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Background Various glomerular pathologies have been reported in patients who have undergone haematopoietic stem cell transplantation (HSCT), but the data on clinico-pathological correlations and clinical outcome remain limited. Methods We analysed the clinical and histopathological data of patients who had biopsy-proven de novo glomerular diseases after HSCT since 1999. Results A total of 2204 patients underwent HSCT during the period 1999–2021, and 31 patients (1.4%) developed de novo glomerular diseases after a mean duration of 2.8 ± 2.7 years after HSCT. Fifteen of these patients (48.4%) had graft-versus-host-disease prior to or concomitant with renal abnormalities. Proteinuria and eGFR at the time of kidney biopsy were 4.1 ± 5.3 g/day and 50.8 ± 25.4 mL/min/1.73 m2, respectively. Kidney histopathologic diagnoses included thrombotic microangiopathy (TMA) (38.7%), membranous nephropathy (MN) (25.8%), mesangial proliferative glomerulonephritis (12.9%), minimal change disease (9.7%), focal segmental glomerulosclerosis (9.7%) and membranoproliferative glomerulonephritis (3.2%). Immunosuppressive treatment was given to patients who presented with nephrotic-range proteinuria and/or acute kidney injury, while renin–angiotensin–aldosterone blockade was given to all patients with proteinuria ≥1 g/day, with complete and partial response rates of 54.8% and 19.4%, respectively. One patient with TMA progressed to end-stage kidney disease after 24 weeks, and two patients, one with TMA and one with MN, (6.4%) progressed to chronic kidney disease (CKD) Stage ≥3. Kidney and patient survival rates were 96.6% and 83.5%, respectively, at 5 years. Conclusion De novo glomerular diseases with diverse histopathologic manifestations affect 1.4% of patients after HSCT, and approximately 10% develop progressive CKD.

Background Current ways to diagnose citrate accumulation (CA) in patients receiving regional citrate anticoagulation (RCA) continuous renal replacement therapy (CRRT) are confounded by various clinical factors. Serum citrate measurement emerges as a more direct way to diagnose CA, but its clinical utility and optimal cut-off values remain undefined. This study examined serum citrate kinetics and its diagnostic performance for CA in patients receiving RCA CRRT. Methods A multicentre prospective study was carried out in two tertiary referral centre intensive care units in Hong Kong with serum citrate levels measured at baseline and 2, 6, 12, 24, 36, 48 and 72 h after initiation of RCA CRRT and their relationships with the development of CA. Results Among the 133 patients analysed, 18 patients (13.5%) developed CA. The serum citrate levels at baseline and 2, 6 and 12 h after initiation of RCA CRRT in patients who had CA were significantly higher than the non-CA group (P Conclusion Serum citrate levels were significantly higher in patients with CA compared with patients without CA. Serum citrate levels showed good performance in diagnosing and predicting the development of CA.

Background: Dysnatraemias are commonly reported in COVID-19. However, the clinical epidemiology of hypernatraemia and its impact on clinical outcomes in relation to different variants of SARS-CoV-2, especially the prevailing Omicron variant, remain unclear. Methods: This was a territory-wide retrospective study to investigate the clinical epidemiology and outcomes of COVID-19 patients with hypernatraemia at presentation during the period from 1 January 2020 to 31 March 2022. The primary outcome was 30-day mortality. Key secondary outcomes included rates of hospitalization and ICU admission, and costs of hospitalization. Results: In this study, 53,415 adult COVID-19 patients were included for analysis. Hypernatraemia was observed in 2688 (5.0%) patients at presentation, of which most cases (99.2%) occurred during the local “5th wave” dominated by the Omicron BA.2 variant. Risk factors for hypernatraemia at presentation included age, institutionalization, congestive heart failure, dementia, higher SARS-CoV-2 Ct value, white cell count, C-reactive protein and lower eGFR and albumin levels (p < 0.001 for all). Patients with hypernatraemia showed significantly higher 30-day mortality (32.0% vs. 5.7%, p < 0.001) and longer lengths of stay (12.9 ± 10.9 vs. 11.5 ± 12.1 days, p < 0.001) compared with those with normonatraemia. Multivariate analysis revealed hypernatraemia at presentation as an independent predictor for 30-day mortality (aHR 1.32, 95% CI 1.14–1.53, p < 0.001) and prolonged hospital stays (OR 1.55, 95% CI 1.17–2.05, p = 0.002). Conclusions: Hypernatraemia is common among COVID-19 patients, especially among institutionalized older adults with cognitive impairment and other comorbidities during large-scale outbreaks during the Omicron era. Hypernatraemia is associated with unfavourable outcomes and increased healthcare utilization.

