Increased risk of cardiovascular events in end-stage renal disease patients with osteoporosis: a nationwide population-based cohort study.

SUMMARY: We investigated the cardiovascular disease risk and mortality in end-stage renal disease (ESRD) patients. A total of 12,535 patients with ESRD undergoing incident dialysis were enrolled, 4,153 (33.13 %) of whom had osteoporosis. The osteoporosis group was associated with a significantly higher risk of coronary artery disease, congestive heart failure, stroke, and mortality. INTRODUCTION: In this study, we aimed to investigate the risk of cardiovascular disease and mortality in a sample of end-stage renal disease patients with osteoporosis. METHODS: We conducted this retrospective cohort study of incident dialysis patients with and without osteoporosis to evaluate the risk of overall mortality and cardiovascular complications including stroke, coronary heart disease, and congestive heart failure between the two groups. A total of 12,535 patients with ESRD undergoing incident dialysis were enrolled, 4,153 (33.13 %) of whom had osteoporosis, from the National Health Insurance Research Database of Taiwan for the years 1998 through 2011. The osteoporosis group had more comorbidities than the group without osteoporosis including hypertension, hyperlipidemia, mental disorders, and hepatitis C infection. RESULTS: After adjusting for age, gender, and related comorbidities, the osteoporosis group was associated with a significantly higher risk of coronary artery disease (hazard ratio (HR)=1.32, 95 % confidence interval (CI)=1.20-1.45) which was significant in both genders (women, HR=1.35, 95% CI=1.20-1.50; men HR=1.27, 95% CI=1.06-1.52) and all age groups (≤49 years HR=1.41, 95% CI=1.16-1.70; >49 years HR=1.30, 95% CI=1.16-1.45). Similar results were observed for the outcomes of congestive heart failure, stroke, and mortality. CONCLUSIONS: The results showed that osteoporosis was significantly associated with the subsequent risk of cardiovascular events in patients with ESRD. When encountering patients with ESRD and osteoporosis, physicians should be alert to the subsequent cardiovascular risk in incident dialysis patients to prevent the subsequent occurrence of these adverse events.

Outcome of peritoneal dialysis in cirrhotic patients with end-stage renal disease: a 24-years' experience in Taiwan.

BACKGROUND: Use of peritoneal dialysis (PD) in liver cirrhosis patients with end-stage renal disease remains controversial. Moreover, the long-term outcome in cirrhotic patients is unclear. The aim of the present study was to analyze the outcome of cirrhotic patients treated with PD in our center during the past 24 years. METHODS: We retrospectively reviewed the data of cirrhotic patients who received PD between 1984 and 2009. A group of noncirrhotic patients who were age- and sex-matched during the same period were selected as controls. Peritonitis rates, complications and outcomes were compared. RESULTS: A total of 30 cirrhotic patients and 60 control patients were included in the analysis. Peritonitis-free survival did not differ between groups. Gram-positive organisms, especially coagulase-negative staphylococcus and streptococcus sp., were the major causes of peritonitis in the cirrhotic patients. Also in the cirrhotic patients, complications such as umbilical hernia, chronic hypotension and erythropoietin resistance were more common as compared with controls. An initially higher solute and water transport capacity was observed in the cirrhotic patients, which became comparable to controls by the end of the 2nd year of treatment. Serum albumin concentrations were lower in cirrhotic patients (p = 0.01), and the decline of renal Kt/V was slower in cirrhotic patients as compared to that of controls (p < 0.0001). There was no significant difference in patient and technique survival between the two groups. CONCLUSION: Our study suggests that PD is an effective therapy with a comparable risk of peritonitis and solute clearance in liver cirrhosis patients with end-stage renal failure.

Evolution of microbiological trends and treatment outcomes in peritoneal dialysis-related peritonitis.

