- NCB301, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, 102 Pokfulam Road, Hong Kong
- +(852)22554385
Desmond Y H Yap
The University of Hong Kong, Medicine, Faculty Member
- Dr. Desmond Yat-Hin YAP joined the University Department of Medicine in 2004 and was appointed as Clinical Assistant ... moreDr. Desmond Yat-Hin YAP joined the University Department of Medicine in 2004 and was appointed as Clinical Assistant Professor in Medicine since 2012. His research interests include the immunopathogenesis and the use of immunosuppressive treatments in glomerular diseases, with special focus on lupus nephritis which is an important cause of renal failure in Asia. Dr. Yap's other research interests pertains to hepatitis B viral infection in patients with kidney diseases, which is a prevalent and important issue among renal transplant recipients in Asia. He received the Young Investigator Award by the Hong Kong Society of Nephrology in 2009 for his investigation on serum immunoglobulin binding activity to human mesangial cells in lupus nephritis. He was awarded the Li Shu Pui Clinical Fellowship (2014-2015) and worked as a visiting clinician-scientist at the Fiebiger-Nikolaus Centre, Friedrich-Alexander University, Germany.edit
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Abstract: Lupus nephritis (LN) is a common and severe organ manifestation of systemic lupus erythematosus (SLE), and is associated with significant patient morbidity and mortality. Autoantibodies and aberrations in lymphocyte subsets have... more
Abstract: Lupus nephritis (LN) is a common and severe organ manifestation of systemic lupus erythematosus (SLE), and is associated with significant patient morbidity and mortality. Autoantibodies and aberrations in lymphocyte subsets have putative roles in the pathogenesis of SLE and LN, and might reflect disease activity and are amenable to immunosuppressive treatments. Anti-DNA is one of the well-studied autoantibodies, which correlates with disease activity and has direct nephritogenic effects on resident renal cells and various glomerular components. Other important autoantibodies in the pathogenesis of LN include anti-C1q, anti-α-actinin and anti-nucleosome antibodies. Changes in naive and memory B cells and plasma cells have been observed in SLE and LN patients. These B cell subsets exert diverse effects during pathogenesis of LN such as production of autoantibodies, secretion of proinflammatory and anti-inflammatory cytokines and presentation of auto-antigens to effector cell...
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BACKGROUND HLA-B*15:11 is associated with carbamazepine (CBZ)-induced severe cutaneous adverse drug reactions (SCARs) in Japanese and some Asian populations, but such data remains relatively limited in Chinese. Routine HLA-B*15:02... more
BACKGROUND HLA-B*15:11 is associated with carbamazepine (CBZ)-induced severe cutaneous adverse drug reactions (SCARs) in Japanese and some Asian populations, but such data remains relatively limited in Chinese. Routine HLA-B*15:02 screening is mandatory before CBZ commencement, however, SCARs related to CBZ were still observed in non-HLA*B-15:02 carriers. OBJECTIVE We aimed to find out the prevalence of HLA-B*15:11 in Chinese patients and its associations with CBZ-induced SCARs. METHOD We screened 8,328 blood samples collected for HLA allele typing before CBZ commencement during the period of January 2014 to December 2019. In HLA-B*15:02 negative Chinese patients, HLA-B*15:11 status were further screened, and the incidence of SCARs in the CBZ group was compared with the control group without CBZ use. RESULT In this cohort, 1416 out of 8328 patients (17%) tested HLA-B*15:02 positive and were advised to avoid CBZ, while 80 (0.96%) were found to be HLA-B*15:11 positive. In 6911 (83%) patients who tested HLA-B*15:02 negative, 70 (1.01%) were HLA-B*15:11 positive. Five out of 70 (7.14%) patients had SCARs. The incidence of SCARs in HLA-B*15:11 carriers who received CBZ was significantly higher than those without CBZ (17.4% [4/23] vs. 2.13% [1/47], P = 0.037*). The odds ratio was 9.68 (95% CI 1.02-92.4, P = 0.048*). These included: one Stevens-Johnson syndrome (SJS), two DRESS, and one MPE after CBZ use, while one developed MPE after phenytoin use in control. CONCLUSION HLA-B*15:11 is a potential risk factor of CBZ-induced SCARs in HLA-B*15:02 negative Chinese patients. Further screening of HLA-B*15:11 status in those HLA-B*15:02 negative patients is recommended to avoid undesirable SCARs.
