A combination of biocompatible peritoneal dialysis solutions and residual renal function, peritoneal transport, and inflammation markers: a randomized clinical trial.

BACKGROUND: The benefits of biocompatible peritoneal dialysis (PD) fluids, particularly for residual renal function (RRF), are controversial. Moreover, the clinical effects of a PD regimen consisting of different biocompatible PD fluids have not been fully established. STUDY DESIGN: Prospective, randomized, controlled, open-label study. SETTING & PARTICIPANTS: Patients with end-stage kidney disease newly started on continuous ambulatory PD therapy (N = 150). INTERVENTION: A 12-month intervention with 3 biocompatible PD fluids (a neutral-pH, low glucose degradation product, 1.5% glucose solution; a solution with 1.1% amino acid; and a fluid with 7.5% icodextrin) or conventional PD fluid. OUTCOMES: The primary outcome was change in RRF and daily urine volume. Secondary outcomes were peritoneal transport and inflammation markers. MEASUREMENTS: RRF, daily urine volume, serum and dialysate cytokine levels. RESULTS: RRF(3.24 ± 1.98 vs 2.88 ± 2.43 mL/min/1.73 m(2); P = 0.9) and rate of decline in RRF (-0.76 ± 1.77 vs -0.91 ± 1.92 mL/min/1.73 m(2) per year; P = 0.6) did not differ between the biocompatible- and conventional-PD-fluid groups. However, patients using the biocompatible PD fluids had better preservation of daily urine volume (959 ± 515 vs 798 ± 615 mL/d in the conventional group, P = 0.02 by comparison of difference in overall change by repeated-measures analysis of variance). Their dialysate-plasma creatinine ratio at 4 hours was higher at 12 months (0.78 ± 0.13 vs 0.68 ± 0.12; P = 0.01 for comparison of the difference in overall change by repeated-measures analysis of variance). They also had significantly higher serum levels of adiponectin and overnight spent dialysate levels of cancer antigen 125, adiponectin, and interleukin 6 (IL-6). No differences between the 2 groups were observed for serum C-reactive protein and IL-6 levels. LIMITATIONS: Unblinded, relatively short follow-up; no formal sample-size calculations. CONCLUSIONS: Use of a combination of 3 biocompatible PD fluids for 12 months compared with conventional PD fluid did not affect RRF, but was associated with better preservation of daily urine volume. The biocompatible PD fluids also lead to changes in small-solute transport and an increase in dialysate cancer antigen 125, IL-6, adiponectin, and systemic adiponectin levels, but have no effect on systemic inflammatory response. The clinical significance of these changes, while of great interest, remains to be determined by further studies.

One year experience of nocturnal home haemodialysis with an alternate night schedule in Hong Kong.

AIM: Nocturnal home haemodialysis (NHHD) was started in Hong Kong in 2006. The experience of 1 year of NHHD with an alternate night schedule in two local centres is reported. METHODS: The clinical parameters of 14 patients who had completed 1 year of NHHD were retrospectively analyzed. All patients were receiving an alternate night schedule (3.5 sessions/week) for 6-8 h/session. RESULTS: After 1 year of NHHD, haemoglobin levels increased from 9.6±1.6 g/dL before NHHD to 11.4±2.2 g/dL (P<0.05) despite a reduction in erythropoietin dose requirement from 120.6±44.3 to 59.4±74.6 U/kg/week (P<0.05). Four patients (29%) were able to stop taking erythropoietin after NHHD. Serum phosphate levels reduced from 2.33±0.41 to 1.59±0.29 mmol/L (P<0.01) and calcium phosphate product decreased from 5.29±0.96 to 3.74±0.90 mmol2/L2 (P<0.01). Phosphate binder dose was greatly reduced and eight patients (67%) were able to stop taking phosphate binders. The number of antihypertensive medications tended to reduced from 2.5±1.3 to 1.6±1.5 (P=0.067) with four patients (29%) able to stop antihypertensives. Left ventricular mass index decreased from 186±62 to 168±60 g/m2 (P=0.463) although this was not statistically significant. Weekly spKt/V during conventional haemodialysis was 3.63±0.95 while that during NHHD was three times higher at 11.09±6.44 (P<0.01). The quality of life indexes also showed improvement. CONCLUSION: This 1 year experience of alternate night NHHD demonstrates benefits in terms of anaemia control, erythropoietin requirement, serum phosphate and calcium phosphate product reduction, blood pressure control, haemodialysis adequacy and quality of life. NHHD with an alternate night schedule is a promising dialytic therapy for patients receiving chronic haemodialysis in this locality.