BACKGROUND AND AIM: Peritoneal dialysis (PD)-related peritonitis is a major risk factor of technique failure and contributes to significant mortality in patients undergoing PD. The aim of this study was to examine the evolution of microbiological trends and treatment outcomes of PD-related peritonitis in our hospital over the past 26 years. METHODS: A total of 630 patients entered our CAPD program from February 1984 to June 2010. Among them, 119 patients (18.9%) experienced 599 episodes of peritonitis. Microbiological trends, treatment responses, techniques and patient survival were analyzed. RESULTS: The incidence rate of total peritonitis showed a steady decline from 1.08 episodes/patient-year in 1984 to 0.25 episode/ patient-year in 2009 (p < 0.001). A similar trend was found in gram-positive (p < 0.001) and gram-negative peritonitis (p = 0.015). In contrast, there was a trend toward an increased proportion of gram-negative peritonitis. This increase was not due to an increased rate of gram-negative peritonitis but to the more dramatic fall in gram-positive peritonitis. Treatment of peritonitis resulted in a complete cure in 78.0% of patients, while 16.7% of patients required catheter removal and 5.3% died. Gram-positive organisms were associated with a more favorable outcome compared to gram-negative pathogens as manifested by a higher cure rate (p = 0.023). The patient survival and technique survival were much improved after 2000 compared to that before 2000 (p < 0.0001). CONCLUSION: A remarkable improvement in the outcome of PD-related peritonitis has been achieved in the past 26 years in our hospital. To further decrease peritonitis rates, attention needs to be directed at reducing gram-negative peritonitis.

Malignant lymphoma of the kidney mimicking rapid progressive glomerulonephritis.

Primary renal lymphoma (PRL) is rare and often presents as rapidly progressive renal failure. Most cases of PRL are large-cell lymphomas of B-cell lineage. Herein, we report a 75-year-old female patient with infiltrative CD20 (+) B-cell lymphoma who underwent 4 consecutive courses of chemotherapy with R-CVP (rituximab, cyclophosphamide, vincristine, and prednisone) and after 12 sessions became free from hemodialysis in good general condition. Her serum creatinine level gradually decreased to 4.1 mg/dl with adequate urine output. Unfortunately, a relapse of CD20 (-) lymphoma developed rapidly involving other organs. She died with severe hospital-acquired pneumonia and febrile neutropenia after the last chemotherapy with R-MINE almost 1 year after onset of symptoms. We conclude that renal biopsy enables prompt diagnosis in rapidly progressive renal failure and immunophenotyping and also staging workup of the lymphoma in case of positive biopsy. Though rituximab improved response rate of PRL, it reduced expression of CD20. This may relate to frequent relapse/resistance after rituximab therapy and poor long-term patient survival.

Clinical Significance of Serum Visfatin in Renal Transplant Recipients.

Chronic antibody-mediated rejection is the most common cause of late graft loss in renal transplant recipients. Visfatin is a pre-B cell colony-enhancing factor secreted by activated lymphocytes. We hypothesize that visfatin may play a role in the augmentation of B cell colonies and facilitate antibody-mediated rejection. Renal transplant recipients were randomly selected for the study. Fasting blood samples were obtained for the assay of visfatin. The participants were prospectively followed up for 3 years. A total of 146 patients were recruited for the study and were divided into 3 groups according to tertile of serum visfatin level. At the end of follow-up, 6 patients had graft loss, including 1 graft loss in tertile 1, 3 in tertile 2, and 2 in tertile 3 (P = .60). Fourteen patients experienced at least 1 episode of acute rejection, while 21 patients were diagnosed as having chronic rejection. The distribution of acute rejection was 10.2% in tertile 1, 10.2% in tertile 2, and 8.3% in tertile 3 (P = .94); chronic rejection occurred in 10.2%, 16.3%, and 16.7%, respectively (P = .59). We conclude that serum visfatin level was not correlated with either graft failure or patient mortality in a 3-year observation period.

Urinary Liver Type Fatty Acid Binding Protein Is Negatively Associated With Estimated Glomerular Filtration Rate in Renal Transplant Recipients With Graft Loss.