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Background and Aims The optimal management for asymptomatic serological reactivation (ASR) in lupus nephritis (LN) patients remains undefined. Our previous retrospective study suggested that pre-emptive treatment with moderate increase of... more
Background and Aims The optimal management for asymptomatic serological reactivation (ASR) in lupus nephritis (LN) patients remains undefined. Our previous retrospective study suggested that pre-emptive treatment with moderate increase of immunosuppression may reduce subsequent clinical flares. Method This prospective study randomized LN patients with ASR (defined as >2-fold increase of anti-dsDNA to >100 IU/mL, with or without change in complement level, and absence of clinical lupus exacerbation) to receive pre-emptive treatment (‘Pre-emptive’ group) or unchanged management (‘Control’ group). Pre-emptive treatment included increasing prednisolone dose to 0.5 mg/kg/D, and the dose of mycophenolate to 1g/D or azathioprine to 75 mg/D, then tapered over 12-16 weeks back to the original dosages. Results Thirty-four patients were randomized (17 in each group). Pre-emptive group showed lower anti-dsDNA and higher C3 levels after 12 weeks compared with Controls (90.3±58.3 IU/mL vs. ...
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Whether the presence or absence of antiphospholipid antibodies (aPL) in patients with lupus nephritis (LN) is associated with differences in clinical outcomes remains unclear. We reviewed LN patients at a single centre during 2000–2017,... more
Whether the presence or absence of antiphospholipid antibodies (aPL) in patients with lupus nephritis (LN) is associated with differences in clinical outcomes remains unclear. We reviewed LN patients at a single centre during 2000–2017, and compared the clinical features and long-term outcomes between patients who were seropositive or seronegative for aPL. aPL was detected in 53/149 (35.6%) patients with biopsy-proven LN, and anticardiolipin IgM, anticardiolipin IgG, anti-β2 glycoprotein I and lupus anticoagulant was detected in 18.8%, 18.1%, 10.7% and 8.1%, respectively. Follow-up was 155.8 ± 61.0 months, and was similar between aPL-seropositive and -seronegative patients. aPL seropositivity persisted in 94.3% of patients during remission. aPL-seropositive patients showed inferior patient survival (91% and 85% at 10 and 15 years, respectively, compared to 99% and 95% in aPL-seronegative patients; p = 0.043). Nine (6.0%) patients died during follow-up, including six aPL-seropositive...
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Lupus nephritis (LN) leads to chronic kidney disease (CKD) through progressive fibrosis. Mycophenolate inhibits inosine monophosphate dehydrogenase and is a standard treatment for LN. The mammalian or mechanistic target of rapamycin... more
Lupus nephritis (LN) leads to chronic kidney disease (CKD) through progressive fibrosis. Mycophenolate inhibits inosine monophosphate dehydrogenase and is a standard treatment for LN. The mammalian or mechanistic target of rapamycin (mTOR) pathway is activated in LN. Rapamycin inhibits mTOR and is effective in preventing kidney transplant rejection, with the additional merits of reduced incidence of malignancies and viral infections. The effect of mycophenolate or rapamycin on kidney fibrosis in LN has not been investigated. We investigated the effects of mycophenolate and rapamycin in New Zealand Black and White first generation (NZB/W F1) murine LN and human mesangial cells (HMCs), focusing on mechanisms leading to kidney fibrosis. Treatment of mice with mycophenolate or rapamycin improved nephritis manifestations, decreased anti-double stranded (ds) DNA antibody titer and reduced immunoglobulin G (IgG) deposition in the kidney. Both mycophenolate and rapamycin, especially the lat...
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Objective.To expand the limited longterm data on sirolimus treatment in patients with lupus nephritis (LN). Our pilot short-term data suggested efficacy of sirolimus treatment in these patients.Methods.We retrospectively reviewed 16 class... more
Objective.To expand the limited longterm data on sirolimus treatment in patients with lupus nephritis (LN). Our pilot short-term data suggested efficacy of sirolimus treatment in these patients.Methods.We retrospectively reviewed 16 class III/IV/V patients with LN who have received prednisolone (PSL) and sirolimus either as initial or maintenance treatment.Results.Sixteen patients received sirolimus treatment (9 because of intolerance to standard immunosuppressants and 7 because of a history of malignancy) for 45.3 ± 36.5 months. In 5 patients, sirolimus and PSL were given as induction for active nephritis, and they showed improvements in proteinuria (2.8 ± 1.9 g/day at baseline, 0.1 ± 0.1 g/day after 36 mos, p = 0.011), anti-dsDNA (107.7 ± 91.9 IU/ml and 37.0 ± 55.4 IU/ml, respectively, p = 0.178), and C3 (54.8 ± 26.1 mg/dl and 86.3 ± 18.6 mg/dl, respectively, p = 0.081). Eleven patients received sirolimus and low-dose PSL as longterm maintenance, and they showed continued improvem...