Streptococcus gordonii peritonitis in a patient on CAPD.

We report the first case of Streptococcus gordonii-related continuous ambulatory peritoneal dialysis (CAPD) peritonitis. He is a 69-year-old man with end-stage renal failure due to chronic glomerulonephritis who had been put on CAPD for 1 year. He was successfully treated with a 2-week course of cefazolin. This case highlights the emerging threat that S. gordonii can be the source of infection in patients on CAPD.

Optimal body mass index that can predict long-term graft outcome in Asian renal transplant recipients.

AIM: There is limited data concerning the impact of recipient body mass index (BMI) on graft outcome in Asian renal transplant recipients. The aim of this study is to identify whether obesity (BMI > or =25 kg/m(2)) and overweight (BMI > or =23 kg/m(2)) can predict graft outcome. METHODS: This is a single-centre retrospective study. All patients who received kidney transplantation between 1997 and 2005 were recruited. Patients were categorized according to two different designated BMI cut-off values. RESULTS: One hundred and thirty-one patients were recruited with a median follow-up duration of 73 months. If a BMI cut-off value of 25 kg/m(2) was used, 86.3% patients were classified as non-obese and 13.7% as obese. Obesity was significantly associated with poor renal graft function and decreased patient and graft survival. On the other hand, 34.3% patients were classified as overweight and 65.7% patients as normal if a BMI cut-off value of 23 kg/m(2) was used. Overweight was significantly associated with a lower glomerular filtration rate only. Cox regression analysis showed that obesity (odds ratio (OR) = 3.09), acute rejection (OR = 5.68), pre-transplant diabetes mellitus (OR = 3.21) and age of recipient (OR = 1.06) were all significant independent risk factors associated with graft failure. CONCLUSION: Recipient BMI > or =25 kg/m(2) is a significant predictive factor for long-term renal graft outcome in the Asian population.

Long-term graft function with tacrolimus and cyclosporine in renal transplantation: paired kidney analysis.

AIM: The first prospective, randomized trial with paired kidney analysis was conducted to compare the efficacy and safety of tacrolimus with cyclosporine-based immunosuppressive therapy in renal transplant recipients. This paper reports the long-term follow-up results of the authors' previously published study, with the main focus on graft survival and renal function. METHODS: Chinese patients transplanted in our centre between June 1998 and June 2005 with their first deceased renal transplant were included. Patients were included if both kidneys were received by the authors' centre, thus allowing a paired analysis. Patients were randomized to receive triple immunosuppressive therapy with either tacrolimus or Neoral cyclosporine, concomitantly with prednisolone and azathioprine therapy. RESULTS: Seventy-six patients received cadaveric kidneys from 38 donors. Each pair of kidneys was randomly assigned to a separate group (38 subjects/group). The mean follow-up duration was 6.1 +/- 1.8 years. The mean calculated creatinine clearance was significantly higher in patients receiving tacrolimus-based therapy. The rate of biopsy-proven acute rejection was lower in the tacrolimus group (18.4% vs 42.1%, P = 0.03). The patient and graft survival were comparable in both treatment arms. Significantly fewer patients on tacrolimus-based therapy developed hypercholesterolaemia (P = 0.05). However, there was no significant difference in the development of post-transplant diabetes mellitus, hypertension, opportunistic infection and malignancy between both groups. CONCLUSION: Using the immunosuppressive regimen, tacrolimus-based therapy provided adequate immunosuppression with better renal function and less acute rejection, as compared with cyclosporine-based therapy.