AIM To evaluate the demographics and long-term patient outcomes of children with end-stage kidney disease in Hong Kong. METHODS We conducted a cohort study at the Paediatric Nephrology Centre, the designated site providing kidney replacement therapy (KRT) for children in Hong Kong. The clinical characteristics and outcomes of all children who initiated chronic KRT before 19 years, between 2001-2020, were analyzed. RESULTS 147 children (50% male) received KRT at a mean age of 11.4±5.7 years. The incidence of ESKD was 6.28 per million age-related population (pmarp). The leading cause of ESKD was congenital anomalies (33%). 10 children (7%) had pre-emptive kidney transplants, 104 (71%) and 33 (22%) patients received automated peritoneal dialysis and haemodialysis as initial KRT. The incidence of ESKD increased over time, and were 4.38, 5.07, 6.15 and 9.17 pmarp during 2001-2005, 2006-2010, 2011-2015 and 2016-2020, respectively (p=0.005). 97 patients (66%) received kidney transplants and the median time to receive a kidney graft was 3.7 years (95% CI 3.1-4.3). Only 10 patients had pre-emptive kidney transplants. The mortality rate was 9.1 deaths per 1000-patient-years (95%CI 4.6-16.2). The survival probabilities at 1-, 5-, 10- and 15-year were 100%, 94.8% (95%CI 90.7-98.9%), 89.7% (95% CI 83.4%-95.9%), 87.1% (95% CI 79.3%-94.9%), respectively. Standardized mortality ratio was 54.5. 72% of deaths were due to infections. Young infants and those without kidney transplants were associated with worse survival (p

Background The impact of contrast-induced acute kidney injury (CI-AKI) on long-term major adverse cardiovascular events (MACE) remains controversial. Method This was a retrospective cohort study from 14 hospitals under the Hospital Authority of Hong Kong between 2004 and 2017. Severe CI-AKI was defined as an increase in serum creatinine of >50% from the baseline value, an absolute increase of >1 mg/dL (88 μmol/L) or requiring dialysis after percutaneous coronary intervention (PCI). Mild CI-AKI was defined as an increase in serum creatinine of >25% from the baseline value or an absolute increase of >0.5 mg/dL (44 μmol/L) after PCI but not fulfilling the criteria for severe CI-AKI. The primary endpoint was MACE, defined as a composite outcome of all-cause mortality, non-fatal myocardial infarction after hospital discharge, stroke or any unplanned coronary revascularization, in a time-to-first-event analysis up to 5 years after PCI. The secondary endpoints were individual components of MACE and cardiovascular mortality. Results A total of 34 576 patients were analysed. After adjustment for cardiovascular risk factors, procedural characteristics and medication use, the risk of MACE at 5 years was significantly higher with mild CI-AKI {hazard ratio [HR], 1.18 [95% confidence interval (CI) 1.12–1.26); P Conclusions Among patients undergoing a first-ever PCI, CI-AKI of any severity was associated with a higher adjusted risk of MACE at 5 years. Severe CI-AKI has a stronger association with MACE and its individual components, with an excess of early and late events.

