Using the chronic kidney disease guidelines to evaluate the renal safety of tenofovir disoproxil fumarate in hepatitis B patients.

BACKGROUND: Renal dysfunction remains an issue in tenofovir disoproxil fumarate (TDF) for chronic hepatitis B (CHB) patients. AIM: To evaluate renal safety of TDF according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. METHODS: We retrospectively recruited CHB patients who received either TDF or entecavir (ETV) monotherapy from January 2008 to August 2015. After excluding confounding conditions, 253 patients who received TDF were randomly matched 1:2 with 506 patients who received ETV through the propensity scores, which consisted of age, gender, cirrhosis, chronic kidney disease (CKD) and estimated glomerular filtration rate (eGFR). Renal function deterioration was defined as a drop in GFR category accompanied with a ≥25% eGFR decline. Cumulative incidences of and hazard ratios (HRs) for renal dysfunction were analysed. RESULTS: The mean eGFR decline was significantly greater in the TDF group over 48 months (TDF vs ETV: 15.73 mL/min/1.73 m2 , 95% confidence interval [CI]: 13.76-17.70 vs 5.96 mL/min/1.73 m2 , 95% CI: 4.72-7.19; P < 0.001). The cumulative incidence of renal function deterioration was significantly higher in the TDF group (TDF vs ETV: 11.1%, 95% CI: 7.4-14.8 vs 1.7%, 95% CI: 1.0-2.4; P < 0.001). After adjusting for age, pre-existing CKD and diabetes, TDF was independently associated with an increased risk of renal function deterioration (HR 5.36, 95% CI: 2.16-13.35; P < 0.001). Pre-existing CKD (HR 6.71, 95% CI: 2.25-17.65), proteinuria (HR 3.39, 95% CI: 1.23-9.39), and haematuria (HR 4.25, 95% CI: 1.32-13.68) were also independent factors of renal dysfunction. CONCLUSION: By following the KDIGO guidelines, we confirmed that TDF was associated with a higher risk of renal dysfunction as compared to ETV.

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.

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.

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.

Serum total p-cresol and indoxyl sulfate correlated with stage of chronic kidney disease in renal transplant recipients.

BACKGROUND: Uremic toxins are considered cardiovascular and mortality risk factors in chronic kidney disease (CKD) patients. Both p-cresol and indoxyl sulfate have been shown to induce oxidative stress in vitro and subsequent endothelial dysfunction in uremic patients. Our study evaluated the levels of p-cresol and indoxyl sulfate, and whether they contribute to the progression of CKD in transplant recipients. METHODS: We retrospectively evaluated 95 patients who had received a transplant from February 1987 to June 2010 in our center; the recipients had a mean transplant duration of 5.3 ± 4.9 years and a mean age of 47.8 ± 14.1 years. Among them, 56.8% (54/95) were male. Patients with glomerular filtration rate (GFR) ≥ 60 mL/min/1.73 m(2) were selected for group 1 (n = 35), and those with GFR < 60 mL/min/1.73 m(2) were selected for group 2 (n = 60). Demographic and clinical data were compared between groups. Serum and urine levels of p-cresol and indoxyl sulfate were also obtained. RESULTS: Baseline serum p-cresol and indoxyl sulfate levels were significantly higher in advanced CKD stages (P = .001 and <.0001, respectively). Patients at advanced CKD stages (group 2) had lower serum levels of hemoglobin and albumin (P < .0001), but higher levels of total cholesterol, triglyceride, and uric acid levels (P = .04, .04 and .001, respectively). Body mass index, C-reactive protein, and serum calcium and phosphate levels showed no significant differences between groups. The cut-off value for serum p-cresol between groups was 1.28 umol/L (P = .01), and that for the indoxyl sulfate level was 0.98 umol/L (P = .0001). CONCLUSION: The serum p-cresol and indoxyl sulfate levels were significantly higher in advanced CKD stages in transplant recipients. To evaluate the use of serum p-cresol and indoxyl sulfate levels as a predictive tool for survival, larger clinical studies are needed.

Gene polymorphisms are associated with posttransplantation diabetes mellitus among Taiwanese renal transplant recipients.

