Influence of cytokine gene polymorphisms on graft rejection in Turkish patients with renal transplants from living related donors

Introduction

Certain cytokine gene polymorphisms (CGPs) have been shown to be associated with renal transplant rejection or graft outcomes. We sought to evaluate the relationship between gene polymorphisms in patients with acute rejection episodes (rejection group, RG, n = 19) versus those with stable graft function (nonrejection group, NRG, n = 71) in comparison with healthy control subjects (HCG, n = 150). The follow-up time period was 18 months. In the present study, 22 single nucleotide polymorphisms distributed across 13 cytokine and cytokine receptor genes were genotyped by polymerase chain reaction sequence-specific primers (PCR-SSP) using the Heidelberg kit.

Results

The interleukin-2 (IL-2) TT/GT haplotype was observed among 36.8% of patients in the RG and 6.7% of those in the HCG but not in any NRG patient (P < .0001; .0007). The IL-2 GG/TT haplotype was observed among 13 NRG and 9 HCG patients (P = .007). The IL-2 GG/GG haplotype was noted in 18.7% of HCG and 4.2% of NRG patients (P = .0033) and the IL-2 TT/TT haplotype in 5 and 8 patients of NRG and HCG, respectively, but not in any RG patient (P > .05). The transforming growth factor beta1 CG/CC haplotype was noted in 15 NRG (21.1%) and 4 HCG patients but not any RG (P < .0001). The IL-2 + 166 GT genotype was detected in 36.8% of RG, 8.5% of NRG, and 14.7% of HCG patients (P = .005, .0244). The IL-2 −330 GG genotype was demonstrated in 32 healthy controls and 3 nonrejection transplant patients (P = .0007). Significant differences were found between NRG and HCG for IL-6 565 AG, IL-1 beta −511 TT and +3962 CC/CT/TT genotypes.

Discussion

We observed significant differences among the frequencies of IL-2 gene polymorphisms between the RG and the NRG, which were consistent with previous clinical but not in vitro studies.     

Human leukocyte antigen and major histocompatibility complex class I-related chain a antibodies after kidney transplantation in Turkish renal transplant recipients

Background

This study was designed to determine whether human leukocyte antigen (HLA) and major histocompatibility complex class I chain-related A (MICA) antibody (Ab) production during the first 6 months posttransplantation correlated with long-term graft survival and rejection rate. The study group included 147 first transplantations from either living related (LRDs) or deceased donors (DDs) who were divided into two subgroups: rejection (RG, n = 28) and nonrejection (NRG, n = 119). Serum samples (n = 441) collected from each patient on posttransplant days 30, 90, and 180 were tested for HLA and MICA Ab using the Luminex technique.

Results

Among 82 Ab-positive patients (55.8%), 40 had both HLA and MICA, 33 only HLA, and 9 only MICA Ab in the posttransplant period. The rates of HLA class I, class II, or both Ab positivities were greater in the RG than the NRG (P = .011, .037, and .0275, respectively). At 180 days posttransplant, 64.3% of patients in the RG had Ab and 41.2% in the NRG (P = .0349). The data for the LRD (n = 116) group were similar to those for the entire group; whereas there was no significant difference in Ab positivity between RG and NRG patients who received organs from DDs. There was no significant difference with respect to HLA class II and/or MICA Ab positivity between RG and NRG among patients who lacked HLA class I Ab.

Discussion

We confirmed that HLA and MICA Ab may be harmful posttransplant, promoting rejection processes and representing an important cause of graft failure. HLA class II and MICA Ab positivities were only important predictors of graft failure when present together with HLA class I positivity. Patients who developed HLA alone or both HLA and MICA Ab rejected their grafts more frequently than Ab-negative recipients.     

Adiponectin gene polymorphisms are associated with posttransplantation diabetes mellitus in Chinese renal allograft recipients

Background

Posttransplantation diabetes mellitus (PTDM) is a well-recognized renal transplantation complication that is associated with increased graft loss, morbidity, and mortality. Adiponectin gene polymorphisms are associated with type 2 diabetes. However, it remains unknown whether these polymorphisms increase the risk for development of PTDM. Therefore, the aim of this study was to investigate the association between the adiponectin gene polymorphism and the risk of PTDM among Chinese renal allograft recipients.

