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Biomedical subjects

T M Chan

Publications and source records attributed to T M Chan.

At least 19 recordsLinked to original sources
PubMed2006

Recurrent glomerulonephritis after kidney transplantation.

Thirty to fifty percent of kidney transplant recipients have glomerular diseases as the underlying causes of end-stage renal failure. While recurrence of glomerulonephritis is an important cause of late renal allograft failure, the risk factors for recurrence are largely unknown or imprecise and prediction remains difficult. Recurrent disease usually presents with similar manifestations as the native disease. With regard to treatment of recurrent glomerular disease in the renal allograft, plasma exchange may be effective in reducing proteinuria in patients with early recurrence of focal and segmental glomerulosclerosis, but immunosuppressive therapy is generally ineffective in the prevention or treatment of recurrent disease. General supportive measures including strict blood pressure control and inhibition or blockade of the rennin-angiotensin pathway are helpful in retarding the rate of deterioration in renal allograft function. Despite the risk of recurrence, kidney transplantation following primary glomerulonephritides enjoys graft and patient survival rates comparable to other causes of end-stage renal failure. With a few exceptions, living related renal transplantation is not contraindicated in view of the favorable outcome and the donor shortage. This review discusses commonly encountered recurrent glomerulonephritides, with special emphasis on the influence of post-transplant prophylactic immunosuppression and emerging treatments.

Diabetic Nephropathies↗
PubMed2006

Non-tuberculous mycobacterial infection in patients with systemic lupus erythematosus.

OBJECTIVES: Patients with systemic lupus erythematosus (SLE) are susceptible to opportunistic infections. To examine the clinical manifestations of non-tuberculous mycobacterial (NTM) infections with those of Mycobacterium tuberculosis (MTB) infections in SLE patients. METHODS: Medical records of a cohort of 725 SLE patients were reviewed for previous NTM infections. Demographic characteristics, predisposing factors and clinical outcomes were compared with patients who had previous MTB infections (n = 39). RESULTS: Eleven (nine female and two male) cases were identified (prevalence 1.5%). The mean +/- S.D. age at the time of infection was 42.8 +/- 13.9 yrs, 9.3 +/- 5.8 yrs after the onset of SLE. The mean +/- S.D. time taken from onset of symptoms to the diagnosis of NTM infection was 5.7 +/- 7.2 months. Sites of involvement included skin and soft tissue (n = 8), chest (n = 2) and disseminated infection (n = 1). NTM infections were more likely to involve extrapulmonary sites (P = 0.006), presented in patients with longer lupus disease duration (P < 0.001), occurred in older patients (P < 0.001) and in those who had a higher cumulative dose of prednisolone (P = 0.01) than MTB infections. Using a stepwise logistic regression, disease duration was found to be the only independent predictive factor (P = 0.005) for NTM infections. Ten (25.6%) patients with MTB infections but none of the patients with NTM infections presented concomitantly at the onset of SLE (P = 0.09). There were no differences in the recurrence rate (P = 0.64) and frequency of disseminated infections (P = 0.40) between NTM and MTB infections. CONCLUSIONS: NTM infections tended to develop in SLE patients later in their disease course than MTB infections. A high index of suspicion is required for its diagnosis.

Adult↗
PubMed2006

Increased mesangial cell hyaluronan expression in lupus nephritis is mediated by anti-DNA antibody-induced IL-1beta.