BACKGROUND: Genetic variations may affect posttransplantation metabolic syndrome and diabetes mellitus (PTDM), which is associated with greater morbidity and progressive impairment of both patient and graft survivals. The aim of this study was to evaluate several candidate gene polymorphisms for their association with the risk of developing PTDM. METHODS: In April 1999, we enrolled 278 renal transplant participants, including 251 subjects free of diabetes and 27 with PTDM. We studied several candidate gene polymorphisms associated with diabetes: 4G/5G polymorphism of plasminogen activator inhibitor 1 (PAI-1) at -675; C/T polymorphism of interleukin-1beta (IL-1ß) at -511; G/C polymorphism of IL-6 at 174; polymorphic XbaI of Glucose transporter 1 (GLUT1); and C/T polymorphism of methylenetetrahydrofolate redutase (MTHFR) at 677. RESULTS: The PTDM group had an older mean age (47.6 ± 9.8 years), greater predominance of men (77.8%), higher number of chronic diseases (CDN ≥2, 96.3%), and more patients using tacrolimus-based immunosuppression (44.4%; P < .05). Using model A, a simple logistic regression, we observed that patients with the IL-6 G/G genotype experienced a lower risk of developing PTDM (odds ratio [OR], 0.08; 95% confidence interval [CI] 0.01-0.86), and multiple logistic regression models B and C, after adjusting for different variables, confirmed this observation (model B: OR, 0.05; 95% CI, 0.00-0.66). The IL-6 G/G genotype showed a borderline effect in model C (OR, 0.02; 95% CI, 0.00-1.16). There were no significant differences between the 2 groups in genotype variations of PAI-1, IL-1ß, GLUT-1, and MTHFR. CONCLUSIONS: The G/G genotype of IL-6 may play an important role to lower the risk for PTDM development.

Serum adiponectin levels in renal transplant recipients with and without metabolic syndrome.

OBJECTIVES: Adiponectin (APN) is an adipocyte-derived protein that has anti-inflammatory, anti-atherogenic, and insulin-sensitizing effects. Lower serum APN level is associated with various inflammatory and metabolic diseases in the general population. Kidney transplant (KT) recipients are at higher risk for developing several metabolic disorders, including metabolic syndrome (MS). The aim of the current study was to assess the change of APN level in KT recipients with and without MS. METHODS: Prevalent KT recipients followed at our hospital were enrolled for the cross-sectional study of MS. The modified Adult Treatment Panel III criteria adopted for the Asian population were used to define MS. Overnight fasting blood samples were obtained for biochemistry and APN. APN was assayed with a commercially available enzyme-linked immunosorbent assay (ELISA) kit. The simplified Modification of Diet in Renal Disease (MDRD) equation was used for the calculation of estimated glomerular filtration rate (eGFR). Univariate and multivariate logistic regression were performed to determine parameters that were associated with serum APN level. RESULTS: A total of 271 KT recipients (male:female = 133:138), with a mean age of 52.3 ± 12.6 years, were enrolled for the study of MS. The mean duration of follow-up posttransplantation was 9.02 ± 5.91 years. MS was found in 72 of 271 KT recipients (26.6%). Patients with MS were older, had significantly higher body weight, waist circumference, serum creatinine, fasting plasma sugar, and hemoglobin A1c, but lower serum APN level and eGFR than did patients without MS. Univariate logistic regression revealed the following variables were associated with APN level: MS, gender, body weight, body height, waist circumference, body mass index, serum creatinine, fasting blood sugar, triglyceride, high-density lipoprotein (HDL) cholesterol, and eGFR. Multivariate analysis revealed that gender, body weight, serum creatinine, triglyceride, and HDL cholesterol were associated with APN level. CONCLUSION: Our results revealed that KT recipients with MS had significantly lower serum APN levels, even in the presence of lower eGFR, than those without MS.

Coronary artery calcification in kidney transplant recipients with long-term follow-up.

OBJECTIVES: Kidney transplantation (KT) is associated with increased incidence of hypertension, hyperlipidemia, metabolic syndrome, and posttransplant diabetes mellitus that promote the development of coronary artery calcification (CAC). The aim of the current study was to elucidate the extent of CAC and its risk factors among KT patients. METHODS: A cross-sectional study was performed to evaluate the severity of CAC in our KT patients. Multidetector computed tomography was performed to assess the coronary artery calcium score (CACS). Patients were further stratified according to the CACS as: group 1: 0-10, group 2: 11-100, group 3: 101-300, group 4: 301-1000, and group 5: >1000. Clinical as well as demographic data were compared among groups. Linear regression analysis was performed to determine factors that were associated with CAC. RESULTS: A total of 99 patients were enrolled in the study. The mean age was 53.5 ± 11.8 years and duration of follow-up post-KT was 11.2 ± 5.9 years. The distribution of CACS in groups 1 through 5 was: 41.4%, 20.2%, 11.1%, 15.2%, and 12.1%, respectively. A significantly higher CACS was found in males, patients with pretransplant diabetes mellitus, older current age, older age at KT, hypertension, higher body weight, higher fasting plasma sugar level and lower high-density lipoprotein (HDL) cholesterol. Twenty-nine (29.3%) patients fulfilled criteria for metabolic syndrome (MS). The CACS was significantly higher in patients with MS than in those without MS. An incremental CACS was found to be correlated with increasing number of MS components (P = .003). Multivariate linear regression revealed that female gender, current age, hypertension, and HDL cholesterol were associated with CAC. CONCLUSION: KT was associated with high CACS in a significant proportion of patients with long-term follow-up. Several risk factors were identified. Some of them were potentially treatable and should be taken into consideration in the management of KT recipients.

