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.

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

OBJECTIVES: To evaluate the use of shear wave elastography in assessment of kidney allograft tubulointerstitial fibrosis. METHODS: Shear wave elastography assessment was carried out by two independent operators in kidney transplant recipients who underwent allograft biopsy for clinical indications (i.e. rising creatinine >15% or proteinuria >1 g/day). Allograft biopsies were interpreted by the same pathologist according to the 2013 Banff Classification. RESULTS: A total of 40 elastography scans were carried out (median creatinine 172.5 µmol/L [interquartile range 133.8-281.8 µmol/L]). Median tissue stiffness at the cortex (22.6 kPa [interquartile range 18.8-25.7 kPa] vs 22.3 kPa [interquartile range 19.0-26.5 kPa], P = 0.70) and medulla (15.0 kPa [interquartile range 13.7-18.0 kPa] vs 15.6 kPa [interquartile range 14.4-18.2 kPa]) showed no significant differences between the two observers. Interobserver agreement was satisfactory (intraclass correlation coefficient of the cortex 0.84, 95% CI 0.70-0.92 and intraclass correlation coefficient of the medulla 0.88, 95% CI 0.78-0.94). The areas under the receiver operating characteristic curves for detection of tubulointerstitial fibrosis were estimated to be 0.75 (95% CI 0.61-0.89), 0.85 (95% CI 0.75-0.95) and 0.65 (95% CI 0.53-0.78) for cortical, medullary tissue stiffness and serum creatinine, respectively. CONCLUSIONS: Shear wave elastography can be used as a non-invasive tool to evaluate kidney allograft fibrosis with reasonable interobserver agreement and superior test performance to serum creatinine in detecting early tubulointerstitial fibrosis.

Rapid reduction of viruria and stabilization of allograft function by fusidic acid in a renal transplant recipient with JC virus-associated nephropathy.

JC virus (JCV)-associated nephropathy has been increasingly recognized as a cause of allograft dysfunction with graft loss in renal transplant recipients. Like many other opportunistic viral infections in transplant recipients, there are currently limited therapeutic options for this condition. Fusidic acid has previously been reported to exhibit antiviral activity against JCV in in vitro assays. We report the first in vivo study to document the rapid reduction of JC viruria and stabilization of allograft function by oral fusidic acid (fusidate sodium) in a deceased donor renal transplant recipient with JCV-associated nephropathy and acute allograft dysfunction which did not improve initially to surgical relief of hydronephrosis and reduction of immunosuppressants. Rapid reduction of JC viruria detected by quantitative PCR and stabilization of renal function were observed. Fusidic acid has several practical advantages in this clinical setting, including a low EC50 against JCV, high plasma C max, long half-life, availability of both oral and intravenous formulations, excellent oral bioavailability, good patient tolerability, and lack of serious drug interactions with other drugs taken by renal transplant recipients. Further mechanistic and clinical studies are necessary to evaluate this treatment option for JCV-associated nephropathy.

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.

Dosing regimen and tolerability of methoxy polyethylene glycol-epoetin beta in Chinese dialysis patients.

AIM: To investigate methoxy polyethylene glycol-epoetin beta dosing regimen in treatment naïve subjects and dose conversion in darbepoetin alpha treated subjects, in Chinese dialysis patients. METHODS: Adult Chinese patients on peritoneal dialysis (PD) or haemodialysis (HD), with no prior treatment with erythropoiesis-stimulating agents and haemoglobin below 8 g/dL (Group I) or receiving darbepoetin alpha and had stable haemoglobin at 10-12 g/dL (Group II) were included in this prospective open-label study. In Group I methoxy polyethylene glycol-epoetin beta was started at 0.6 µg/kg subcutaneously fortnightly till haemoglobin reached 10 g/dL, after which it was given monthly. A dose conversion table was devised for Group II. Follow-up was 36 weeks. RESULTS: Forty-five patients were included. Haemoglobin in Group I (n=23, PD/HD:19/4) increased from 7.5 ± 0.9 g/dL at baseline to 10.7 ± 1.0 g/dL after 16 weeks, while it remained stable at 10.4 ± 1.0 g/dL after conversion in Group II (n=22, PD/HD:15/7). Actual dose required after stabilization was 1.7 µg/kg per month in Group I and 2.3 µg/kg per month in Group II. Median number of dose adjustment was three in Group I and one in Group II, while haemoglobin overshoot to 13 g/dL or above occurred in 4.4% and 9.1%, respectively. No significant side-effect was observed. CONCLUSIONS: Our dosing regimen for methoxy polyethylene glycol-epoetin beta, for treatment naïve subjects or for conversion from darbepoetin alpha, is safe and effective. The dose required to achieve a haemoglobin concentration of 10-11 g/dL in Chinese dialysis patients is approximately 2 µg/kg monthly.