Blockade of the binding between neonatal Fc receptor and IgG‐Fc reduces circulating IgG, and thus emerges as a potential therapy for IgG‐mediated autoimmune conditions. This was a double blind, randomized, single ascending dose study to evaluate the safety, pharmacokinetics, and pharmacodynamics of HBM9161 (a fully humanized Fc receptor monoclonal antibody) in healthy Chinese volunteers. Subjects were randomized to receive a single s.c. dose of HBM9161 or placebo in a 3:1 ratio in 3 dosing cohorts (340 mg, 510 mg, or 680 mg, respectively), and then followed up for 85 days. Study end points included incidence of adverse event (AE), serum drug concentration, IgG and its subclasses, and anti‐drug antibodies (ADAs). Twenty‐four subjects were randomized. Dose‐dependent reduction of total IgG occurred rapidly from baseline to reach nadir at day 11, then recovered steadily from day 11 to day 85. The mean maximum percentage reductions from baseline total IgG were 21.0 ± 9.3%, 39.8 ± 5.13%, and 41.2 ± 10.4% for subjects receiving HBM9161 340 mg, 510 mg, and 680 mg, respectively. The exposure of HBM9161 (areas under the curve [AUCs] and peak plasma concentration [Cmax]) increased in a more than dose‐proportional manner at the dose examined. All reported AEs were mild in severity. The most reported AEs in the HBM9161 groups were influenza‐like illness and rash. Two subjects developed ADA during the study period. A single s.c. dose of HBM9161 results in sustained and dose‐dependent IgG reduction, and was well‐tolerated at a dose up to 680 mg in Chinese subjects. The data warrant further investigation of its effects in IgG‐mediated autoimmune disorders.

Human leukocyte antigen (HLA)-B*58:01 allele is a significant risk factor for allopurinol-induced severe cutaneous adverse reactions (SCARs) which is potentially fatal. In some studies, chronic kidney disease (CKD) was also implicated to compound the risk of SCARs. We aim to investigate if pre-treatment HLA-B*58:01 screening can prevent allopurinol-induced SCARs in Chinese patients with CKD and its cost-effectiveness. We prospectively recruited Chinese CKD patients who required allopurinol during 2011–2015 and performed pre-treatment HLA testing (HLA screening group). Patients tested positive for HLA-B*58:01 were refrained from allopurinol while those tested negative were prescribed allopurinol. The incidence of SCARs in the HLA screening group was compared with the historical control in previous 5 years and the cost-effectiveness of HLA testing was analyzed. In the historical control (2006–2010), 3605 patients on allopurinol were screened, 22 out of 1027 (2.14%) CKD Chinese patients newly started on allopurinol developed SCARs, including 6 SJS/TEN. In the HLA screening group, 28 out of 192 patients (14.6%) tested HLA-B*58:01 positive were advised to avoid allopurinol; 156 out of 164 HLA-B*58:01-negative patients received allopurinol and none developed SCARs. The incidence rate of SCARs was significantly lower in the HLA screening group compared with controls (0% vs 2.14% respectively, p = 0.037*). The targeted HLA screening approach was associated with lower healthcare costs compared with no HLA screening (US$ 92,430 vs US$ 281,226). Pre-treatment HLA-B*58:01 screening is cost-effective to target on patients with CKD in Chinese to prevent allopurinol-induced SCARs.