Prevalence of abnormal glucose metabolism in Chinese renal transplant recipients: a single centre study.

BACKGROUND: Post-transplant diabetes mellitus (PTDM) after renal transplantation is associated with adverse outcome on patient and graft survival. Fasting blood glucose alone will underestimate diabetes and also ignores diagnosis of impaired glucose tolerance (IGT). IGT has a strong correlation with diabetes and cardiovascular risk. METHODS: In this cross-sectional study, we estimate the prevalence of abnormal glucose metabolism (AGM) using oral glucose tolerance test (OGTT) and identify its predictive factors. Patients who received kidney transplantation in our centre without pre-transplant diabetes were recruited. OGTT was performed in patients with fasting glucose levels between 5.6 and 6.9 mmol/L for at least two occasions 6 months post-transplantation. RESULTS: Of 119 patients recruited, 31 had OGTT performed. The prevalence of PTDM, IGT and IFG was 21.8 (26/119)%, 6.7 (8/119)% and 3.4 (4/119)% respectively. Thus the overall prevalence of AGM was 31.9%. Age (P = 0.003), body mass index (P = 0.032), hepatitis B seropositivity status (P = 0.01), CMV infection (P = 0.02) and acute rejection (P = 0.002) were all associated with development of AGM. Using multivariate analysis, only older age at transplant (OR 1.09), history of acute rejection (OR 3.40) and hepatitis B seropositivity (OR 3.13) were significantly associated with the development of AGM. CONCLUSION: AGM is common in our renal transplant recipients.

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.

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.

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.

ASPD: A prospective study of adequacy in Asian patients on long term, small volume, continuous ambulatory peritoneal dialysis.

BACKGROUND: The impact of small solute clearance on patient survival in continuous ambulatory peritoneal dialysis (CAPD) is not yet solidified. Previously, we demonstrated that CAPD using small volume (6 L) daily exchanges provides adequate dialysis for most Asian patients. METHODS: We conducted a prospective, long-term observational study to determine the optimal dialysis adequacy that may provide better patient survival for Asian patients who receive small-volume CAPD. We recruited 294 patients. The initial CAPD regime was 3 x 2-L exchanges daily. The same regime was maintained unless there was significant loss of ultrafiltration or fluid retention despite the use of hypertonic dialysate. RESULTS: Median study period was 38.9 (range 5 - 76.5) months, with 81% and 27% of patients remaining in the study at 24 and 48 months respectively. The overall survival rates at 2 and 4 years were 94.0% and 74.8% respectively. Our long-term data revealed that survival rate was related to Kt/V values. Survival rates were significantly higher for patients with total Kt/V > 2.0 than for patients with Kt/V < 1.7 (p = 0.02). The former group had lower body mass index and higher residual renal function and peritoneal Kt/V than the Latter group. On analysis using Cox proportional hazards regression models, cardiovascular disease (CVD), lower urine volume, and higher body mass index were independent predictors of mortality. Patients with higher renal Kt/V had a significantly lower risk of mortality (RR = 0.018, p = 0.01) after adjusting for the effects of CVD and diabetes mellitus. CONCLUSION: Our data recommend that 1.7 be the minimal target for total Kt/V in patients on long-term CAPD. Patients with high body mass index, low residual urine volume, and significant CVD need close monitoring.

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.

A study of the clinical and biochemical profile of peritoneal dialysis fluid low in glucose degradation products.