Renal registry and peritoneal dialysis management: the Hong Kong perspective.

The Hong Kong Renal Registry (HKRR) is an electronic paperless registry that services as database for patients on various renal replacement therapies in the territory. The database consists of demographic data, dialysis and transplant treatments, complications, and inquiries and reports. The HKRR can be helpful for individual patient's management, for renal center management, and for territory-wide management.

Risk factors and outcomes of extended-spectrum beta-lactamase-producing E. coli peritonitis in CAPD patients.

OBJECTIVE: To determine the risk factors and outcomes of peritonitis caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli in continuous ambulatory peritoneal dialysis (CAPD). PATIENTS AND METHODS: Episodes of E. coli CAPD peritonitis in our unit from October 1994 to August 2003 were reviewed. Demographic data, underlying medical conditions, recent use of gastric acid inhibitors (including H2 antagonist and proton pump inhibitor), recent antibiotic therapy, antibiotic regimen for peritonitis episodes, sensitivity test results of the E. coli isolated, and clinical outcomes were examined. RESULTS: Over a 10-year study period, 88 episodes of E. coli peritonitis were recorded; 11 of the 88 cases were caused by ESBL-producing E. coli. Recent use of cephalosporins and gastric acid inhibitor were associated with the development of ESBL-producing E. coil peritonitis. Compared with non-ESBL-producing E. coli peritonitis, more cases in the ESBL-producing E. coli group developed treatment failure (45.5% vs 13.0%, p = 0.02) and died of sepsis (27.3% vs 3.9%, p = 0.02). Peritoneal failure rate was higher in the ESBL-producing E. coli group, although the difference was not statistically significant (18.2% vs 3.9%, p = 0.12). CONCLUSION: Peritonitis caused by ESBL-producing E. coli is associated with worse clinical outcomes. The use of cephalosporins and gastric acid inhibitors may contribute to its development. Further studies are warranted to investigate and determine the predisposing factors for ESBL-producing E. coli peritonitis.

Recurrent hemoperitoneum complicating continuous ambulatory peritoneal dialysis.

OBJECTIVES: To study the clinical features, clinical outcomes, and peritoneal transport characteristics of patients with recurrent hemoperitoneum complicating continuous ambulatory peritoneal dialysis (CAPD). DESIGN: Single-center retrospective case review of patients on CAPD over a 10-year period. SETTING: Renal Unit in Queen Mary Hospital, a tertiary-care referral center in Hong Kong. PATIENTS: 549 patients were available for review. 46 patients (8.4%) had at least one episode of hemoperitoneum during their course of CAPD; 25 patients had only one episode of hemoperitoneum and they were excluded. The remaining 21 patients (3.8%) had two or more episodes of hemoperitoneum and they were included for review. MAIN OUTCOME MEASURES: Basic demographic factors and the etiology and episodes of hemoperitoneum were recorded. Clinical outcomes included continuation on peritoneal dialysis, conversion to hemodialysis (HD), renal transplantation, and death. The reason for conversion to HD, the causes of death, and serial peritoneal equilibration tests (PET) using dialysate-to-plasma ratio of creatinine (D/P creat) and ratio of dialysate glucose at hours 4 and zero of the dwell (D4/D0) with standard 2-L 2.5% glucose dialysate were assessed. RESULTS: There were 549 patients with total of 91 episodes of recurrent hemoperitoneum affecting 21 patients (3.8%). Mean age was 50.2 years (range 24-76 years) and mean duration of dialysis was 61.6 months (range 2-166 months). There were 14 female patients (66.7%) and 7 male patients (33.3%). The average number of hemoperitoneum episodes was 4.3 per patient (range 2-12). The mean time interval of the first hemoperitoneum episode from commencement of peritoneal dialysis was 10.5 months (range 1-37 months, SD 9.7 months). Most cases were due to retrograde menstruation in females and unknown cause in males. Two patients had intra-abdominal pathology accounting for hemoperitoneum. Thirteen patients (61.9%) continued CAPD, 2 (9.5%) underwent renal transplantation, and 2 (9.5%) were converted to long-term HD. The reason for conversion to HD was related to hemoperitoneum in 1 patient (4.8%) only. Four patients (19.0%) died; the causes of death were unrelated to hemoperitoneum. There was no correlation between recurrent hemoperitoneum and peritonitis episodes (p = 0.18). There was no significant association between hemoperitoneum episodes and clinical outcomes (p = 0.91) or survival (p = 0.52). None of the patients developed ultrafiltration failure on long-term follow-up. CONCLUSIONS: Recurrent hemoperitoneum is a benign complication of CAPD, with no significant long-term effects on patient survival, predisposition to peritonitis, or ultrafiltration failure.

