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ABSTRACT: Lupus nephritis (LN) is usually associated with widespread effacement of the podocytes' foot processes leading to proteinuria. Induction of urokinase receptor (uPAR) signaling in podocytes leads to foot process effacement and urinary protein loss via promoting podocytes' motility and kidney permeability in the glomerulus. Very little is known about uPAR signaling in LN. Mycophenolate mofetil (MMF), an immunosuppressive agent, efficiently modulates the development of LN in humans and mice, but there are no data concerning the direct uPAR involvement on podocytes in LN. The MMF efficiency and uPAR involvement signaling in NZB×NZW F1 lupus-prone mice were examined by proteinuria, renal function and pathology, immune complex deposits, and uPAR expression of podocytes by immunofluorescence staining and quantitative RT-PCR. After MMF treatment, the proteinuria (p < 0.01), BUN level (p < 0.05) and immunodeposition in glomeruli (p < 0.001) were significantly improved. Most important, the renal uPAR mRNA levels (p < 0.001) and uPAR protein level of podocytes (p < 0.001) were significantly reduced. The beneficial effect of MMF on LN could be attributed, at least in part, to the inhibition of uPAR expression in podocytes. These findings demonstrated uPAR could have potential as a predictive index for response to LN therapeutics.
Lupus 03/2013; · 2.34 Impact Factor
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ABSTRACT: 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.
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.
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).
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.
Transplantation Proceedings 04/2012; 44(3):621-4. · 1.00 Impact Factor
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ABSTRACT: 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.
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-1β) 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.
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-1β, GLUT-1, and MTHFR.
The G/G genotype of IL-6 may play an important role to lower the risk for PTDM development.
Transplantation Proceedings 04/2012; 44(3):667-71. · 1.00 Impact Factor
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ABSTRACT: 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.
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.
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.
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.
Transplantation Proceedings 04/2012; 44(3):676-9. · 1.00 Impact Factor
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ABSTRACT: 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.
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.
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.
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.
Transplantation Proceedings 04/2012; 44(3):687-90. · 1.00 Impact Factor
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ABSTRACT: 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.
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.
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-β1 (TGF-β1). 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-β1 was lower in HSCs cocultured with MLR than in the control group, except in the early period.
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.
Transplantation Proceedings 04/2012; 44(3):725-9. · 1.00 Impact Factor
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ABSTRACT: Nonadherence to immunosuppressive drugs is a concern among kidney transplantation recipients (KTRs). The adverse effects of immunosuppressive drugs can trigger nonadherence and lead to a great impact on the allograft survival. The aim of this prospective controlled study is to determine the major adverse effects of immunosuppressive drugs and their correlation with the nonadherence in kidney transplantation recipients.
All data were collected from medical and pharmacy records. We use modified Immunosuppressant Therapy Adherence Scale combined with Modified Transplant Symptom Occurrence and Symptom Distress scale to explore the relationship between symptom experience related to side effects of immunosuppressants and adherence. The risk of nonadherence was estimated by stepwise logistic regression while controlling for age, gender, education, and immunosuppressive medications. Multivariable analysis was performed using a single random effect of P < .2.
In total, 412 KTRs completed the structured self-report instrument. The weekly pill counts were 84.2 ± 39.8. Overall, 21.4% of patients were nonadherent to immunosuppressive drugs. The most common adverse effects of immunosuppressive drugs were memory impairment (28.4%), insomnia (26.0%), gastrointestinal discomfort (21.4%), easy fatigue (22.1%), hand tremor (23.8%), and vision variation (29.1%). Multivariate analysis revealed that the adherence increased in patients with awareness of memory impairment (odds ratio 2.320, 95% confidence interval: 1.259-4.274, P = .007). There was no significant difference in the incidence of acute rejection, gender, age, and education between adherent and nonadherent patients.
In summary, these results indicate a significant prevalence of nonadherence to immunosuppressive drugs in kidney transplantation recipients. Awareness of memory impairment significantly affected adherence to immunosuppressive drugs.
Transplantation Proceedings 04/2012; 44(3):746-8. · 1.00 Impact Factor
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ABSTRACT: 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.
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.
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.
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.
Transplantation Proceedings 01/2012; 44(1):7-10. · 1.00 Impact Factor
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S-F Tsai,
K-H Shu,
H-C Ho, M-J Wu,
C-H Cheng,
J-D Lian,
M-C Wen,
C-K Su,
T-M Yu,
Y-W Chuang,
S-T Huang,
C-H Chen
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ABSTRACT: 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.
We retrospectively retrieved medical data of living kidney donors at our hospital over the past 28 years.
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).
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.
Transplantation Proceedings 01/2012; 44(1):39-42. · 1.00 Impact Factor
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ABSTRACT: 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.