OBJECTIVE: Although peritoneal dialysis (PD) is a widely accepted form of renal replacement therapy, concerns remain regarding the bioincompatible nature of standard PD fluid (PDF). Short-term studies of new biocompatible PDFs low in glucose degradation products (GDPs) reveal divergent results with respect to peritoneal integrity. METHODS: We studied 125 patients on maintenance PD who were assigned, by simple randomization, to receive either conventional or low-GDP PDF at PD initiation. Parameters of dialysis adequacy and peritoneal transport of small solutes were determined at initiation and after a period of maintenance PD at the time when serum and overnight effluent dialysate were simultaneously collected and assayed for various cytokines, chemokines, adipokines, and cardiac biomarkers. All patients were further followed prospectively for an average of 15 months from the day of serum and effluent collection to determine patient survival and cardiovascular events. RESULTS: Patients treated with conventional or low-GDP PDF were matched for sex, age, duration of dialysis, dialysis adequacy, and incidence of cardiovascular disease or diabetes. After an average of 2.3 years of PD treatment, the weekly total and peritoneal creatinine clearance, and the total and peritoneal Kt/V were comparable in the groups. However, urine output was higher in patients using low-GDP PDF despite there having been no difference between the groups at PD initiation. Patients using low-GDP PDF also experienced a slower rate of decline of residual glomerular filtration and urine output than did patients on conventional PDF. Compared with serum concentrations, effluent concentrations of tumor necrosis factor α, hepatocyte growth factor, macrophage migration inhibitory factor, interleukins 8 and 6, C-reactive protein, and leptin were found to be higher in both groups of patients after long-term PD, suggesting that the peritoneal cavity was the major source of those mediators. Compared with patients on low-GDP PDF, patients on conventional fluid showed elevated leptin and reduced adiponectin levels in serum and effluent. The effluent concentration of interleukin 8 was significantly lower in patients using low-GDP PDF. The survival rate and incidence of cardiovascular complications did not differ between these groups after maintenance PD for an average of 3.6 years. CONCLUSIONS: It appears that low-GDP PDF results in an improvement of local peritoneal homeostasis through a reduction of chronic inflammatory status in the peritoneum.

Renal cell carcinoma of native kidney in Chinese renal transplant recipients: a report of 12 cases and a review of the literature.

OBJECTIVES: To present and discuss the epidemiological and clinical aspects, as well as therapeutic options and outcome of de novo renal cell carcinoma (RCC) of the native kidneys in a series of Chinese renal transplant recipients. PATIENTS AND METHODS: A retrospective, cohort study examining all renal transplant recipients with the diagnosis of RCC of native kidney followed up in two major regional hospitals in Hong Kong between January 2000 and December 2009. Clinical data included age, gender, cause of renal failure, symptoms at presentation, duration of transplantation, immunosuppressive therapy, and history of acquired cystic kidney disease (ACKD). Laboratory, radiographic, operative, and pathology reports were used to assess the tumor extent. RESULTS: Among the 1,003 renal transplant recipients recruited, 12 transplant recipients had a nephrectomy for a total of 13 RCC. The prevalence of de novo RCC was 1.3%. The mean age at diagnosis of RCC was 48.4 years, and the median time from transplantation to diagnosis was 6.1 years. ACKD was found in 6 (50%) of the patients. All patients except one were asymptomatic. pT1 disease was found in ten patients with a mean tumor size of 3.2 cm. All patients were treated successfully with radical nephrectomy. After a median follow-up of 38 months, two patients (16.7%) died. One died of sepsis, and the other died of metastatic carcinoma. CONCLUSIONS: With increasing data showing a better prognosis if RCC is detected early by screening, it is time to consider screening all kidney transplant recipients for ACKD and RCC.

Dried blood spot measurement: application in tacrolimus monitoring using limited sampling strategy and abbreviated AUC estimation.

Dried blood spot (DBS) sampling and high-performance liquid chromatography tandem-mass spectrometry have been developed in monitoring tacrolimus levels. Our center favors the use of limited sampling strategy and abbreviated formula to estimate the area under concentration-time curve (AUC(0-12)). However, it is inconvenient for patients because they have to wait in the center for blood sampling. We investigated the application of DBS method in tacrolimus level monitoring using limited sampling strategy and abbreviated AUC estimation approach. Duplicate venous samples were obtained at each time point (C(0), C(2), and C(4)). To determine the stability of blood samples, one venous sample was sent to our laboratory immediately. The other duplicate venous samples, together with simultaneous fingerprick blood samples, were sent to the University of Maastricht in the Netherlands. Thirty six patients were recruited and 108 sets of blood samples were collected. There was a highly significant relationship between AUC(0-12), estimated from venous blood samples, and fingerprick blood samples (r(2) = 0.96, P < 0.0001). Moreover, there was an excellent correlation between whole blood venous tacrolimus levels in the two centers (r(2) = 0.97; P < 0.0001). The blood samples were stable after long-distance transport. DBS sampling can be used in centers using limited sampling and abbreviated AUC(0-12) strategy as drug monitoring.

