Hepatocellular carcinoma after kidney transplantation: analysis of Hong Kong Renal Registry.

Kidney transplant recipients have increased risk of cancers when compared with the general population. Hepatocellular carcinoma (HCC) is extremely important in Asia where hepatitis B virus (HBV) infection is endemic. The aim is to study the epidemiological and clinical aspects of all de novo HCC in our kidney transplant recipients. Moreover, various preventive strategies which may help to optimize the outcome will also be discussed. A retrospective review of all patients who developed HCC after kidney transplantation between May 1972 and December 2011 in Hong Kong, based on the data from Hong Kong Renal Registry. After a follow-up period of 40,246 person-years, 20 patients (males 15: females 5) developed HCC. The annual incidence was 49.7/100,000 persons per year. Among them, 16 were HBV carriers, 2 were hepatitis C (HCV) carriers and 2 had HBV and HCV co-infection. Presence of HBV infection was associated with 78-fold higher risk for HCC development. Majority (85%) were asymptomatic when HCC was diagnosed by ultrasound or alpha-fetoprotein surveillance. All patients diagnosed by surveillance received active treatment while 2/3 of symptomatic patients could only receive symptomatic care and died rapidly. In conclusion, HBV infection is the major etiological factor for HCC development in kidney transplant recipients in HBV endemic areas. Regular HCC surveillance appeared to be able to detect early stage cancers which are amenable to treatment and offer the best hope of cure.

Influence of different allelic variants of the CYP3A and ABCB1 genes on the tacrolimus pharmacokinetic profile of Chinese renal transplant recipients.

Tacrolimus has a narrow therapeutic window and a wide interindividual variation in its pharmacokinetics. The cytochrome P450 3A (CYP3A) and the ATP-binding cassette B1 (ABCB1) genes play an important role in the tacrolimus disposition. Therefore, the aim of this study was to evaluate whether CYP3A and ABCB1 polymorphisms are associated with the area under the time concentration curve (AUC0-12) calculated using a two time point sample strategy. The CYP3A and ABCB1 genotypes were determined by real-time polymerase chain reaction (RT-PCR) fluorescence resonance energy transfer (FRET) assays in 103 Chinese renal transplant recipients and consequently related to their dose-normalized (dn)AUC0-12. A significant allele-dependent effect (Kruskal-Wallis; p < 0.001) was observed between the CYP3A5*3 polymorphism and the dnAUC0-12. Multiple regression analysis showed that the CYP3A5*3 polymorphism is the most significant independent variable and explained 35% of the dose requirement variability in relation to tacrolimus use. Regarding the ABCB1 G2677T/A and C3435T polymorphisms, a trend was observed between the different genotypes and the dnAUC0-12. In conclusion, the CYP3A5*3 polymorphism may be an important factor in determining the dose requirement for tacrolimus and genotyping can help determine the initial daily dose required by individual patients for adequate immunosuppression.

Use of allopurinol in slowing the progression of renal disease through its ability to lower serum uric acid level.

BACKGROUND: Hyperuricemia is associated strongly with the development of hypertension, renal disease, and progression. Allopurinol decreases serum uric acid levels by inhibiting the enzyme xanthine oxidase. We hypothesized that administrating allopurinol to decrease serum uric acid levels to the normal range in hyperuricemic patients with chronic kidney disease may be of benefit in decreasing blood pressure and slowing the rate of renal disease progression in these patients. METHODS: We conducted a prospective, randomized, controlled trial of 54 hyperuricemic patients with chronic kidney disease. Patients were randomly assigned to treatment with allopurinol, 100 to 300 mg/d, or to continue the usual therapy for 12 months. Clinical, hematologic, and biochemical parameters were measured at baseline and 3, 6, and 12 months of treatment. We define our study end points as: (1) stable kidney function with less than 40% increase in serum creatinine level, (2) impaired renal function with creatinine level increase greater than 40% of baseline value, (3) initiation of dialysis therapy, and (4) death. RESULTS: One patient in the treatment group dropped out because of skin allergy to allopurinol. Serum uric acid levels were significantly decreased in subjects treated with allopurinol, from 9.75 +/- 1.18 mg/dL (0.58 +/- 0.07 mmol/L) to 5.88 +/- 1.01 mg/dL (0.35 +/- 0.06 mmol/L; P < 0.001). There were no significant differences in systolic or diastolic blood pressure at the end of the study comparing the 2 groups. There was a trend toward a lower serum creatinine level in the treatment group compared with controls after 12 months of therapy, although it did not reach statistical significance (P = 0.08). Overall, 4 of 25 patients (16%) in the allopurinol group reached the combined end points of significant deterioration in renal function and dialysis dependence compared with 12 of 26 patients (46.1%) in the control group (P = 0.015). CONCLUSION: Allopurinol therapy significantly decreases serum uric acid levels in hyperuricemic patients with mild to moderate chronic kidney disease. Its use is safe and helps preserve kidney function during 12 months of therapy compared with controls. Results of this study need to be confirmed with an additional prospective trial involving a larger cohort of patients to determine the long-term efficacy of allopurinol therapy and in specific chronic kidney disease subpopulations.

Fatal case of Aspergillus coinfection in a renal transplant recipient suffering from cytomegalovirus pneumonitis.

Cytomegalovirus (CMV) disease is common in postrenal transplant recipients, and may predispose the patients to secondary bacterial or fungal infections. However, simultaneous coinfection is rare and often makes diagnosis difficult. We report a case of CMV pneumonitis in a renal transplant recipient presenting with elevated CMV pp65 antigen level and abnormal chest radiograph. Despite potent and broad-spectrum antimicrobial therapy, his condition deteriorated rapidly - he soon went into respiratory failure, septic shock and died several days later. Transbronchial biopsy and bronchoalveolar lavage obtained before the patient's death showed evidence of invasive pulmonary aspergillosis with concomitant CMV pneumonitis. High index of suspicion and early and empirical initiation of antifungal therapy may be necessary for successful management of fulminant pneumonia in solid organ transplant recipients.