AIM Darbepoetin alpha is available as Aranesp® and NESP®, which differ in the inactive component and maximum dose-strength of prefilled syringes. We conducted an observational cohort study to investigate optimal conversion strategies and the feasibility of extending dosing intervals with higher-dose preparations in dialysis patients converting from Aranesp® to NESP®. METHODS Adult dialysis patients on Aranesp® with stable haemoglobin of 9-12 g/dL were converted to NESP® at the same monthly total dose according to one of three conversion regimens. Group A included patients on ≤80 mcg/month of Aranesp® who converted with dosing regimen unchanged. Group B patients converted to NESP® with extended dosing intervals using higher individual dose preparations. Group C were patients on 100 mcg Aranesp® who converted to NESP® 120 mcg with extended dosing intervals. Patients were observed for 6 months. RESULTS Fifty patients were included. All 24 Group A patients maintained stable haemoglobin. In Group B, 10 patients (50%) maintained stable haemoglobin with extension of dosing interval from 1.04 ± 0.14 to 3.03 ± 1.28 weeks. Factors associated with success in extending dosing interval included a lower prevalence of cardiovascular disease and a higher Kt/Vurea in peritoneal dialysis patients. Four patients (80%) in Group C maintained stable haemoglobin after conversion to NESP® 120 mcg with extended dosing interval. The use of NESP® 120 mcg was well tolerated, and was associated with reduced patient-reported pain score and 38% reduction of drug cost. CONCLUSION Dialysis patients on Aranesp® can be successfully converted to NESP® and the dosing interval can be extended successfully in a significant proportion of patients, which could reduce discomfort and drug cost.

BACKGROUND Structured advance care planning (ACP) program is an important service in the end-of-life care for patients with advanced medical illness. We pioneered a structured and coordinated ACP program for patients with advanced malignancies and end-stage organ failure in Hong Kong. This study investigated the impact of a structured ACP program on the concordance rate for patients' final wishes, patient/family satisfaction, and the number of acute admissions (AA) and length of stay (LOS) in hospital. METHODS Patients with advanced malignancy or end-stage organ failure who were able to complete ACP forms during the current admission to medical units were recruited. Patients who could not complete ACP forms or

Renal anaemia is a common and important complication in patients with chronic kidney disease (CKD). The current standard‐of‐care treatment for renal anaemia in CKD patients involves ensuring adequate iron stores and administration of erythropoietin stimulating agents (ESA). Hypoxia inducible factor (HIF) is a key transcription factor primarily involved in the cellular regulation and efficiency of oxygen delivery. Manipulation of the HIF pathway by the use of HIF‐prolyl hydroxylase inhibitors (HIF‐PHI) has emerged as a novel approach for renal anaemia management. Despite it being approved for clinical use in various Asia‐Pacific countries, its novelty mandates the need for nephrologists and clinicians generally in the region to well understand potential benefits and harms when prescribing this class of drug. The Asian Pacific society of nephrology HIF‐PHI Recommendation Committee, formed by a panel of 11 nephrologists from the Asia‐Pacific region who have clinical experience or have been investigators in HIF‐PHI studies, reviewed and deliberated on the clinical and preclinical data concerning HIF‐PHI. This recommendation summarizes the consensus views of the committee regarding the use of HIF‐PHI, taking into account both available data and expert opinion in areas where evidence remains scarce., SUMMARY AT A GLANCE The Asian Pacific society of nephrology HIF‐PHI Recommendation Committee summarizes the consensus views of the committee regarding the use of HIF‐PHI, taking into account both available data and expert opinion in areas where evidence remains scarce.

Aim To study the epidemiology and clinical outcomes of catheter-related infections of Serratia species in peritoneal dialysis (PD) patients. Methods We retrospectively reviewed the patient characteristics, antibiotics susceptibility/resistance patterns and treatment outcomes of exit site infection (ESI) and peritonitis due to Serratia in PD patients during the period of 2004 to 2017. Results One hundred and sixty-one patients had Serratia ESI, of which 10 (6.2%) progressed to tunnel tract involvement and 11 (6.8%) developed PD peritonitis. Nineteen (11.8%) patients with Serratia ESI failed to respond to medical treatment and required catheter removal. Fifty-six (34.8%) patients had repeat Serratia ESI, which occurred at 12.9 ± 13.6 months after the previous episode. Twenty-two patients had Serratia peritonitis, which accounted for 1% of peritonitis during the study period. Ten (45.5%) patients responded to medical treatment while 12 (54.5%) patients required catheter removal. Nine patients (36.4%) failed to resume PD and were converted to long-term haemodialysis. Two patients had repeat peritonitis at 2 months and 3 years, respectively, after the initial episode. Serratia species in PD patients showed high rates of resistance to ampicillin, and first- and second-generation cephalosporins, but were generally susceptible to aminoglycosides, carboxy-/ureido-penicillins and carbapenems. Conclusion Our results suggest that Serratia ESI show low risk of progression to peritonitis and favourable response to medical therapy, while Serratia peritonitis was associated with high rates of catheter removal and peritoneal failure.