BACKGROUND: Liver type fatty acid binding protein (L-FABP) is abundant not only in the liver but also in the kidney and is excreted in urine. Its primary function is to facilitate intracellular long chain fatty acid transport and it might also act as an endogenous antioxidant molecular. The purpose of this study was to investigate whether plasma or urinary L-FABP levels were associated with graft function in renal transplant recipients. PATIENTS AND METHODS: Sixty-seven renal transplant recipients with a mean age of 48.8 years were recruited. The mean duration of renal transplantation was 4131 days. Recipients were divided into 2 groups based on their estimated glomerular filtration rate (eGFR) values: moderate graft function (eGFR ≥60 mL/min/1.73 m2) and low graft function (eGFR <60 mL/min/1.73 m2). Fasting plasma and urinary L-FABP levels were measured. RESULTS: There was no significant difference in plasma L-FABP level between the 2 groups, although recipients in the low graft function group had significantly lower urinary L-FABP level when compared with recipients in the moderate graft function group. Plasma and urinary L-FABP levels were not associated with eGFR in the 67 recipients; however, urinary L-FABP level (ß = -1.24, P = .037) and level adjusted by urinary creatinine (ß = -0.75, P = .046) were significantly negatively associated with eGFR in recipients with low graft function after adjusting for potential confounders. CONCLUSION: Increased urinary L-FABP level seems to be a significant indicator of decreased graft function in renal transplant recipients with loss of graft function.

Severe emphysematous pyelonephritis in a renal allograft: successful treatment with percutaneous drainage and antibiotics.

Emphysematous pyelonephritis is a rare, severe gas-forming infection of the kidney. Herein we report a case of a 51-year-old man who had received a cadaveric renal transplant 12 years ago. Post-transplant diabetes mellitus occurred 8 years later. He experienced urinary tract infection with graft pain one week before admission and presented with septic shock at the emergency room. Plain X-ray of the abdomen showed retroperitoneal air. A computed tomography scan of the abdomen showed retroperitoneal and extraperitoneal air being released from the graft kidney. These findings were compatible with extensive emphysematous pyelonephritis. The patient underwent percutaneous drainage. Blood culture and urine culture yielded Escherichia coli. After repeated percutaneous drainage and strong antibiotics for a prolonged period, the patient finally recovered.

Prognosis of Kidney Transplant Recipients With Pretransplantation Malignancy: A Nationwide Population-Based Cohort Study in Taiwan.

OBJECTIVE: The objective of this study was to evaluate the prognosis of kidney transplant recipients with pretransplantation malignancy and the incidence of recurrent malignancy in kidney transplant recipients using claims data from Taiwan's universal health insurance program. METHOD: A total of 4350 transplant recipients were retrospectively analyzed. The rates of pretransplantation or recurrent malignancy, which was defined by their inclusion in the catastrophic illness patient registry using the International Classification of Diseases, 9th Revision, were evaluated. Cox proportional hazard regression and Kaplan-Meier curves were used for the analyses. RESULTS: In total, there were 4350 kidney transplant recipients, 52.1% of patients were male, the mean age at transplantation was 45.8 years old, and the percentages of diabetes mellitus, hypertension, hepatitis B viral infection, and hepatitis C viral infection were 14%, 63.2%, 4.2%, and 2.4%, respectively. There were 95 patients (2.2%) with pretransplantation malignancy. The top 3 pretransplantation malignancies, in decreasing order, were urinary tract, kidney, and breast cancers. After kidney transplantation, 10 recipients had recurrent cancer. The overall cancer recurrence rate was 10.5%. These 10 cancers included urothelial carcinoma (n = 5), renal cell carcinoma (n = 3), breast cancer (n = 1), and thyroid cancer (n = 1). Eleven recipients had a secondary cancer. Patients without pretransplantation and post-transplantation malignancy had the best survival. Patients with pretransplantation malignancy had a greater occurrence of cancers and increased mortality regardless of whether or not they had recurrence of cancer. CONCLUSION: Our results suggest the higher risk of cancer, recurrent or secondary, and mortality after kidney transplantation. Adequate waiting time before transplantation and preventive strategies are strongly suggested in kidney transplant recipients with cancer history.