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Concomitant chronic kidney disease (CKD) is common in patients with significant valvular heart disease (VHD). This study sought to evaluate the clinical benefit of valvular surgery in patients with concomitant CKD.We evaluated 349... more
Concomitant chronic kidney disease (CKD) is common in patients with significant valvular heart disease (VHD). This study sought to evaluate the clinical benefit of valvular surgery in patients with concomitant CKD.We evaluated 349 patients with significant VHD who were referred for surgery. Patients were divided into those with CKD stage ≥ 3 (CKD patients; n = 88) and those with CKD stage 1 or 2 (no CKD patients; n = 261). 63 patients did not receive surgery, of which 20 patients had CKD and 43 had no CKD. Mortality and change in eGFR were assessed after a median follow-up of 21 months.In the whole study population, 25% of the patients had CKD and these patients had higher mortality than those with no CKD. The annual mortality rates of patients with CKD who did and did not undergo surgery were 7.9% and 28.0%, respectively. In patients with no CKD, the annual mortality rates of those who did and did not undergo surgery were 1.8% and 2.3%, respectively. Importantly, surgery was associ...
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To evaluate the use of shear wave elastography in assessment of kidney allograft tubulointerstitial fibrosis. Shear wave elastography assessment was carried out by two independent operators in kidney transplant recipients who underwent... more
To evaluate the use of shear wave elastography in assessment of kidney allograft tubulointerstitial fibrosis. Shear wave elastography assessment was carried out by two independent operators in kidney transplant recipients who underwent allograft biopsy for clinical indications (i.e. rising creatinine >15% or proteinuria >1 g/day). Allograft biopsies were interpreted by the same pathologist according to the 2013 Banff Classification. A total of 40 elastography scans were carried out (median creatinine 172.5 μmol/L [interquartile range 133.8-281.8 μmol/L]). Median tissue stiffness at the cortex (22.6 kPa [interquartile range 18.8-25.7 kPa] vs 22.3 kPa [interquartile range 19.0-26.5 kPa], P = 0.70) and medulla (15.0 kPa [interquartile range 13.7-18.0 kPa] vs 15.6 kPa [interquartile range 14.4-18.2 kPa]) showed no significant differences between the two observers. Interobserver agreement was satisfactory (intraclass correlation coefficient of the cortex 0.84, 95% CI 0.70-0.92 and ...
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Serological activity may precede clinical flares of lupus nephritis (LN) but the management of asymptomatic serological reactivation (ASR) remains undefined. We conducted a retrospective analysis of 138 episodes of ASR, which included 53... more
Serological activity may precede clinical flares of lupus nephritis (LN) but the management of asymptomatic serological reactivation (ASR) remains undefined. We conducted a retrospective analysis of 138 episodes of ASR, which included 53 episodes in which immunosuppression was increased preemptively and 85 episodes in which treatment was unaltered. Preemptive immunosuppressive treatment comprised increasing the dose of prednisolone to ∼0.5 mg/kg/day, and in patients already on mycophenolate mofetil (MMF) or azathioprine (AZA), increasing the dose to 1.5 g/day and 100 mg/day, respectively. Thirty-four episodes of renal flare occurred during follow-up (88.8 ± 77.3 and 82.8 ± 89.7 months in the preemptive group and controls, respectively), following 5 (9.4%) of preemptively treated ASR and 27 (31.8%) of untreated ASR [hazard ratio 0.3 (confidence interval 0.1-0.7), P = 0.012]. Preemptive treatment was associated with superior survival free of renal relapse (99, 92 and 90% at 6, 12 and ...
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To examine the disease flare rate in lupus nephritis (LN), focusing on renal flares, and the factors associated with relapse risk in recent years. We analyzed data on 139 Chinese patients with class III/IV ± V LN diagnosed from January... more
To examine the disease flare rate in lupus nephritis (LN), focusing on renal flares, and the factors associated with relapse risk in recent years. We analyzed data on 139 Chinese patients with class III/IV ± V LN diagnosed from January 1983 to December 2013. We also compared data before and after 1998, when maintenance immunosuppression was changed from azathioprine (AZA) to mycophenolic acid (MPA). Over 112.5 ± 88.4 months, 135 episodes of renal flare occurred, giving a flare rate of 0.108 episodes per patient-year. The renal relapse-free survival rate was 96%, 90%, 86%, 80%, 69%, and 57% after 1, 2, 3, 4, 5, and 10 years, respectively, calculated from the start of induction treatment. Reduced risk of flare was associated with MPA maintenance (OR 0.314, 95% CI 0.099-0.994, p = 0.049), complete remission after induction immunosuppression (OR 0.329, 95% CI 0.133-0.810, p = 0.016), and diagnosis after 1998 (OR 0.305, 95% CI 0.133-0.700, p = 0.005). Relapse-free survival was significan...
