Can daclizumab reduce acute rejection and improve long-term renal function in tacrolimus-based primary renal transplant recipients?

AIMS: To evaluate the efficacy and safety of a tacrolimus-based immunosuppressive regimen with and without induction therapy using daclizumab in first cadaveric renal transplant recipients. METHODS: Since January 2001, we studied the effect of daclizumab in a non-randomized and prospective study of 36 sequential first cadaveric renal transplant recipients. They were compared with a historical control group of 21 sequential first cadaveric renal transplant recipients without induction therapy. All patients received tacrolimus, azathioprine and corticosteroids as concomitant immunosuppressive therapy. Daclizumab was given at 1 mg/kg infusion 2 h before transplantation and then every 14 days for four more doses. Outcomes measured included incidence of acute rejection, patient survival, graft survival, annualized change in creatinine clearance (CrCl), cardiovascular risk profile, infection and malignancy. RESULTS: Fewer biopsy proven acute rejections were observed in the induction treatment group: 11.1% (4/36) versus 19% (4/21) but the rejection free survival was similar (P = 0.37). The patient survival and graft survival were comparable. The renal function was similar in both groups. There were also no significant difference in infection, malignancy and cardiovascular risk profile in both groups. CONCLUSION: Adding daclizumab to a tacrolimus-based therapy is safe but cannot further improve clinical efficacy.

Prevalence of chronic kidney disease in Chinese HIV-infected patients.

BACKGROUND: To evaluate the prevalence of chronic kidney disease (CKD) in Chinese HIV-infected population. METHODS: This was a cross-sectional point prevalence study. All Chinese HIV-infected patients who were followed up in a tertiary referral center in Hong Kong were recruited. Spot urine was saved for each patient to calculate urine protein-to-creatinine ratio (urine P/Cr). Those with urine P/Cr > 0.3 would have 24-h urine collection to determine the exact amount of proteinuria. Glomerular filtration rate (GFR) was estimated using MDRD formula. CKD was defined as GFR <60 ml/min/1.73 m2 and/or urine P/Cr > 0.3. Baseline demographic and clinical data were extracted from patients' records. RESULTS: In total 322 patients were recruited. The mean age was 45.2 +/- 11.7 years. The duration of follow up was 6.0 +/- 4.0 years. There were 264 male and 58 female patients. The prevalence of hypertension, diabetes mellitus and CKD were 7.4%, 10.6% and 16.8%, respectively. Eighteen patients (5.6%) had GFR < 60 ml/min/1.73 m2 while 44 patients (13.7%) had spot urine P/Cr > 0.3. Among those with urine P/Cr > 0.3, 38 patients had 24-h urine collection. Using univariate analysis, CKD was found to be significantly (P < 0.05) associated with age, hypertension, diabetes, use of indinavir, lower CD4 count and peak viral load. Multivariate logistic regression revealed older age (P < 0.001), lower CD4 count (P = 0.02) and use of indinavir therapy (P = 0.04) were associated with development of CKD. CONCLUSION: CKD is prevalent in Chinese HIV-infected patients. Patients with CKD were more likely to be older, associated with use of indinavir and CD4 nadir less than 100 cells/mul.

A veno-caliceal fistula related to ureteric stricture in a kidney allograft masquerading as renal failure.

We report an unusual case of veno-caliceal fistula that developed because of high ureteric pressure caused by graft ureteric stricture after kidney transplantation in a 60-year-old patient. We further confirmed its presence with radiological images. Recirculation of creatinine and other uremic toxins resulted in a biochemical picture of renal failure in the presence of normal kidney function, confirmed by normal scintigraphy findings. Drainage of the pelvi-caliceal system could not be assessed accurately by means of diuretic renogram using technetium-99m diethylenetriaminepentaacetic acid with frusemide because of the rapid clearance of tracer activity from the system in the presence of a veno-caliceal fistula. The patient's renal function improved rapidly after interrupting urine recirculation by using percutaneous drainage, confirming "pseudo renal failure" as the cause of his persistently increased serum creatinine concentration. The ureter was re-implanted later, and the veno-caliceal fistula was not seen in the nephrostogram after the operation. He remains well with stable renal function at 3 years' follow-up. Clinicians should exercise judgment when evaluating patients with allograft dysfunction, especially when the investigation and clinical findings show contradicting results.

Paired kidney analysis of tacrolimus and cyclosporine microemulsion-based therapy in Chinese cadaveric renal transplant recipients.