The hybrid grey-based models for temperature prediction.

In this paper several grey-based models are applied to temperature prediction problems. Standard normal distribution, linear regression, and fuzzy techniques are respectively integrated into the grey model to enhance the embedded GM(1, 1), a single variable first order grey model, prediction capability. The original data are preprocessed by the statistical method of standard normal distribution such that they will become normally distributed with a mean of zero and a standard deviation of one. The normalized data are then used to construct the grey model. Due to the inherent error between the predicted and actual outputs, the grey model is further supplemented by either the linear regression or fuzzy method or both to improve the prediction accuracy. Results from predicting the monthly temperatures for two different cities demonstrate that each proposed hybrid methodology can somewhat reduce the prediction errors. When both the statistics and fuzzy methods are incorporated with the grey model, the prediction capability of the hybrid model is quite satisfactory. We repeat the prediction problems in neural networks and the results are also presented for comparison.

Influence of pretransplantation dialysis time and lupus activity on outcome of kidney transplantation in systemic lupus erythematosus.

BACKGROUND: Kidney transplantation (KT) has better outcome compared with dialysis in lupus patients. The duration lupus patients need to wait before KT remains debatable, especially in patients with lupus activity. We analyzed a renal transplantation database to elucidate if pretransplantation dialysis (PTD) time and lupus activity affected outcome. METHODS: From 1984 to 2012, 31 Chinese lupus nephritis patients underwent KT at our hospital. The lupus activity was defined as nonrenal systemic lupus erythematosus disease activity index (SLE-DAI) score. Biopsy-proven acute rejection/recurrent lupus nephritis (RLN) were recorded. Chronic allograft dysfunction (CAD) was defined as doubling of serum creatinine level. Graft failure was defined as return to dialysis. We calculated relative hazard ratios (HR) with 95% confidence intervals (CI) from Cox proportional-hazards regression models. RESULTS: In total, 31 lupus patients with KT (7 men and 24 women), with a mean age of 35.3 years at transplantation, were enrolled in this study. The mean follow-up duration was 8.2 years. The mean PTD time was 3.3 years. Both PTD time and lupus activity before transplantation had no effect on CAD and graft failure. Longer PTD time was associated with more acute rejection (HR = 1.20; 95% CI, 1.02-1.41). Also, maximal lupus activity after transplantation was associated with more CAD (HR = 6.44; 95% CI, 1.36-30.57). CONCLUSION: For Chinese lupus patients with KT, longer PTD time was associated with worse outcome. Patients should undergo KT immediately if a kidney is available for donation, even with active lupus disease. It is necessary to monitor lupus activity after transplantation due to its effect on outcome.

Serum Endocan correlated with stage of chronic kidney disease and deterioration in renal transplant recipients.

Earlier detection and intervention for chronic renal allograft injury (CRAI) remain major challenges for transplantation physicians. Endocan plays a key role in the regulation of cell adhesion, inflammatory disorders, and tumor progression. We conducted this cross-sectional study of 97 renal transplant (RT) recipients with mean RT duration of 7.0 ± 5.7 years to determine whether Endocan could be a diagnostic and prognostic marker. The patients' mean age was 43.6 ± 13.2 years, and 55.7% (54/97) were male. Higher Endocan levels were found in more advanced chronic kidney disease (CKD) stages in a dose-dependent manner. Interestingly, the Endocan ≥ 643.19 pg/mL group had higher creatinine (Cr; 1.2 ± 0.4 vs 1.6 ± 1.1 mg/dL; P = .029) and lower estimated glomerular filtration rate (eGFR; 67.8 ± 23.8 mL/min vs 54.4 ± 22.0; P = .006) than the Endocan <643.19 pg/mL group after 3 months of follow-up, respectively. Linear regression analysis found tumor necrosis factor (TNF)-α correlated well with Endocan. To elucidate the response of endothelium activation, we stimulated human umbilical vein endothelial cells (HUVECs) with TNF-α in vitro, and found the levels of Endocan (P = .022) and transforming growth factor (TGF)-ß1 (P = .034) increased with time, but interleukin (IL)-10 decreased (P = .013). In summary, Endocan may reflect the degree of endothelial cell injury in renal allografts, and showed a trend of elevation in late-stage CKD. An in vitro study demonstrated TNF-α-activated HUVECs secreted high levels of Endocan and TGF-ß1, which could lead to a better understanding of the role of endothelium in immune balance. In conclusion, Endocan may have potential as a useful long-term indicator of CRAI in RT recipients, but further study is needed to verify our findings.

