Hepatitis C core antigen testing to diagnose active hepatitis C infection among haemodialysis patients.

BACKGROUND: Hepatitis C virus (HCV) infects more than 71 million people worldwide and chronic HCV infection increases the risk of liver cirrhosis and failure. Haemodialysis (HD) is one of the renal replacement therapies with risk of HCV transmission. Anti-HCV antibodies are the serological screening test for HCV infection that does not detect active phase of infection. Majority HCV infected HD patients in Malaysia do not have further HCV RNA performed due to high cost and thus HCV treatment is less frequently offered. HCV Core Antigen (HCV Ag) can potentially be used to diagnose active HCV infection in HD population in comparison to HCV RNA, at lower cost. METHODS: We conducted a cross-sectional study to assess the correlation between HCV Ag and HCV RNA and to identify the prevalence of active HCV infection among HCV seropositive HD patients from dialysis centres across West Malaysia from July 2019 to May 2020. Pre-dialysis blood was taken and tested for both HCV Ag and HCV RNA tests. HCV Ag was tested with Abbott ARCHITECT HCV Ag test. RESULTS: We recruited 112 seropositive HD patients from 17 centres with mean age of 54.04 ± 11.62 years, HD vintage of 14.1 ± 9.7 years, and male constitute 59.8% (67) of the study population. HCV Ag correlates well with HCV RNA (Spearman test coefficient 0.833, p < 0.001). The sensitivity was 90.7%, specificity 100%, positive predictive value (PPV) 100%, negative predictive value (NPV) 76.5%, and accuracy 92.9%. For HCV RNA level > 3000 IU/mL, HCV Ag had a higher sensitivity of 95.1% and greater correlation (Spearman test coefficient 0.897, p < 0.001). The prevalence of active HCV infection was 76.8% among HCV seropositive HD patients. CONCLUSIONS: Although HCV Ag is less sensitive, it shows an excellent correlation with HCV RNA and has 100% PPV. HCV Ag can be considered as an alternative diagnostic tool for chronic active HCV infection among HD cohort, who can then be considered for HCV treatment. For seropositive HD patient with negative HCV Ag, we recommend to follow-up with HCV RNA test.

Efficacy and safety of low dose, weight-based subcutaneous enoxaparin protocol in recurrent arteriovenous access thrombosis.

BACKGROUND: This study aims to evaluate the safety and efficacy of a short-term, low dose, weight-based subcutaneous enoxaparin protocol (SEP) in maintaining the patency of arteriovenous (AV) access with recurrent thrombosis. METHODS: Prospective follow-up of 25 patients who presented to a tertiary institution with recurrent AV access thrombosis and treated with anticoagulation according to SEP following successful thrombectomy. Patency and safety outcomes of SEP were studied. RESULTS: The participants were 66.4 ± 10.2 years old and predominantly male (60%) and of Chinese ethnicity (72%). The AV accesses had a median age of 1.4 (0.6, 5.6) years with 60% being non-autogenous arteriovenous access while 40% were autogenous arteriovenous access. Thrombolytic agents (urokinase (72%) or alteplase (28%)) were used in all procedures while adjunct thrombectomy device was used in only four procedures. The mean dose of enoxaparin was 36.0 ± 8.2 mg or 0.64 ± 0.1 mg/kg/day for a mean duration 30.0 days (Interquartile range: 27.5, 31.0). One patient developed minor bleeding episode. Kaplan-Meier analysis demonstrated that the mean thrombosis-free survival pre- versus post-SEP adoption was 27.3 (95% CI 17.9-36.7) versus 183.5 (95% CI 100.1-266.9) days (p < 0.001). After adjusting for the type of thrombolytic agent, use of adjunct thrombectomy device, cutting balloon, drug-coated balloon, and stent graft, SEP remained a significant factor associated with longer thrombosis-free patency (HR 0.166: 95% CI 0.070-0.392, p < 0.001). DISCUSSION: SEP appears to be a feasible and safe thromboprophylaxis method to improve thrombosis-free patency for AV access with recurrent thrombosis.

Metabolic Changes In Living Kidney Donors After Donation In University Malaya Medical Centre.