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.
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.
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.
Transplantation Proceedings 01/2012; 44(1):80-2. · 1.00 Impact Factor
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ABSTRACT: Trends in maintenance immunosuppressive drugs used among Taiwanese kidney transplant recipients have not been reported before. We examined the National Health Insurance Research Database to analyze trends in maintenance immunosuppressive drugs used in Taiwanese kidney transplant recipients for the years 2002-2009. The new case number of kidney transplant recipients ranged from 302 to 673 per year. In 2009, 5276 kidney transplant recipients received immunosuppressive therapy. The 5-year renal graft survival rate of kidney transplant recipients was 93%. In 2009, the most common immunosuppressive therapy among Taiwanese kidney transplant recipients was a triple regimen that included tacrolimus, mycophenolate mofetil, and corticosteroid. There was a significant increase in the use of a tacrolimus-based regimen from 35.1%-58.2%, while the use of cyclosporine decreased from 62.2%-24.8% (P < .05). The percentage of calcineurin inhibitor-free regimen increased from 2.7%-17%. Moreover, the use of Rapamune dramatically increased from 8.2%-22.6% in 2002-2004. However, the percentage of kidney transplant recipients using Rapamune maintained 23 ± 1.6% in 2004-2009. The use of mycophenolic acid remained stable at about 74.9 ± 3.2% in 2002-2009. As predicted, the use of Imuran decreased from 6.9%-3.5%. In summary, although calcineurin inhibitors remained the mainstay of immunosuppressive drugs, these findings suggest a general trends toward individualized regimens and the use of calcineurin inhibitor-free and mammalian target of rapamycin inhibitors-based regimens in Taiwanese kidney transplant recipients.
Transplantation Proceedings 01/2012; 44(1):190-2. · 1.00 Impact Factor
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ABSTRACT: 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.
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.
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.
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.
Clinical nephrology 10/2011; 76(4):306-13. · 1.17 Impact Factor
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ABSTRACT: Peritoneal dialysis (PD)-related peritonitis is a major risk factor of technique failure and contributes to significant mortality in patients undergoing PD. The aim of this study was to examine the evolution of microbiological trends and treatment outcomes of PD-related peritonitis in our hospital over the past 26 years.
A total of 630 patients entered our CAPD program from February 1984 to June 2010. Among them, 119 patients (18.9%) experienced 599 episodes of peritonitis. Microbiological trends, treatment responses, techniques and patient survival were analyzed.
The incidence rate of total peritonitis showed a steady decline from 1.08 episodes/patient-year in 1984 to 0.25 episode/ patient-year in 2009 (p < 0.001). A similar trend was found in gram-positive (p < 0.001) and gram-negative peritonitis (p = 0.015). In contrast, there was a trend toward an increased proportion of gram-negative peritonitis. This increase was not due to an increased rate of gram-negative peritonitis but to the more dramatic fall in gram-positive peritonitis. Treatment of peritonitis resulted in a complete cure in 78.0% of patients, while 16.7% of patients required catheter removal and 5.3% died. Gram-positive organisms were associated with a more favorable outcome compared to gram-negative pathogens as manifested by a higher cure rate (p = 0.023). The patient survival and technique survival were much improved after 2000 compared to that before 2000 (p < 0.0001).
A remarkable improvement in the outcome of PD-related peritonitis has been achieved in the past 26 years in our hospital. To further decrease peritonitis rates, attention needs to be directed at reducing gram-negative peritonitis.
Clinical nephrology 05/2011; 75(5):416-25. · 1.17 Impact Factor
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ABSTRACT: Primary renal lymphoma (PRL) is rare and often presents as rapidly progressive renal failure. Most cases of PRL are large-cell lymphomas of B-cell lineage. Herein, we report a 75-year-old female patient with infiltrative CD20 (+) B-cell lymphoma who underwent 4 consecutive courses of chemotherapy with R-CVP (rituximab, cyclophosphamide, vincristine, and prednisone) and after 12 sessions became free from hemodialysis in good general condition. Her serum creatinine level gradually decreased to 4.1 mg/dl with adequate urine output. Unfortunately, a relapse of CD20 (-) lymphoma developed rapidly involving other organs. She died with severe hospital-acquired pneumonia and febrile neutropenia after the last chemotherapy with R-MINE almost 1 year after onset of symptoms. We conclude that renal biopsy enables prompt diagnosis in rapidly progressive renal failure and immunophenotyping and also staging workup of the lymphoma in case of positive biopsy. Though rituximab improved response rate of PRL, it reduced expression of CD20. This may relate to frequent relapse/resistance after rituximab therapy and poor long-term patient survival.