Outcome of lupus nephritis after entering into end-stage renal disease and comparison between different treatment modalities: a nationwide population-based cohort study in Taiwan.

BACKGROUND: Systemic lupus erythematosus (SLE) is not a rare disease among the Chinese and the incidence is higher in the female population. Lupus nephritis (LN) often develops in patients with SLE and may progress to end-stage renal disease (ESRD). Although there are studies that suggest postponement of the scheduling of kidney transplantation (KT) for these patients, there are still some other studies with conflicting results. Our study aimed to analyze the outcome of patients with LN after progression to ESRD and to try to elucidate whether deferral of KT is necessary in the Chinese population. METHODS: We used the National Health Insurance Research Database to perform this cohort study. The study cohort was observed between 1998 and 2009 after being diagnosed as having SLE. The cases of SLE and ESRD were identified according to the catastrophic illness database. RESULTS: In total, 1998 SLE patients with ESRD were identified. They received hemodialysis, peritoneal dialysis, or KT with the proportion of 82.1%, 9.8%, and 8.1%, respectively. The 1-year, 5-year, 10-year patient survival rates were best for those who underwent KT (100%, 98.1%, and 94.4%, respectively), followed by peritoneal dialysis (88.3%, 79.1%, and 76%, respectively), and hemodialysis (53.6%, 46.0%, and 41.6%, respectively). For those who underwent KT within 1 year after ESRD, no significant worse patient survival and graft survival were observed than those who underwent KT 1 year later. CONCLUSION: KT provides a better survival benefit for SLE patients with ESRD than hemodialysis and peritoneal dialysis. No obvious clinical benefit of KT deferral was observed in our study and the deferral may not be necessary for our population.

Hyperuricemia predicts kidney disease progression after acute allograft dysfunction.

BACKGROUND: Hyperuricemia is associated with the development of new cardiovascular events and chronic allograft nephropathy in patients with decreased allograft function. This study investigates whether hyperuricemia in kidney transplant recipients should be considered as an independent predictor of kidney disease progression after acute allograft dysfunction. METHODS: Between September 1, 2010, and December 31, 2012, 124 patients who underwent kidney graft biopsy for acute allograft dysfunction were enrolled. Participants were divided into 2 groups: A hyperuricemic group (n = 57) and a normouricemic group (n = 67). The mean serum uric acid (UA) level was obtained by averaging all measurements, once per month for 3 months, before the study began. Clinical and laboratory data were collected. We investigated the role of hyperuricemia on the composite end point (CEP) of doubling of serum creatinine and graft failure by using Cox regression and Kaplan-Meier plots. RESULTS: Over a mean follow-up of 14.27 months, the hyperuricemic group had a poor cumulative survival and easily reached the CEP of doubling of serum creatinine and graft failure (P = .025) with a first-year cumulative incidence of 29.84% and a second-year cumulative incidence of 35.09%. Cox regression models revealed that age at biopsy (unadjusted hazard ratio [HR], 1.03; 95% CI, 1.00-1.06), hyperuricemia (HR, 2.24; 95% CI, 1.13-4.46), and interstitial fibrosis and tubular atrophy (IF/TA), including <25% of parenchyma affected (HR, 3.71; 95% CI, 1.34-10.31) and ≥ 25% of parenchyma affected (HR, 5.10; 95% CI, 1.83-14.19), were highly associated with poor outcome. After adjusting different variables, hyperuricemia and IF/TA were still significant. CONCLUSION: Persistently high serum UA and IF/TA both contribute to the risk of kidney disease progression after acute allograft dysfunction.

