II receptor antagonists, dipyridamole, low dose warfarin including protein restriction and therapy aimed at hypercholesterolaemia in an attempt to retard progression to end stage renal failure. This paper presents a therapeutic approach for the various forms of primary GN.

Angiotensin II↗

A case series of falciparum malaria-induced acute renal failure.

Falciparum malaria is a disease of tropical climates which affects 270 million people annually and has an overall mortality of 1%. While the incidence of acute renal failure in malaria is less than 1%, mortality is reported to be as high as 45% in those with renal failure. We report the clinical course and outcome in 5 patients with falciparum malaria-induced acute renal failure treated at the Singapore General Hospital between June and July 1997. All 5 males, with mean age of 35.2 +/- 13.1 years, were admitted with history of fever and reported travel to a known malarious zone. Mean laboratory parameters upon admission included serum creatinine 725 +/- 515 mumol/L and serum urea 47 +/- 31 mmol/L. Three patients with hypotension on admission were started on haemodiafiltration, of whom 2 were subsequently converted to haemodialysis as their haemodynamics improved. Two remaining patients were started on intermittent bicarbonate haemodialysis. The overall mortality in our series was 20%, with 1 patient having died of complications of adult respiratory distress syndrome, disseminated intravascular coagulation and multiorgan failure. The remaining 4 survived and recovered their renal function. The single patient mortality occurred in the patient with admission serum creatinine of 1632 mumol/L, a value significantly higher than that of the 4 patients who survived (mean serum creatinine, 499 +/- 106 mumol/L, P < 0.002). These results suggest that falciparum malaria associated with acute renal failure is associated with a high morbidity, but early presentation and intervention with appropriate antimalarial and renal replacement therapy is associated with improved survival and recovery of renal function.

Acute Kidney Injury↗

Renal transplantation in cyclosporine-treated recipients at the Singapore General Hospital.

1. The 5-year patient and graft survival rates for live-donor renal transplants undergoing transplantation with CsA-based immunosuppression at the Singapore General Hospital from 1985-1999 were 97.0% and 91.6%, respectively. The 5-year patient and graft survival rates for cadaveric renal transplant recipients from the same institution were significantly lower at 91.6% and 79.4%, respectively. Long-term graft survival as described by half-lives (T1/2) were 28.6 years and 20.4 years for live-donor and cadaveric grafts, respectively. 2. Tissue matching had no impact on graft or patient survivals in either live-donor or cadaveric renal transplants. However, sensitisation was associated with significantly worse graft survival in cadaveric transplant recipients. 3. Primary cadaveric transplant recipients enjoyed significantly better graft survival rates than retransplanted recipients (5-year survival rates of 80.1% and 65.0%, respectively; p = 0.032). 4. Among cadaveric renal transplant recipients, a single acute rejection episode was associated with worse long-term graft survival (T1/2 of 14.6 years and 37.0 years for those with and without rejection, respectively, p = 0.001). Likewise, delayed graft function was associated with worse overall graft survival (5-year graft survival rates of 70.7% vs. 86.8% in patients with and without DGF, respectively, p < 0.001). 5. Among cadaveric transplant recipients with a functioning kidney at 5 years after transplantation, 61.4% had normal renal function with serum creatinine levels < 141 mumol/L while 33.9% had mild renal dysfunction with SCr of 141-250 mumol/L. 6. The high graft and patient survival rates in this Asian population as reported from this single centre study may be attributed to selection of younger patients without overt ischaemic heart disease for transplantation and to good patient compliance to CsA therapy. Thus, recipient selection and ensuring patient compliance to treatment are key strategies in optimizing the use of a scarce resource such as organ transplants.

Adolescent↗

Pattern of proteinuria in tubular injury and glomerular hyperfiltration.

Proteinuria is one of the bad prognostic indices in renal disease. This study compares the pattern of protein excretion in 10 patients with IgA nephropathy (IgAN), 10 patients with chronic glomerulonephritis approaching end-stage renal failure (ESRF) who still had proteinuria and 10 other patients with diabetic nephropathy (DN) with proteinuria but normal renal function. The pattern of proteinuria was analysed by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE), isoelectric focusing (IEF) and assayed for orosomucoid, alpha-1-microglobulin, retinol-binding protein, lysozyme, beta-2-microglobulin and N-acetyl-beta-D-glucosaminidase activity. Our data showed much similarity in the pattern of proteinuria between the DN and ESRF groups but significant differences with the IgAN group. The pattern of proteinuria in the IgAN group reflects glomerulonephritis whereas the similar pattern between the ESRF and DN groups may reflect hyperfiltration as well as tubular injury.

Adolescent↗

Hepatitis C antibodies in patients on peritoneal dialysis: prevalence and risk factors.

Our objective was to determine the prevalence of the antibody to hepatitis C (anti-HCV) in a population of end-stage renal failure patients on continuous peritoneal dialysis (CPD) and study the possible risk factors associated with anti-HCV seropositivity and seroconversion. A cross-sectional study included 155 adult patients enrolled in the CPD program in a single renal unit of a teaching hospital who were screened for anti-HCV by second-generation enzyme immunoassay, which was confirmed by recombinant immunoblot assay. Serum was also assayed for hepatitis B surface antigen (HBsAg). History of renal transplantation, blood transfusions, and exposure to hemodialysis was obtained from medical records. Ten of 155 patients (6.5%) in this study population were anti-HCV positive [anti-HCV(+)] and 11/155 (7.1%) were HBsAg positive; no patient was positive for both. All the anti-HCV(+) patients were on continuous ambulatory peritoneal dialysis (CAPD); no continuous cycling peritoneal dialysis (CCPD) patient was anti-HCV(+). Exposure to hemodialysis was a risk factor for anti-HCV seropositivity, with 7 out of 10 (70%) anti-HCV(+) patients having been on hemodialysis compared to 55/134 (41%) anti-HCV(-) (p < 0.05, Fisher's exact test). No difference was noted between anti-HCV(+) and anti-HCV(-) groups in relation to age, gender, duration on CPD, renal transplantation, or exposure to blood transfusions. Seroconversion occurred in only one patient after a mean observation period of 20 +/- 0.6 months. The prevalence of anti-HCV seropositivity in this population of CPD patients is 6.5%, and HBsAG 7.1%. Exposure to hemodialysis is a significant risk factor for development of anti-HCV seropositivity. Seroconversion rate appears to be low.

Adolescent↗

Plasma activity of contact coagulation factors in patients with IgA nephritis.

Intraglomerular coagulation, initiated by the local activation of contact coagulation factors, has been suggested as one possible factor causing glomerular injury in IgA nephritis. The plasma activity of factor XII, prekallikrein and high molecular weight (HMW) kininogen were measured in 24 patients with biopsy-proven IgA nephritis and in 123 normal controls, using an activated partial thromboplastin time assay with the appropriate factor-deficient plasma as substrate. IgA patients had significantly lower plasma activity of factor XII (45.5% +/- 28.3% against 80.7% +/- 31.8%; mean +/- standard deviation, P < 0.001), prekallikrein (37.7% +/- 24.5% against 119.8% +/- 37.7%; P < 0.001) and HMW kininogen (72.8% +/- 37.8% against 119.1% +/- 42.8%; P < 0.001) when compared with controls. In the IgA patients, there was no significant correlation between factor XII, prekallikrein and HMW kininogen activity and 24-hour total urinary protein excretion, suggesting that the reduced plasma activity was not due to increased urinary loss of the coagulation factors. One possible explanation for these results is that the intrinsic coagulation pathway is activated in patients with IgA nephritis.

Adult↗