Application of virtual reality for peritoneal dialysis exchange learning in patients with end-stage renal disease and cognitive impairment.

Cognitive impairment is not uncommon in patients with end-stage renal disease and can make it more difficult for these patients to carry out peritoneal dialysis (PD) on their own. Their attempts to do so may result in adverse consequences such as peritonitis. PD exchange is a complex procedure demanding knowledge and skill which requires close supervision and guidance by a renal nurse specialist. In this study, a non-immersive virtual reality (VR) training program using a Leap motion hand tracking device was developed to facilitate patients' understanding and learning of the PD exchange procedure before attempting real task practice. This study was a two-center single-blinded randomized controlled trial on 23 incident PD patients. Patients in the experimental group received 8 sessions of VR training, while patients in the control were provided with printed educational materials. The results showed that there were significant differences between the two groups in performance of the overall PD exchange sequence, especially on the crucial steps. VR had a patient satisfaction rate of 89%, and all patients preferred to have the VR aid incorporated in PD training. Our findings conclude VR can be a useful aid in the training and reinforcement of PD exchange procedures, with distinct merits of being free from restrictions of time, space, and manpower.

Direct Renin Inhibition in Non-diabetic chronic Kidney disease (DRINK): a prospective randomized trial.

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.

Conversion from Aranesp® to NESP® in dialysis patients-Exploration of dosing strategies and the feasibility of extending the dosing interval.

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.

Pharmacokinetics and pharmacogenomics of mycophenolic acid and its clinical correlations in maintenance immunosuppression for lupus nephritis.

BACKGROUND: There is little data on mycophenolic acid (MPA) pharmacokinetics and pharmacogenomics and optimal MPA exposure in lupus nephritis (LN) patients during long-term maintenance. METHODS: 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. RESULTS: 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 inversely correlated with hemoglobin, immunoglobulins and leukocyte levels (P < 0.05 for all). Five renal flares, 11 episodes of infection and 10 episodes of anemia (hemoglobin <10 g/dL) occurred over 96 weeks, with a corresponding C12 of 1.3 ± 0.5, 4.3 ± 2.6 and 2.9 ± 1.5 mg/L, respectively (versus 2.4 ± 1.2, 1.8 ± 1.2 and 1.7 ± 1.1 mg/L in patients without these complications; P = 0.041, <0.001 and 0.004). SNP rs2273697 A/G in the ABCC2 gene was associated with lower MPA exposure compared with G/G (1075.9 ± 239.9 versus 1891.5 ± 918.9 mgh/L per g/kg; P = 0.003). SNPs of OATP and UGT were unrelated to MPA level. CONCLUSION: MPA C12 correlates with the AUC0-12 and is related to renal flare, infection and anemia. SNP rs2273697 A/G is associated with lower MPA exposure.

Effect of mycophenolate and rapamycin on renal fibrosis in lupus nephritis.

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 ß1 (TGF-ß1), 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-ß1. 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.

Preemptive immunosuppressive treatment for asymptomatic serological reactivation may reduce renal flares in patients with lupus nephritis: a cohort study.

BACKGROUND: Serological activity may precede clinical flares of lupus nephritis (LN) but the management of asymptomatic serological reactivation (ASR) remains undefined. METHODS: 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. RESULTS: 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 24 month, respectively, compared with 94, 69 and 64% in controls; P = 0.011), whereas survival rate free of extrarenal relapse was similar in the two groups. Preemptively treated patients who did not develop renal flares showed better renal function preservation (estimated glomerular filtration rate slope +0.54 ± 0.43 mL/min/1.73 m2/year, compared with -2.11 ± 0.50 and -1.00 ± 0.33 mL/min/1.73 m2/year, respectively, in controls who did and did not develop subsequent renal flares; P = 0.001 and 0.012, respectively). Preemptive treatment was associated with an increased incidence of gastrointestinal side effects attributed to MMF (P = 0.031), whereas infection rate did not differ between the two groups. CONCLUSION: A preemptive moderate increase of immunosuppression for ASR in LN patients may reduce renal flares and confer benefit to long-term renal function.

Long-term data on entecavir treatment for treatment-naive or lamivudine-resistant chronic hepatitis B infection in kidney transplant recipients.