Uric acid is highly associated with kidney allograft survival in a time-varying analysis.

BACKGROUND: Hyperuricemia may be associated with the development of new cardiovascular events and graft loss in renal transplant recipients. This study was conducted to clarify whether hyperuricemia is a persistently independent predictor of long-term graft survival and patient outcome. METHODS: Renal allograft recipients (n = 880) who underwent transplantation from December 1999 to March 2013 were included. Participants were divided into 2 groups: a hyperuricemic group (n = 389) and a normouricemic group (n = 491). The mean serum uric acid (UA) level was obtained by averaging all measurements, once per month for 3 months, before the study began. Clinical and laboratory data were collected. We investigated the role of hyperuricemia in the primary endpoint of graft failure by using time-varying analysis and Kaplan-Meier plots. All-cause mortality in renal transplant recipients was also surveyed. RESULTS: During a mean follow-up of 43.3 ± 26.3 months, the major predisposing factors in the 389 patients with hyperuricemia were male predominance (62.98%), high entry serum UA (7.70; range 6.70-8.80 mg/dL), more hypertension (92.29%), previous hemodialysis mode (29.56%), hepatitis C infection (24.42%), more frequent use of UA-lowering agents (43.44%), and use of more drugs for inducing high serum UA (17.74%). After 12 months, the hyperuricemic group had persistently high serum UA (7.66 ± 2.00 vs 6.17 ± 1.60 mg/dL, P < .001) and poor renal function (serum creatinine 2.96 ± 3.20 vs 1.61 ± 1.96 mg/dL, P < .001) compared with the normouricemic group. Survival analysis showed the hyperuricemic group had poorer graft survival (60.47%) than the normouricemic group (75.82%, P = .0069) after 13-year follow-up. However, there was no difference in all-cause mortality between the 2 groups. CONCLUSION: Persistently high serum UA seems to be implicated in elevation of serum creatinine, which could increase the risk for allograft dysfunction.

Universal valganciclovir prophylaxis significantly reduces episodes of first-year cytomegalovirus disease and biopsy-proven acute rejection in kidney transplant recipients.

BACKGROUND: Cytomegalovirus (CMV) remains the most critical viral pathogen after kidney transplantation (KTx). The universal prophylaxis, but not pre-emptive therapy, could avoid the wide range of indirect effects induced by CMV infection. This study aims to examine the effect of universal prophylaxis with oral valganciclovir for the first year of CMV disease after KTx. METHODS: The universal prophylaxis therapy was started in May 2008. Patients who received KTx between January 2006 and September 2010 were included in the study. Oral valganciclovir (Valcyte) was used for 3 months with dosage adjusted by eGFR. CMV disease was defined by typical CMV syndrome with positive viremia or tissue proven. The study end points are episode of CMV disease and first-year biopsy-proven acute rejection. RESULTS: In total, 68 KTx patients who received universal prophylaxis for 3 months (study group) and another 50 KTx recipients without universal prophylaxis (control group) were enrolled. The incidence of CMV disease was 8.0% (4 of 50) in the control group. The universal prophylaxis significantly reduced the first-year episodes of CMV disease to 0% (0 of 68). There were 8 episodes of biopsy-proven acute rejection (8 of 50, 16%) within 1 year after KTx in the control group, but only 2 episodes of biopsy-proven acute rejection (2 of 68, 2.9%) in the treatment group (P < .05). CONCLUSIONS: Universal prophylaxis with oral valganciclovir for 3 months significantly reduced episodes of first-year CMV disease and biopsy-proven acute rejection in kidney transplant recipients.

Serum adipokine levels in renal transplant recipients.