Hepatic stellate cells attenuate the immune response in renal transplant recipients with chronic hepatitis.

BACKGROUND: Chronic viral hepatitis is no longer a contraindication to renal transplantation (RT), owing to our better understanding of the hepatitis virus. Hepatitis patients may receive RT depending on their response to viral therapy. RT patients with hepatitis generally do not have an inferior prognosis compared with RT patients without the disease. Hepatic stellate cells (HSCs) are activated during chronic viral hepatitis. The role of HSCs in immunoregulatory effects in RT recipients has not been fully elucidated. METHODS: We recruited 22 RT recipients with chronic viral hepatitis, who composed the chronic liver disease (CLD) group, and 25 disease-free recipients, who served as the control group. We retrieved their clinical data and collected serum to measure cytokine levels. To investigate the immunoregulatory effect of HSCs, we cocultured HSCs with allogeneic antigen-presenting cell-activated T cells (mixed lymphocyte reaction [MLR]) in Transwell plates. RESULTS: The liver biopsy disclosed activation HSCs in 1 chronic hepatitis C virus recipient without treatment. Serum monocyte chemoattractant protein-1 (MCP-1) levels in the CLD group (41.6 ± 27.4 pg/mL) were significantly higher than those in the control group (28.1 ± 12.8 pg/mL; P = .008). There were similar levels of transforming growth factor-ß1 (TGF-ß1). In allogeneic MLR, HSCs inhibited T-cell activation through the soluble factors in the Transwell assays. There was a high level of MCP-1 in the supernates of the HSC group in the allogeneic MLR, but TGF-ß1 was lower in HSCs cocultured with MLR than in the control group, except in the early period. CONCLUSIONS: HSCs may play an immunoregulatory role in chronic viral hepatitis recipients to minimize the effect of immunosuppressants without affecting rejection. The immunomodulatory effects may be attributed to soluble factors in HSCs.

Imaging evaluation of kidney using multidetector computerized tomography in living-related renal transplantation.

BACKGROUND: Multidetector computerized tomography (MDCT) is lesser invasive than conventional angiography and has the advantage of assessment of vessels and surrounding anatomic variants before laparoscopic nephrectomy. METHODS: From May 2005 to March 2011, 62 consecutive living kidney donors of mean age 45.3 ± 12.7 years (range 24-70 y, male:female 26:36) underwent laparoscopic nephrectomy to paired recipients of mean age 44.8 ± 14.0 years (range 17-74 y, male:female 38:24). The clinical characteristics and laboratory data of donors and recipients were collected for analysis. Graft function as indicated by estimated glomerular filtration rate (eGFR) was obtained from the last stable visit of the donors and the best value displayed by the recipients. RESULTS: There was no significant correlation between CT kidney volume and and eGFR. By univariate analysis, donor age was associated with worse graft function (-0.51 mL/min lower eGFR per 1 year of donor age; P < .0001). Female sex and higher effective renal plasma flow/body mass index ratio were associated with better graft function; conversely, body weight and BMI were associated with poor graft function upon univariate and multivariate analysis. An ERPF of <220 mL/min and a donor age >45 y showed significantly lower eGFR. There was no effect of CT kidney volume <100 mL. CONCLUSIONS: Our preliminary data suggest that CT kidney volume does not predict posttransplantation graft function, but MDCT is still important for analysis of anatomy before laparoscopic nephrectomy among living donors.

Long-term outcomes of living kidney donors over the past 28 years in a single center in Taiwan.