Clinical nephrology 12/2010; 74(6):480-4. · 1.17 Impact Factor
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ABSTRACT: Human polyomaviruses (PV), including JC and BK virus, have been reported to cause polyomavirus-associated nephropathy (PVAN), in renal transplant patients. PV infection has been demonstrated to be associated with malignancies in animals; however, the association between malignancy and viral infections in humans is not clear. We retrospectively reviewed our 864 (M:F=502:362) kidney transplant patients over the past 25 years. We identified PVAN in 6 patients (0.69%), including BK nephropathy (n=5) and JC nephropathy (n=1). Three patients (50%) improved after reducing the immunosuppression, but 3 (50%) progressed to graft loss despite this reduction. Malignancy occurred in 5 out of the 6 patients (83%; P<.0001 compared with patients without PVAN), including transitional cell carcinoma (n=2), renal cell carcinoma (n=1), squamous cell carcinoma of skin (n=1) and Kaposi sarcoma (n=1). We concluded that kidney transplant patients with PVAN are at a significantly greater risk to develop malignancy. Whether this is due to a direct effect of PV infection or the result of overimmunosuppression remains to be determined in a future study.
Transplantation Proceedings 04/2010; 42(3):817-8. · 1.00 Impact Factor
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ABSTRACT: 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<.01). We concluded that HSCs may reduce T-cell proliferation against alloantigens and suppress acute GVHD to prolong recipient survival. Our study sheds some light on the immunosuppressive nature of the liver, suggesting a biological manipulation of alloreactivity for transplantation medicine.
Transplantation Proceedings 04/2010; 42(3):971-5. · 1.00 Impact Factor
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ABSTRACT: The efficacy of sirolimus is strictly dose-dependent; an inappropriate exposure may cause either rejection episodes or drug toxicity. The variability of sirolimus trough levels (C0) may also have an impact on renal allograft function. We prospectively evaluated the impact of the dose-normalized C0 of sirolimus and the intrapatient coefficient of variation (% CV) on renal allograft function at 6 months after the administration of sirolimus to kidney transplant recipients with chronic allograft nephropathy (CAN). We enrolled 51 recipients with CAN who were treated with sirolimus. The dose-normalized C0 of sirolimus was 3.8 +/- 1.9 ng/mL/mg. The intra- and interpatient variabilities of sirolimus C0 were 26.1% and 51.9%, respectively. Based on receiver operating characteristic analysis, patients were divided into 2 groups: group I, sirolimus % CV <22.9% (n = 36) versus group II, sirolimus % CV >22.9% (n = 15). Patients in group II experienced significantly greater risk for progressive deterioration of allograft function (group I vs group II: 11.1% vs 73.3%; P < .05). Multiple logistic regression analysis revealed that higher baseline serum creatinine, but not age, gender, or concomitant immunosuppressants, positively correlated with the sirolimus % CV. In conclusion, both higher baseline serum creatinine and higher intraindividual variability of sirolimus C0 impact the outcome of renal allograft function in CAN. Thus, we suggest that close monitoring of sirolimus C0 is necessary for recipients treated with sirolimus, especially for patients with CAN.
Transplantation Proceedings 10/2008; 40(7):2202-5. · 1.00 Impact Factor
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ABSTRACT: Emphysematous pyelonephritis is a rare, severe gas-forming infection of the kidney. Herein we report a case of a 51-year-old man who had received a cadaveric renal transplant 12 years ago. Post-transplant diabetes mellitus occurred 8 years later. He experienced urinary tract infection with graft pain one week before admission and presented with septic shock at the emergency room. Plain X-ray of the abdomen showed retroperitoneal air. A computed tomography scan of the abdomen showed retroperitoneal and extraperitoneal air being released from the graft kidney. These findings were compatible with extensive emphysematous pyelonephritis. The patient underwent percutaneous drainage. Blood culture and urine culture yielded Escherichia coli. After repeated percutaneous drainage and strong antibiotics for a prolonged period, the patient finally recovered.
Clinical nephrology 08/2007; 68(1):42-6. · 1.17 Impact Factor
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ABSTRACT: Chronic allograft nephropathy (CAN) is characterized by a progressive deterioration of renal function with various degrees ofproteinuria. Currently, there is no effective treatment despite the introduction of new generations of immunosuppressants. Pentoxifylline (PTX) is a phosphodiesterase inhibitor that possesses antiproteinuric effect and has been proved to be effective in treating several glomerular diseases. The purpose of the current study was to examine the effect of PTX on renal transplant patients with established CAN.