The short- and long-term outcome of donations from living donors of kidneys (LKDs) remains controversial. Information regarding metabolic changes after donation in Malaysia remains limited despite Malaysia having the highest record prevalence of diabetes, obesity, and hypertension in Asia. There were 159 LKDs in our center from 2010 to 2020. We analyzed pre and post donation clinical data and laboratory results from 140 LKDs, retrospectively, from electronic medical records and looked for any metabolic changes. Among these 140 LKDs, 99 were women (70.7%), with a mean age of 47.23 ± 11.67 before donation. The median follow-up was 4 years (range, 2-6 years). Median body mass index increased from 24.35 kg/m2 (range, 22.11-26.93) to 25.56 kg/m2 (range, 22.78-28.57; Z=-3.934, P = .000) after donation. Prevalence of obesity increased from 24.18% to 30.77%. Only 2.8% of LKDs developed proteinuria postnephrectomy (P = .250). Serum creatinine increased from 60 mmol/L (range, 52-74) to 87 mmol/L (range, 74-108) 1 year after donation (P = .000), and the latest results decrease to 83 mmol/L (range, 73-101; P = .000). Systolic blood pressure increased from 127.83 ± 12.25 mm Hg to 131.30 ± 18.16 mm Hg, (t[97] = -2.012; P = .047); and prevalence of hypertension increased from 19.81% to 23.58% (P = .125), with 22.64% requiring treatment. We noted that 22.54% of the LKDs had dyslipidemia before donation, a number that increased to 50% after donation (P = .000). LKDs with hyperuricemia increased significantly from 7.92% to 34.65%, with uric acid level increasing from 311.94 ± 78.51umol/L to 381.87 ± 86.96 umol/L (t[94] = -10.805; P = .000). Fasting blood glucose and glycated hemoglobin level recorded no significant changes after donation. Post donation kidney function of LKDs compensated well and stable in short term. We noted statistically significant increment of weight, post donation body mass index, systolic blood pressure, uric acid, and lipids. We suggest prospective studies with longer follow-up and more subjects for clinical correlation.

The Effects of Different Induction Regimes on Serial Lymphocyte Subsets in Kidney Transplant Recipients: A Single Tertiary Center Experience.

BACKGROUND: Immunosuppressive therapy is the backbone of kidney transplantation in preventing acute rejection. T-cell depletion after doses of thymoglobulin is dose-dependent, as are their side effects. At the same time, basiliximab and other maintenance immunosuppressive drugs act at different signals on T lymphocytes. Therefore, studying the pattern of lymphocyte subset depletion depending on the induction regime given at transplantation could be an added tool in managing post-transplant recipients. METHODOLOGY: This prospective observational study recruited kidney transplant recipients from August 2019 through April 2021 at the University of Malaya Medical Centre. Blood tests for lymphocyte subsets were taken at pre-transplant, 1 week, 1 month, 3 months, and 6 months post-transplantation. At transplantation, recipients received either basiliximab, low-dose thymoglobulin (cumulative dose: 1.5 mg/kg), or standard-dose thymoglobulin (cumulative dose: 5 mg/kg). RESULTS: A total of 39 patients were recruited: 38.5% received basiliximab (15 of 39), 15.4% received low-dose thymoglobulin (6 of 39), and 46.2% received standard-dose thymoglobulin (18 of 39). Absolute lymphocyte counts 1 week post-transplantation were 1.5 ± 0.84 × 109/L for basiliximab, 0.7 ± 0.57 × 109/L for low-dose thymoglobulin, and 0.1 ± 0.08 × 109/L for standard-dose thymoglobulin (P < .001). The CD4+ and CD8+ counts were severely depleted in the standard-dose thymoglobulin group, with a statistically significant differenceup to 6 months post-transplantation. In the low-dose thymoglobulin group, the CD4+ and CD8+ counts were depleted at 1 week post-transplantation and recovered at 1 month post-transplantation. There was no difference in allograft function and incidence of allograft rejection across groups. CONCLUSIONS: The effects on lymphocyte counts, CD4+ and CD8+, vary depending on the type and dose of induction immunosuppression. This could be a guiding tool in managing immunosuppression post-transplantation depending on the patient's immunologic risk.

The Outcome of the Elderly Living Kidney Donors in a Single Tertiary Center in Malaysia.

Living-kidney transplantation increases with years, however, the rate is comparatively low to support local needs. Marginal living donors like the elderly were used to increase the donor pool. We retrospectively evaluate the outcome of 25 elderly living kidney donors (eLKDs) who were ≥60 years old at the time of donation in our center. Their medical history and laboratory results were analyzed retrospectively from e-medical records. There are 16 females (64.0%) with a median age of 63 (60.5-66.0). The mean follow-up duration was 4.36 ± 2.46 years. Their mean body mass index increased from 23.70 ± 3.07 kg/m2 to 24.21 ± 2.93 kg/m2 (t[14] = -2.176, P = .047) post donation. Systolic blood pressure (SBP) increased from 133.33 ± 11.65 mm Hg to 140.56 ± 17.78 mm Hg (t[17] = -2.124, P = .049). However, the prevalence of overweight and hypertension were not significant. Only 5.56% of the eLKDs developed proteinuria post nephrectomy (P =1.000). Serum creatinine increased from 62.33 ± 14.39 mmol/L to 104.63 ± 28.53 mmol/L post 1-month donation (t[23] = -9.720, P = .000) and decreased to 99.67 ± 22.39 mmol/L post 1-year donation (t[17] = -8.415, P = .006), and latest results were 94.28 ± 20.74mmol/L (t[17] = -6.630, P = .033). Fasting blood glucose and HbA1c level recorded no significant changes post donation. We noted that 47.62% of the eLKDs had dyslipidemia pre donation, which increased to 76.20% post donation (P = .031). eLKDs with hyperuricemia increased significantly from 5.88% to 52.94%; with uric acid level from 306.12 ± 68.67 umol/L to 412.24 ± 74.14 umol/L (t[16] = -7.726, P = .000). None of the eLKDs were diagnosed with metabolic syndrome pre and post kidney donation. Postdonation kidney function of the eLKDs compensated well and were stable in the short term. We noted statistically significant increments of weight, body mass index, SBP, uric acid, and lipid levels, which did not translate to clinical significance post donation. Elderly living-kidney donation can be done safely with close monitoring post donation.