Methods

We genotyped 398 unrelated renal allograft recipients without a prior diagnosis of diabetes, including 97 PTDM and 301 without PTDM, for adiponectin gene variants: single nucleotide polymorphisms at position 45 and 276, that is, SNP-45: T/G, SNP-276: G/T, using the polymerase chain reaction-restriction fragment length polymorphism assay. No prisoners or organs from prisoners were used in the study.

Results

The G allele of SNP-276 was significantly more frequent in PTDM than non-PTDM subjects (P = .041). For SNP-45 and SNP-276, the incidence of PTDM was significantly higher in patients with the GG genotype than those with the TG and TT genotypes (48.1% vs 21.5% and 23.6% and 30.7% vs 18.5% and 22.8%; (P = .011 and .024, respectively). Even after adjusting for age and sex, the effects of the SNP-45 genotypes for GG compared to TT (odds ratio [OR] = 3.108, P = .009) and GG compared to TG (OR = 3.620, P = .004) as well as for SNP-276 genotypes GG compared to TG (OR = 2.203, P = .002) and body mass index at transplantation (OR = 1.099, P = .024) remained significant.

Conclusions

These data suggested that SNP-45 and SNP-276 of the adiponectin gene were significantly associated with an increased risk for PTDM among Chinese renal allograft recipients.     

Influence of interleukin-6 promoter polymorphism -174 g/c on kidney graft outcome

Background

The cytokine interleukin-6 (IL-6) is important in both immune responses and cardiovascular diseases. The IL-6 promoter polymorphism −174 G/C is associated with increased plasma concentrations of IL-6. The relationship between IL-6 polymorphisms and graft survival, cardiovascular events, and new-onset diabetes mellitus after kidney transplantation is controversial.

Objective

To analyze whether IL-6 (−174 G/C) polymorphism influences kidney graft survival or development of chronic allograft nephropathy, cardiovascular events, or new- onset diabetes.

Methods

The IL-6 promoter polymorphism (−174 G/C) was analyzed using the polymerase chain reaction with sequence-specific primers in 335 kidney transplant recipients. Data for graft survival, chronic graft nephropathy, cardiovascular events, and new-onset diabetes were obtained retrospectively from clinical records. Categorical variables were compared between individuals with CC, GG, and GC genotypes using χ² tests. Survival analysis was performed using the Kaplan-Meier method, comparing groups using the log-rank test.

Results

No significant differences were observed in 5-year graft survival between individuals with CC and GC/GG genotypes (85.3% vs 77.1%; P = .22). Nor were significant differences noted in the rates of chronic allograft nephropathy (37.5% vs 33.8%; P = .48), cardiovascular events (10.0% vs 23.0%; P = .10), or new-onset diabetes (7.5% vs 11.8%; P = .28).

Conclusion

There is no association between IL-6 (−174 G/C) polymorphism and graft survival or development of chronic allograft nephropathy, cardiovascular events, or new- onset diabetes.     

Clinical characteristics and outcomes of renal transplantation in elderly recipients

Background

Elderly renal transplant candidates constitute one the fastest-growing populations among end-stage renal disease patients. Since the impacts of advanced recipient age have not yet been fully defined, we evaluated the clinical characteristics and outcomes of elderly renal transplant recipients.

Methods

Among 564 adult renal transplant recipients, at our center between 2000 and 2009, 64 were at least 60 years of age (Elderly group), and 500 were younger than 60 years (Young group) at the time of the procedure. We compared their clinical features and surgical management.

Results

There were significant differences in mean donor age (55.6 years vs. 53.2 years, P = .030) and gender mismatch (77.0% vs. 63.4%, P = .035). However, there were no significant differences between the two groups in patient and graft survivals (P = .177 and P = .365, respectively). Malignancy after transplantation was a significant risk factor upon univariate evaluation but only ABO incompatibility upon multivariate analysis of patient and graft survival. The main cause of graft loss among the Elderly group was death with a functioning graft due to heart failure.

Conclusions

Renal transplantation is a feasible, safe option for the elderly and should be actively implemented. However, screening for cancer and heart disease should be mandatory to improve outcomes.     

High incidence of postoperative bowel obstruction in newborns and infants

Background

Postoperative bowel obstruction (PBO) plagues patients of all ages after intraabdominal surgery. We examined the incidence, risk factors, and the need for operative intervention of PBO.

