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.

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.

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.

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.

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.

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.

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.

A Longitudinal Study on the Prevalence and Risk Factors for Depression and Anxiety, Quality of Life, and Clinical Outcomes in Incident Peritoneal Dialysis Patients.

BACKGROUND: Starting dialysis is an important life event. The prevalence and evolution of psychological symptoms at commencement of long-term dialysis is unclear. We examined the prevalence of and risk factors for depression and anxiety, and the quality of life (QOL) of incident peritoneal dialysis (PD) patients, and also the change of these parameters in the first year of PD in relation to clinical outcomes under the PD-first policy. METHODS: All patients commencing long-term PD from March 2011 to April 2015 were asked to complete the Hospital Anxiety and Depression Scale (HADS), World Health Organization Quality of Life-BREF and the Kidney Disease Quality of Life Instrument Short Form questionnaire. Patient demographics and the incidence of hospitalization, peritonitis, exit-site infection, and all-cause mortality were studied. The HADS was repeated after 9 - 12 months. RESULTS: A high depression score was present in 39.6% of 191 patients at commencement of PD and was more common in diabetes patients (odds ratio [OR] 2.03, 95% confidence interval [CI] 1.09 - 3.81). A high anxiety score was present in 23.6%, and the risk factors included younger age (OR 0.96 per year, 95% CI 0.94 - 0.99) and diabetes (OR 2.59, 95% CI 1.20 - 5.57). Both high depression and anxiety scores were associated with an inferior QOL, overall and across most QOL domains. Depression and anxiety symptoms did not change in the first year of PD and were not associated with short-term clinical outcomes. CONCLUSIONS: High depression and anxiety scores were prevalent in incident PD patients where PD-first policy is adopted and were associated with inferior QOL. There was no improvement after 1 year of PD. The impact of strategic interventions targeting patient groups at risk such as those with diabetes or of younger age warrants further investigation.

Longterm Data on Sirolimus Treatment in Patients with Lupus Nephritis.

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.

mTOR Inhibition and Kidney Diseases.

Mammalian or mechanistic target of rapamycin (mTOR) is a serine-threonine kinase that plays essential roles in cell growth, proliferation, metabolism, and survival. Increased activation of the mTOR pathway is observed in patients and animal models of renal transplant rejection, autosomal dominant polycystic kidney disease, renal cell carcinoma, diabetic nephropathy, lupus nephritis, and angiomyolipoma. Agents that inhibit mTOR, such as sirolimus and everolimus, are incorporated in immunosuppressive regimens to prevent renal allograft rejection and are often used to facilitate calcineurin inhibitor minimization or to reduce the incidence of tumor recurrence. There are data from basic or animal studies to suggest that sirolimus and its analogs may also benefit patients with autosomal dominant polycystic kidney disease and metabolic- or immune-mediated renal diseases through its ability to reduce glomerular hypertrophy, renal parenchymal inflammation and fibrosis, but translation into clinical use has proved challenging. This review summarizes the current understanding of mTOR signaling pathway under physiological and pathological conditions and recent findings on mTOR inhibitors in the management of kidney transplantation and nontransplant kidney diseases.

Toward Establishing Core Outcome Domains For Trials in Kidney Transplantation: Report of the Standardized Outcomes in Nephrology-Kidney Transplantation Consensus Workshops.

BACKGROUND: Treatment decisions in kidney transplantation requires patients and clinicians to weigh the benefits and harms of a broad range of medical and surgical interventions, but the heterogeneity and lack of patient-relevant outcomes across trials in transplantation makes these trade-offs uncertain, thus, the need for a core outcome set that reflects stakeholder priorities. METHODS: We convened 2 international Standardized Outcomes in Nephrology-Kidney Transplantation stakeholder consensus workshops in Boston (17 patients/caregivers; 52 health professionals) and Hong Kong (10 patients/caregivers; 45 health professionals). In facilitated breakout groups, participants discussed the development and implementation of core outcome domains for trials in kidney transplantation. RESULTS: Seven themes were identified. Reinforcing the paramount importance of graft outcomes encompassed the prevailing dread of dialysis, distilling the meaning of graft function, and acknowledging the terrifying and ambiguous terminology of rejection. Reflecting critical trade-offs between graft health and medical comorbidities was fundamental. Contextualizing mortality explained discrepancies in the prioritization of death among stakeholders-inevitability of death (patients), preventing premature death (clinicians), and ensuring safety (regulators). Imperative to capture patient-reported outcomes was driven by making explicit patient priorities, fulfilling regulatory requirements, and addressing life participation. Specificity to transplant; feasibility and pragmatism (long-term impacts and responsiveness to interventions); and recognizing gradients of severity within outcome domains were raised as considerations. CONCLUSIONS: Stakeholders support the inclusion of graft health, mortality, cardiovascular disease, infection, cancer, and patient-reported outcomes (ie, life participation) in a core outcomes set. Addressing ambiguous terminology and feasibility is needed in establishing these core outcome domains for trials in kidney transplantation.

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.

A Rare Case of Famotidine-Induced Delirium in a Peritoneal Dialysis Patient.

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.

Mortality among Younger and Older Recipients of Kidney Transplants from Expanded Criteria Donors Compared with Standard Criteria Donors.

