Preliminary report of a nationwide case-control study for identifying risk factors of tuberculosis following renal transplantation

Background. Tuberculosis (TB) is an important infection encountered posttransplantation, especially among patients in developing countries, where there are high incidences of morbidity and mortality. Materials and Methods. One hundred and twenty subjects (1) from 15 major kidney transplantation centers in Iran from 1984 to 2003 were compared with 440 controls who were matched for operative time, treatment center, and surgical team. Results. Mean ages of research subjects and controls were 38.6 and 36.6 years (P = .04), respectively. The mean duration of pretransplantation hemodialysis was 29 months (range, 2 to 192 months) in research subjects and 20 months (range, 1 to 180 months) in controls (P = .003). Positive past history of tuberculosis was detected in 4 (3.3) research subjects and in 7 (1.5) controls (P = .2). Fifty-two research subjects (43.3) and 241 controls (54.8) had pretransplantation purified protein derivative of tuberculin less than 5 mm (P = .02). Mean dosages of initial and maintenance immunosuppressive drugs in research subjects and in controls were not significantly different. Sixty research subjects (50) and 152 controls (34.5) had rejection prior to diagnosis of TB (P = .03). Conclusion. To our knowledge, this is the first study that demonstrates an increased risk of posttransplant TB by prolonged duration of pretransplant hemodialysis and number of posttransplant rejection episodes. Further study is needed to clarify these findings specifically with respect to various immunosuppressive regimens. © 2005 by Elsevier Inc. All rights reserved

Dynamic variation of kidney injury molecule-1 mRNA and protein expression in blood and urine of renal transplant recipients: a cohort study

BACKGROUND: Acute renal dysfunction still constitutes a highly significant obstacle to renal transplantation outcome. Kidney injury molecule-1 is highly upregulated in proximal tubular cells and shed into the urine and blood circulation following kidney injury. The aim of current cohort study was to evaluate the urine KIM-1 (uKIM-1) mRNA expression level and its protein concentration in blood and urine samples to determine whether sequential monitoring of KIM-1 in renal allograft recipients is a reliable biomarker for predicting the clinical status and outcome. METHODS: Both uKIM-1 mRNA expression level and the level of serum and uKIM-1 protein concentration in the 52 renal transplant recipients were respectively quantified using real-time PCR and ELISA methods at 2, 90 and 180 days after transplantation. RESULT: KIM-1 mRNA and protein expression level in the blood and urine samples of patients with graft dysfunction was significantly higher than patients with well-functioning graft on days 2, 90 and 180 after transplantation. Receiver-operating characteristic curve analysis of mRNA and protein expression levels showed that urinary and blood KIM-1 at months 3 and 6 could predict acute renal dysfunction at 6 months and 1 year after transplantation. CONCLUSION: Sequential monitoring of uKIM-1 mRNA expression level and its protein concentration in the serum and urine samples of renal transplant patients suggests that KIM-1 could be a sensitive and specific biomarker for early diagnosis and prognosis of kidney allograft injury

High expression of TIM-3 and KIM-1 in blood and urine of renal allograft rejection patients

Background-T cell immunoglobulin and mucin domain 3 (TIM-3) is involved in alloimmune and autoimmune responses, as well as tolerance induction in kidney transplantation. Kidney injury molecule-1 (KIM-1) is highly expressed in epithelial cells of the injured proximal tubule. In this study, we have investigated both urinary and blood TIM-3 mRNA expressions, urinary KIM-1 mRNA expression, and urinary and serum KIM-1 proteins in renal allograft recipients diagnosed with acute allograft rejection (AR) and chronic allograft dysfunction (CAD), as well as those with well-functioning transplants (WFG). Methods: We divided 85 patients into the following groups: AR (n = 24), CAD (n = 19), and WFG (n = 42). TIM-3 and KIM-1 mRNA expressions were quantified using real-time reverse-transcription TaqMan probe polymerase chain reaction (RT-PCR). An ELISA test was used to measure the amount of KIM-1 protein in serum and urine samples. Results: AR and CAD patients had significantly greater urinary and blood TIM-3 mRNA expressions, urinary KIM-1 mRNA expression, and urinary and serum KIM-1 proteins compared to WFG patients. Receiver operating characteristic (ROC) analysis showed that these molecules discriminated Allograft rejections from WFG. Conclusion: Quantification of TIM-3 and KIM-1 mRNA expressions, along with KIM-1 protein measurements in urine and blood could be employed as promising tools for noninvasive diagnosis of allograft dysfunction

Expression patterns of Toll like receptor (TLR)-2, TLR-4 and myeloid differentiation primary response gene 88 (MYD88) in renal transplant patients developing allograft dysfunction; a cohort study

This cohort intends to determine the sequential dynamic changes in Toll-like receptor (TLR)-4, TLR-2, and myeloid differentiation primary response gene 88 (MYD88) mRNA expressions in PBMCs and biopsy samples from kidney allograft recipients in relation to graft function. This study enrolled 52 renal transplant patients, 27 with well functioning graft (WFG) and 25 graft dysfunction (GD). Peripheral blood samples pre- and post-transplantation (days 2, 90 and 180) were collected to analyze mRNA expression levels of TLR-2, TLR-4, and MYD88 genes in relation to allograft function during one-year follow up. The mean dynamic changes of post-transplant TLR-2, TLR-4, and MYD88 mRNA expressions were significantly higher in GD compared to WFG patients (P = .001). ROC curve analysis based on glomerular filtration rate (GFR) index showed the area under curve (AUC) values for the genes: TLR-2(0.89;P < .001), TLR-4(0.86;P < .001), and MYD88(0.75;P = .003) in the third month post-transplantation for GD diagnosis. The calculated AUCs for the expressions of genes in allograft biopsies were 0.94(TLR-2), 0.95(TLR-4), and 0.98(MYD88) in the sixth month post-transplant based on pathology report (P < .001). Our results indicate that sequential monitoring of the expression patterns of TLR-2, TLR-4, and MYD88 in PBMCs and biopsy samples could be considered as predictive biomarkers for early and late kidney allograft function