Long-term outcome of renal transplant recipients with chronic hepatitis B infection-impact of antiviral treatments.

BACKGROUND: Antiviral treatment has improved the short-term outcome of kidney transplant recipients with chronic hepatitis B infection, but its long-term impact, especially in patients who have developed drug resistance, remains uncertain. METHODS: Sixty-three hepatitis B surface antigen positive (HBsAg+) and 63 HBsAg- patients who have undergone kidney transplantation from 1985 to 2008 were retrospectively reviewed and their clinical outcomes were compared. RESULTS: With lamivudine as initial treatment, 62% of patients developed drug resistance after 4 years. Lamivudine resistance was associated with a higher incidence of chronic hepatitis but had no significant impact on liver stiffness score or patient survival during follow-up. Salvage treatment with adefovir or entecavir was well tolerated, and resulted in a three-log decrease in hepatitis B deoxynucleic acid after 6 months and normalization of alanine aminotransferase in 75% of patients. The survival rate of HBsAg+ patients transplanted in the recent era of antiviral treatment was 81% at 10 years. Treatment of hepatitis B with nucleoside/nucleotide analogues resulted in significantly improved patient survival (83% vs. 34% at 20 years, P=0.006). Although antiviral treatment was associated with reduced mortality because of liver complications (P=0.036), liver-related deaths still accounted for 40% of mortalities in HBsAg+ patients in the era of antiviral therapies and 22.2% of all deaths that occurred in patients who had received antiviral treatment. CONCLUSION: Treatment of HBsAg+ renal transplant recipients with nucleoside/nucleotide analogues confers long-term survival benefit, and that rescue therapy with adefovir or entecavir is effective and well tolerated in patients who had developed resistance to lamivudine.

Renal transplantation in patients with primary immunoglobulin A nephropathy.

BACKGROUND: Opinions on the clinical course and outcome of renal transplantation in patients with primary immunoglobulin A nephropathy (IgAN) have been controversial. METHODS: We conducted a retrospective single-centre study on 542 kidney transplant recipients over the period 1984-2001. Long-term outcome and factors affecting recurrence in recipients with primary IgAN were analysed. RESULTS: Seventy-five patients (13.8%) had biopsy-proven IgAN as the cause of renal failure, and their mean duration of follow-up after transplantation was 100 +/- 5.8 months. Fourteen (18.7%) of the 75 patients had biopsy-proven recurrent IgAN, diagnosed at 67.7 +/- 11 months after transplantation. The risk of recurrence was not associated with HLA DR4 or B35. Graft failure occurred in five (35.7%) of the 14 patients: three due to IgAN and two due to chronic rejection. Three (4.9%) of the 61 patients without recurrent IgAN had graft failure, all due to chronic rejection. Graft survival was similar between living-related and cadaveric/living-unrelated patients (12-year graft survival, 88 and 72%, respectively, P = 0.616). Renal allograft survival within the first 12 years was better in patients with primary IgAN compared with those with other primary diseases (80 vs 51%, P = 0.001). Thereafter, IgAN patients showed an inferior graft survival (74 vs 97% in non-IgAN patients, P = 0.001). CONCLUSIONS: Our data suggested that around one-fifth of patients with primary IgAN developed recurrence by 5 years after transplantation. Recurrent IgA nephropathy in allografts runs an indolent course with favourable outcome in the first 12 years. However, the contribution of recurrent disease to graft loss becomes more significant on long-term follow up.