BACKGROUND: Metabolic syndrome (MS) is a common complication in renal transplant (RTx) recipients. This study aimed to explore the alterations and interrelationship of various adipokines in RTx recipients with and without MS. METHODS: RTx recipients followed at our hospital were randomly selected for the cross-sectional study of MS. The modified Adult Treatment Panel III criteria adopted for Asian populations were used to define MS. Overnight fasting blood samples were obtained for determination of adipokines, including adiponectin, leptin, resistin, and visfatin. Univariate and multivariate logistic regressions were performed to determine parameters that were associated with serum adipokine levels. Pearson correlation analysis was performed between adipokines. RESULTS: A total of 280 RTx recipients were enrolled for the study. Seventy-three cases (26.1%) fulfilled the criteria of MS. A significantly higher serum leptin level was found in MS patients (16.61 ± 13.90 vs 8.00 ± 7.42 µg/mL; P < .0001). There was no significant difference in serum levels of adiponectin, resistin, and visfatin between the 2 groups. Serum adiponectin level was positively correlated with serum resistin (r = 0.422; P < .0001) and visfatin levels (r = 0.224; P < .0001). Serum resistin level was positively correlated with serum visfatin level. All but serum visfatin level were negatively correlated with estimated glomerular filtration rate. Univariate logistic regression revealed the following variables to be associated with serum leptin level: metabolic syndrome, sex, body weight, waist circumference, body mass index (BMI), hypertension, serum creatinine, fasting blood sugar, HbA1c, serum triglyceride, and uric acid. Multivariate analysis revealed that sex, body weight, BMI, and serum creatinine were associated with serum leptin level. CONCLUSIONS: Compared with RTx recipients without MS, patients with MS were associated with significantly higher serum leptin levels and similar adiponectin, resistin, and visfatin levels. A close interrelationship was also found in the serum levels of these adipokines.

Reduced variability of tacrolimus trough level in once-daily tacrolimus-based Taiwanese kidney transplant recipients with high-expressive genotype of cytochrome P450 3A5.

BACKGROUND: Our previous study results indicated that conversion from twice-daily Prograf to once-daily Advagraf associated with lower variability of tacrolimus blood trough level. Some factors, such as frequency of interaction by food exposure, expression of cytochrome P450 3A5 genetic polymorphism, and other interactions of unknown factors, could be the reasons for the change of variability. We aimed to clarify the impact of cytochrome P450 3A5 genetic polymorphism on the variability of tacrolimus blood trough level in Taiwanese kidney transplant recipients. METHODS: We collected blood samples from kidney transplant recipients to prepare DNA and then performed single-nucleotide polymorphism genotyping by using the restriction fragment length polymorphism. RESULTS: We found that 79 (52.7%) of 150 kidney transplant recipients had the low-expressive genotype (CYP3A5*3/*3), whereas the other 71 (47.3%) kidney transplant recipients had high-expressive genotype (CYP3A5*1/*1 and CYP3A5*1/*3). The prevalence of high-expressive genotype is higher than previous reports from western countries. Compared with the patients with high-expressive genotype, the average dose-normalized trough level of tacrolimus was significantly higher in patients with low-expressive genotype. Interestingly, when patients converted from twice-daily Prograf to once-daily Advagraf, the percent coefficient of variation of tacrolimus trough level was significantly decreased in patients with high-expressive genotype. CONCLUSION: This study suggested that there is a potential benefit for kidney transplant recipients with cytochrome P450 3A5 high-expressive genotype (*1/*1 or *1/*3) to convert from Prograf to once-daily Advagraf.

Changing pattern of mortality in renal transplant recipients: a single-center, 30-year experience.

INTRODUCTION: Patient survival among kidney transplant (KTx) recipients has improved remarkably in the past decades. The most common causes of death are cardiovascular disease in the West; in Taiwan, the answer remains uncertain. METHODS: From 1983 to 2012, KTx patients who underwent transplantation and were followed at our hospital were recruited for the study. For comparison, patients were stratified according to the transplant time as group 1, 1983-1989 (the initial era); group 2, 1990-1998 (the cyclosporine era); and group 3, 1999-2012 (the modern era, in which tacrolimus and mycophenolate mofetil were available). RESULTS: A total of 520 KTx patients (male:female ratio of 285:235) were performed in our hospital during the study period. A progressive improvement in patient survival rates (P < .0001) was noted among the 3 groups. At a mean follow-up duration of 9.55 ± 8.20 years, 83 recipients had died. Overall, the most common cause of death was infection (44.6%), followed by cardiovascular disease (21.7%), malignancy (12.0%), and hepatic failure (10.8%). Infection was the main cause of death in groups 1 and 2 (44.1% and 52.6%, respectively) but not in Group 3 (18.2%), although this trend did not reach statistical significance. Death owing to cardiovascular diseases became the most common cause of death (27.3%) in the modern era (group 3). CONCLUSION: The pattern of mortality among Taiwanese KTx patients has changed over the past 30 years. Infection is no longer the commonest cause of death.