BACKGROUND: The chronic shortage of kidneys for transplantation has increased the number of living donations, but demand remains high, which has created a long waiting list of end-stage kidney disease patients. Donors with decreased renal mass may suffer a higher risk of developing proteinuria, hypertension (HTN), and chronic renal disease (CKD) during long-term follow-up. METHODS: We retrospectively retrieved medical data of living kidney donors at our hospital over the past 28 years. RESULTS: There were 45 male and 60 female donors with a mean donation age of 46.34 ± 12.47 years (range = 20-70y). The mean follow-up duration was 4.67 ± 4.78 years. The serum creatinine (Cr) at donation was 0.93 ± 0.22 mg/dL, while the latest Cr was 1.26 ± 0.45 mg/dL (P < .001). The mean age at follow-up was 50.95 ± 14.57 years. At last follow-up, eight subjects (7.6%) displayed HTN requiring treatment, 10 (9.5%), proteinuria and 55.4%, an estimated glomerular filtration rate (eGFR) of less than 60 mL/min, including one with diabetic nephropathy at 10 years after donation who required long-term hemodialysis. Although gender did not correlate with occurrence of HTN, proteinuria, and CKD, the occurrence of CKD was associated with age at donation (P < .001, odds ratio [OR] = 1.076), and age at follow-up (P < .001, OR = 1.071). HTN donors were older (P = .036, OR = 1.057) with longer follow-up durations (P = .007, OR = 1.166) and had higher Cr values at donation (P = .044, OR = 94.4). Donors with proteinuria were not related to gender, follow-up duration, initial Cr, warm ischemic time, or duration of admission. eGFR was indeed worse after donation (P = .002). CONCLUSIONS: Our results indicated a significant proportion of living donors may develop CKD upon long-term follow-up. The factors affecting donor risk of CKD were baseline renal function, older age, and duration after kidney donation.

Follow-up and treatment of renal transplantation with nephropathic cystinosis in central Taiwan.

BACKGROUND: Cystinosis is a rare autosomal recessive disease caused by a defect in lysosomal cystine. The intracellular cystine accumulation causes damage in multiple organs and renal failure. We retrospectively evaluated the outcomes and complications of patients with nephropathic cystinosis after renal transplantation (RT) in Taiwan. METHODS: Only 2 nephropathic cystinosis patients (siblings) had RT out of the 1,196 RTs in our hospital over the past 30 years. The younger sister received a living-related RT from her mother. The elder sister received a second cadaveric RT owing to chronic allograft rejection one-half year before. RESULTS: They were diagnosed with cystinosis at ages 5 and 9 years, and received allografts at ages 13.4 (younger) and 19.8 and 26.4 (elder) years. They each experienced 1 episode of acute rejection at 6 months after the first RT. The elder sister suffered from obstructive nephropathy with progressive graft failure at age 26.4 years and was treated for vulvar condyloma and carcinoma in situ of cervix. The second graft kidney then maintained good kidney function. The younger sister delivered a girl without complication during gestation, and her renal function also remained good. At latest follow-up, they both had crystalline keratopathy and nephropathy, but no other system involvement. CONCLUSIONS: The extrarenal complications with nephropathic cystinosis are high. These 2 siblings had only have ocular involvement without further cysteamine therapy. However, long-term follow-up is required to monitor development of complications and determine their prognoses.

Study on factors affecting the occurrence of upper gastrointestinal bleeding in elderly acute stroke patients undergoing rehabilitation.

OBJECTIVE: To investigate factors affecting upper gastrointestinal bleeding (UGIB) in elderly first-time acute stroke patients undergoing rehabilitation. PARTICIPANTS AND SETTING: Three hundred and thirty-one elderly first-time acute stroke patients (age ≥65 years) transferred to our rehabilitative ward from July 2002 to June 2009 were included in the study. DESIGN: We divided patients into UGIB and non-UGIB groups. Demographic data and possible precipitating factors were analyzed. RESULTS: Sixty-eight (20.5%) patients experienced UGIB. The patients with UGIB were of older age (75.4 vs. 72.92 years, P = 0.003), had a longer rehabilitative ward stay (26.32 vs. 21 days, P = 0.002), more frequently had stroke-induced consciousness impairment (60.3 vs. 38%, P = 0.001), had a higher incidence of bilateral brain lesion (7.4 vs. 1.9%, P = 0.034), and more frequently used anticoagulants (17.6 vs. 9.1%, P = 0.044) than patients in the non-UGIB group. In multivariate logistic regression analysis, stroke-induced impaired consciousness (odds ratio: 2.806, 95% CI = 1.588-4.957, P = 0.000) was the most important risk factor for UGIB. CONCLUSIONS: UGIB may prolong a patient's length of stay in a rehabilitative ward. These identified factors may help clinicians identify risks of UGIB before it develops.

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.