Maggie M.Y. Mok

Amiodarone-Induced Thyrotoxicosis Is a Predictor of Adverse Cardiovascular Outcome

BACKGROUND Amiodarone-induced thyrotoxicosis (AIT) is a clinical condition that is notoriously difficult to manage; the relative risk of adverse cardiovascular events in these patients compared with euthyroid patients is largely unknown. OBJECTIVE We compared the clinical characteristics and major adverse cardiovascular events (MACE) in AIT and euthyroid patients. METHOD Patients at a tertiary referral center who had been prescribed amiodarone for at least 3 months were retrospectively analyzed. Baseline clinical characteristics, laboratory parameters, and outcome events were evaluated. MACE was defined as cardiovascular mortality, myocardial infarction, stroke and heart failure, or ventricular arrhythmias that required hospitalization. RESULTS A total of 354 patients (61.8 +/- 14.1 yr; 64.7% male) with a mean follow-up of 48.6 +/- 26.7 months were studied. AIT, euthyroid status, and amiodarone-induced hypothyroidism were identified in 57 (16.1%), 224 (63.3%), and 73 (20.6%) patients, respectively. No differences in baseline clinical characteristics were observed between AIT and euthyroid patients. Nonetheless AIT patients demonstrated a higher MACE rate (31.6 vs. 10.7%, P < 0.01), mostly driven by a higher rate of ventricular arrhythmias that required admission (7.0 vs. 1.3%, P = 0.03). Cox-regression multivariate analysis revealed that AIT (hazard ratio 2.68; confidence interval 1.53-4.68; P < 0.01) and left ventricular ejection fraction less than 45% (hazard ratio 2.52; confidence interval 1.43-4.42; P < 0.01) were independent predictors of MACE. CONCLUSION In patients prescribed long-term amiodarone therapy, occurrence of AIT is associated with a 2.7-fold increased risk of MACE. Regular and close biochemical surveillance is thus advisable to identify and treat this high-risk group of patients.

Long-term data on corticosteroids and mycophenolate mofetil treatment in lupus nephritis

OBJECTIVE We investigated the long-term outcome of patients with proliferative LN treated with CSs and MMF. METHODS This was a single-centre retrospective study on patients with biopsy-proven class III/IV ± V LN treated with prednisolone and MMF continuously as both early and maintenance immunosuppression. RESULTS Sixty-five patients were included, and followed for 91.9 (47.7) months. All received prednisolone and MMF as induction immunosuppression. In 31 patients, maintenance immunosuppression comprised prednisolone and MMF only (MMF-MMF group). MMF was replaced with AZA in 23 patients (MMF-AZA), and with calcineurin inhibitors (CNIs) in 11 patients (MMF-CNI) at sometime during follow-up. Ten-year patient and renal survival rates were 91% and 86%, respectively, and were similar in the three groups. MMF-MMF group showed better relapse-free survival than MMF-AZA and MMF-CNI patients (76% vs 56% vs 43%, respectively at 5 years; 69% vs 32% vs 0%, respectively at 10 years; MMF-MMF vs MMF-AZA or MMF-CNI, P = 0.049 or 0.019, respectively; MMF-AZA vs MMF-CNI, P = 0.490). Patients treated with MMF for >24 months had better relapse-free survival than those treated for shorter durations (88% vs 48% at 5 years; 81% vs 28% at 10 years; P < 0.001). Renal function at 10 years was better in the MMF-MMF group. Anaemia was associated with MMF treatment. Other adverse events were comparable and relatively minor with MMF, AZA or CNI as maintenance. CONCLUSION Long-term treatment with CSs and MMF from induction to maintenance phase is associated with relatively favourable long-term outcome in Chinese LN patients. Discontinuation of MMF before 24 months may increase the risk of flares.