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H2 receptor antagonists are commonly employed to manage gastro-esophageal reflux and peptic ulcer diseases with a very low incidence of side effects. Herein, we report an extremely rare incidence of famotidine-induced acute confusion in a... more
H2 receptor antagonists are commonly employed to manage gastro-esophageal reflux and peptic ulcer diseases with a very low incidence of side effects. Herein, we report an extremely rare incidence of famotidine-induced acute confusion in a patient with end-stage renal failure. We also discuss the pharmacokinetic properties of famotidine and its interplay with compromised renal function to result in neuropsychiatric manifestations, highlighting the importance of dosage ad ustment in individuals with renal insufficiency.
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Annexin II on mesangial cell surface mediates the binding of anti-dsDNA antibodies and consequent downstream inflammatory and fibrotic processes. We investigated the clinical relevance of circulating annexin II-binding immunoglobulins... more
Annexin II on mesangial cell surface mediates the binding of anti-dsDNA antibodies and consequent downstream inflammatory and fibrotic processes. We investigated the clinical relevance of circulating annexin II-binding immunoglobulins (Igs) in patients with severe proliferative lupus nephritis, and renal annexin II expression in relation to progression of nephritis in New Zealand Black and White F1 mice (NZBWF1/J) mice. Annexin II-binding Igs in serum were measured by ELISA. Ultrastructural localization of annexin II was determined by electron microscopy. Seropositivity rates for annexin II-binding IgG and IgM in patients with active lupus nephritis were significantly higher compared with controls (8.9%, 1.3% and 0.9% for annexin II-binding IgG and 11.1%, 4.0% and 1.9% for annexin II-binding IgM for patients with active lupus nephritis, patients with non-lupus renal disease and healthy subjects respectively). In lupus patients, annexin II-binding IgM level was higher at disease flar...
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BackgroundBurkholderia cepacia is a hardy bacterium with intrinsic resistance to multiple antibiotics and high transmissibility. Opportunistic healthcare-associated B. cepacia infections among immunocompromised or critically ill patients... more
BackgroundBurkholderia cepacia is a hardy bacterium with intrinsic resistance to multiple antibiotics and high transmissibility. Opportunistic healthcare-associated B. cepacia infections among immunocompromised or critically ill patients have been reported, but there is limited data on the clinical characteristics and treatment outcomes of exit-site infection (ESI) in peritoneal dialysis (PD) patients.Patients and methodsPatients who suffered from B. cepacia ESI from 1 January 2004 to 31 December 2014 were reviewed. The clinical characteristics and treatment outcomes of the patients and the antibiotic susceptibility patterns of the bacterial isolates were analyzed.ResultsTwenty-two patients were included for analysis. Eight patients (36.4%) had medical conditions which impaired host immunity, while 7 (31.8%) had pre-existing skin abnormalities. Three patients (13.6%) progressed to tunnel-tract infection and another 3 patients (13.6%) developed associated peritonitis. Fifteen patient...
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Lupus nephritis (LN) is a common and severe organ manifestation of systemic lupus erythematosus (SLE), and is associated with significant patient morbidity and mortality. Autoantibodies and aberrations in lymphocyte subsets have putative... more
Lupus nephritis (LN) is a common and severe organ manifestation of systemic lupus erythematosus (SLE), and is associated with significant patient morbidity and mortality. Autoantibodies and aberrations in lymphocyte subsets have putative roles in the pathogenesis of SLE and LN, and might reflect disease activity and are amenable to immunosuppressive treatments. Anti-DNA is one of the well-studied autoantibodies, which correlates with disease activity and has direct nephritogenic effects on resident renal cells and various glomerular components. Other important autoantibodies in the pathogenesis of LN include anti-C1q, anti-α-actinin and anti-nucleosome antibodies. Changes in naive and memory B cells and plasma cells have been observed in SLE and LN patients. These B cell subsets exert diverse effects during pathogenesis of LN such as production of autoantibodies, secretion of proinflammatory and anti-inflammatory cytokines and presentation of auto-antigens to effector cells. Aberrat...