INTRODUCTION: Entecavir (ETV) showed short-term efficacy and safety in HBsAg-positive kidney transplant recipients (KTRs), but long-term data are lacking. METHODOLOGY: We retrospectively reviewed 30 HBsAg-positive KTRs who received ETV during 2007-2017. RESULTS: Eighteen treatment-naïve (Group I) and 12 lamivudine-resistant (Group II) patients received ETV for 48.4 ± 35.2 and 66.0 ± 26.0 months, respectively. Both groups show significant HBV DNA decline, but Group I achieved earlier undetectability after 11.9 ± 9.6 months (compared with 28.8 ± 24.2 months in Group II, P = .033). Group I showed higher rates of undetectable HBV DNA (89%, 94%, 94%, 100%, and 100% at 12, 24, 36, 48, and 60 months, respectively, compared with 25%, 50%, 50%, 91%, and 91% in Group II, P = .003). ALT normalized after 6.0 ± 1.9 and 6.8 ± 2.1 months in Group I and Group II, respectively. Four patients (33.3%) in Group II developed drug resistance (2 had persistent viraemia and 2 had virological breakthrough, at 40.3 ± 15.0 months). Group II showed higher liver stiffness after 5 years (7.7 ± 4.1 kPa, compared with 5.0 ± 1.6 kPa in Group I, P = .046) and incidence of cirrhosis (4 patients [33.3%], compared with 1 [5.6%] patient in Group I, P = .049). Two patients (one in each group) developed hepatocellular carcinoma. Renal allograft function remained stable during follow-up of 63.2 ± 33.4 months for both groups. There was no difference in patient and graft survival between two groups at 5 years (P = .62 and .36, respectively). CONCLUSION: ETV showed favorable long-term efficacy and tolerability in treatment-naïve KTRs. One-third of lamivudine-resistant subjects showed non-response or viral breakthrough after ETV treatment.

Screening Algorithm for BK Virus-Associated Nephropathy Using Sequential Testing of Urinary Cytology: A Probabilistic Model Analysis.

BACKGROUND: Incorporating urinary cytology in BK virus (BKV) screening algorithm potentially reduces the screening cost for BK viral nephropathy. We aimed to evaluate the test performances and screening cost of sequential 2-stage screening consisting of urine cytology followed by BKV serum quantitative polymerase chain reaction (PCR). METHODS: Ninety-five kidney transplant recipients who had BKV serum quantitative PCR/urine cytology tested and verified with histopathology (the reference gold standard) were included. A probabilistic model was constructed to evaluate the test performance and screening cost of 2-stage screening, and was compared with screening with urine cytology or serum viral load alone. RESULTS: At a viral load threshold of ≥104 copies/ml, the sensitivity and specificity of quantitative PCR alone were 83% (95% CI 69-96) and 91% (95% CI 83-97), respectively. The sensitivity and specificity of urine cytology alone were 91% (95% CI 79-100) and 74% (95% CI 60-91), respectively. Sequential 2-stage screening resulted in loss in sensitivity but a net gain in specificity (viral load threshold ≥104 copies/ml - sensitivity, 75% (95% CI 60-91); specificity, 98% (95% CI 95-99)). Two-stage screening also had superior positive predictive value and is cost effective when BKV-associated nephropathy prevalence is below 94%. CONCLUSIONS: Our study had demonstrated a favorable test performance and cost efficiency of 2-stage BKV screening.

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.

Acute drug toxicity related to drinking herbal tea in a kidney transplant recipient.

Calcineurin and mTOR inhibitors are commonly used immunosuppressive agents with narrow therapeutic range. As the drugs are mainly metabolized by the P450 cytochrome system, the interaction between food and herbs are also commonly seen and affect the drug levels. We present a case of a kidney transplant recipient with toxic therapeutic levels of cyclosporine A and sirolimus due to interaction between the immunosuppressive agents and Chinese herbal tea. Ingredients within the herbal tea were reported to have inhibitory effect on cytochrome CYP3A4 in-vitro studies. Transplant recipients should be alert that there may be potent interaction between the immunosuppressive drugs and herbs resulting in adverse effect on allograft function.

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.

Charlson co-morbidity index and albumin significantly associated with fracture risk in peritoneal dialysis patients.

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.

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.

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.

Survival analysis and causes of mortality in patients with lupus nephritis.

BACKGROUND: This study aimed to define the causes and associated risks of death compared with the local general population in Chinese patients with lupus nephritis in the recent era. METHODS: The records of all lupus nephritis patients followed in a single centre during 1968-2008 were reviewed. The causes of death were identified, the survival curves constructed and the standardized mortality ratios (SMRs) of potential risk factors were calculated with reference to the local general population. RESULTS: Two hundred and thirty systemic lupus erythematosus patients with history of renal involvement (predominantly Class III/IV lupus nephritis with or without membranous features) were included. The follow-up was 4076.6 person-years (mean 17.7 ± 8.9 years). Twenty-four patients (10.4%) died, and 85% of the deaths occurred after 10 years of follow-up. The 5-, 10-, and 20-year survival rates were 98.6, 98.2 and 90.5%, respectively. The leading causes of death were infection (50.0%), cardiovascular disease (20.8%) and malignancy (12.5%). The renal survival rates at 5, 10 and 20 years were 99.5, 98.0 and 89.7%, respectively. The SMR in patients with renal involvement, end-stage renal disease (ESRD), malignancy or cardiovascular disease was 5.9, 26.1, 12.9 and 13.6, respectively. CONCLUSIONS: Lupus nephritis is associated with a 6-fold increase in mortality compared with the general population. Lupus patients who develop ESRD have a 26-fold excess in the risk of death, which is more than twice the risk associated with malignancy or cardiovascular disease in these patients.