Long-term data on tacrolimus treatment in lupus nephritis

OBJECTIVE Calcineurin inhibitors are effective immunosuppressants. They also reduce proteinuria in glomerular diseases but are potentially nephrotoxic. Short-term data suggest that tacrolimus (TAC) combined with corticosteroids is effective in LN, but long-term data are lacking. This study examined the long-term outcomes and tolerability of TAC for the treatment of LN. METHODS We retrospectively reviewed 29 LN patients who received TAC treatment for 46.9 months (s.d. 37.9). RESULTS In 17 patients with class III/IV or V LN and persistent proteinuria >2 g/day despite induction immunosuppression, response rates after 12 and 24 months of add-on TAC treatment were 66.7% and 80.0%, respectively. In 10 patients with nephrotic syndrome due to class V LN who were given prednisolone and TAC as initial treatment, the response rate was 60.0% and 90.0% after 12 and 24 months, respectively. TAC facilitated steroid minimization in two patients with lupus podocytopathy. As a group, proteinuria decreased from 3.6 g/day (s.d. 2.6) to 1.0 (s.d. 1.1) (P < 0.05). Four patients developed end-stage renal failure, with 3-, 5- and 8-year renal survival rates of 93%, 83% and 83%, respectively. In the remaining patients, serum creatinine and estimated GFR remained stable after 36 months. One patient with pre-existing chronic renal failure developed TAC nephrotoxicity. Four renal flares occurred, all associated with low TAC blood levels. Six patients (20.1%) had deterioration of hypertension and one patient (3.4%) had new-onset diabetes mellitus. Six patients (20.1%) had infections that required hospitalization. Two deaths occurred: one due to pneumonia and one to breast cancer. CONCLUSION The results suggest efficacy of TAC in LN, especially in reducing proteinuria, and its role as a long-term maintenance agent warrants further investigation.

Entecavir Treatment in Kidney Transplant Recipients Infected with Hepatitis B

Although nucleotide/side analogs improve the clinical outcome of hepatitis B surface antigen‐positive (HBsAg+) kidney transplant recipients (KTR), a significant proportion of subjects have developed resistance to lamivudine (LAM). We retrospectively analyzed the efficacy and tolerability of entecavir (ETV) in HBsAg+ KTR at Queen Mary Hospital during 2005–2013. Twenty‐one patients (10 treatment‐naïve, 11 with LAM resistance) were included (duration of ETV treatment 34.7 ± 22.9 months, range 6–75 months). ETV treatment led to a decline of hepatitis B virus (HBV) DNA titer compared to baseline and is more significant in the treatment‐naïve group (treatment‐naïve: p = 0.028, <0.001 and <0.001; LAM‐resistant p = 0.273, 0.180, and 0.109 after 12, 24, and 36 months). The cumulative rate of HBV DNA undetectability at 12, 24, and 36 months was 60%, 100%, and 100% for treatment‐naïve group, and 27%, 45%, and 45% for LAM‐resistant group, respectively. Time‐to‐HBV DNA undetectability and time‐to‐alanine transaminase (ALT) normalization were 15.7 ± 4.6 and 12.6 ± 3.7 months for treatment‐naïve patients, and 24.5 ± 4.2 and 28.2 ± 3.5 months for those with LAM resistance. Genotypic resistance to ETV emerged after 20.0 ± 3.5 months with increase in ALT and HBV DNA in two patients with LAM resistance, but was not observed in the treatment‐naïve group. Allograft dysfunction, de novo cirrhosis, or hepatocellular carcinoma did not occur during follow‐up.

Significant reduction of Tacrolimus trough level after conversion from twice daily Prograf to once daily Advagraf in Chinese renal transplant recipients with or without concomitant diltiazem treatment.

Abstract 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.

Longterm Data on Disease Flares in Patients with Proliferative Lupus Nephritis in Recent Years

Objective. To examine the disease flare rate in lupus nephritis (LN), focusing on renal flares, and the factors associated with relapse risk in recent years. Methods. 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). Results. 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 significantly better in patients treated with prednisolone and MPA as maintenance immunosuppression (91% after 5 yrs and 83% after 10 yrs, respectively) compared with prednisolone and AZA (70% and 52%, respectively, p = 0.044). LN diagnosed in 1998–2013 showed 5-year and 10-year relapse-free survival rates of 93% and 86%, respectively, compared with 81% and 66%, respectively (p = 0.017) for LN that presented in 1983–1997. Conclusion. Our data show a relatively low flare rate for LN in the more recent era, attributed to effective induction of immunosuppression and MPA as maintenance treatment.

High Prevalence of Vitamin D Insufficiency in Southern Chinese Renal Transplant Recipients