Methods

We reviewed all children who underwent a laparotomy or laparoscopy. Parameters included age, diagnosis, type and number of procedures, complications, time interval to PBO, treatment of PBO, morbidity, and mortality.

Results

From 2001 to 2005, 2187 abdominal operations were performed. Overall, 61 patients (2.8%) developed a PBO; 43 (70.5%) required reoperation. Postoperative bowel obstruction was more common in patients younger than 1 year (28/601, 4.7%) compared with older children (33/1586, 2.1%; P = .01, β = .80). In infants, PBO was not influenced by initial diagnosis (P = .26) or whether the initial operation was clean/clean-contaminated or contaminated/dirty (P = .12). In children older than 1 year, nonoperative treatment was more likely to be successful if PBO occurred within 12 weeks of initial operation (12/16 vs 3/14; P = .01). In contrast, all but one infant (16/17) with early PBO required reoperation.

Conclusion

The incidence of PBO is significantly higher in newborns and infants than in older children (who have rates comparable to those reported in adults). Infants are significantly more likely to require operative intervention, particularly if PBO occurs early after the initial operation.     

Preincisional local infiltration of tramadol at the trocar site versus intravenous tramadol for pain control after laparoscopic cholecystectomy

Study Objective

To compare the effects of preoperative intravenous (IV) tramadol and preoperative tramadol infiltration of trocar sites on postoperative pain and postoperative nausea and vomiting (PONV) after laparoscopic cholecystectomy.

Design

Prospective, randomized study.

Setting

Operating room, recovery room, and surgical ward.

Patients

70 ASA physical status 1 and 2 patients, aged 20-70 years, scheduled for elective laparoscopic cholecystectomy.

Interventions

In Group I, patients received IV 2.0 mg/kg of tramadol; in Group II, trocar insertion points were infiltrated with 2.0 mg/kg of tramadol in 20 mL of 0.9% NaCl.

Measurements

Pain scores, sedation scores, postoperative analgesic requirement, and PONV were recorded at 0 and 30 minutes and one, three, 6, 12, and 24 hours. At 30 minutes and one hour, pain localization (incisional or diffuse abdominal) was also recorded.

Main Results

Visual analog scale scores at 30 minutes were significantly lower in Group II [3 (0-7)] than Group I [6 (3-8)] (P < 0.001). In Group I, 91.4% of patients received sodium diclofenac, while 68.6% of Group II patients received sodium diclofenac (P = 0.002). The time to first analgesic requirement was significantly lower in Group II (P = 0.004). At the 30-minute measurement time, a significant difference was recorded between the groups in incisional pain (P < 0.001). There was also a significant difference between groups in the frequency of PONV.

Conclusions

Trocar site infiltration of tramadol improves early postoperative pain and decreases PONV.     

Angiotensinogen t235 and angiotensin-converting enzyme insertion/deletion polymorphisms associated with the development of posttransplantation diabetes mellitus in renal allograft recipients

Background

Genetic polymorphisms of the renin-angiotensin system (RAS) have been reported to play an important role in the pathogenesis of diabetes mellitus and hypertension. In addition, a close association has been reported between RAS and the progression of both diabetes and hypertension. But the role of RAS on the development of posttransplantation diabetes mellitus (PTDM) is not known. For this purpose we investigated the association of polymorphisms in the genes for angiotensin-converting enzyme (ACE) and angiotensinogen (AGT) with the development of PTDM.

Methods

Genotyping for ACE insertion/deletion (I/D) and AGT M235T polymorphisms was performed in 50 patients who underwent renal transplantation during a 5-year period. Group 1 consisted of 23 recipients who developed PTDM and group 2 consisted of 27 recipients that did not have PTDM.

Results

Of 50 patients, 13 (26%) showed the ACE DD, 21 (42%) the ACE ID, and 16 the ACE II genotype. The frequencies of AGT MM, AGT MT, and AGT TT were 0, 54%, and 46%, respectively. Compared with group 2, there were high frequencies of the AGT TT genotype in group 1 recipients (P < .001). In addition the ACE DD genotype was found significantly higher in group 1 patients compared with group 2 patients (P = .001).

Conclusion

The high frequencies of the AGT TT genotype and ACE DD genotype in recipients may contribute to the high prevalence of PTDM. Our data suggest a synergistic effect between the ACE and AGT polymorphism in the risk of PTDM, but to support this theory a larger patient group must be studied.     