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.

Conversion of ciclosporin A to tacrolimus in kidney transplant recipients with chronic allograft nephropathy.

BACKGROUND: Tacrolimus and ciclosporin might have different effects on intra-renal fibrosis and allograft function in chronic allograft nephropathy (CAN). It is difficult to predict the response to calcineurin inhibitor minimization in patients with CAN. METHODS: This prospective randomized study compared ciclosporin A (CsA)-to-tacrolimus conversion (group A, target tacrolimus trough level 6-8 ng/ml) vs CsA minimization (group B, target CsA trough level 80-100 ng/ml) with regard to efficacy and safety in patients with CAN and deteriorating allograft function. The primary efficacy endpoint was improvement in the slope of inverse serum creatinine (1/SCr) vs time plot. RESULTS: There were 34 evaluable patients (n=16 in group A; n=18 in group B), with similar baseline characteristics. Both groups reached target drug levels after a 3-month run-in period. Over the ensuing 12 months, nine (56.3%) subjects in group A and 10 (55.6%) in group B reached the primary end point (P=0.968). Both groups showed considerable improvement in the slope of 1/SCr vs time plot. There was no significant difference in the slope between groups before and after intervention. Graft survival was 87% in group A and 100% in group B (P=0.121). Acute rejection was encountered in two group A subjects. There was no significant change or difference in blood glucose, lipids, and blood pressure between groups. CONCLUSION: Our results suggest that in patients with CAN and deteriorating allograft function, CsA-to-tacrolimus conversion or CsA minimization achieved comparable efficacies in retarding the decline of graft function. Such contention may be biased by the low patient number. Further studies with a larger cohort are needed for validation.

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.

Diltiazem co-treatment in renal transplant patients receiving microemulsion cyclosporin.

BACKGROUND: Usage of cyclosporin (the Hong Kong Hospital Authority's single largest item of drug expenditure) continues to increase, mainly due to increasing numbers of renal allograft patients taking it as long-term antirejection therapy. Diltiazem, an antihypertensive agent, interferes with the first pass extraction of oral cyclosporin, thus serving to conserve its dosage. AIMS: In renal transplant patients, to assess whether diltiazem co-treatment could achieve worthwhile dosage conservation of Neoral (a relatively new microemulsified cyclosporin formulation), safely. METHODS: A randomized, placebo-controlled, double-blind clinical trial was undertaken at three local hospitals. Renal transplant recipients receiving Neoral as prophylactic immunosuppression were randomized to two treatment arms. Active treatment consisted of diltiazem tablets 30 or 60 mg twice daily for patients weighing < 60 or >or= 60 kg, respectively. One hundred and ten eligible patients gave their informed consent, and were followed up for at least six months. The mean difference in the dollar cost in the sixth month was the primary outcome. Secondary/ancillary outcomes included changes in cyclosporin dosage and blood level, and untoward clinical events including rejection. Outcomes were evaluated by intention to treat analyses. RESULTS: During weeks 23-26 (sixth month) post randomization, diltiazem co-treatment yielded an estimated average cost saving per patient on drugs of 15%[the 95% confidence interval (CI) of the difference being HK dollars 609 +/- 517 or pound 50 +/- 42], with no apparent excess of untoward or adverse events, complications, hospitalization, outpatient visits, or inferior quality of life. CONCLUSIONS: This diltiazem co-treatment regime applied to the nearly 1800 surviving renal allograft patients followed up in Hospital Authority hospitals could have saved approximately HK dollars 14.3 million ( pound 1.17 million) annually, without adverse sequelae.