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Gitelman syndrome (GS) is an autosomal recessive renal tubulopathy because of mutations in the gene for the thiazide-sensitive sodium chloride co-transporter in the distal convoluted tubule. GS is characterized by hypokalaemia, secondary... more
Gitelman syndrome (GS) is an autosomal recessive renal tubulopathy because of mutations in the gene for the thiazide-sensitive sodium chloride co-transporter in the distal convoluted tubule. GS is characterized by hypokalaemia, secondary hyperaldosteronism, hypocalciuria and hypomagnesaemia. Little is known about GS in pregnancy. Eplerenone is an aldosterone antagonist and potassium-sparing diuretic used to treat hypertension and cardiac failure. We report the use of eplerenone to treat GS in pregnancy with a successful outcome for mother and baby. A 21 years old nulliparous woman presented with longstanding lethargy, muscle cramps, nausea, thirst and nocturia. Serum potassium was 2.6 mmol/L, urine potassium was inappropriately high consistent with renal loss, there was mild hypomagnesaemia, hypocalcuria and secondary hyperaldosteronism. She denied diuretic use. She had otherwise been well with no significant past medical history. GS was confirmed by DNA sequence analysis revealing compound heterozygosity with pathogenic mutations in exon 18 (2186G > T) and exon 25 (2872A > T) in the SLC12A3 gene. She was intolerant of oral potassium and magnesium supplements, spironolactone and non-steroidal anti-inflammatory drugs because of nausea, and intolerant of amiloride because of tinnitus. Treatment with a combination of eplerenone 50 mg twice a day and perindopril 2.5 mg each morning resulted in resolution of her symptoms and a serum potassium at the lower end of the normal range. After preconception counselling her perindopril was ceased, and she elected to fall pregnant while continuing treatment with eplerenone. Other than intermittent vomiting in first trimester her confinement was uneventful, with her serum potassium ranging between 2.6 and 2.9 mmol/L, a healthy baby girl weighing 3630 g born by vaginal delivery at 39 weeks gestation. The babies’ potassium was normal. Two years post delivery mother and baby are well. Twelve pregnancies to mothers with GS have been described previously, all with an uneventful pregnancy course and excellent outcome, despite inability to normalize maternal serum potassium and magnesium levels even with large doses of oral supplements. The aim in pregnancy should be to give adequate therapy to prevent maternal symptoms. Spironolactone and amiloride have been used in pregnancies complicated by GS syndrome in addition to electrolyte supplementation. Amniotic fluid levels should be monitored as oligohydramnios was reported in 5 of the 12 pregnancies. Eplerenone was used in our mother because of her intolerance to spironolactone, amiloride and oral potassium and magnesium supplements. We are only aware of one previous report of eplerenone use in pregnancy, commenced at 32 weeks gestation in a 41 years old woman with diastolic heart failure. A healthy newborn was delivered, the gestation was not stated. In animal studies the only noticeable risk of foetal abnormalities occurred when laboratory animals were given doses well over 1000 times the recommended daily dose of eplerenone. Eplerenone is category B in pregnancy. The most common side-effect of eplerenone is hyperkalemia, necessitating close monitoring in individuals with diabetes mellitus and proteinuria, heart failure or those who are taking moderate CYP450 3A inhibitors. In conclusion, we report the safe and effective use of eplerenone throughout pregnancy by a mother with GS.
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A dose ratio of 1:1 was recommended for the conversion from Standard-release Tacrolimus (Prograf) to Prolonged-release Tacrolimus (Advagraf). We investigated the trough tacrolimus blood level in Chinese kidney transplant recipients after... more
A dose ratio of 1:1 was recommended for the conversion from Standard-release Tacrolimus (Prograf) to Prolonged-release Tacrolimus (Advagraf). We investigated the trough tacrolimus blood level in Chinese kidney transplant recipients after conversion, including subjects receiving concomitant treatment with diltiazem. Eighteen stable renal allograft recipients were followed prospectively for 12 weeks after conversion from Prograf to Advagraf at the same daily dose. Tacrolimus blood trough level decreased significantly within 8 weeks after conversion (p < 0.01). Twelve patients required escalation of the Advagraf dose by 1.10 ± 0.36 mg. For the whole group the daily tacrolimus dose was increased from 0.057 ± 0.032 mg/kg to 0.068 ± 0.033 mg/kg (p < 0.0001). At week 12 the daily dose of Advagraf was 127 ± 32% of the original daily dose of Prograf. In the subgroup of patients receiving diltiazem, their tacrolimus trough level decreased significantly after conversion (p = 0.001), and the daily tacrolimus dose was increased from 0.060 ± 0.036 mg/kg to 0.073 ± 0.036 mg/kg (p < 0.0001). At week 12, their daily dose of Advagraf was 131 ± 34% of the original daily dose before conversion. To conclude, conversion from Prograf to Advagraf in renal allograft recipients with or without diltiazem co-treatment necessitated an increase in the daily dose by approximately 30% to maintain the target blood trough level unchanged.