The influence of flourodeoxyglucose positron emission tomography on the management of gastroesophageal junction carcinoma

Background

The influence of positron emission tomography (PET) scanning with flourodeoxyglucose (FDG) on decision making for the treatment of patients with esophagogastric junction (EGJ) carcinoma is unclear as is the utility of the maximum standardized uptake value (SUV) as a prognostic indicator.

Methods

This study was a retrospective review of EGJ carcinoma cases at a single institution during a 5-year period.

Results

FDG-PET altered treatment in 13 of 64 patients (20%). Of these, 21 patients had PET scans before and after undergoing neoadjuvant chemoradiation (CRT) as well as surgery. Patients who had a decrease in SUV >50% had a 12-month disease-free survival advantage over patients a decrease in SUV <50% (93% vs 43%, P = .025).

Conclusions

FDG-PET alters treatment in a significant number of patients with EGJ carcinoma. A >50% decrease in SUV after CRT is associated with an improved prognosis.     

Impact of early lymph node procurement to facilitate histocompatibility testing on long-term cadaveric kidney graft survival

Background

Prolonged cold ischemia time (CIT) is a clinically important causes of delayed graft function (DGF) after kidney transplantation. As DGF has been previously shown to have a deleterious influence on long-term graft survival, in the present study we analyzed the impact of early lymph node (LN) procurement on CIT, HLA mismatches, and long-term kidney graft outcome.

Materials and Methods

We evaluated 394 consecutive cadaveric procedures performed from 2001 to 2006, including 289 recipients, in whom LN were obtained before kidney procurement seeking to shorten the total time for HLA typing and crossmatch procedures.

Results

During 58 ± 6 months, 24 patients died (918 [8.3%] in the early and 6 [5.7%] in late procurement group, P = ns) and 52 lost their kidney grafts (31 [10.7%] vs 21 [20%]; P = .025). Early procurement of LN performed in 73.4% of all kidney graft recipients shortened CIT by almost 7 hours (22.9 vs 16.1 hours; P < .001), with a nonsignificantly lower incidence of DGF (32.2% vs 41.0%; P = .13). However, a Cox proportional hazards regression model revealed that early procurement reduced the risk of death-censored kidney graft loss by roughly 40% (log-rank, P = .013).

Conclusion

Early LN procurement in significantly shorten CIT and subsequently reduced the risk of long-term kidney graft loss.     

Heat Shock Protein Polymorphism Predisposes to Urinary Tract Malformations and Renal Transplantation in Children

Background

Anatomical malformations of the kidney and urinary tract account for 17% of pediatric renal transplantation procedures. Heat shock proteins (HSPs) are molecular chaperones with a protective function that promotes cell survival. HSP72 is an endogenous ligand for toll-like receptor TLR4, thereby stimulating innate immunity. Both in adults and children, decreased expression of HSP70s is associated with a number of kidney diseases.

Objective

To assess the prevalence of HSPA1A G(190)C, HSPA1B A(1267)G, and TLR4 A(896)G polymorphisms in children who had undergone kidney transplantation.

Patients and Methods

Genotypes were analyzed using allele-specific polymerase chain reaction in 41 pediatric recipients. Allelic prevalence was related to reference values in 65 age- and sex-matched healthy children.

Results

Clinical data did not reveal a difference between any of the groups. HSPA1B (1267)GG genotype and HSPA1B (1267)G allele were observed more frequently in the transplant recipients compared with the control group: AA vs AG: odds ratio [OR], 12.6; 95% confidence interval [CI], 1.58-100.0; P = .004; AA vs GG: OR, 20.80; 95% CI, 2.32-187.00; P = .01; and A vs G: OR, 2.10; 95% CI, 1.19-3.07; P = .01. Furthermore, the prevalence of the HSPA1B (1267)GG genotype was greater in transplant recipients with vs without urinary tract malformations: AG vs GG: OR, 0.10; 95% CI, 0.09-0.48; P = .007. No differences were observed in the other studied polymorphisms.

Conclusion

Our findings suggest an association between the carrier status of HSPA1B (1267)G with urinary tract malformations, leading to end-stage renal disease requiring kidney transplantation. This observation raises further questions about the clinical and therapeutic relevance of this polymorphism to pediatric nephrology.     