Study protocol for a Prospective, Randomized controlled trial of stEnt graft and Drug-coated bAlloon Treatment for cephalic arch stenOsis in dysfunctional arteRio-venous fistulas (PREDATOR).

BACKGROUND: Treatment of cephalic arch stenosis (CAS) is associated with high risk of failure and complications. Although stent-graft (SG) placement has improved patency rates, stent edge restenosis has been raised as a potential limiting factor for SG usage in CAS. This study aims to evaluate the safety and efficacy of combining stent graft placement with paclitaxel-coated balloon (PCB) angioplasty versus PCB alone in the treatment of CAS. METHODS: This is an investigator-initiated, prospective, international, multicenter, open-label, randomized control clinical trial that plans to recruit 80 patients, who require fistuloplasty from dysfunctional arteriovenous fistula (AVF) from CAS. Eligible participants are randomly assigned to receive treatment with SG and PCB or PCB alone in a 1:1 ratio post-angioplasty (n = 40 in each arm). Randomization is stratified by de novo or recurrent lesion, and the participants are followed up for 1 year. The primary endpoints of the study are target lesion primary patency (TLPP) and access circuit primary patency (ACPP) rates at 6-months. The secondary endpoints are TLPP and ACPP at 3- and 12-month; target lesion and access circuit assisted primary and secondary patency rates at 3, 6, and 12-months and the total number of interventions; complication rate; and cost-effectiveness. DISCUSSION: This study will evaluate the clinical efficacy and safety of combination SG and PCB implantation compared to PCB alone in the treatment of CAS for hemodialysis patients.

One-Year Outcomes of Living Related Kidney Transplant in Patients With Preformed HLA Donor-Specific Antibodies: A Single-Center Experience in Malaysia.

The shortage of deceased donors led to an increase of living related renal transplant performed in the presence of donor-specific antibodies (DSAs) or ABO incompatibilities. There are various desensitization protocols that have been proposed. Here, we describe the outcome of these sensitized patients. This is a prospective cohort study recruiting all kidney transplant recipients from August 2016 until June 2018. Deceased donations, ABO incompatible patients, and sensitized patients who were not prescribed on our desensitization protocol were excluded. Recipients were screened for the presence of HLA-antibodies 1 month before transplant. Those with positive DSA will undergo flow cytometry (risk stratification). We are using a protocol that consisted of intravenous rituximab 200 mg (day -14), intravenous antithymocyte globulin 5mg/kg (day 0-4), plasma exchange post transplant for patients with mean fluorescent intensity (MFI) < 3000, and negative flow cytometry. Those patients with MFI ≥ 3000 or positive flow cytometry need extra cycles pretransplant. A total of 40 patients were recruited, and 20 were sensitized patients. Among the sensitized group 4 of 20 had flow cytometry crossmatch positive, while all had preformed HLA-DSA. A total of 8 of 20 had class I HLA-DSA, 11 of 20 had class II HLA-DSA, and 1of 20 was positive for both class I and II HLA-DSA. Mean immunodominant MFI was 2133.4 (standard deviation [SD], 4451.24) and 1383.7 (SD, 2979.02) for class I and class II, respectively. At 1 year, mean serum creatinine was 108.90 (SD, 25.95) and 118.42 (SD, 31.68) in sensitized and unsensitized patients, respectively. One of 20 unsensitized patients had Banff 1B rejection at 3 months, and there was no significant rejection in sensitized patients at 6 months and 1 year. There was no difference in the occurrence of de novo HLA-DSA between the groups. Desensitization protocols may help to overcome incompatibility barriers in living donor renal transplant. The combination of low-dose rituximab, antithymocyte globulin, and judicious use of plasma exchange has worked well for our cohort.