The mechanism by which anti-DNA antibodies contribute to the pathogenesis of lupus nephritis (LN) remains to be fully elucidated. Hyaluronan (HA) is an important extracellular matrix constituent that accumulates during tissue injury, and participates in lymphocyte recruitment to sites of inflammation. The role of HA in the pathogenesis of LN has not been defined. We investigated the expression of HA in renal biopsies and circulating HA levels in patients with diffuse proliferative LN, and the effect of human anti-DNA antibodies on HA synthesis in cultured human mesangial cells (HMC). HA expression was increased in the mesangium, and in the periglomerular and tubular distribution in LN kidney biopsies. LN patients showed increased levels of circulating HA, especially during active disease, which correlated with anti-DNA antibody titers (r=0.35, P=0.0234). Anti-DNA antibodies isolated during active LN but not remission increased de novo synthesis of (3)H-labeled HA, which was accompanied by induction of HA synthase (HAS) II transcription, and enhanced IL-1beta, IL-6, and tumor necrosis factor-alpha secretion in HMC (P<0.001 for all). Only anti-DNA antibody induction of IL-1beta enhanced HA synthesis, which was abrogated by inhibitors of de novo mRNA or protein synthesis. Our findings demonstrate that HA expression is significantly increased within the mesangium in diffuse proliferative LN mediated through anti-DNA antibody-induced IL-1beta. Given that HA plays a pivotal role during inflammatory responses, influences cellular behavior and assists in the recruitment of lymphocytes to sites of injury, it is likely that HA contributes to the pathogenesis of LN.

Adult↗
PubMed2006

Quality of life comparison between corticosteroid- and-mycofenolate mofetil and corticosteroid- and-oral cyclophosphamide in the treatment of severe lupus nephritis.

There is accumulating evidence that mycophenolate mofetil (MMF), when combined with corticosteroid, is an effective induction treatment for severe proliferative lupus nephritis and is associated with fewer adverse effects compared to cyclophosphamide (CTX), but the quality of life (QOL) associated with these regimens as perceived by the patient has not been compared. This study included patients who had experienced both treatment regimens, for distinct episodes of diffuse proliferative lupus nephritis. QOL parameters during the first six months of each treatment were assessed through SF36 and WHOQOL questionnaires. Twelve patients and 24 episodes of severe lupus nephritis were studied. CTX-treated and MMF-treated episodes showed comparable baseline characteristics and response rate, with complete remission occurring in 83.3%. MMF treatment was associated with higher numerical scores for all domains across both QOL instruments than CTX. MMF treatment was associated with significantly less fatigue, less impediment of physical and social functioning, and better psychological well being compared to CTX. When each patient served as her/his own control, most patients ascribed higher QOL domain scores to the MMF-treated episode. Seventy-five percent of patients found MMF treatment more acceptable and preferred when compared with CTX, and the complications that most concerned them included Cushingoid features, alopecia, menstrual disturbance and infections. These data showed that MMF-based induction immunosuppression for severe lupus nephritis was associated with better QOL than CTX as perceived by patients, which was most likely attributed to the reduced side-effects during MMF treatment.

Activities of Daily Living↗
PubMed2006

Necrotizing fasciitis in rheumatic diseases.

Necrotizing fasciitis is an uncommon but life-threatening complication in immunocompromised hosts. We reported four patients with rheumatic diseases complicated by necrotizing fasciitis and reviewed 14 others from literature search. Most patients were on corticosteroid treatment. Septic shock, disseminated intravascular coagulopathy and acute renal deterioration were common giving rise to an overall mortality rate of 27.8%. Septic arthritis may also complicate the condition. Statistical analysis on the series showed the lack of major surgical debridement as the only risk factor associated with increased mortality (RR 7.5, 95% CI 2.1-27.3, P = 0.01). Timely debridement of necrotic tissue is important for reducing mortality.

Adult↗
PubMed2005

Long-term outcome of patients with diffuse proliferative lupus nephritis treated with prednisolone and oral cyclophosphamide followed by azathioprine.