A high model for end-stage liver disease score should not be considered a contraindication to living donor liver transplantation

Objective

To analyze the outcomes of patients with high Model for End-Stage Liver Disease (MELD) scores who underwent adult-to-adult live donor liver transplantation (A-A LDLT).

Materials and Methods

From September 2002 to October 2010, a total of 152 adult patients underwent A-A LDLT in our institution. Recipients were stratified into a low MELD score group (Group L; MELD score ≤30) and a high MELD score group (Group H; MELD score >30) to compare short-term and long-term outcomes.

Results

Of the 152 adult patients who underwent A-A LDLT, 9 were excluded from the analysis because they received ABO-incompatible grafts. Group H comprised 23 and Group L 120 patients. The median follow-up was 21.5 months (range, 3 to 102 m). The mean MELD score was 15.6 in Group L and 36.7 in Group H. There were no significant differences in the mean length of stay in the intensive care unit (Group L: 3.01 days vs Group H: 3.09 days, P = .932) or mean length of hospital stay (Group L: 17.89 days vs. Group H: 19.91 days, P = 0.409). There were no significant differences in 1-, 3-, or 5-year survivals between patients in Groups L versus H (91.5% vs 94.7%; 86.4% vs 94.7%; and 86.4% vs 94.7%; P = .3476, log rank).

Conclusion

The short-term and long-term outcomes of patients with high MELD scores who underwent A-A LDLT were similar to those of patients with low MELD scores. Therefore, we suggest that high MELD scores are not a contraindication to LDLT.     

Serine Protease Inhibitor Aprotinin Ameliorates Renal Injury in a Rat Model of Ischemia-Perfusion Injury

Background

Renal ischemia-reperfusion (I/R) injury may occur after renal transplantation, thoracoabdominal aortic surgery, and renal artery interventions.

Objective

To investigate the therapeutic effects of aprotinin on tissue protection against I/R injury in a rat model. N-acetylcysteine (NAC), a potent antioxidant, was also tested to assess the experimental model.

Materials and Methods

Twenty-four rats were categorized into 3 groups of 8 rats each: those receiving isotonic sodium chloride solution (control group); NAC, 150 mg/kg; and aprotinin, 40,000 KIU/kg. The animals underwent unilateral nephrectomy after 60 minutes of warm ischemia and 60 minutes of reperfusion of the kidney. Malondialdehyde, a lipid peroxidation marker, and antioxidant glutathione levels were measured in the kidney parenchyma. Tissue samples were obtained for histologic analysis.

Results

Compared with the control group, the NAC group demonstrated significantly low levels of malondialdehyde (P = .04) and high levels of glutathione (P = .01). At histopathologic analysis, less acute tubular necrosis (ATN) and cellular swelling was noted in the NAC group (P = .002 and P = .005, respectively). In the aprotinin group, histopathologic analysis revealed less tissue damage in terms of ATN (P < .001, cellular swelling (P < .001), and vacuolysis (P = .002). Compared with the NAC group, ATN (P = .01), vacuolysis (P = .04), and congestion (P = .05) were significantly less in the aprotinin group.

Conclusions

Our results suggest that administration of aprotinin attenuates renal I/R injury. This observation has potential application for kidney preservation for transplantation, for aortic surgery, and for renal artery interventions by protecting cells from free radical damage.     

Oesophageal atresia: improved outcome in high-risk groups?

Purpose

The Spitz classification of oesophageal atresia (OA) based on the birth weight and the presence of a major cardiac anomaly was proposed 1994. Advances in neonatal care have led us to question if these outcome figures are still valid. We tested the hypothesis that the outcome of neonates with OA has improved during the last decade.

Methods

The records of all neonates (n = 188) born with OA and treated in a single institution between 1993 and 2004 were reviewed and compared with data from the original Spitz study. Data were obtained on the birth weight, presence of a major cardiac anomaly, and survival. Differences in survival were compared using the Yates-corrected χ² test.

Results

In the early period, 326 neonates survived (87.6%) compared with 174 (91.5%) in the most recent decade (P = .10). Based on Spitz classification, the outcome comparing both periods was the following: group I, 97% (283/293) and 98.5% (130/132) (P = .44); group II, 59% (41/70) and 82% (41/50) (P = .01); group III, 22% (2/9) and 50% (3/6) (P = .57), respectively.