Sequential monitoring of TIM-3 mRNA expression in blood and urine samples of renal transplant recipients

BACKGROUND: T cell immunoglobulin and mucin domain 3 (TIM-3), as a co-inhibitory receptor expressed on Th1, Th17, CD8T, FoxP3+Treg and innate immune cells, plays an important role in suppression of T cell-mediated immune responses, tolerance induction and T cell exhaustion. In this study, we evaluated sequential alterations of TIM-3 mRNA expression level in blood and urine samples of renal transplant recipients to predict approaching clinical episodes. METHODS: A total of 52 adult renal transplant recipients (31 male and 21 female) were enrolled in this study. All the patients received kidney transplant from living unrelated donors. TIM-3 mRNA expression in peripheral blood mononuclear cells (PBMCs) and urinary cells were quantified using Real Time TaqMan polymerase chain reaction (PCR) at 4 different time points (pre-transplantation, 2, 90 and 180days post-transplantation). RESULT: TIM-3 mRNA expression level on days 2, 90 and 180 after transplantation was significantly higher in blood and urine samples of patients with graft dysfunction (GD) compared with patients with well-functioning graft (WFG). Our results also showed a high correlation between blood and urinary level of TIM-3 mRNA expression. The data from Receiver Operating Characteristic (ROC) Curve Analysis showed that blood and urinary TIM-3 mRNA expression level at month 3 and 6 could discriminate graft dysfunction (GD) from well-functioning graft (WFG) with high specificity and sensitivity. CONCLUSION: Our data suggested that serial monitoring of TIM-3 mRNA level in the blood and urine samples of renal transplant recipients could be a useful non-invasive biomarker for prediction and diagnosis of allograft dysfunction

The risk factors and laboratory diagnostics for post renal transplant tuberculosis: A case-control, country-wide study on definitive cases

Background. Tuberculosis (TB) is an important cause of morbidity and mortality in renal transplant recipients and, because of its infrequency and the lack of medical awareness, it is usually misdiagnosed. This study was carried out to determine frequency and weight of multiple risk factors for post kidney transplantation TB. Methods. A total of 44 cases (0.3), out of 12,820 patients from 12 major kidney transplantation centers in Iran from 1984 to 2003, were compared with 184 healthy transplant subjects who were transplanted by the same surgical team. Results. The mean age of cases and controls was 37.7 (13-63) and 35.6 (8-67) years (P=0.3), respectively. The mean duration of pre-transplantation hemodialysis was 30.3 (3-168) months in cases and 18.2 (1-180) months in controls (P=0.03). A positive past history of TB was detected in 2 cases and 1 control (P=0.3). The mean doses of initial and maintenance immunosuppressive drugs in cases and controls were not significantly different. A total of 25 cases (56.8) and 60 controls (32.6) had rejection before diagnosis of TB (P=0.004; OR=2.7, CI95: 1.3-5.6). Conclusions. To our knowledge, this is the first study that demonstrated an increase in the risk of post-transplant TB by increasing the duration of pre-transplant hemodialysis and the number of post-transplant rejection episodes as 2 immunocompromised states. Further study is needed to clarify our new findings, specifically in relation to different immunosuppressive regimens. © 2008 Wiley Periodicals, Inc

Risk factors and laboratory diagnostics for post renal transplant tuberculosis: A case-controlled, country-wide study on definitive cases

Background: Tuberculosis (TB) is a common cause of morbidity and mortality in renal transplant recipients. It is usually misdiagnosed because of lack of medical awareness and its infrequency in renal transplant recipients. Materials and Methods: 44 cases (0.3) with post-transplant TB out of 12820 patients who had renal transplants performed between 1984 to 2003 were found from the hospital records of 12 major kidney transplantation centers in Iran. These cases were compared with 184 healthy transplant subjects whose transplants were performed by the same surgical team as the controls. Results: The mean age of cases and controls was 37.7 (13-63) and 35.6 (8-67) years (p=0.3), respectively. The mean duration of pre-transplantation hemodialysis was 30.3 (3-168) months in cases and 18.2(1-180) months in controls (p=0.03). A past history of tuberculosis was detected in 2 cases and 1 control (p=0.3). The mean doses of initial and maintenance immunosuppressive drugs in cases and controls were not significantly different. A total of 25 cases (56.8) and 60(32.6) controls had rejection prior to diagnosis of TB (p=0.004; OR=2.7, Cl95 1.3-5.6). Conclusion: To our knowledge, this is the first study that demonstrated increasing risk of post-transplant TB by extending the duration of pre-transplant hemodialysis and the number of post-transplant rejection episodes. Further study is needed to clarify our new findings specifically in respect of different immunosuppressive regimens. © 2006 NRITLD, National Research Institute of Tuberculosis and Lung Disease, Iran