Background/Aims: Data on treatment efficacy and safety of glecaprevir/pibrentasvir (GLE/PIB) for chronic hepatitis C virus (HCV) infection in Asian patients with severe renal impairment are limited. This study aimed to study the treatment and side effects of GLE/PIB in these patients infected with non-1 genotype (GT) HCV.Methods: We prospectively recruited patients with Child’s A cirrhosis and eGFR 2 in Hong Kong and Taiwan during 2017–2018 to receive GLE/PIB treatment.Results: Twenty-one patients (GT2, n=7; GT3, n=6; and GT6, n=8) received GLE/PIB for 11.2±1.8 weeks. All except one were treatment-naïve. GLE/PIB was initiated in 16 patients while on dialysis (seven on peritoneal dialysis [PD] and nine on hemodialysis) and in five patients before dialysis. One patient died of PD-related peritonitis during treatment and two were lost to follow up. The SVR12 rate in the remaining 18 patients was 100%. All patients achieved undetectable levels at 4-, 12-, 24- and 48-week after treatment. Patients with deranged alanine aminotransferase showed normalization after 4 weeks and the response was sustained for 48 weeks. No significant adverse event was observed.Conclusions: GLE/PIB treatment was associated with high efficacy and tolerability in HCV-infected patients with severe renal impairment.

Background The potential long-term safety and efficacy of aliskiren in nondiabetic chronic kidney disease (CKD) are unknown. We sought to investigate the renoprotective effect of aliskiren on nondiabetic CKD patients. Methods In this open-label, parallel, randomized controlled trial, nondiabetic CKD Stages 3–4 patients were randomized to receive aliskiren added to an angiotensin II receptor blocker (ARB) at the maximal tolerated dose, or ARB alone. Primary outcome was the rate of change in estimated glomerular filtration rate (eGFR). Secondary endpoints included rate of change in urine protein-to-creatinine ratio (UPCR), cardiovascular events and hyperkalemia. Composite renal outcomes of doubling of baseline serum creatinine or a 40% reduction in eGFR or incident end-stage renal disease or death were analyzed as post hoc analysis. Results Seventy-six patients were randomized: 37 to aliskiren (mean age 55.1 ± 11.1 years) and 39 to control (mean age 55.0 ± 9.4 years). Their baseline demographics were comparable to eGFR (31.9 ± 9.0 versus 27.7 ± 9.0 mL/min/1.73 m2, P = 0.05) and UPCR (30.7 ± 12.6 versus 47.8 ± 2.8 mg/mmol, P = 0.33) for treatment versus control subjects. After 144 weeks of follow-up, there was no difference in the rate of eGFR change between groups. Six patients in the aliskiren group and seven in the control group reached the renal composite endpoint (16.2% versus 17.9%, P = 0.84). The cardiovascular event rate was 10.8% versus 2.6% (P = 0.217). The hyperkalemia rate was 18.9% versus 5.1% with an adjusted hazard ratio of 7.71 (95% confidence interval 1.14 to 52.3, P = 0.04) for the aliskiren arm. Conclusion Aliskiren neither conferred additional renoprotective benefit nor increased adverse events, except for more hyperkalemia in nondiabetic CKD patients.