Conclusions

The Spitz classification remains valid. It may be of use when counselling parents and in comparing outcome among centres. In our centre, the overall survival of neonates with OA has not significantly changed in the recent decade. The improvement in survival of neonates in group II, however, demonstrated the recent advances in neonatal, paediatric surgical, and cardiac care.     

The estrogen receptor α gene (XbaI,PvuII) polymorphisms and susceptibility to idiopathic scoliosis: a meta-analysis

Study design

A genetic association meta-analysis of estrogen receptor α gene (ERα) polymorphisms with idiopathic scoliosis.

Objective

To determine whether the ERα gene polymorphisms correlate with idiopathic scoliosis.

Summary of background data

Idiopathic scoliosis represents a complex genetic trait under the influence of multiple predisposition genes. Several studies showed that single nucleotide polymorphism (SNP) in ERα was associated with idiopathic scoliosis, but the results from some studies were conflicting.

Methods

We searched PubMed, EMBASE, and Cochrane CENTRAL databases from January 1994 to January 2014. All the case–control studies included should mainly study the relationship between XbaI A/G, PvuII T/C polymorphisms and the susceptibility of idiopathic scoliosis.

Results

A total of 299 articles were found, six of which fulfilled the inclusion criteria after being assessed by two reviewers. A pooled odds ratio (OR) with 95 % confidence interval (95 % CI) was calculated to assess the associations. Subgroup meta-analyses were performed according to ethnicity. Overall, ERα Xbal A/G polymorphism was not associated with risk of idiopathic scoliosis (G versus A, OR 1.07, 95 % CI 0.88–1.30, P = 0.51; AG versus AA, OR 1.03, 95 % CI 0.89–1.21, P = 0.67; GG versus AA, OR 1.12, 95 % CI 0.72–1.73, P = 0.61; AG/GG versus AA, OR 1.05, 95 % CI 0.91–1.22, P = 0.49; GG versus AG/AA, OR 1.10, 95 % CI 0.75–1.63, P = 0.62). ERα PvuII T/C polymorphism was also not associated with risk of idiopathic scoliosis under five models (C versus T, OR 0.93, 95 % CI 0.75–1.14, P = 0.48; TC versus TT, OR 0.99, 95 % CI 0.80–1.23, P = 0.93; CC versus TT, OR 1.05, 95 % CI 0.80–1.39, P = 0.72; TC/CC versus TT, OR 1.01, 95 % CI 0.83–1.23, P = 0.93; CC versus TC/TT, OR 1.05, 95 % CI 0.82–1.33, P = 0.72).

Conclusion

ERα Xbal and ERα PvuII polymorphisms are not obviously associated with risk of idiopathic scoliosis.     

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-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.

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-1β, GLUT-1, and MTHFR.

Conclusions

The G/G genotype of IL-6 may play an important role to lower the risk for PTDM development.     

Inflammation, metalloproteinases, and growth factors in the development of carotid atherosclerosis in renal transplant patients

Background

Cardiovascular disease is the leading cause of death in renal transplant (RT) patients. Both traditional and emerging risk factors, some of which are controversial, have been described in the pathogenesis of cardiovascular disease. Carotid ultrasound (CUS) is considered to be an excellent diagnostic tool for subclinical atherosclerosis.

Objective

To evaluate the relationship between biomarkers of inflammation, growth factors, metalloproteinases, and the development of subclinical atherosclerosis diagnosed by using CUS.

Methods

We studied 93 RT patients (aged 54 ± 12 years; 67.9% men; 13.5% with pre-RT diabetes mellitus). The following biomarkers were determined in the patients' blood hours before RT: C-reactive protein (CRP) and serum amyloid A using nephelometry; interleukin (IL) 2, 6, 8, and 10 and soluble IL-2 receptor, tumor necrosis factor (TNF) α, vascular endothelial growth factor (VEGF), epidermal growth factor, and monocyte chemotactic peptide using chemoluminescence; and pregnancy-associated plasma protein (PAPP)A using ELISA. A CUS was carried out during the first month after RT.

