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.

Higher Variability of Tacrolimus Trough Level Increases Risk of Acute Rejection in Kidney Transplant Recipients.

BACKGROUND: Tacrolimus is the most commonly prescribed immunosuppressive drug after kidney transplantation (KTx). The trough level of tacrolimus (T0) is currently used for routine monitoring after KTx. The purpose of this study was to examine the association between the variability of T0 and acute rejection. METHODS: All kidney transplant recipients (KTR) with tacrolimus-based regimen and episode of biopsy-proven acute rejection (BPAR) between January 2012 and October 2014 were enrolled in the acute rejection (AR) group. KTR with tacrolimus-based regimen and without episode of AR were enrolled in the control group. All of the results of T0 within 6 months before episode of acute rejection were used for the calculation of within-patient variability of T0. The percent coefficient of variation, which is calculated as (standard deviation of mean/mean) × 100%, was used to represent the concentration variability of tacrolimus. RESULTS: In all, 25 KTR with AR and another 136 KTR without BPAR were enrolled in the study. The mean age of all 161 patients was 50.1 ± 10.4 years, and the mean duration after KTx was 4.3 ± 4.7 years. The average daily dose of tacrolimus was 5.7 ± 2.6 mg, and T0 was 5.4 ± 1.8 ng/mL. Age, sex, duration after KTx, daily dose of tacrolimus, and T0 were similar in both groups. Compared with the control group, the percent coefficient of variation of T0 was significantly higher in patients with BPAR 12.1% ± 7.9% vs 39% ± 15.6%, P<.001. CONCLUSIONS: The study results suggest that, in KTR, higher variability of tacrolimus trough level is associated with higher risk of acute rejection.

Long-Term Outcome of Liver Transplant Recipients After the Development of Renal Failure Requiring Dialysis: A Study Using the National Health Insurance Database in Taiwan.

BACKGROUND: The aims of this study were to identify the incidence of renal failure requiring dialysis and to investigate the long-term outcome after renal failure in liver transplantation (LT) patients. METHODS: The primary database used was the Taiwan National Health Insurance Research Database. Subjects with LT from 1997 to 2009 were included. Patients were grouped into the dialysis cohort if they once received hemodialysis owing to any pattern of renal failure during peri-transplantation periods or after LT. Otherwise, they were categorized into the nondialysis cohort. We conducted a retrospective observational study on the correlation of renal failure requiring dialysis and its effect on LT recipients. RESULTS: The analysis included data of 1,771 LT recipients with a mean follow-up time of 3.8 ± 2.9 years. The mean age was 43.2 ± 19.3 years, and 69.4% were male. Overall patient survival was 86.2% at 1 year, 82.2% at 3 years, and 80.5% at 5 years. Renal failure requiring dialysis had developed in the 323 patients (18.2%). Among them, 26 individuals (1.5%) had progressed to end-stage renal disease without renal recovery after perioperative hemodialysis. Individuals who developed renal failure requiring dialysis had a higher mortality compared with LT recipients never requiring dialysis (hazard ratio, 8.75; 95% confidence interval, 7.0-10.9). CONCLUSIONS: Renal failure requiring dialysis development after LT is common and carries high mortality in Chinese liver allograft recipients. Recognizing risk factors permits the timely institution of proper treatment, which is the key to reducing untoward outcomes.

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.

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.

Kidneys from standard-criteria donors with different severities of terminal acute kidney injury.