Immunogenicity of intradermal hepatitis B vaccination in renal transplant recipients.

We investigated intradermal hepatitis B (HBV) vaccination in 24 renal transplant recipients who failed to develop hepatitis B surface antibody (anti-HBs) with intramuscular (i.m.) vaccination. All patients received recombinant HBV vaccine 5 microg intradermally every 2 weeks for 8 doses. Nine patients developed protective levels of anti-HBs (> 10 miu/mL) and two patients developed low levels of anti-HBs (4-6 miu/mL), giving an overall initial response rate of 45.8%. A booster of 40 microg was administered intramuscularly after 1 year. All initial responders developed an anti-HBs response (322.6 +/- 92.0 miu/mL). In addition, four patients who did not respond initially to the intradermal vaccination seroconverted after the booster. Responders (62.5%) and nonresponders had comparable age, gender, immunosuppressive medications, and duration of transplant. In conclusion, renal transplant patients who fail to respond to intramuscular HBV vaccination may benefit from intradermal vaccination followed by an intramuscular booster.

Tuberculous infection in southern Chinese renal transplant recipients.

A retrospective study of the prevalence and pattern of tuberculosis among renal transplant patients in a single centre in southern China was performed. Twenty-three cases of tuberculosis were diagnosed among 440 patients between January 1991 and December 2002. There were 18 men and five women. The mean age of the patients was 39.3 +/- 13.4 yr. There were 13 living-related and 10 cadaveric renal transplants. The interval between renal transplantation and the development of tuberculosis ranged from 3 to 127 months with a median of 46 months. There were 18 cases of pulmonary tuberculosis, two cases of pulmonary plus laryngeal tuberculosis, two cases of disseminated tuberculosis, and one case of tuberculosis involving the urinary tract. Diagnosis was established by positive culture for Mycobacterium tuberculosis in 21 patients and response to empirical anti-tuberculosis treatment in two patients. The duration of symptoms before the diagnosis of tuberculosis was 27 +/- 12 d. The patients were treated with standard anti-tuberculosis drugs for 11 +/- 3 months. The anti-tuberculosis treatment was in general well-tolerated. Five patients developed transient hepatitis, three patients developed thrombocytopenia and five patients developed gouty arthritis. One patient died 2 months after initiation of anti-tuberculosis therapy. All other patients completed anti-tuberculosis treatment. No recurrence of tuberculosis was observed after a median follow-up of 90 months. We concluded that (i) tuberculosis is prevalent among southern Chinese renal transplant recipients; (ii) high index of suspicion for tuberculosis among renal transplant recipients is warranted to ensure early diagnosis and prompt initiation of treatment; and (iii) treatment with standard anti-tuberculosis drugs for an extended period of time is well-tolerated and is associated with favourable outcome.

Idiopathic minimal change nephrotic syndrome in older adults: steroid responsiveness and pattern of relapses.

INTRODUCTION: Minimal change nephrotic syndrome (MCNS) is a common form of nephrotic syndrome in children and young adults. We investigated its clinical presentations, steroid responsiveness, subsequent clinical course and patterns of relapse in older adults in whom it was diagnosed after the age of 50 years. METHODS: The clinical records of renal patients followed-up in a single out patient clinic were retrieved and those patients with biopsy-proven MCNS were included. Patients in the 18-50-year age range (Group A) at the time of biopsy were compared with those older than 50 years (Group B) with regard to baseline demographic data, clinical features and outcome of treatment. RESULTS: In all, 50 patients were studied, 35 in Group A (age at diagnosis: 38.8+/-11.91 years) and 15 in Group B (age at diagnosis: 70+/-6.85 years), with an overall follow-up duration of 72.08+/-63.42 months. Group B had a higher prevalence of hypertension and lower creatinine clearance at presentation, but the values of creatinine clearance for both groups were comparable with age-matched controls. One patient from Group B and two from Group A had spontaneous remission. Complete remission was achieved in 9.09, 45.45, 90.91 and 100% of Group B patients and 15.63, 62.5, 87.5 and 93.75% of Group A patients after 2, 4, 8 and 16 weeks of steroid therapy, respectively. The median time to complete remission and the duration of steroid treatment were similar for both groups. From Group B five patients and 22 patients from Group A relapsed during follow-up (P=0.055), with similar proportions of each group being early relapsers or frequent relapsers. The average number of relapses was 2.06 episodes for Group A, compared with 0.87 episodes for group B (P=0.062). Second agents were used in 20 Group A and four Group B patients (P=0.048). Complications of treatment were more common in Group A. None of the patients developed doubling of serum creatinine during follow-up. CONCLUSIONS: Clinical presentations of older patients with MCNS were similar to younger patients apart from the age-related decline of renal function and higher prevalence of hypertension. Both groups have similar steroid responsiveness, but older patients tend to have fewer relapses and require fewer second agents for treatment of relapses.