Research Interests: Urology, Kidney transplantation, Drug interactions, China, Treatment Outcome, and 15 moreMedicine, Tacrolimus, Therapeutic drug monitoring, Prospective studies, Humans, Female, Renal failure, Male, Clinical Sciences, Middle Aged, Adult, Chi Square Distribution, Graft Rejection, Immunosuppressive Agents, and Antihypertensive agents
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There is little data on mycophenolic acid (MPA) pharmacokinetics and pharmacogenomics and optimal MPA exposure in lupus nephritis (LN) patients during long-term maintenance. We measured blood MPA levels at 1, 2, 4, 8, 10 and 12-h... more
There is little data on mycophenolic acid (MPA) pharmacokinetics and pharmacogenomics and optimal MPA exposure in lupus nephritis (LN) patients during long-term maintenance. We measured blood MPA levels at 1, 2, 4, 8, 10 and 12-h post-dose (i.e. C1, C2, C4, C8, C10 and C12) in 88 stable LN patients receiving maintenance prednisolone and mycophenolate mofetil, repeated every 6 months. The relationship between MPA exposure and single nucleotide polymorphisms (SNPs) of adenosine triphosphate-binding cassette subfamily C member 2 (ABCC2; rs2273697, rs3740066, rs717620 and rs17222723), organic anion-transporting polypeptides (OATPs; rs7311358 and rs4149117) and uridine diphosphate glucuronosyltransferase (UGT; rs17863762, rs6714486, rs17868320 and rs72551330) was also investigated. C1, C2 and C12 were 8.3 ± 6.6 , 7.2 ± 5.2 and 2.0 ± 1.4 mg/L and all correlated with the 12-h area under the curve (AUC0-12; r = 0.51, 0.85 and 0.73; P = 0.02, <0.001 and <0.001, respectively). C12 inver...
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ABSTRACT We report a case of epistaxis due to post-transplant lymphoproliferative disease (PTLD) in a kidney transplant recipient. A 42-year-old Chinese gentleman suffered from end stage renal failure and received living related kidney... more
ABSTRACT We report a case of epistaxis due to post-transplant lymphoproliferative disease (PTLD) in a kidney transplant recipient. A 42-year-old Chinese gentleman suffered from end stage renal failure and received living related kidney transplantation in 2008. He had an episode of antibody-mediated rejection when he was treated with plasmapheresis, intravenous immunoglobulins and pulse corticosteroids. His subsequent maintenance immunosuppression consisted of prednisolone, tacrolimus and mycophenolate mofetil (MMF). He presented with epistaxis 1 year after this episode of rejection. His serum creatinine level was 150 μmol/L and his lactate dehydrogenase level was 290 U/L (ref. range 118-221 U/L). Physical examination revealed no lymphadenopathy. PET-CT scan showed diffuse soft tissue swelling at the right nasopharynx with increase fludeoxyglucose (FDG) uptake (Figure 1). Endoscopic examination revealed a fungating mass and confirmed monomorphic T-cell PTLD. He was managed with reduction of immunosuppression followed by chemotherapy with favorable response.
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Telbivudine is a relatively novel oral nucleoside analogue with favorable efficacy and tolerability in treatment-naïve chronic hepatitis B virus (HBV) infection but its data in kidney transplant recipients (KTRs) was lacking. The efficacy... more
Telbivudine is a relatively novel oral nucleoside analogue with favorable efficacy and tolerability in treatment-naïve chronic hepatitis B virus (HBV) infection but its data in kidney transplant recipients (KTRs) was lacking. The efficacy and tolerability of telbivudine in four treatment-naïve HBsAg-positive KTRs were reviewed [treatment duration: 54 (36-72 moths)]. HBV DNA declined from 2.6x10(5) (7.8x10(3) -1.5x10(7) ) copies/mL at baseline to 170 (0-3.2x10(4) ) copies/mL at 12 months, and became undetectable at 24 and 36 months (p = 0.060, 0.118 and 0.005 compared with baseline). ALT levels dropped from 46.5 (30-48) IU/mL at baseline to 28 (13-45) IU/mL, 34.5 (15-71) IU/mL and 26 (12-41) IU/mL at 12, 24 and 36 months respectively (p = 0.109, 0.715 and 0.068 compared with baseline). Serum creatinine level and eGFR remained stable after 36 months of treatment (p all &amp;amp;amp;amp;gt;0.05 compared with baseline). No virological breakthrough, cirrhosis or hepatocellular carcinoma occurred. Our pilot data suggests that telbivudine has favorable efficacy and renal safety profiles in HBsAg-positive KTRs.