OBJECTIVES: High terminal serum creatinine level in a deceased donor has been reported as the second most frequent cause of refusal for kidney transplantation. A growing body of evidence has shown a comparable outcome of kidney transplantation from deceased donors with acute kidney injury (AKI). However, the influence of the severity of AKI on graft outcomes remains to be elucidated. METHODS: In this retrospective cohort study, 84 consecutive kidney transplants from 57 standard-criteria donors were classified into 4 groups by RIFLE (Risk, Injury, Failure, Loss of function, and End-stage renal disease) classification according to donor AKI severity before kidney procurement. The donor and recipient characteristics and graft outcomes were compared. RESULTS: Of 84 kidney transplants, 56, 11, 10, and 7 recipients were in the Non-AKI, Risk, Injury, and Failure groups. The mean terminal creatinine was 1.1, 1.6, 2.3, and 4.4 mg/dL in these 4 groups. However, the graft outcomes, including primary nonfunction rate, delayed graft function rate, acute rejection rate, renal function, graft survival and overall survival over the first 5 years had no statistical difference. A trend toward increasing delayed graft function rate as the severity of AKI increased was observed (Non-AKI, Risk, Injury, and Failure: 26.8%, 36.4%, 60.0%, and 57.1%, P = .099). CONCLUSIONS: Our study demonstrates that AKI before procurement does not cause adverse long-term graft outcomes. Standard-criteria donors with AKI are suitable for kidney transplantation, even with a high severity of AKI.

Rapamycin promotes podocyte migration through the up-regulation of urokinase receptor.

Conversion to rapamycin from calcineurin inhibitors may contribute to improvement of graft function in kidney transplant recipients, especially in patients with calcineurin inhibitor-related nephrotoxicity. The conversion from calcineurin inhibitors to rapamycin in kidney transplant recipients has been associated with a higher incidence of proteinuria. It could be explained by possible hemodynamic changes due to withdrawal of calcineurin inhibitors. Podocyte damage occurs commonly in rapamycin-related proteinuria. The vascular endothelial growth factor system has been suggested to be implicated in mammalian target of rapamycin inhibitor-associated proteinuria. However, induction of urokinase receptor (uPAR) signaling in podocytes leads to foot process effacement and urinary protein. In this study, we assessed the role of uPAR in primary cultured podocytes with rapamycin treatment. Our results indicate that 24-hour rapamycin treatment promotes podocyte migration on the wound scratch assay in a dose-dependent manner. Rapamycin treatment for 2 days does not increase the apoptosis of podocytes or affect the podocyte cell viability and morphology. The up-regulation of uPAR in podocytes was confirmed by immunofluorescence staining, real-time polymerase chain reaction (1.8 ± 0.3-fold increase of relative quantification; P < .01) and Western blot analysis. Rapamycin treatment also causes the activation of FAK and ILK in a dose-dependent manner. In summary, rapamycin could promote podocyte migration through the up-regulation of uPAR. This finding provides a new mechanism of rapamycin-associated proteinuria. It also suggests that pharmacologic inhibition of uPAR signaling cascade may have therapeutic potential in the setting of rapamycin-related proteinuria.

Anticancer benefits of early versus late use of rapamycin in a rat model of urothelial carcinoma.

BACKGROUND: We previously reported both in vivo and in vitro effects of rapamycin on urothelial carcinoma. Clinically, the use of rapamycin could not completely prevent the recurrence of urothelial carcinoma. Therefore, we designed this study to compare the difference of efficacy between early and late use of rapamycin in a rat model of urothelial carcinoma. METHODS: The rat model of urothelial carcinoma was induced by adding 0.05% N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) to the drinking water for up to 20 weeks in male Fisher-344 rats. Rapamycin was fed orally from the 1st day, 5th week, 9th week, 13th week, and 17th week. The antitumor effects of different periods of rapamycin treatment were assessed grossly and microscopically. RESULTS: Papillary tumors of urinary bladder were successfully induced in the BBN group. Simultaneous use of rapamycin and BBN from the 1st day of treatment significantly reduced the tumor growth in urinary bladder: 80% of the rats had no tumor and 20% had low-grade tumors. Adding rapamycin from the 5th week was associated with more tumor growth: 20% of the rats had no tumors, 20% had low-grade tumors, and 60% had high-grade tumors. Moreover, in the groups with rapamycin treatment from the 9th week, 13th week, and 17th week, all rats developed high-grade papillary tumors in urinary bladder, as did the control group that received no rapamycin. CONCLUSIONS: The study results suggest that the anticancer effect of rapamycin on urothelial carcinoma is stage dependent. Early use of rapamycin provides better anticancer effect, whereas late use of rapamycin fails to inhibit the cancer growth.