Renal transplant recipients with biopsyproven CAN were recruited for the study. All the patients had been on angiotensin-converting enzyme inhibitor or angiotensin receptor blocker for more than 1 year and were on a triple immunosuppressive regimen including corticosteroid, calcineurine inhibitor and mycophenolate mofetil. PTX in a dose of 1,200 mg/day was administered for at least 6 months. The following parameters were assessed at baseline, the 3rd and the 6th month post treatment: systolic and diastolic blood pressure, number of anti-hypertension drugs, serum creatinine (sCr),estimated glomerular filtration rate (eGFR), 24-hour urinary protein excretion (U/P), urinary N-acetylglucosaminidase (NAG) and intracytoplasmic Thl/Th2 cytokines production of peripheral blood CD4+ cells.
A total of 17 (11 male and 6 female) patients were enrolled in the study. The mean duration of follow-up post transplant was 10.6+/- 4.4 years. The baseline data of sCr, eGFR and U/P were 1.83+/-0.46 mg/dl, 38+/-8 ml/min and 2.65+/-2.15 g/day, respectively. Corresponding values at the 3rd and 6th month post treatment were 1.90+/-0.43 mg/dl (p = NS), 33+/-7 ml/min (p=NS), 2.13 +/-1.13 g/day (p < 0.05) and 2.03+/-0.64 mg/dl (p < 0.05), 32+/-10 ml/min (p < 0.05), 2.74 +/-0.93 g/day (p = NS), respectively. When individual data were analyzed, five cases (29.4%) showed a U/P significant reduction of more than 50% of baseline value, while in 10 cases (58.8%) the graft function remained either stable (9 cases) or improved (1 case) at the end of treatment. Urinary NAG was elevated at the 3rd month, but stabilized thereafter. The Thl/Th2 intracytoplasmic cytokine pattern of peripheral blood CD4+ cells showed a significant decrease of cells bearing TNF-alpha (15.0+/-14.4% vs 14.2+/-17.0%, p < 0.05) and cells bearing IL-10 (1.60 +/-1.23% vs 0.90+/-0.66%, p < 0.05) at the 3rd month.
In this pilot study, PTX seemed to be temporarily effective in reducing proteinuria. The graft function was stabilized in more than half of patients at the end of follow-up.
Clinical nephrology 04/2007; 67(3):157-63. · 1.17 Impact Factor
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ABSTRACT: Tuberculosis (TB) is one of the major causes of morbidity and mortality worldwide. Post-transplant (post-Tx) TB is a problem in successful long-term outcome of renal transplantation recipients. It is a life-threatening opportunistic infection that is frequently encountered, but the diagnosis is often delayed. With the emergence of newer potent immunosuppressive regimens and an increased incidence of TB in the general population, post-Tx TB among transplant recipients can be anticipated. Our objective was to describe the pattern and risk factors of TB infection, and the prognosis in an endemic area.
This study was a retrospective review of the records of 756 renal transplant recipients in our hospital during the period from January 1983 to December 2003. The demographic data, transplant characteristics, clinical manifestations, diagnostic criteria, treatment protocol, and long-term outcome of this cohort of patients were analyzed.
Thirty-one episodes developed into TB in 29 patients (3.8%) with a mean age of 45.5 (range: 24.2-66.2) years and a mean post-Tx period of 57.9 (range: 1.2-145.2) months. The forms of the diseases were pulmonary in 22/31 (71%), disseminated in 1/31 (3%), miliary in 1/31 (3%), and extrapulmonary in 7/31 (23%). All patients initially received 4-drug combination therapy, and then dosage was adjusted based on clinical condition. Because of drug interaction, a mean 2-fold increase in the dose of calcineurium inhibitor, but no change in steroid, was required. Twenty-two patients (71%) had an elevated creatinine (Cr) level, and 6 (19%) patients did not recover owing to tissue-proof acute rejection (3 cases) and chronic allograft nephropathy (3 cases), respectively, after treatment. The serum Cr level on diagnosis of TB was 1.9+/-0.7 mg/dL; it then deteriorated to 2.4+/-1.5 mg/dL (P=0.134). Hepatotoxicity developed in 11 patients (35.5%) during treatment. Twenty-five patients were successfully treated, 2 patients remain under treatment, and 4 (12.9%) died. Based on univariate analysis, we found the post-Tx TB risk factors were diabetes and more than 3 episodes of rejection, modalities for acute rejection (high-dose steroid and anti-lymphocyte globulin), and maintenance therapy with steroid.
Post-Tx 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 renal transplant patients. The use of optimal immunosuppressive agents to minimize acute rejection seems reasonable to prevent TB infection in endemic areas like Taiwan. More than 9 months of treatment may be necessary to prevent recurrence.
Transplant Infectious Disease 10/2006; 8(3):148-56. · 2.22 Impact Factor
