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Background Several comparison studies have suggested that kidney transplant (KT) could reduce stroke risk in patients with end-stage renal disease (ESRD). To avoid the selection criteria bias of using dialysis patients as control groups, we compared the risk of stroke between KT recipients and comparable propensity score-matched dialysis patients. Methods We used Taiwan's National Health Insurance Research Database to identify patients with newly diagnosed ESRD between 2000 and 2009. We separated them into 2 groups: a KT group and a non-KT dialysis-only group. To evaluate the stroke outcome, we compared each patient with KT to a patient on dialysis without KT using propensity score matching. Results In total, 2735 KT recipients and 10,940 propensity score-matched dialysis patients were identified. The incidence rates of overall stroke were 9.1 and 23.4 per 1000 person-years in KT recipients and non-KT dialysis patients. Compared with the propensity score-matched dialysis patients, the patients who received KT exhibited significantly lower overall stroke risk, hemorrhagic stroke, and ischemic stroke, the adjusted hazard ratios were 0.37 (95% CI, 0.31–0.45), 0.19 (95% CI, 0.12–0.29), and 0.46 (95% CI, 0.37–0.56), respectively (all P Conclusions Through a propensity score-matched cohort, this study confirms that KT is associated with a reduced risk of stroke more than dialysis alone in patients with newly diagnosed ESRD.

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 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 (β = −1.24, P = .037) and level adjusted by urinary creatinine (β = −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.

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.

Background The online percent coefficient of variation reporting system could monitor the variation of tacrolimus trough level (T0) and identify kidney transplant recipients (KTRs) with a higher percent coefficient of variation (%CV) instantly. Consequently, transplant doctors and pharmacists could take actions to improve drug variability. The purpose of this study was to determine the efficacy of the system for higher intrapatient variability of T0 in KTRs. Methods The T0 data were collected with KTRs routinely followed up at an outpatient clinic between June 2016 and November 2016. The %CV was calculated with T0 data within 6 months before and after the index date. The last outpatient clinic visit date was before December 1, 2016. The KTRs with %CV of T0 greater than 22% were enrolled. Results The study consisted of 183 KTRs (96 male, 87 female), the median age was 50 years (interquartile range [IQR], 41.0–57.0), and the median years post-kidney transplantation was 7 years (IQR, 3.0–12.4). The median T0 and creatinine level at baseline were 6.09 ng/mL (IQR, 4.80–7.52) and 1.33 mg/dL (IQR, 1.03–1.72), respectively. After the intervention, the median %CV of T0 was significantly lower than before, 32% (IQR, 26%–42%) vs 22% (IQR, 15%–33%), P Conclusions The results of this study indicate that continuously aggressive intervention with an online %CV reporting system effectively improves intrapatient variability of T0 in KTRs.

Pneumococcal disease leads to renal complications ranging from persistent proteinuria to end-stage renal disease (ESRD) in pediatric patients. However, long-term renal effects after pneumococcal pneumonia infection in adult patients remains largely unknown. To evaluate this we conducted a population-based retrospective cohort study consisting of 18,733 adult patients at the time of pneumococcal pneumonia diagnosis, using claims data from Taiwan's National Health Insurance Research Database (NHIRD) with a comparison cohort of 73,409 age- and gender-matched patients without pneumococcal pneumonia. The overall incidence rate ratio of ESRD was 23% higher in those with pneumococcal pneumonia than in those without pneumococcal pneumonia (5.26 vs. 3.10 per 1000 person-years), with an adjusted hazard ratio of 1.14 (95% confidence interval 1.01-1.29). In addition, the risk of developing ESRD was associated with covariates including age, gender, chronic kidney disease, diabetes mellitus, hypertension, hyperlipidemia, chronic obstructive pulmonary disease, and heart failure. The ESRD cumulative incidence curve showed a considerably higher risk of ESRD in those with pneumococcal pneumonia than in those without pneumococcal pneumonia (significant by log-rank test). Thus, pneumococcal pneumonia may be associated with an increased risk of ESRD in adult patients. A long-term follow-up of renal function is recommended for adult hospitalized patients with pneumococcal pneumonia infection.

Renal fibrosis is the common final pathological hallmark of most progressive renal diseases. Unilateral ureteral obstruction (UUO) is a well-documented hydronephrosis model which shows interstitial inflammatory-cell infiltration and tubular dilatation, followed by tubulointerstitial fibrosis. Polyphenols possess antioxidative and anti-inflammatory properties. This study is aimed to investigate the effect of apple polyphenols (AP) on the inflammatory response and subsequent fibrotic change of the kidneys in UUO rats. After completing the UUO, 0.05, 0.1, or 0.15% of AP was given to the rats for 3 weeks. The results show that AP attenuates tubular dilatation and interstitial volume in UUO rats. It decreases the expression of inflammatory markers, ED-1 and MCP-1. AP also significantly down-regulate the expression of profibrotic markers, TGF-β and α-SMA, in UUO rats. The findings show the beneficial effects of AP in UUO induced renal injury, and it is also given the alternative medical function of AP.