Background Patients on dialysis are hyporesponsive to the hepatitis B virus vaccines (HBVv). We examined intradermal (ID) HBVv Sci-B-Vac, with topical Toll-like receptor 7 (TLR7) agonist imiquimod pretreatment in dialysis patients. Methods We enrolled and prospectively followed adult patients on dialysis between January 2016 and September 2018. Eligible patients were randomly allocated (1:1:1) into 1 treatment group, topical imiquimod cream followed by ID HBVv (IMQ + ID); and 2 control groups: topical aqueous cream (placebo) followed by ID HBVv (AQ + ID) or topical aqueous cream followed by intramuscular HBVv (AQ + IM). The primary endpoint was the seroprotection rate (hepatitis B surface antibody ≥10 mIU/mL) at 52 weeks. Results Ninety-four patients were enrolled, among which 57.4% were previous nonresponders. Seroprotection rate was significantly better at week 52 for the IMQ + ID group with 96.9% compared to 74.2% and 48.4% for AQ + ID and AQ + IM groups, respectively (P < .0001). The geometric mean concentration was significantly higher at week 52 for the IMQ + ID group: 1135 (95% confidence interval [CI], 579.4–2218.2) mIU/mL, compared to 86.9 (95% CI, 18.5–409.3) mIU/mL and 7.2 (2.0–26.5) mIU/mL for the AQ + ID and AQ + IM groups, respectively (P < .0001). IMQ + ID vaccination (odds ratio, 3.70 [95% CI, 1.16–11.81]; P = .027) was the only factor independently associated with higher 52-week seroprotection rate. Adverse reaction was infrequent. Conclusions Pretreatment with topical imiquimod before ID HBVv Sci-B-Vac was safe with favorable seroprotection in dialysis patients. Clinical Trials Registration NCT02621112.

Palliative care (PC) has expanded to medical conditions beyond its conventional scope of terminal malignancy and end-stage organ failure. This editorial showed our opinion in care model for the integration of PC into rheumatology and the growing needs of both rheumatology and PC services in view of increasing comorbidities and novel therapies. We anticipate an escalating demand for PC in this special group of patients who have concomitant long-standing systemic rheumatic diseases and age-related comorbidities. In addition, patients with advanced malignancy who develop rheumatological problems and require PC is also an emerging area of service need.

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 (four thrombotic events and two bleeding complications related to anticoagulation) and three aPL-seronegative patients. aPL seropositivity was associated with more rapid decline in estimated glomerular filtration rate (–1.44 mL/min/year compared to –0.38 mL/min/year in aPL-seronegative patients; p = 0.027) and inferior long-term renal survival (82% and 74% at 10 and 15 years, respectively, compared to 91% and 87% in aPL-seronegative patients; p = 0.034). aPL-seropositive patients also had a higher incidence of thrombotic events and miscarriage (32.1% and 13.2%, respectively, compared to 16.7% and 2.1% in the aPL-seronegative group; p = 0.030 and 0.006). We concluded that aPL seropositivity was associated with inferior long-term patient and renal survival and more frequent thrombotic events and miscarriage in LN patients.

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 latter, decreased glomerular mTOR Ser2448 phosphorylation. Renal histology in untreated mice showed mesangial proliferation and progressive glomerulosclerosis with tubular atrophy, and increased expression of transforming growth factor β1 (TGF-β1), monocyte chemoattractant protein-1 (MCP-1), α-smooth muscle actin (α-SMA), fibronectin (FN) and collagen. Both mycophenolate and rapamycin ameliorated the histopathological changes. Results from in vitro experiments showed that both mycophenolate and rapamycin decreased mesangial cell proliferation and their binding with anti-dsDNA antibodies. Mycophenolate and rapamycin also down-regulated mTOR and extracellular signal-regulated kinase (ERK) phosphorylation and inhibited fibrotic responses in mesangial cells that were induced by anti-dsDNA antibodies or TGF-β1. Our findings suggest that, in addition to immunosuppression, mycophenolate and rapamycin may reduce fibrosis in LN, which has important implications in preventing CKD in patients with LN.

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.