BACKGROUND AND OBJECTIVES: The quality and age of donor organs are known to have a major effect on patient and graft outcomes, but it is uncertain whether this association is uniform for all recipients. We aimed to determine whether the use of expanded criteria deceased donor (ECD) kidneys for transplantation compared with standard criteria deceased donor (SCD) kidneys has a different association with survival in younger (age <60 years old) compared with older (age ≥60 years old) recipients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Using data from the Australian and New Zealand Dialysis and Transplant Registry (1997-2009), we compared the risk of all-cause mortality and death with functioning graft among younger and older recipients who had received either an SCD or an ECD kidney using the adjusted Cox proportional hazard models. RESULTS: In total, 3822 patients were transplanted between 1997 and 2009. Over a follow-up period of 21,249 person-years (a median duration of 5.3 years [interquartile range, 2.22-8.6 years]), 567 recipients (n=385 for those age <60 years old; n=182 for those age ≥60 years old) died. Recipient age was an effect modifier between donor types, all-cause mortality, and death with functioning graft (P values for interaction were 0.05 and 0.04, respectively). In younger recipients, there was an excess risk of all-cause mortality (adjusted hazard ratio [HR], 1.55; 95% confidence interval [95% CI], 1.23 to 1.97) and death with functioning graft (adjusted HR, 1.72; 95% CI, 1.28 to 2.29) after transplantation with ECD kidneys compared with SCD kidneys, but there was no statistically significant association among older recipients (adjusted HR, 1.11; 95% CI, 0.80 to 1.54 and adjusted HR, 1.30; 95% CI, 0.89 to 1.89, respectively). This excess risk was largely caused by death from cardiovascular disease. CONCLUSIONS: There was an excess risk of all-cause mortality and death with functioning graft when younger recipients were transplanted with ECD kidneys compared with SCD kidneys. These findings suggest that caution is needed in allocating ECD kidneys to younger recipients.

Impact of a low-glucose peritoneal dialysis regimen on fibrosis and inflammation biomarkers.

BACKGROUND: The impact of a low-glucose peritoneal dialysis (PD) regimen on biomarkers of peritoneal inflammation, fibrosis and membrane integrity remains to be investigated. METHODS: In a randomized, prospective study, 80 incident PD patients received either a low-glucose regimen comprising Physioneal (P), Extraneal (E) and Nutrineal (N) (Baxter Healthcare Corporation, Deerfield, IL, USA) (PEN group), or Dianeal (control group) for 12 months, after which both groups continued with Dianeal dialysis for 6 months. Serum and dialysate levels of vascular endothelial growth factor (VEGF), decorin, hepatocyte growth factor (HGF), interleukin-6 (IL-6), macrophage migration inhibitory factor (MIF), hyaluronan (HA), adiponectin, soluble-intracellular adhesion molecule (s-ICAM), vascular cell adhesion molecule-1 (VCAM-1) and P-selectin, and dialysate cancer antigen 125 (CA125), were measured after 12 and 18 months. This paper focuses on results after 12 months, when patients in the PEN group changed to glucose-based PD fluid (PDF). RESULTS: At the end of 12 months, effluent dialysate levels of CA125, decorin, HGF, IL-6, adiponectin and adhesion molecules were significantly higher in the PEN group compared to controls, but all decreased after patients switched to glucose-based PDF. Macrophage migration inhibitory factor level was lower in the PEN group but increased after changing to glucose-based PDF and was similar to controls at 18 months. Serum adiponectin level was higher in the PEN group at 12 months, but was similar in the 2 groups at 18 months. Body weight, residual renal function, ultrafiltration volume and total Kt/V did not differ between both groups. Dialysate-to-plasma creatinine ratio at 4 h was higher in the PEN group at 12 months and remained so after switching to glucose-based PDF. CONCLUSION: Changes in the biomarkers suggest that the PEN PD regimen may be associated with better preservation of peritoneal membrane integrity and reduced systemic vascular endothelial injury.

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.

The risk of cancer in recipients of living-donor, standard and expanded criteria deceased donor kidney transplants: a registry analysis.

BACKGROUND: Kidneys from expanded criteria deceased donors may elicit a strong inflammatory response, predisposing recipients to an increased risk of cancer after transplantation. We aimed to determine the association between donor types and cancer risk after kidney transplantation. METHODS: Using the Australian and New Zealand Dialysis and Transplant Registry, we assessed the association between different donor types (living donor, standard, and expanded criteria deceased donors) and the risk of cancer after kidney transplantation using adjusted Cox proportional hazard and competing risk models. RESULTS: Over a median follow-up period of 4.4 years in 7,040 patients (34,684 patient-years), 468 patients (6.6%) developed cancer. The overall risks for cancer were 1,080, 1,444, and 2,018 per 100,000 patient-years for recipients of living donor, standard, and expanded criteria deceased donor kidneys, respectively. Compared to recipients of living-donor kidneys, recipients of expanded criteria deceased donor kidneys were at an increased risk of cancer (adjusted hazard ratio [HR], 1.52; 95% confidence interval [95% CI], 1.15-2.02; P = 0.004), particularly for genitourinary cancer (adjusted HR, 1.79; 95% CI, 1.03-3.10; P = 0.038) and post-transplant lymphoproliferative disease (adjusted HR, 2.72; 95% CI, 1.38-5.37; P = 0.004). CONCLUSION: Recipients of expanded criteria deceased donor kidneys are at substantially increased risk of cancer, especially cancers with a viral etiology. Allocation of expanded criteria deceased donor kidneys to potential recipients should balance the harms, such as the excess risk of cancer against the survival gains and quality-of-life benefits associated with transplantation.

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.