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.

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.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.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.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.

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.

Liver allografts seem to be immunologically privileged; they are the only solid transplant that can protect cotransplanted organs from rejection. The mechanisms of this "hepatic tolerance" are poorly understood. The aim of this study was to examine the immunomodulatory effect of hepatic stellate cells (HSCs) in mixed lymphocyte reactions in vitro and in graft-versus-host disease (GVHD) in vivo. Using a carboxyfluorescein diacetate succinimidyl ester-labeling method, we observed that the percentage of proliferative T cells was reduced when HSCs were present in a mixed lymphocyte culture. In addition, the degree of reduction was the same when HSCs were co-cultured in transwell inserts. Thus, soluble factors may participate in the immunomodulatory effect of HSCs. In GVHD experiments, irradiated BALB/c (H-2d) mice simultaneously received an intravenous mixture of bone marrow and splenic T cells from C57BL/6 (H-2b) mice. The HSCs prominently reduced symptoms and pathologic severity of GVHD in target organs. HSC cotransplanted mice survived for 57.5+/-30.6 days whereas the control hosts only survived for 15.3+/-5.2 days (P

Constipation is a frequent health concern for long-term dialysis patients. The increased incidence of constipation in long-term dialysis patients is based mainly on self-reported data. Our aim is to investigate this problem objectively by using colonic transit time in long-term hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) patients.Segmental and total colonic transit time studies measured by means of radiopaque markers were conducted in 56 HD patients, 63 CAPD patients, and 25 healthy control subjects. Segmental colonic transit times were calculated separately for 3 segments of the colon (right, left, and rectosigmoid) and total transit time, which was the sum of all 3 segment times.Colonic transit time was significantly prolonged in HD patients (43.0 +/- 22.2 versus 32.7 +/- 13.7 hours in CAPD patients and 24.3 +/- 11.9 hours in controls; P0.001). Increased colonic transit times in the right and rectosigmoid segments, but not the left segment, contributed to the prolongation in total colonic transit time. Age and interdialytic weight gain correlated well with prolongation of total and segmental colonic transit times in HD patients (P0.01). Diabetes and female sex in all groups were associated with longer total and segmental colonic transit times, but this trend was not statistically significant.Total, right segmental, and rectosigmoid segmental colonic transit times are prolonged in long-term HD patients compared with CAPD patients and healthy controls. We believe colonic transit time measurement is helpful to tailor therapy because it helps define the pathogenesis of constipation.

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.

Intracellular calcium plays an important role on the pathogenesis of hypoxia-induced cellular injury. Calbindin-D(28k), a cytosolic vitamin D-dependent calcium binding protein, can serve as a buffer to limit a surge in intracellular Ca2+ concentration ([Ca2+]i) induced by various stimulations. To evaluate the possible cytoprotective effect of calbindin-D(28k) against hypoxic injury in proximal tubular cells, a plasmid containing calbindin-D(28k) cDNA under the control of CMV immediate-early gene promoter was transfected into the murine proximal tubular epithelial (MCT) cells. The expression of calbindin-D(28k) in the transfected cells was verified with Northern blot analysis, Western blot analysis, and immunofluorescent staining. The non-transfected and transfected MCT cells were subjected to chemical hypoxia induced by antimycin A (10 microM) and glucose deprivation for 30-120 min. The transfection of calbindin-D(28k) reduced lactate dehydrogenase (LDH) release by 41%, 41%, 24%, and 24%, respectively, at 30, 60, 90 and 120 min after hypoxia when compared to the non-transfected cells (all p < 0.05). Cell viability after hypoxic injury was also significantly higher in transfected cells than non-transfected cells. Transfection with the plasmid without calbindin-D(28k) cDNA did not affect LDH release or cell viability after chemical hypoxic injury. [Ca+2]i was measured ratiometrically with fura-2 after exposure to chemical hypoxia. The rate of initial rise in [Ca2+]i and final [Ca+2]i at 30-120 min were significantly lowered in transfected cells. In conclusion, this study demonstrated that transfection of calbindin-D(28k) gene into MCT cells provide protective effects against chemical hypoxic injury probably through its buffering effects on [Ca+2]i.