The short-term outcome of patients with diffuse proliferative lupus nephritis (DPLN) has improved with advances in immunosuppressive treatment. However, the impact of different immunosuppressive regimens on long-term renal function remains to be defined. This prospective cohort study examined the long-term renal function and disease relapse in adults with biopsy-proven DPLN, significant proteinuria, and hypoalbuminemia, who had been treated with sequential immunosuppression comprising prednisolone and oral cyclophosphamide as induction followed by low-dose prednisolone and azathioprine as maintenance. Sixty-six patients with 68 episodes of DPLN were included, with follow-up of 91.7 +/- 36.7 months. 82.4% achieved complete remission and 39.1% relapsed during follow-up. Patients in partial remission were at higher risk of relapse compared with those in complete remission (hazard ratio 6.2, P < 0.001). Serum creatinine remained stable over time (P = 0.931), while creatinine clearance showed a significant increase with time after treatment (P = 0.032). Three (4.4%) patients had doubling of baseline creatinine, but none reached end-stage renal failure or died. Univariate and mixed model analyses showed that the evolution of long-term renal function was significantly influenced by the chronicity score and creatinine clearance at baseline, and by the renal function at one year after treatment. These data demonstrate the efficacy of sequential immunosuppression in preserving renal function in most Chinese subjects with DPLN. The results also indicate that irreversible renal scarring (as reflected by baseline chronicity score), renal reserve (as reflected by renal function at baseline and one year), and an induction regimen that is effective in preserving the nephron mass are critical determinants of long-term renal outcome.

Administration, Oral↗
PubMed2005

Lupus nephritis: induction therapy.

Effective induction therapy is of pivotal importance in minimizing renal parenchymal damage by the active immune-mediated inflammatory processes in severe proliferative lupus nephritis. Preservation of nephron mass is prerequisite to long-term renal survival. Data from US-based studies have shown improved efficacy with induction treatment comprising corticosteroid and cyclophosphamide, compared with corticosteroid treatment alone. Data from European studies have shown similar efficacy with a modified treatment regimen, in which smaller doses of cyclophosphamide were given at weekly or fortnightly intervals over a shortened treatment duration, and the treatment related adverse effects appeared less frequent with the reduced-dose regimen. We have also reported that sequential immunosuppression with prednisolone and oral cyclophosphamide as induction followed by azathioprine maintenance was associated with a high incidence of remission and relatively favourable long-term renal outcome in Chinese patients. However, cyclophosphamide treatment is associated with considerable adverse effects, which could be potentially fatal. Mycophenolate mofetil selectively inhibits lymphocyte proliferation, and thus targets an instrumental step in the pathogenesis of systemic lupus erythematosus. There is accumulating evidence that the combined use of mycophenolate mofetil and corticosteroid presents an effective treatment for severe proliferative lupus nephritis in different ethnic groups, and is associated with much fewer adverse effects compared with cyclophosphamide-based regimens. Recent data from our group also demonstrate the long-term efficacy of mycophenolate mofetil in preserving renal survival, when used continuously as both induction and maintenance therapy.

Anti-Inflammatory Agents↗
PubMed2005

Angiotensin inhibition or blockade for the treatment of patients with quiescent lupus nephritis and persistent proteinuria.

Angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) reduces proteinuria and the rate of renal function deterioration in diabetic nephropathy and other glomerular diseases, but its role in quiescent lupus nephritis has not been established. We conducted a retrospective study to investigate the effects of ACEI/ARB on proteinuria and renal function in patients with persistent proteinuria (>1 g/day) despite resolution of acute lupus nephritis following immunosuppressive treatment. Fourteen out of 92 patients were included. The duration of treatment with ACEI/ARB was 52.1 +/- 35.7 months. The levels of proteinuria, serum albumin, serum creatinine, systolic and diastolic blood pressure were 1.10 to 6.90 g/day, 35.8 +/- 3.6 g/L, 102.54 +/- 34.48 micromol/L, 137.6 +/- 10.9 and 81.9 +/- 9.2 mmHg at baseline. Proteinuria and serum albumin showed significant sustained improvements after 6 and 24 months of treatment. Comparison of slopes for serial proteinuria, albumin and reciprocal of serum creatinine before and after treatment showed significant improvements in six (43%), eight (57%) and two patients, respectively. At last follow-up proteinuria remained significantly lower (0.36 g/day, P = 0.043) and albumin higher (41.3 +/- 2.2 g/L, P = 0.023). Eleven (78.6%) patients had proteinuria improved by >50%, and five had insignificant proteinuria at last follow-up. Systolic blood pressure was significantly reduced from 6 months onwards, but this did not correlate with proteinuria reduction. Diastolic blood pressure, serum creatinine, creatinine clearance, anti-dsDNA, C3 and haemoglobin were not altered. We conclude that ACEI/ARB effectively reduces proteinuria and improves serum albumin in patients with persistent proteinuria despite quiescent lupus nephritis.