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ABSTRACT Introduction: Renal involvement affects over half of the patients with systemic lupus erythematosus. Lupus nephritis (LN) is an important cause of morbidity, mortality and renal failure. Treatment of LN has evolved over the past... more
ABSTRACT Introduction: Renal involvement affects over half of the patients with systemic lupus erythematosus. Lupus nephritis (LN) is an important cause of morbidity, mortality and renal failure. Treatment of LN has evolved over the past few decades with the advent of new therapeutic options, and the clinical outcome of patients has improved substantially. Areas covered: This review covers data from the clinical studies to date, focusing on the short- and long-term efficacy and safety, on different immunosuppressives, including corticosteroids, cyclophosphamide (CYC), azathioprine (AZA), mycophenolate mofetil (MMF), calcineurin inhibitors (CNI), biologic agents (e.g., anti-CD20, anti-BAFF, CTLA4-Ig) and other novel immunomodulatory drugs. Expert opinion: Initial treatment for active proliferative and/or membranous LN should be corticosteroids combined with either CYC or MMF. MMF has the advantages of improved tolerability and ease of administration, and also higher efficacy in patients of African or Hispanic descent. Preliminary data suggest that CYC treatment may lead to a more sustained response, especially in patients with most severe disease. Low-dose corticosteroids with either MMF or AZA, or CNI, can be used as long-term maintenance immunosuppression, and the choice depends on prior induction treatment, history of relapse, and considerations of pregnancy and finance.
Lupus nephritis (LN) is a common and severe manifestation of systemic lupus erythematosus in Asian patients, and is an important cause of renal failure in Asian countries. Immunosuppressive treatments of LN have evolved over the past few... more
Lupus nephritis (LN) is a common and severe manifestation of systemic lupus erythematosus in Asian patients, and is an important cause of renal failure in Asian countries. Immunosuppressive treatments of LN have evolved over the past few decades and resulted in improvements in patient outcomes. Treatment guidelines have been recently published by rheumatology and nephrology communities in the USA and Europe, but the emphasis was more on patients of African or Hispanic descent and Caucasians. There is increasing evidence that racial and ethnic variations are associated with differences in disease manifestations, pharmacogenomics/kinetics, response to therapy and complications of disease or treatment. There is substantial data confirming the efficacy of combined corticosteroids and either cyclophosphamide or mycophenolate mofetil (MMF) as initial treatments for active Class III/IV LN in Asian patients. Azathioprine, MMF or a calcineurin inhibitor, or possibly mizoribine which requires further investigation in non-Japanese patients, in combination with low-dose corticosteroids, can be considered as maintenance immunosuppression to prevent disease flares, and the optimal choice needs to take into account tolerability and prior induction therapy. Treatment costs and accessibility to specialist healthcare facilities, compliance which in turn is related to socio-economic and education status, as well as regional variations in risk of infections, including subacute infection such as tuberculosis or chronic infections such as hepatitis B or C, are issues that are distinctly pertinent in Asia.
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Chronic hepatitis B virus (HBV) infection adversely influences the clinical outcomes of renal transplant recipients owing to increased hepatic complications. Management of HBV infection in kidney transplant recipients presents a challenge... more
Chronic hepatitis B virus (HBV) infection adversely influences the clinical outcomes of renal transplant recipients owing to increased hepatic complications. Management of HBV infection in kidney transplant recipients presents a challenge to clinicians, especially in endemic regions. Interferon precipitates renal allograft dysfunction. Treatment with lamivudine, the first oral nucleoside analogue available, resulted in effective viral suppression, reduced liver-related complications, and improved patient survival so that medium-term data showed comparable patient survival rates between hepatitis B surface antigen-positive and HBsAg-negative kidney transplant recipients in the era of effective antiviral therapies. Entecavir has replaced lamivudine as first-line therapy for treatment-naïve subjects in view of the propensity for drug resistance with the latter. Management of HBV infection in kidney transplant patients needs to take into consideration the nephrotoxicity of nucleoside/tide analogues such as adefovir and tenofovir. Prevention of HBV-related complications in kidney transplant recipients starts much earlier prior to transplantation, with vaccination of patients with chronic kidney disease and donor-recipient matching with regard to HBV status. In addition to anti-viral treatment, patients with chronic HBV infection must have regular surveillance for liver cancer and assessment for the development of cirrhosis.