QT dispersion (the difference between maximum and minimum QT across the 12-lead electrocardiogram [ECG]), which reflects regional variations in ventricular repolarization, is a predictor of arrhythmia and cardiovascular mortality. The present study was undertaken to assess the difference in QT dispersion between uremic and nonuremic patients with acute myocardial infarction (AMI) and its relationship to post-AMI clinical outcome. Twelve-lead ECG recordings were obtained the first and third days after the onset of AMI in 21 uremic and 21 nonuremic patients. QT intervals were measured on 12-lead ECGs and corrected by heart rate (QTc). Our findings show that uremic patients with AMI had greater QTc dispersion (84 ± 35 versus 55 ± 15 milliseconds; P P = 0.003), and underwent fewer reperfusion therapies (5 of 21 versus 17 of 21 patients; P = 0.002) compared with nonuremic patients with AMI. Patients with AMI who died had greater QTc dispersion than those who survived (102 ± 40 versus 67 ± 40 milliseconds; P = 0.015). An optimal QTc dispersion cutoff value of 60 milliseconds had a sensitivity of 100% and specificity of 55% in predicting 1-year mortality in uremic patients with AMI. Uremic patients with AMI administered thrombolytic therapies (n = 5) had reduced 1-year mortality rates (0% versus 63%; P = 0.003) and shortened QTc dispersion from days 1 to 3 (changes in QTc dispersion between days 1 and 3, 29% ± 9% decrease versus 13% ± 5% increase; P = 0.001) compared with those without therapies (n = 16). Our findings suggest that greater QT dispersion is associated with greater total mortality, and thrombolytic therapies could reduce QTc dispersion and mortality in uremic patients with AMI. It is prudent to refine our current management regimen for uremic patients with AMI to improve the poor clinical outcome. © 2002 by the National Kidney Foundation, Inc.

Impact of interleukin-1 receptor antagonist and tumor necrosis factor-α gene polymorphism on IgA nephropathy.BackgroundIt is evident that cytokines play an important role in the pathogenesis as well as disease progression in IgA nephropathy (IgAN). The level of cytokine production is influenced by different genotypes that reflect gene polymorphism of the pertinent cytokine. Interleukin-1 receptor antagonist (IL-1ra) and tumor necrosis factor-α (TNF-α) gene polymorphism have been found to affect disease susceptibility and activity in several inflammatory diseases. However, the impact of these polymorphisms in IgAN patients has not previously been thoroughly studied.MethodsWe investigated 111 cases of biopsy-proven IgAN and 100 healthy, normal controls for their IL-1ra and TNF-α gene polymorphism. IL-1ra gene polymorphism was characterized as a variable number of tandem repeats of a 86 bp sequence within intron 2. Five alleles were identified and were designated as IL1RN*1, IL1RN*2, IL1RN*3, IL1RN*4, and IL1RN*5, corresponding to 4, 2, 5, 3, 6 repeats, respectively. A polymorphism in the promoter region of the TNF-α gene was also studied. This polymorphism involved a guanidine to adenosine transition at position -308 and was designated as TNF1 (-308G) and TNF2 (-308A).ResultsThere were 54 male and 57 female patients with a mean age of 30.3 ± 12.5 years and a disease duration of 66.8 ± 47.2 months. The mean duration of the follow-up period was 47.3 ± 32.6 months. In the patient group, the allele frequencies of IL1RN*1, IL1RN*2, IL1RN*3, IL1RN*4, and IL1RN*5 were 89.6%, 9.9%, 0%, 0.5%, and 0%, respectively, whereas the corresponding carriage rates were 100%, 19.8%, 0%, 0.9%, and 0%, respectively. An excessive carriage of IL2RN*2 was found in the patients when compared with normal controls (allele frequency, 9.9 vs. 2.5%, P < 0.0001). The allele frequencies of TNF1 and TNF2 were 94.1 and 5.9%, respectively, and the carriage rates were 99.1 and 10.8%, respectively, in the patients, which was not significantly different from those of normal controls. When the patients were stratified into mild and severe groups according to their initial presentation, none of the studied alleles correlated with the severity. However, patients with gross hematuria were associated with a higher carriage rate of TNF2 when compared with patients without gross hematuria (allele frequency, 15.4 vs. 4.6%, P = 0.0552; carriage rate, 30.8% vs. 8.2%, P = 0.0272). Renal survival analysis revealed that the TNF2 carrier had a renal survival comparable with TNF2 (-) patients. However, the carriage of the IL1RN*2 allele was associated with a significantly poorer long-term outcome with a median survival time of 72 months, as compared with those without IL1RN*2 (134 months, P < 0.01).ConclusionIL-1ra and TNF-α gene polymorphism may affect disease susceptibility as well as disease activity and long-term outcome in human IgAN. Treatment with an IL-1ra or IL-1 blocking agent may be relevant in those carrying the IL1RN*2 allele.