Vitamin D deficiency is common globally. There is evidence that vitamin D status may be related to immune function and cardiovascular disease. The vitamin D status of Chinese kidney transplant recipients has never been investigated. We performed a cross-sectional study and measured the level of 25-hydroxyvitamin D [25(OH)D] in 94 Chinese renal transplant recipients with stable allograft function. Vitamin D deficiency and insufficiency were detected in 43.6% and 54.2% of patients, respectively. About 53.2% of the patients also had elevated parathyroid hormone (PTH) levels. The level of 25(OH)D was lower in kidney transplant recipients compared with healthy controls matched for age and sex (52.5 ± 15.6 nmol/L vs. 57.5 ± 19.0 nmol/L, p = 0.05), but the level of serum creatinine was higher in kidney transplant recipients (120.3 ± 48.5 μmol/L and 78.3 ± 15.3 μmol/L, p < 0.01). The level of 25(OH)D was negatively correlated with that of PTH (p = 0.001). The latter was associated with serum creatinine (p = 0.001) and duration of dialysis (p = 0.001). Patients with a history of acute rejection showed lower levels of 25(OH)D (45.3 ± 11.9 nmol/L vs. 54.2 ± 16.0 nmol/L, p = 0.003). We conclude that vitamin D deficiency is prevalent among Chinese renal transplant recipients. In view of the potential immunomodulatory effect of vitamin D, the relationship between vitamin D level and rejection and the effect of vitamin D supplementation in renal transplant recipients warrant further investigations.

Non‐invasive assessment of kidney allograft fibrosis with shear wave elastography: A radiological‐pathological correlation analysis

To evaluate the use of shear wave elastography in assessment of kidney allograft tubulointerstitial fibrosis.

Arthrobacter sanguinis: An uncommon cause of peritonitis in a peritoneal dialysis patient

We report the first case of Arthrobacter sanguinis peritonitis in a peritoneal dialysis (PD) patient. This 63-year-old gentleman suffered from end stage renal failure due to unknown cause and had been on peritoneal dialysis (PD) since 2013. He also had chronic eczema and received long-term topical corticosteroids. He presented with turbid PD effluent (total PD fluid cell count 1096/cm (neutrophil 91%)) but with no abdominal pain or exit site infection. He was empirically treated with intraperitoneal clindamycin and amikacin due to allergy to vancomycin and penicillin. Gram smear of PD fluid showed coryneform Gram-positive bacilli and the identity of Arthrobacter sanguinis was confirmed by Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry (MALDI-TOF-MS) (Bruker Daltonik, Bremen, Germany) and 16S rRNA sequencing. The strain was tested to be sensitive to Penicillin G but moderately sensitive to clindamycin. His peritonitis resolved with 2 weeks of intravenous ceftriazone after desensitization in the intensive care unit. Arthrobacter are Gram-positive bacilli commonly found in the environment. Fulminant Arthrobacter infection have been reported to cause endophthalmitis after intra-ocular implantation, infective endocarditis in intravenous drugabuser, fetal demise and disseminated intravascular coagulation in a pregnant woman and catheter-related bacteremia in a leukemic patient. The possible predisposing factors in this patient include renal failure, malnutrition and the long-term use of topic corticosteroids. Arthrobacter infection often presents a diagnostic challenge due to the difficulty of identification by conventional biochemical assays. Identification by sophisticated molecular methods such as MALDI-TOF-MS and gene sequencing is often required. Our experience suggested that Arthrobacter peritonitis can be successfully treated with appropriate parenteral antibiotics without the need for catheter removal.

Epistaxis in a kidney transplant recipient: An uncommon presentation of post-transplant lymphoproliferative disease

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 one year after this episode of rejection. His serum creatinine level was 150 mmol/L and his lactate dehydrogenase level was 290 U/L (ref. range 118–221 U/L). Physical examination revealed no lymphadenopathy. Positron emission tomography (PET)-computed tomography (PET-CT) scan showed diffuse soft tissue swelling at the right nasopharynx with increase fludeoxyglucose (FDG) uptake (Fig. 1). Endoscopic examination revealed a fungating mass and confirmed monomorphic T-cell PTLD. He was managed with reduction of immunosuppression followed by chemotherapy with favourable response. Epistaxis is usually related to benign causes like local trauma, rhinitis or sinusitis. However, in the Asia-Pacific region where there is high prevalence of Epstein-Barr virus (EBV)-positivity, sinister conditions like nasopharyngeal carcinoma and lymphoproliferative diseases should also be considered. PTLD is a serious complication after solid organ transplantation, occurring in 1–5% of kidney allograft recipients. Although PTLD are usually of B-cell lineage, Tand NK-cell lymphoma is not uncommon in patients of Asian descent. The intense immunosuppressive treatment for rejection had predisposed our patient to this complication. In line with one recent report, our patient had favourable treatment response to reduction of immunosuppression and chemotherapy. In Asian renal transplant recipients who presented with epistaxis, especially those who had received potent immunosuppression previously, clinicians should be vigilant of post-transplant malignancies like PTLD and nasopharyngeal carcinoma.