Objective We investigated the clinico-pathological associations of serum VCAM-1 and ICAM-1 levels in patients with biopsy-proven Class III/IV±V lupus nephritis (LN). Methods Serum VCAM-1 and ICAM-1 levels were determined by ELISAs. Sera from patients with non-renal SLE or non-lupus chronic kidney disease (CKD), and healthy subjects served as controls. Results Seropositivity rate for VCAM-1 and ICAM-1 was 93.10% and 37.93% respectively at the time of nephritic flare, and 44.83% and 13.79% respectively at remission, with both showing higher levels during flare ( P Conclusion Our findings suggest potential utility of serum VCAM-1 and ICAM-1 in clinical management. Monitoring VCAM-1 may facilitate early diagnosis of flare. Combining selected biomarkers may be advantageous in diagnosing active LN. VCAM-1 may have a pathogenic role in renal parenchymal inflammation in active LN.

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. 153.8±92.9 IU/mL, and 98.7±33.4 mg/dL vs. 81.8±26.2 mg/dL, respectively; p Conclusion Our results suggest that pre-emptive moderate increase of immunosuppressive treatment reduces the risk of disease flare in LN patients with ASR and is well tolerated.

Introduction Renal relapses adversely affect the long-term outcomes of patients with lupus nephritis (LN), but the pathogenic mechanisms remain elusive. B cell signatures of miR-148a, BACH1, BACH2, and PAX5 expression are relevant to the regulation of B lymphocyte homeostasis. It is unknown whether B cell signature is related to the relapse of LN. Methods We compared B lymphocyte subsets and cellular signatures during disease quiescence between LN patients with multiple relapses (MR, ≥3 LN relapses within 36 months) and those with no relapse (NR). Also, circulating B lymphocytes were isolated from treatment-naive patients with active LN and treated with antagomir-148a in vitro to investigate the relationship between miR-148a, BACH1, BACH2, and PAX5. Results MR patients (n = 19), when compared with NR (n = 14), showed significantly lower percentage of circulating naive B cells and higher memory B cell-to-naive B cell ratio. MR patients also showed higher miR-148a levels in sera and B cells, and lower BACH1, BACH2, and PAX5 expression in naive and memory B cells. Antagomir-148a upregulated BACH1, BACH2, and PAX5 expression, and reduced B cell proliferation upon stimulation, in naive and memory B cells isolated from treatment-naive active LN patients. Conclusion Altered B cell subsets and cellular signatures of miR-148a, BACH1, BACH2, and PAX5 may be associated with distinct patient phenotypes related to the risk of LN relapse.

Hepatitis B virus (HBV), influenza, pneumococcus and herpes zoster are important infections which could result in significant morbidity and mortality in patients with chronic kidney disease (CKD). While seroconversion rates after vaccination are often lower in CKD patients compared with healthy adults due to impaired innate and adaptive immunity, vaccinations for HBV, influenza, pneumococcus and herpes zoster are generally effective in reducing the transmission and/or severity of these infections. Practical issues that have an impact on the efficacy of vaccination in the CKD population include the timing, dose, schedule of vaccination, the route of administration, and adjuncts applied at time of vaccination. This review discusses the vaccination regimens and the efficacy of HBV, influenza, pneumococcus and zoster vaccines in CKD patients, and highlights recent advances in enhancing vaccine seroconversion rates.

Objectives We investigated circulating syndecan-1, HA and thrombomodulin levels in patients with biopsy-proven Class III/IV ± V LN and their clinico-pathological associations. Patients with non-renal SLE or non-lupus chronic kidney disease, and healthy subjects served as controls. Methods Serum syndecan-1, HA and thrombomodulin levels were determined by ELISAs. Results Syndecan-1, HA and thrombomodulin levels were significantly higher during active LN compared with remission (P Conclusion Our findings suggest potential utility of serum syndecan-1, thrombomodulin and HA levels in clinical management, and their potential contribution to LN pathogenesis.

