Prevalence and impact of anxiety and depression in Chinese peritoneal dialysis patients: A single centre study.

AIM: Anxiety and depression are prevalent among patients with end stage renal failure. However, data concerning their role in the subsequent peritonitis and hospitalization was scarce. The aim of this study was to examine the prevalence of psychological problems in our Chinese peritoneal dialysis (PD) patients and its association with subsequent clinical outcome. METHODS: This was a single-centre prospective cohort study. All patients newly started on PD between 1 September 2012 and 31 December 2014 were recruited. Hospital Anxiety Depression Scale was used to categorize the patients into high score group (HSG) and low score group (LSG). Higher score reflects higher emotional distress. RESULTS: A total of 132 patients were recruited. Seventy-five patients (55%) were categorized as HSG. Higher overall peritonitis rate and Gram-positive organism associated peritonitis rate were observed in HSG (P = 0.012 and P = 0.016, respectively). The hospitalization rates in HSG and LSG were 1.20 episodes per patient-year and 1.05 episodes per patient-year respectively. Both high CCI (OR 1.33, 95% CI 1.10-1.62, P < 0.01) and HSG (OR 3.17, 95% CI 1.27-7.93, P = 0.01) were independent risk factors for PD peritonitis. CONCLUSION: Anxiety and depression were also common among Chinese PD patients. Those in HSG were more likely to develop PD peritonitis. These psychological symptoms deserved early detection. Further studies are needed to investigate whether intervention can improve the clinical outcome of these patients.

Hemodialysis catheter insertion using transrenal approach.

We report a patient suffering from end-stage renal disease (ESRD) because of lupus nephritis presented with exhausted vascular access after multiple arteriovenous grafts creation and hemodialysis catheters insertion. A rare percutaneous transrenal approach was finally used for the insertion of dialysis catheter. After 2 years, this hemodialysis catheter was complicated by blockage but was successfully replaced by a new catheter via the same site. Our report shows that the transrenal route of hemodialysis catheter insertion can provide a glimpse of hope for those ESRD patients with exhausted vascular access.

Screening Algorithm for BK Virus-Associated Nephropathy Using Sequential Testing of Urinary Cytology: A Probabilistic Model Analysis.

BACKGROUND: Incorporating urinary cytology in BK virus (BKV) screening algorithm potentially reduces the screening cost for BK viral nephropathy. We aimed to evaluate the test performances and screening cost of sequential 2-stage screening consisting of urine cytology followed by BKV serum quantitative polymerase chain reaction (PCR). METHODS: Ninety-five kidney transplant recipients who had BKV serum quantitative PCR/urine cytology tested and verified with histopathology (the reference gold standard) were included. A probabilistic model was constructed to evaluate the test performance and screening cost of 2-stage screening, and was compared with screening with urine cytology or serum viral load alone. RESULTS: At a viral load threshold of ≥104 copies/ml, the sensitivity and specificity of quantitative PCR alone were 83% (95% CI 69-96) and 91% (95% CI 83-97), respectively. The sensitivity and specificity of urine cytology alone were 91% (95% CI 79-100) and 74% (95% CI 60-91), respectively. Sequential 2-stage screening resulted in loss in sensitivity but a net gain in specificity (viral load threshold ≥104 copies/ml - sensitivity, 75% (95% CI 60-91); specificity, 98% (95% CI 95-99)). Two-stage screening also had superior positive predictive value and is cost effective when BKV-associated nephropathy prevalence is below 94%. CONCLUSIONS: Our study had demonstrated a favorable test performance and cost efficiency of 2-stage BKV screening.

Dialysis outcomes of elderly Indigenous and non-Indigenous Australians.

AIM: Whilst increasing numbers of elderly people in Australia are commencing dialysis, few Indigenous patients are aged ≥ 65 years and their outcomes are unknown. We compared the long-term survival, mortality hazards and causes of death between elderly Indigenous and elderly non-Indigenous dialysis patients. METHODS: This was a retrospective cohort study of adults aged ≥ 65 years who commenced dialysis in Australia from 2001-2011, identified from the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry. Indigenous (n = 263) and non-Indigenous (n = 10,713) patients were followed until death, loss to follow-up, recovery of renal function or 31 December 2011. Mortality was compared using a multivariate Cox proportional-hazards model with age, gender, body mass index, smoking, primary renal disease, comorbidities, late referral and initial treatment modality as predictive variables. RESULTS: Median follow-up was 26.9 months (interquartile range 11.3-48.8 months). Overall 166 Indigenous and 6265 non-Indigenous patients died during the 11-year follow-up period. Mortality rates per 100 patient-years were 23.9 for Indigenous patients and 21.2 for non-Indigenous patients. The overall 1-, 3- and 5-year survival rates were 81%, 49% and 27% for Indigenous patients and 82%, 55% and 35% for non-Indigenous patients respectively. Indigenous patients had a 20% increased risk of mortality compared with non-Indigenous patients (adjusted hazard ratio 1.20, 95% confidence interval, 1.02, 1.41; P = 0.02). 'Social deaths' (predominantly dialysis withdrawal) and cardiac deaths were the main causes of death for both groups. CONCLUSION: Among elderly dialysis patients in Australia, Indigenous status remains an important factor in predicting survival.

Risk factors for dialysis withdrawal: an analysis of the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry, 1999-2008.

BACKGROUND AND OBJECTIVES: Dialysis withdrawal (DW) in patients with ESRD is increasing in importance. This study assessed causes of death and risk factors for DW in Australia and New Zealand in the first year of dialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This retrospective observational cohort study included all adult Australians and New Zealanders beginning renal replacement therapy in 1999-2008. RESULTS: A total of 24,884 patients with 10,073 deaths were included. Deaths from cardiac and social causes (predominantly DW) accounted for 38% and 28% of all deaths, respectively. Cumulative incidence of DW was 3.5% at 1 year (95% confidence interval [CI], 3.3%-3.8%), 9.0% at 3 years (95% CI, 8.6%-9.4%), and 13.4% at 5 years (95% CI, 12.8%-13.9%). In multivariate analysis, predictors for DW in the first year were older age (subhazard ratio [SHR], 1.70 per decade [95% CI, 1.59-1.83]; P<0.001), late referral (SHR, 1.83 [95% CI, 1.59-2.11]; P<0.001), comorbid conditions (SHR, 1.33 per each additional comorbid condition [95% CI, 1.25-1.41]; P<0.001), and diabetes (SHR, 1.16 [95% CI, 1.00-1.34]; P=0.05). Negative predictors for DW included male sex (SHR, 0.75 [95% CI, 0.66-0.87]; P<0.001), indigenous ethnicity (SHR, 0.74 [95% CI, 0.58-0.95]; P=0.02), other nonwhite race (SHR, 0.66 [95% CI, 0.48-0.91]; P=0.01), and peritoneal dialysis user (SHR, 0.59 [95% CI, 0.49-0.72]; P<0.001). CONCLUSIONS: DW is common among dialysis patients in Australia and New Zealand. Risk factors include older age, female sex, white race, diabetes, higher comorbidity burden, hemodialysis user, and late referral to nephrologist.

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.

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.

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.