A nationwide population-based study of the risk of tuberculosis in different solid organ transplantations in Taiwan.

Advances in immunosuppressants for solid organ transplantation (SOT) have improved prevention and treatment of acute rejection as well as reduced the risk of chronic graft damage. However, SOT recipients are prone to developing opportunistic infections because of their long-term immunosuppressed status. Tuberculosis (TB) is a serious opportunistic infection that is associated with increased morbidity and mortality in SOT recipients. However, nationwide population-based research specifically focused on the associations between kidney transplantation (KTx), liver transplantation (LTx), and heart transplantation (HTx), and subsequent TB infection is lacking. This study was conducted using Taiwan's National Health Insurance Research Database, which provided claims data for SOT recipients from 2000 to 2009. Clinical features, treatment, and outcomes were analyzed to determine the risk for TB after SOT. In total, 153 (3.2%) RTx, 19 (1.1%) LTx, and 26 (2.8%) HTx recipients became infected with TB. Compared with non-TB patients, HTx recipients with TB had significantly higher prevalence of older age (P = .037), hypertension (P < .001), and coronary artery disease (CAD) (P = .002). There were also greater percentages of male sex (P = .018), diabetes (P = .029), hyperlipidemia (P = .016), CAD (P < .001), and chronic obstructive pulmonary disease (COPD) (P < .001) in RTx recipients with TB than in those without. In conclusion, posttransplantation TB is a serious problem worldwide, and a high index of suspicion is warranted to ensure early diagnosis and prompt initiation of treatment for TB among SOT patients. In this preliminary study, KTx recipients had a higher risk of TB infection than LTx and HTx recipients, and the high-risk factors were male sex, diabetes, hyperlipidemia, CAD, and COPD. The use of optimal immunosuppressive agents to minimize acute rejection, monitoring of high-risk recipients, prompt diagnosis, and appropriate treatment are required for the management of TB infection in endemic areas such as Taiwan.

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.

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.

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.

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.

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.

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.

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.

Trend of outcomes in renal transplant recipients with hepatitis B virus: a longitudinal analysis using a national database.

INTRODUCTION: Manifestations of hepatitis B virus (HBV) infection in renal transplant (RTx) recipients tend to be worse because of the higher viral load. RTx recipients with Asian heritage have a higher HBV infection rate and have unique characteristics. To date, no large-scale study on the outcomes of Asian RTx recipients has been conducted. Furthermore, there are few longitudinal studies comparing outcomes before and after availability of anti-HBV drugs. MATERIAL AND METHODS: We conducted a nationwide, population-based study to elucidate patient survival, graft survival, and hepatic outcome (incidence of hepatoma) in Asian RTx recipients. The study includes all RTx recipients in Taiwan from 1997 to 2006. Patients were divided into 2 groups according to HBV infection status to examine the effect of antiviral drug therapy. RESULTS: In all, 3826 RTx recipients were followed for a mean of 7.4 years, with a mean age of 43.7 years. There were no differences between the HBV and non-HBV groups in patient or graft survival rates. At 5 years after RTx, 89.2% of the patients were still alive and 84.5% RTx recipients were still dialysis free. In the era before anti-HBV drugs were available (1997-2001), patient survival in the HBV and non-HBV groups were similar (P = .614). This result can also be seen in the anti-HBV drug era, from 2002 to 2006 (P = .148). The unusual lack of a significant effect of drug anti-HBV administration on HBV-related mortality in RTx patients may be explained by the short duration of follow-up in the 2 eras. Another explanation may be the confounding effect of the different health status of RTx patients in the pre-anti-HBV drug era, when cardiovascular and infection-related mortality rates were considerably greater than HBV-related mortality rates. CONCLUSION: These results demonstrate that HBV is not a contraindication for RTx. Asian recipients with HBV can still achieve a similar graft outcome and survival rate compared with those of patients without HBV.