Background: Fluid management is a clinical challenge in patients with end-stage renal disease (ESRD), especially among those who opted for conservative treatment. We initiated a comprehensive program of psychosocial interventions. Objectives: To study the impact of this psychoeducational (Appropriate amount of intake, Self-efficacy, and Adherence [ASA]) program on symptom burden and acute admission rates related to fluid overload (FO) in this group of elderly ESRD patients attending renal palliative care outpatient clinic under our division. Methods: All elderly (age >60 years) patients who were followed in our renal palliative clinic had one or more acute admissions related to FO during the first three months were identified and invited to participate in this program. The palliative care nurse assessed each pair of patient/caregiver before doctor consultation, documented the symptom burden by the Edmonton Symptom Assessment Scale, provided symptom advice with use of pamphlets, monitored fluid and drug compliance, and provided psychosocial-spiritual support. The patient symptom score, body weight (BW), and three month acute admission episodes were compared before and after psychoeducation interventions by paired t test. Results: Data from 138 patients were analyzed. Of them, edema, shortness of breath, and insomnia occurred in 131 (95%), 67 (49 %), and 44 (32%) patients, respectively. A total of 125 patients (90.6%) had poor fluid/diet compliance, whereas 59 patients (42.7%) had poor drug compliance. The BW decreased significantly from 57.1 (12.8) kg at baseline to 52.5 (13.6) kg after three months of the ASA program. The acute admission rate related to FO dropped significantly from 7.6 episodes/patient/year to 6.4 episodes/patient/year. Conclusion: Our data demonstrated that the ASA program could improve patient symptoms and reduce acute hospital admissions, and thus improve the overall patient wellbeing and reduce health care utilization. Further studies are required to delineate the efficacy of different components in this ASA program and how to enhance its delivery.

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 improvement in C3 (90.4 ± 18.1 mg/dl and 117.7 ± 25.1 mg/dl at commencement and after 36 mos, respectively, p = 0.025), stable renal function (estimated glomerular filtration rate 58.6 ± 25.8 ml/min and 63.0 ± 29.6 ml/min, respectively, p = 0.239), and proteinuria (0.8 ± 0.7 g/day and 0.7 ± 0.7 g/day respectively, p = 0.252). Renal flare occurred in 1 patient, and another patient who had stage 4 chronic kidney disease when sirolimus was started developed endstage renal failure after 27 months. Sirolimus was discontinued in 5 patients, in 4 cases related to drug side effects. Deterioration of dyslipidemia occurred in 4 patients, but was adequately controlled with statin therapy.Conclusion.The preliminary evidence suggests that sirolimus may serve as an alternative treatment for patients with LN who do not tolerate standard treatment or who had a history of malignancy, and it has an acceptable longterm safety profile.

Immunosuppressive therapies for lupus nephritis (LN) have improved significantly over the past few decades, resulting in growing number of choices for treatment individualization and improved renal and patient outcomes. Corticosteroids combined with mycophenolate or cyclophosphamide induces a satisfactory response in a high proportion of Asian and Caucasian patients, but the rate of improvement varies considerably between patients. Relatively low disease flare rate was observed in Chinese patients receiving low-dose prednisolone and mycophenolate maintenance. Short-term results with calcineurin inhibitors (CNI) are encouraging, attributed both to their immunosuppressive efficacy and the action of these agents on podocyte biology leading to more rapid proteinuria suppression. Additional data, especially on the avoidance of nephrotoxicity and metabolic side effects, is required to facilitate selection of patients appropriate for this treatment. Modifications of standard regimens such as reducing corticosteroid exposure or using enteric-coated mycophenolate might help reduce treatment-related toxicities without compromising efficacy. While clinical outcomes of patients have improved with recent therapeutic advances, individual and ethnic variations in disease manifestations and treatment response, as well as the prevention of infections and long-term complications still present challenges to frontline clinicians. Recent data from histological examination and translational studies also suggest that complement activation via the alternative pathway, immune deposition on renal tubular basement membrane, and local inflammatory responses involving resident kidney cells are of pathogenic relevance in LN. The progress of clinical and translational studies has improved not only the understanding of disease mechanisms but also clinical decision making in the management of LN.