Short-term prospective study of metabolic syndrome in renal transplant recipients.

BACKGROUND: Metabolic syndrome (MS) may affect patient and graft survival in renal transplant recipients. However, the evolution of MS during prospective follow-up remains uncertain. METHODS: Renal transplant patients were recruited for a study of MS in 2010 and then prospectively followed for 2 years. The modified Adult Treatment Panel III criteria adopted for Asian populations were used to define MS. RESULTS: A total of 302 cases (male:female = 154:148) with a mean duration of 10.5 ± 5.7 years after transplantation were enrolled. At initiation, 71 cases (23.5%) fulfilled the criteria of MS. At the end of follow-up, 11 cases had died and 21 had graft failure. Nine cases had insufficient data for reclassification. The remaining 261 cases completed a 2-year follow-up, and the prevalence of MS was 26.1% at the end of study. Of these, 7.79% (18 cases) of patients without MS had developed new-onset MS. Conversely, 16.9% (12 cases) with MS were free from MS at the end of study (P = .362). Patients with MS were associated with older age (57.1 ± 10.4 vs 52.6 ± 12.4 y; P = .006), more chronic allograft nephropathy (17.4% vs 7.1%; P = .01), proteinuria (22.5% vs 10.8%; P = .012), and use of more antihypertensive agents (1.49 ± 0.86 vs 0.80 ± 0.98; P < .0001). There was no significant change in serum creatinine in each subgroup. CONCLUSIONS: The status of MS in renal transplant patients is dynamic. MS patients were associated with more chronic allograft nephropathy and proteinuria.

Comparison of tuberculosis infection rates in a national database of renal transplant patients with data from a single center in Taiwan.

Successful renal transplantation (RT) improves quality of life and patient survival. Advances in immunosuppressants for RT have improved the prevention and treatment of acute rejection as well as reduced the risk of chronic graft damage, but immunodeficiency may render patients vulnerable to opportunistic infections. We conducted this study to compare the difference in tuberculosis (TB) infection rates between a single institution and a national database of RT recipients in Taiwan. There were 153 patients with TB (3.2%) among 4,835 RT recipients in the database during the period 2000-2009, with a higher prevalence of men (P = .018) and diabetes patients (P = .029). In our institution's registry, 33 patients (2.7%) developed 35 episodes of TB infection among 1,209 RT recipients, but there were no significant differences in general characteristics among different subgroups. Interestingly, the use of cyclosporine was significantly more frequent in RT recipients with TB than in those without in both the national database and in our institution. In contrast, TB infection was negatively correlated with the use of tacrolimus (TAC) and mycophenolate (MPA). RT recipients with TB infection had poor survival (P = .0013) and low graft survival (P = .0003). Taken together, analyses of the national database and the RT patients in our institution revealed that the use of long-term cyclosporine-based immunosuppressive agents was associated with a greater risk of developing post-transplantation TB compared with that of other immunosuppressive agents, but the chronicity and accumulation effect of TAC and MPA should be observed despite the negative correlation found herein. In conclusion, post-transplantation TB is a serious health threat and one of the major causes of death among RT recipients, and a high index of suspicion to ensure early diagnosis and prompt initiation of treatment for TB is crucial. The use of optimal immunosuppressive agents to minimize acute rejection, monitoring of high-risk recipients, prompt diagnosis, and appropriate treatment are required to manage TB infection in endemic areas such as Taiwan.