Adult↗
PubMed2005

Benign metastasising leiomyoma: a rare but possible cause of bilateral pulmonary nodules in Chinese patients.

We report three cases of benign metastasising leiomyoma, which is a rare cause of multiple lung nodules, in three Hong Kong Chinese females. One patient presented with pleuritic chest pain, another was asymptomatic, while the last presented with haemoptysis. All three patients had previously undergone surgical resection of uterine leiomyomas. Multiple lung nodules mimicking lung metastases were demonstrated on chest radiographs, and all three diagnoses were obtained from lung biopsies. Hormonal therapy was given to two patients with variable responses. To the best of our knowledge, this is the first report of benign metastasising leiomyoma in Hong Kong Chinese population. It highlights the importance of considering this rare and benign disease in premenopausal females presenting with multiple lung nodules.

Adult↗
PubMed2004

Antiviral therapy for hepatitis B after kidney transplantation.

The clinical outcome of HBsAg-positive renal transplant recipients has been adversely affected by potentially fatal acute hepatitic exacerbations and chronic liver disease, in addition to the increased risk of hepatocellular carcinoma. The difficulty in predicting the evolution and severity of liver disease after kidney transplantation further confounds the management of these patients. The clinical course of HBsAg-positive renal transplant recipients can be modified favorably after nucleoside analogue therapy and quantitative HBV DNA assays have become available. The latter allow earlier detection of increased viral replication, before the onset of biochemical abnormality. We have combined serial HBV DNA monitoring with preemptive lamivudine therapy, and our results showed that this strategy markedly improved patient survival. Prolonged treatment, however, was associated with the selection of drug-resistant YMDD variants. Hepatitic flares were common after the development of drug resistance and could lead to decompensation in a small proportion of patients. With careful selection, discontinuation of antiviral treatment was feasible in 18.5% of treated subjects. While the outcome of HBsAg-positive renal allograft recipients should continue to improve with the availability of more effective antiviral agents, financial constraints and the paucity of research data could hamper the optimal adoption of recent advances into clinical practice.

DNA, Viral↗
PubMed2004

A survey on the prevalence and management of hepatitis B after renal transplantation in Asian-Pacific countries.

The carrier rate for hepatitis B virus (HBV) varies from 1% to 2% to 10% in Asian-Pacific countries. A survey involving 12 transplant centers from 11 countries in this region showed that 1% to 25% of kidney transplant recipients were infected with HBV, and up to 60% of these subjects showed abnormal liver biochemistry. While nearly all centers tested anti-HBs in potential kidney transplant recipients, HBV vaccination of nonimmune subjects was routine in only 66.7%. One-third of the surveyed units rejected HBsAg-positive subjects as kidney donors, while the others demonstrated differing policies in choosing the respective recipients. Two units (16.7%) excluded HBsAg-positive patients from kidney transplantation, whereas the others only excluded those with severe liver disease. Heterogeneity also applies to the immunosuppressive regimens, the use of HBV DNA in serial monitoring, and the timing of antiviral therapy in HBsAg-positive kidney transplant recipients. The data showed that despite HBV infection being a significant problem in kidney transplantation, there is a lack of uniform management policy, attributable to the clinical complexity and deficiency of research data. Although improvement in clinical outcome is likely with the advent of nucleoside analogue therapy and better monitoring, the financial implications in the adoption of these recent advances remain realistic concerns.