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A dose ratio of 1:1 was recommended for the conversion from Standard-release Tacrolimus (Prograf) to Prolonged-release Tacrolimus (Advagraf). We investigated the trough tacrolimus blood level in Chinese kidney transplant recipients after... more
A dose ratio of 1:1 was recommended for the conversion from Standard-release Tacrolimus (Prograf) to Prolonged-release Tacrolimus (Advagraf). We investigated the trough tacrolimus blood level in Chinese kidney transplant recipients after conversion, including subjects receiving concomitant treatment with diltiazem. Eighteen stable renal allograft recipients were followed prospectively for 12 weeks after conversion from Prograf to Advagraf at the same daily dose. Tacrolimus blood trough level decreased significantly within 8 weeks after conversion (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01). Twelve patients required escalation of the Advagraf dose by 1.10 ± 0.36 mg. For the whole group the daily tacrolimus dose was increased from 0.057 ± 0.032 mg/kg to 0.068 ± 0.033 mg/kg (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001). At week 12 the daily dose of Advagraf was 127 ± 32% of the original daily dose of Prograf. In the subgroup of patients receiving diltiazem, their tacrolimus trough level decreased significantly after conversion (p = 0.001), and the daily tacrolimus dose was increased from 0.060 ± 0.036 mg/kg to 0.073 ± 0.036 mg/kg (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001). At week 12, their daily dose of Advagraf was 131 ± 34% of the original daily dose before conversion. To conclude, conversion from Prograf to Advagraf in renal allograft recipients with or without diltiazem co-treatment necessitated an increase in the daily dose by approximately 30% to maintain the target blood trough level unchanged.
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Published literature on fracture in dialysis patients seldom addressed the effect of co-morbidity and malnutrition. In this study, we reported the incidence and risk factors for fracture in peritoneal dialysis patients. Peritoneal... more
Published literature on fracture in dialysis patients seldom addressed the effect of co-morbidity and malnutrition. In this study, we reported the incidence and risk factors for fracture in peritoneal dialysis patients. Peritoneal dialysis patients who had fractures between 2006 and 2011 were recruited. Demographic data, details of fracture, Charlson Co-morbidity Index (CCI) and biochemical parameters were also collected. Non-fracture controls, matched for age, gender and duration of dialysis, were also recruited at ratio 1:1 for fracture risk analysis. The incidence of fracture was 1 in 37 patient-years. The commonest site of fracture was neck of femur (n = 16, 55.2%). Twenty-four patients (82.8%) developed fracture after slip and fall injury. Eight out of 17 self-ambulatory patients (47.1%) became non-ambulatory after fracture. Infection was the commonest complication during hospitalization. Univariant analysis demonstrated high CCI (P = 0.001), hypoalbuminaemia (P < 0.001), loss of self autonomy (P = 0.006) and non-ambulatory state (P = 0.011) significantly associated with increased fracture risk. However, only CCI (odds ratio (OR) 1.373, P = 0.028) and albumin (OR 0.893, P = 0.025) increased fracture risk significantly on multivariant analysis. Bone profile and parathyroid hormone were not significant risk factors. To conclude, fracture associated with adverse outcome in peritoneal dialysis patients. High CCI score and hypoalbuminaemia significantly increase risk of fracture.
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The prevalence and severity of sleep apnea (SA) in the chronic kidney disease (CKD) population is not well characterized. Recent studies have yielded highly variable prevalence rates due to cohort heterogeneity and interstudy... more
The prevalence and severity of sleep apnea (SA) in the chronic kidney disease (CKD) population is not well characterized. Recent studies have yielded highly variable prevalence rates due to cohort heterogeneity and interstudy inconsistencies in defining SA. This study sought to determine the association of SA with CKD by recruiting a uniform cohort to undertake overnight polysomnography (PSG). A total of 141 male Chinese CKD patients, ages 40-60 years, underwent overnight PSG to delineate the prevalence and severity of SA and nocturnal hypoxemia (NH). Body mass index (BMI), neck girth, estimated glomerular filtration rate, urinary protein excretion and Epworth sleepiness scale (ESS) score were collected at baseline to determine associative factors. The prevalence rates of SA and NH were 35.5 and 10.6%, respectively, in this study population [mean (±SD) age 51.44 ± 6.05 years; BMI 26.05 ± 4.22 kg/m(2)]. The adjusted odds ratios (ORs) for SA by BMI and proteinuria were 1.18 [95% confi...
Research Interests:
Hydralazine is an effective antihypertensive drug which acts by vasodilatation. It is well known to cause drug-induced lupus erythematosus. Nevertheless, the overall safety profile is good and cutaneous adverse effects are uncommon. To... more
Hydralazine is an effective antihypertensive drug which acts by vasodilatation. It is well known to cause drug-induced lupus erythematosus. Nevertheless, the overall safety profile is good and cutaneous adverse effects are uncommon. To the best of our knowledge, hydralazine has never been reported to cause Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN). We herein report the first case of hydralazine-induced TEN in a patient with end-staged renal failure. Despite meticulous wound management and intensive medical care, the patient died of a sudden cardiac arrest on day 10 of admission. We speculate that patients with renal failure may be predisposed to a higher risk of allergy to drug entities that are rarely associated. Physicians should be aware that hydralazine can be a potential cause for severe allergic reaction such as SJS or TEN, particularly in the setting of poor renal excretory function. Patient education and cautious monitoring by physicians are essentia...