Aliskiren combined with losartan in immunoglobulin A nephropathy: an open-labeled pilot study.

BACKGROUND: Aliskiren is a relatively new oral direct renin inhibitor (DRI) that has been increasingly used for the treatment of diabetic nephropathy and hypertension. Its potential efficacy in nondiabetic chronic kidney diseases that are driven by renin-angiotensin system activation remains to be explored. METHODS: From a teaching and regional hospital in Hong Kong between July 2009 and March 2010, patients with biopsy-proven immunoglobulin A nephropathy (IgAN) in whom the ratio of protein to creatinine, as measured in early morning urine samples, remained >113 mg/mmol (1000 mg/g), despite receiving the maximum recommended dose of losartan (100 mg daily) were recruited to receive additional DRI treatment. They were followed prospectively for 12 months with changes in proteinuria as the main outcome measure. RESULTS: Twenty-five consecutive patients were enrolled. Treatment with aliskiren for 12 months reduced the mean urinary protein-to-creatinine ratio by 26.3% (95% confidence interval, 20.1-43.6; P = 0.001 versus baseline), with a reduction of ≥ 50% in 24% of patients. There were significant reductions in plasma renin activity (P < 0.0001) and serum interleukin-6 (P < 0.05) and transforming growth factor-ß (P = 0.01) levels, compared with baseline. Two patients (8%) developed mild allergic reactions and six (24%) had transient hyperkalemia (K >5.5 mmol/L) during the study. CONCLUSION: Aliskiren confers an antiproteinuric effect in IgAN patients with significant residual proteinuria, despite receiving the recommended renoprotective treatment. Further prospective randomized trials are warranted to examine its long-term renoprotective potential. This trial is registered with the ClinicalTrials.gov number NCT00922311.

Proliferation signal inhibitors in the treatment of lupus nephritis: preliminary experience.

AIM: Proliferation signal inhibitors (PSI) have demonstrated efficacy in prevention and treatment in an animal model of lupus nephritis (LN) but there are no data regarding the use of PSI in human LN. We report here our experience of using PSI treatment in seven patients with severe proliferative lupus nephritis. METHODS: This is a retrospective study on patients with proliferative lupus nephritis who had received PSI treatment. RESULTS: Seven patients were included. Two patients had concomitant membranous lupus nephropathy. The indications for PSI included mycophenolate mofetil intolerance (n = 4), history of malignancy (n = 2) and leucopoenia (n = 1). Five patients were given PSI when disease was active. Two had treatment discontinued because of acute cholecystitis and leucopoenia, respectively. In the other three patients combined steroid and PSI treatment as induction therapy led to improvements in serology, renal function and proteinuria. In two patients treated with PSI and low-dose steroid as maintenance immunosuppression, both maintained stable lupus serology, renal function and proteinuria over 18 months. Side-effects included dyslipidemia and oral ulcers. CONCLUSION: Proliferation signal inhibitors warrants further investigation as an alternative immunosuppressive treatment in lupus nephritis.

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.

Transplantation in Asia during the coronavirus disease-19 (COVID-19) pandemic: briefs from member countries of the Asian Society of Transplantation.

The coronavirus disease-19 (COVID-19) pandemic has affected 1,029,968 people in Asia as of May 16, 2020. Although Asia was the first continent to be affected, many countries in the region continue to battle COVID-19, which challenges the way transplant programs provide their services. Given the diversity of healthcare systems in Asia, the countermeasures in response to COVID-19 are as potentially diverse. This review reports the experiences of transplant services in member countries of the Asian Society of Transplantation (AST) as well as provides a platform for sharing of best practices during the COVID-19 pandemic. AST invited member countries to provide a short description of their transplant experiences during the COVID-19 pandemic. Whenever information is available, countries were asked to provide information on COVID-19 related statistics, status of transplant programs, mitigation measures taken to prevent COVID-19, and other areas of transplant programs impacted by COVID-19. Ten countries responded to the invitation of which seven still have active transplant programs at varying levels of activity. All countries have protocols for donor/recipient screening and countermeasures to prevent COVID-19 infections in recipients and healthcare providers. Interestingly, these countries report only 16 transplant recipients with COVID-19 infection but no cases of donor-transmitted COVID-19 infection. Despite the diversity of healthcare systems in Asia, transplant centers in Asia have taken appropriate precautions to avoid COVID-19 infections, though the long-term impact of COVID-19 remains unclear.