Few studies used paired kidneys for comparison between tacrolimus and cyclosporine in renal transplantation. Most of the published data used whole blood trough levels for drug monitoring. However, the use of limited sampling strategy and abbreviated formula to estimate the 12-h area under concentration-time curve (AUC(0-12)) allowed better prediction of drug exposure. Sixty-six first cadaveric renal transplant recipients receiving paired kidneys were randomized to receive either tacrolimus-based (n = 33) or cyclosporine microemulsion (Neoral)-based therapies (n = 33). Abbreviated AUC(0-12) was used for drug monitoring and dose titration. Mean follow-up duration was 2.8 +/- 2 years. The patient and graft survival were comparable. Fewer incidence of acute rejection was observed in tacrolimus group (15% vs. 27.3%) though the difference was not significant (P = 0.23). The absolute value and the rate of decline of creatinine clearance were both significantly better in tacrolimus-treated patients. Prevalence of hypertension, post-transplant diabetes mellitus, infection, and malignancy were similar in both groups. Prevalence of hypercholesterolemia (11/33 vs. 4/33) and gum hypertrophy (6/33 vs. 1/33) was more common in cyclosporine-treated patients (P = 0.04 in both parameters). This was the first prospective, randomized study with paired kidney analysis showing the renal function was significantly better in tacrolimus-treated patients than in cyclosporine-treated patients.

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.

A report with consensus statements of the International Society of Nephrology 2004 Consensus Workshop on Prevention of Progression of Renal Disease, Hong Kong, June 29, 2004.

This report summarizes the discussions of the International Society of Nephrology (ISN) 2004 Consensus Workshop on Prevention of Progression of Renal Disease, which was held in Hong Kong on June 29, 2004. Three key areas were discussed during the workshop: (1) screening for chronic kidney disease; (2) evaluation and estimating progression of chronic kidney disease; and (3) measures to prevent the progression of chronic kidney disease. Fifteen consensus statements were made in these three areas, as endorsed by the participants of the workshop. The ISN can make use of and take reference to these statements in formulating its policy for tackling chronic kidney disease, a disease with significant global impact.

Prevalence of silent kidney disease in Hong Kong: the screening for Hong Kong Asymptomatic Renal Population and Evaluation (SHARE) program.

BACKGROUND: End-stage renal disease (ESRD) is epidemic worldwide. In Hong Kong, the annual incidence of ESRD has risen from 100 pmp (per million population) in 1996 to 140 pmp in 2003. SHARE (Screening for Hong Kong Asymptomatic Renal Population and Evaluation program) is a population-based screening program aimed at identifying the prevalence of unrecognized renal disease in asymptomatic individuals, allowing further evaluation and disease-modifying interventions. METHODS: From November to December 2003, SHARE was conducted in several large residential communities in Hong Kong. The screening tool included a questionnaire documenting demographics and history or family history of diabetes mellitus (DM), hypertension (HT), and chronic kidney disease (CKD), together with on-site measurements of blood pressure (BP) and urine dipstick for protein, blood, and glucose. RESULTS: There were a total of 1811 participants. One thousand two hundred and one subjects were entered into the final analysis. Among the 1201 who were apparently "healthy" (asymptomatic and without history of DM, HT, or CKD), the prevalence of positive (> or =1+) urine dipstick for protein, glucose, blood, protein or blood, any urine abnormality, and HT (BP> or =140/90) was 3.2%, 1.7%, 13.8%, 16%, 17.4%, and 8.7%, respectively. Thirty three percent of the age over 60 years old group had either hypertension or urine abnormalities, compared with 24.0% in the 41- to 60-year-old group and 9.7% in the 20- to 40-year-old group. Having a family history of diabetes or hypertension increases the risk of having urine abnormalities, while a family history of hypertension also increases the risk of high blood pressure. CONCLUSION: It is concluded that subclinical abnormalities in urinalysis or BP readings are prevalent across all age groups in the adult population. An effective screening program at the primary care level that identifies these subjects for further evaluation is warranted, and the public in Hong Kong should be educated toward the significance of such findings in order to have regular health check for asymptomatic renal diseases.

Efficacy and side effects of intradermal hepatitis B vaccination in CAPD patients: a comparison with the intramuscular vaccination.

BACKGROUND: This prospective randomized study aims to assess the effectiveness of intradermal (ID) hepatitis B virus (HBV) vaccination in patients on continuous ambulatory peritoneal dialysis (CAPD) therapy. METHODS: Sixty patients were randomly divided into 2 groups. The ID group was treated with 5 microg of recombinant HBV vaccine intradermally every week for a total of 10 doses, and the intramuscular (IM) group, with 20 microg intramuscularly at 0, 1, and 6 months. RESULTS: ID HBV vaccination was associated with a greater seroconversion rate (81.5% versus 62.1%), although the difference did not reach statistical significance (P = 0.14). The cumulative seroconversion rate was significantly greater with ID vaccination by 6 months after the first vaccine dose (P = 0.03). There was no difference between the 2 groups in time required to convert, peak antibody to HBV surface antigen (anti-HBs), and proportion of patients with anti-HBs levels maintained at greater than 10 mIU/mL or 100 mIU/mL in the 2-year observation period. Although the ID group achieved a peak anti-HBs titer significantly earlier than the IM group (P = 0.001), we found a significant trend for the ID group to achieve a lower peak anti-HBs titer (chi-square test for trend, P = 0.005). The incidence of local reactions was significantly greater with ID immunization; however, reactions were mild and transient. CONCLUSION: ID HBV vaccination is associated with significant improvement in seroconversion rate in CAPD patients at 6 months, but this difference diminishes at 2 years. Larger studies are warranted to confirm this finding.