A prospective randomized study on three different peritoneal dialysis catheters.

OBJECTIVE: We compared outcomes for catheters with different configurations: conventional straight, swan-neck straight tip, and swan-neck curled tip. DESIGN: The study was conducted as a prospective randomized controlled trial in the continuous ambulatory peritoneal dialysis (CAPD) unit of a university center. PATIENTS AND METHODS: We randomized 93 new regular CAPD patients without prior peritoneal dialysis (PD) catheter insertion to receive a conventional straight, double-cuffed catheter (CS), a swan-neck straight catheter (SNC), or a swan-neck curled tip catheter (SNC) in 2:1:1 ratio. RESULTS: The exit-site infection (ESI) rate was slightly lower with swan-neck catheters as compared with straight catheters, but the difference was not statistically significant. The peritonitis rate and overall catheter survival were similar. In Staphylococcus aureus nasal non carriers as compared with carriers, ESI-free catheter survival was significantly better with swan-neck catheters (p = 0.0302 and p = 0.82 respectively). As compared with SC catheters, SNC catheters had a significantly higher migration rate (p = 0.022). CONCLUSIONS: Swan-neck catheters were associated with a slightly better ESI rate, but SNC catheters are not routinely recommended because of a high migration rate. The SNS catheter is therefore recommended as the first-line catheter of choice, particularly in populations with a low rate of S. aureus nasal carriage.

Incidence and outcome of antiglomerular basement membrane disease in Chinese.

BACKGROUND: Antiglomerular basement membrane (anti-GBM) disease is an uncommon disease, especially among Asian population. Many reports and studies on this condition in the Caucasian population are available, but little information exists on anti-GBM disease in Asians. To study the incidence and clinical characteristics of anti-GBM disease among Chinese patients, we reviewed our experience of anti-GBM disease in our hospital (Queen Mary Hospital, Hong Kong) from 1992 to 2003. METHODS: All patients who were admitted for acute renal impairment, which was caused by crescentic glomerulonephritis associated with linear immunoglobulin G (IgG) staining on immunofluorescence, were included in the analysis. Serum anti-GBM antibodies were detected by either enzyme-linked immunofluorescence or indirect immunofluorescence. Ten patients were treated for anti-GBM disease during this 11-year period, yielding an incidence of approximately 0.6 cases per million population per year. RESULTS: In this cohort, anti-GBM disease predominantly affected older patients (mean age: 58.6 +/- 21.7 years). Eight patients were aged between 60 and 80 years and there was a female preponderance (M:F = 2:8). The 1-year renal and patient survival was 15% (95% CI 0-40%) and 70% (95% CI 42-98%), respectively. Most patients presented with non-specific symptoms as well as impaired renal function. Detection of anti-GBM antibody provided a good screening test for the disease. Antiglomerular basement membrane antibodies were not detected in two patients. All but two patients received steroid, cyclophosphamide and intensive plasmapheresis therapy. Haemoptysis occurred in four patients (40%), and usually lagged behind the renal presentation and commencement of treatment. Six patients required long-term dialysis after the acute disease. Three patients died from the disease, two died from pulmonary complications and one died suddenly after a partial recovery of renal function. CONCLUSION: Antiglomerular basement membrane disease is uncommon among the Chinese population. It predominantly affects older patients, and prognosis is poor. Long-term preservation of renal function after the initial attack is unusual.