Clinical outcomes of systemic lupus erythematosus patients undergoing continuous ambulatory peritoneal dialysis.

OBJECTIVES: The purpose of this study was to evaluate the outcome of systemic lupus erythematosus (SLE) patients on continuous ambulatory peritoneal dialysis (CAPD). METHODS: Eighteen SLE patients who had been undergoing CAPD for at least 3 months in our unit were compared with 36 other age- and gender-matched non-diabetic CAPD patients with an underlying primary chronic glomerulonephritis (CGn). The clinical outcome, infective complications, lupus activities, biochemical parameters, haemoglobin level and the use of erythropoietin were reviewed. RESULTS: The duration of dialysis of the two studied groups was not different, with a mean of 35.4 months for the SLE group and 36.7 months for the CGn group. Before dialysis, SLE patients had a significantly lower albumin level (30.4+/-6.6 vs 35.4+/-5.59 g/dl, P<0.01), while the mean haemoglobin levels of the two groups were similar (8.5+/-1.8 g/dl for SLE vs 9.0+/-1.9 g/dl for the control group). However, the weekly dose of erythropoietin (EPO) used was significantly higher in the SLE group (6000 vs 3818 U/week, P<0.01) to maintain a similar haemoglobin level during dialysis. Regarding the infective complications, the SLE group had a higher peritonitis rate (5.7 episodes/100 patient-months vs 2.4 episodes/100 patient-months, P<0.05), and an increase in the non catheter related infection rate (6.67 episodes/100 patient-months vs 1.1 episodes/100 patient-months, P<0.001). However, no significant difference could be demonstrated in the Tenckhoff catheter exit site infection rate (2 episodes/100 vs 1.7 episode/100 patient-months). The number of patients who received a kidney transplant or required a change of mode to haemodialysis was similar among the two groups. Seven patients died during the follow-up period, and the overall mortality rate was much higher in the SLE group than in the control group (0.83/100 vs 0.15/100 patient-months, P<0.05). CONCLUSIONS: SLE patients on CAPD have a significantly lower pre-dialysis serum albumin level and use a higher dose of Epo to achieve a comparable haemoglobin level than other non-diabetic CGn CAPD patients. They also have a poorer prognosis in terms of infective complications and mortality rate.

Use of intraperitoneal urokinase for resistant bacterial peritonitis in continuous ambulatory peritoneal dialysis.

Intraperitoneal (IP) urokinase is a fibrinolytic agent that has been used in the adjunctive treatment of continuous ambulatory peritoneal dialysis (CAPD) and resistant and relapsing peritonitis. However, its efficacy and role in treating resistant CAPD bacterial peritonitis remain unclear and results from previous prospective studies have been conflicting. We prospectively randomized 88 CAPD patients with bacterial peritonitis resistant to initial empirical IP antibiotics into two groups: IP urokinase 60,000 IU and a placebo group. Patients were treated concomitantly with susceptible antibiotics according to culture results. Peritoneal dialysate grew pseudomonas aeruginosa in 13 patients (14.8%), non-pseudomonas bacteria in 63 patients (71.6%) and negative cultures in 12 patients (13.6%). For the clinical outcomes, there were no significant differences in the primary response rates (61.4 vs. 50%), relapse rates (9.1 vs. 13.6%), Tenckhoff catheter removal rates (22.7 vs. 29.5%) and mortality rates (6.8 and 6.8%) between the urokinase group and the controls (p=ns). Subgroup analysis of culture negative patients (n=12) also demonstrated no sgnificant benefit for urokinase treatment. No significant adverse effects were encountered with the IP urokinase instillation. Total median peritonitis-related length of hospitalization for the urokinase group and controls were 7 and 11 days, respectively (p=0.32). We concluded that IP urokinse plays no significant role as an adjuvant therapy in the treatment of bacterial CAPD peritonitis resistant to initial IP antibiotic therapy.

Ultrasonography in the management of exit site infections in peritoneal dialysis patients.

AIM: To assess the efficacy of using ultrasonography (USG) in monitoring the progress of exit site infection (ESI) in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). METHODS: Twenty-two cases of newly diagnosed ESI and 20 cases with normal exit sites as controls were assessed by using USG. The exit sites were reassessed by using USG after finishing a course of antibiotic therapy, and the sonographic findings were correlated with the clinical outcome. RESULTS: Out of the 22 cases of ESI, 21 cases had definite sonolucent zones around the external cuffs, while one case had normal sonographic findings. Of the 20 control cases of normal exit sites, 16 had normal sonographic findings, and four had sonolucent zones around the external cuffs. Exit site infections correlated with positive sonographic findings as compared to normal exits (P <0.0001). The 21 cases of ultrasonic-positive ESI were re-examined after antibiotic therapy, and 10 of these had a post-treatment sonolucent rim around the distal cuff < or =1 mm thick, while 11 cases were persistently > mm thick. The former group was shown to have a more favourable outcome (P=0.013). And despite variable USG findings, all eight patients with Pseudomonas aeruginosa-related ESI had an unfavourable clinical outcome. CONCLUSION: Ultrasonography of the exit sites in CAPD patients is a useful adjunctive tool in the management of ESI. A sonolucent zone around the external cuff >1 mm thick following a course of antibiotic treatment and the involvement of the proximal cuff are associated with poor clinical outcome. In ESI caused by Pseudomonas aeruginosa, the clinical outcome was uniformly poor irrespective of the sonographic findings.