Asia↗
PubMed2004

Association of interleukin-10 promoter polymorphisms with systemic lupus erythematosus.

Several lines of evidence suggest interleukin-10 gene (IL-10) is a candidate gene in susceptibility to systemic lupus erythematosus (SLE). We investigated the association of IL-10 promoter single-nucleotide polymorphisms (SNPs) (-3575T/A, -2849G/A, -2763C/A, -1082A/G, -819T/C and -592A/C) and microsatellites (IL10.R, IL10.G) with SLE in 554 Hong Kong Chinese patients and 708 ethnically matched controls. Six haplotypes (hts) were identified from the SNPs. The genotype distribution of the ht1 (T-C-A-T-A), which is associated with low IL-10 production, was different in patients and controls (P=0.009). The homozygous genotype of non-ht1 was significantly increased in patients (P=0.009, odds ratio (OR)=1.80, 95% CI: 1.15-2.82). The frequency of IL10.G4 of IL10.G was also significantly increased in patients (P=0.017, OR=2.53, 95% CI: 1.18-5.40). We found that the homozygous non-ht1 combined with short allele (CA repeat number < or =21) of IL10.G has a dose-dependent effect on SLE susceptibility: non-ht1/non-ht1 with homozygous short allele showed a higher OR (OR=4.11, 95% CI: 1.27-13.2, P=0.018) of association with SLE than the genotype of non-ht1/non-ht1 with heterozygous short/long allele (OR=2.98, 95% CI: 1.26-7.07, P=0.013) and homozygous long allele (OR=1.05, 95% CI: 0.62-1.78, P=0.848). The frequency of non-ht1 was significantly increased in patients with serositis (P<0.0001, OR=2.42, 95% CI: 1.55-3.80). In conclusion, the high expression promoter genotype is associated with SLE in Chinese.

Adult↗
PubMed2004

Differential expression of receptors for advanced glycation end-products in peritoneal mesothelial cells exposed to glucose degradation products.

Autoclaving peritoneal dialysate fluid (PDF) degrades glucose into glucose degradation products (GDPs) that impair peritoneal mesothelial cell functions. While glycation processes leading to formation of advanced glycation end-products (AGE) were viewed commonly as being mediated by glucose present in the PDF, recent evidence indicates that certain GDPs are even more powerful inducers of AGE formation than glucose per se. In the present study, we examined the expression and modulation of AGE receptors on human peritoneal mesothelial cells (HPMC) cultured with GDPs, conventional PDF or PDF with low GDP content. HPMC cultured with GDPs differentially modulated AGE receptors (including RAGE, AGE-R1, AGE-R2 and AGE-R3) expression in a dose-dependent manner. At subtoxic concentrations, GDPs increased RAGE mRNA expression in HPMC. 2-furaldehyde (FurA), methylglyoxal (M-Glx) and 3,4-dideoxy-glucosone-3-Ene (3,4-DGE) increased the expression of AGE-R1 and RAGE, the receptors that are associated with toxic effects. These three GDPs up-regulated the AGE synthesis by cultured HPMC. In parallel, these GDPs also increased the expression of vascular endothelial growth factor (VEGF) in HPMC. PDF with lower GDP content exerted less cytotoxic effect than traditional heat-sterilized PDF. Both PDF preparations up-regulated the protein expression of RAGE and VEGF. However, the up-regulation of VEGF in HPMC following 24-h culture with conventional PDF was higher than values from HPMC cultured with PDF containing low GDP. We have demonstrated, for the first time, that in addition to RAGE, other AGE receptors including AGE-R1, AGE-R2 and AGE-R3 are expressed on HPMC. Different GDPs exert differential regulation on the expression of these receptors on HPMC. The interactions between GDPs and AGE receptors may bear biological relevance to the intraperitoneal homeostasis and membrane integrity.

Animals↗