Results

Carotid intima-media thickness (IMT) was elevated in 51% of the patients, and 50.5% of the patients had atherosclerotic plaque. Both plaque (P = .004) and IMT (P = .001) correlated with age, and the increase of IMT was progressive, on both the left and the right side. Pre-RT CRP, IL-8, TNF-α, VEGF, MCP-1, and PAPP-A were significantly more elevated in patients with plaque. In the multivariate analysis adjusted for clinical variables, age (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.01-1.10; P = .04), CRP (OR, 7.5; 95% CI, 2.05-27.3; P = .002), IL-8 (OR, 4.73; 95% CI, 1.27-17.6; P = .02), and PAPP-A (OR, 4.45; 95% CI, 1.22-16.2; P = .023) were independent markers of the presence of plaque.

Conclusions

Age, CRP, IL-8, and PAPP-A, and not growth factors, are markers of carotid atheromatous plaque in RT patients.     

Total thyroidectomy for benign disease in the pediatric patient—feasible and safe

Purpose

Total thyroidectomy (TT) is a safe and efficacious treatment of malignant thyroid disease in children. The role of TT in benign thyroid disease is less well-defined. The goal of this study was to compare the safety of TT performed for benign and malignant disease.

Methods

The medical records of 31 patients undergoing TT from January 2000 to June 2007 at a single center were reviewed. The benign cohort totaled 15 patients consisting of 12 with Graves' disease, 2 with hyperthyroidism, and 1 with large and symptomatic multinodular goiter. The malignant cohort totaled 16 patients consisting of 9 with malignant disease, 4 with a nodule and history of cancer or radiation exposure, and 3 with RET proto-oncogene mutations.

Results

The most common complication was transient hypocalcemia observed in 7 (46%) of 15 patients with benign disease and 9 (56%) of 16 patients with malignancy (P = .72). Permanent hypocalcemia, defined as need for calcium supplement 6 months postprocedure, was observed in 1 patient with benign disease (6.67%) and 1 patient with malignancy (6.25%; P = 1.0). A single parathyroid gland was reimplanted in 2 patients with malignancy and 2 patients with benign disease (P = 1.0). One case of keloid scar was noted, and no cases of recurrent laryngeal nerve palsy, nerve paralysis, tracheal injury, tracheostomy, or wound infection were encountered in either cohort. There were no cases of relapse hyperthyroidism in the benign cohort.

Conclusions

Similar rates of postoperative complications can be expected with TT for benign thyroid disease as compared to TT for malignant disease. Total thyroidectomy is a safe treatment option for benign thyroid disease in children.     

Serum levels of interleukin (IL)-10, IL-17, transforming growth factor (TGF)-β1, and interferon-γ cytokines and expression levels of IL-10 and TGF-β1 genes in renal allograft recipients after donor bone marrow cell infusion

Background

Cytokine storm generated by an alloimmune response after transplantation can lead to either graft survival or rejection. The aim of this study was to evaluate the serum levels of interleukin (IL)-10, IL-17, transforming growth factor (TGF)-β1, and interferon (IFN)-γ and expression levels of IL-10 and TGF-β1 in renal allograft recipients with or without donor bone marrow cell infusion (DBMI).

Methods

We retrospectively followed 28 living unrelated kidney recipients, including 14 with and 14 without DBMI infusion for 2 years. Also, 14 healthy subjects were included as a normal control group. PBMC gene expression analysis for mRNA levels of IL-10 and TGF-β1 cytokines relative to β-actin as a reference gene was performed using quantitative fluorescence real-time polymerase chain reaction at the end of 2 years posttransplantation. Also, serum levels of IL-10, TGF-β1, IFN-γ, and IL-17 in the 3 groups were measured by enzyme-linked immunosorbent assay at the same time.

Results

Both patient groups showed increased gene expression and serum content of IL-10 compared with normal controls. The expression levels were only significant between control patients and normal subjects (P = .02). Serum levels of IFN-γ and IL-17 were higher in untreated patients compared with normal controls (P = .03 and P = .07, respectively). DBMI patients showed significantly lower levels of serum TGF-β1 and IL-17 compared with normal subjects (P = .05 and P = .06, respectively). Also, infused patients showed a positive correlation between circulating levels of IL-17 and IL-10 (r = 0.692; P = .006), and an inverse correlation between serum creatinine and TGF-β1 levels (r = −0.580; P = .03).

Conclusion

The decreased levels of inflammatory cytokines besides IL-10 with increased TGF-β1 levels and better allograft function with improved clinical outcomes were observed among infused patients, possibly indicating immunomodulatory effects of this approach in kidney allograft patients.